Lynn Million specializes in the treatment of cancer. She has practiced Radiation Oncology for more than 30 years. Dr. Million has a special interest in the treatment of sarcoma’s of soft tissue, bone and cartilage in children, young adolescents and adults.

Clinical Focus

  • Cancer > Radiation Oncology
  • Cancer > Sarcoma
  • Radiation Oncology
  • Soft Tissue Sarcoma
  • Pediatric cancer
  • Skin cancer
  • Cutaneous lymphoma
  • Lymphoma, Non-Hodgkin
  • Hodgkin Lymphoma
  • Transplant related disease

Academic Appointments

Boards, Advisory Committees, Professional Organizations

  • Soft tissue sarcoma Committe member, Childrens Oncology Group (COG) (2008 - Present)
  • Bone sarcoma panel member, NCCN (2015 - Present)

Professional Education

  • Fellowship: Stanford University Dept of Radiation Oncology (2020) CA
  • Fellowship: Stanford University Dept of Radiation Oncology (1991) CA
  • Internship: Wellstar Atlanta Medical Center Internal Medicine Residency (1987) GA
  • Medical Education: University of Florida Office of Student Affairs (1986) FL
  • Residency: Stanford University Radiation Oncology Residency (1990) CA
  • Board Certification: American Board of Radiology, Radiation Oncology (1991)

Clinical Trials

  • Low-dose (12 Gy) TSEBT+Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides Not Recruiting

    The purpose of this study is to determine if vorinostat combined with low-dose total skin electron beam therapy (TSEBT) offers superior clinical benefit (efficacy & safety) over low-dose TSEBT alone in participants with mycosis fungoides (MF) Treatment in this study is TSEBT +/- vorinostat, with participants stratified by MF stage.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, 650-421-6370.

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  • Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma Not Recruiting

    Non-myeloablative approach for allogeneic transplant is a reasonable option, especially given that the median age at diagnosis is 55-60 years and frequently present compromised skin in these patients, which increases the risk of infection. Therefore, we propose a clinical study with allogeneic hematopoietic stem cell transplantation (HSCT) using a unique non-myeloablative preparative regimen, TLI/ATG, to treat advanced mycosis fungoides/Sezary syndrome (MF/SS).

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Chin, 650-721-4183.

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  • Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery Not Recruiting

    This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether these therapies can be safely combined and if they work better when given together in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa M. Marina, 650-498-7061.

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2023-24 Courses

All Publications

  • Clinical features and outcomes of young patients with low-grade non-rhabdomyosarcoma soft tissue sarcomas treated with a risk-based strategy: A report from Children's Oncology Group study ARST0332. Pediatric blood & cancer Douglass, D. P., Coffin, C. M., Randall, R. L., Yang, Y., Barkauskas, D. A., Million, L., McCarville, M. B., Pappo, A. S., Weiss, A. R., Spunt, S. L. 2024: e31062


    In retrospective analyses, the Pediatric Oncology Group [POG) and the Federation National des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade predict outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), but prospective data on grading, clinical features, and outcomes of low-grade NRSTS are limited.We analyzed patients less than 30 years of age enrolled on Children's Oncology Group (COG) study ARST0332 (NCT00346164) with POG grade 1 or 2 NRSTS. Low-risk patients were treated with surgery alone. Intermediate-/high-risk patients received ifosfamide/doxorubicin and radiotherapy, with definitive resection either before or after 12 weeks of chemoradiotherapy.Estimated 5-year event-free and overall survival were 90% and 100% low risk (n = 80), 55% and 78% intermediate risk (n = 15), and 25% and 25% high risk (n = 4). In low-risk patients, only local recurrence was seen in 10%; none with margins greater than 1 mm recurred locally. Sixteen of 17 intermediate-/high-risk patients who completed neoadjuvant chemoradiotherapy underwent gross total tumor resection, 80% with negative margins. Intermediate-/high-risk group events included one local and seven metastatic recurrences. Had the FNCLCC grading system been used to direct treatment, 29% of low-risk (surgery alone) patients would have received radiotherapy ± chemotherapy.Most low-risk patients with completely resected POG low-grade NRSTS are successfully treated with surgery alone, and surgical margins greater than 1 mm may be sufficient to prevent local recurrence. Patients with intermediate- and high-risk low-grade NRSTS have outcomes similar to patients with high-grade histology, and require more effective therapies. Use of the current FNCLCC grading system may result in overtreatment of low-risk NRSTS curable with surgery alone.

    View details for DOI 10.1002/pbc.31062

    View details for PubMedID 38757485

  • Embryonal sarcoma of the liver in pediatric and young adult patients: A report from Children's Oncology Group study ARST0332. Cancer Spunt, S. L., Xue, W., Gao, Z., Hayes Dixon, A., Million, L., Polites, S. F., Vasudevan, S. A., Kao, S. C., McCarville, M. B., Parham, D. M., Barkauskas, D. A., Cai, Z., Cost, C., Mascarenhas, L., Weiss, A. R. 2024


    BACKGROUND: Embryonal sarcoma of the liver (ESL) is a rare mesenchymal tumor most common in childhood; the optimal treatment approach is uncertain. The clinical features and outcomes of patients with ESL enrolled in a Children's Oncology Group (COG) clinical trial that evaluated a risk-based strategy for treating soft tissue sarcomas in patients aged <30 years were evaluated.METHODS: This subset analysis included patients with ESL enrolled in COG study ARST0332. Central review of records, pathology, and imaging confirmed the diagnosis, presenting features, and surgery extent and complications. All patients received dose-intensive ifosfamide/doxorubicin chemotherapy, with cycle timing dependent on surgery and radiotherapy. Tumor resection occurred before study entry or after four cycles of chemotherapy; radiotherapy for residual tumor was optional.RESULTS: Thirty-nine eligible/evaluable patients with ESL were analyzed. All tumors were >10 cm in diameter; four were metastatic. Tumor resection was performed upfront in 23 and delayed in 16. Positive surgical margins (n=6) and intraoperative tumor rupture (n=6) occurred only in upfront resections. Eight patients received radiotherapy. Estimated 5-year event-free and overall survival were 79% (95% confidence interval [CI], 65%-93%) and 95% (95% CI, 87%-100%), respectively. Positive margins increased the local recurrence risk. One of 13 patients with documented hemorrhagic ascites and/or tumor rupture developed extrahepatic intra-abdominal tumor recurrence.CONCLUSIONS: The treatment strategy used in ARST0332 achieved favorable outcomes for patients with ESL despite a substantial proportion having high-risk disease features. Deferring tumor resection until after neoadjuvant chemotherapy may decrease the risk of intraoperative tumor rupture and improve the likelihood of adequate surgical margins.

    View details for DOI 10.1002/cncr.35305

    View details for PubMedID 38567652

  • Patterns of local recurrence and risk of skin recurrence in soft tissue sarcomas after surgical resection. Practical radiation oncology Ewongwo, A., Oladipo, E. D., Hui, C., Avedian, R. S., Steffner, R. J., Mohler, D. G., Kalbasi, A., Chin, A. L., Million, L., Hiniker, S. M., Moding, E. J. 2023


    Although there is a theoretical risk of skin seeding during surgical resection of soft tissues sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during RT. However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT.We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007-2021. For patients who developed LR, the depth was evaluated. Progression free survival (PFS) and overall survival (OS) were analyzed from time of first LR using Kaplan-Meier method. Cumulative incidence of distant metastasis (CIDM) was calculated with competing risk analysis from date of LR.Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, five patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had pre-operative RT, 53.3% had post operative RT, and bolus was used in 46.7%. Surgical margins were close (<1mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within RT field in 13 patients (86.7%). At 1 year after LR, PFS was 70.3%, OS was 81.7%, and CIDM was 5.9%.Skin recurrences were rare after surgical resection of STSs, and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

    View details for DOI 10.1016/j.prro.2023.09.006

    View details for PubMedID 37804883

  • Shaping success: clinical implementation of a 3D-printed electron cutout program in external beam radiation therapy. Frontiers in oncology Schulz, J. B., Gibson, C., Dubrowski, P., Marquez, C. M., Million, L., Qian, Y., Skinner, L., Yu, A. S. 2023; 13: 1237037


    The integration of 3D-printing technology into radiation therapy (RT) has allowed for a novel method to develop personalized electron field-shaping blocks with improved accuracy. By obviating the need for handling highly toxic Cerrobend molds, the clinical workflow is significantly streamlined. This study aims to expound upon the clinical workflow of 3D-printed electron cutouts in RT and furnish one year of in-vivo dosimetry data.3D-printed electron cutouts for 6x6 cm, 10x10 cm, and 15x15 cm electron applicators were designed and implemented into the clinical workflow after dosimetric commissioning to ensure congruence with the Cerrobend cutouts. The clinical workflow consisted of four parts: i) the cutout aperture was extracted from the treatment planning system (TPS). A 3D printable cutout was then generated automatically through custom scripts; ii) the cutout was 3D-printed with PLA filament, filled with tungsten ball bearings, and underwent quality assurance (QA) to verify density and dosimetry; iii) in-vivo dosimetry was performed with optically stimulated luminescence dosimeters (OSLDs) for a patient's first treatment and compared to the calculated dose in the TPS; iv) after treatment completion, the 3D-printed cutout was recycled.QA and in-vivo OSLD measurements were conducted (n=40). The electron cutouts produced were 6x6 cm (n=3), 10x10 cm (n=30), and 15x15 cm (n=7). The expected weight of the cutouts differed from the measured weight by 0.4 + 1.1%. The skin dose measured with the OSLDs was compared to the skin dose in the TPS on the central axis. The difference between the measured and TPS doses was 4.0 + 5.2%.The successful clinical implementation of 3D-printed cutouts reduced labor, costs, and removed the use of toxic materials in the workplace while meeting clinical dosimetric standards.

    View details for DOI 10.3389/fonc.2023.1237037

    View details for PubMedID 37621682

    View details for PubMedCentralID PMC10445153

  • Outcomes After Preoperative Chemoradiation With or Without Pazopanib in Non-Rhabdomyosarcoma Soft Tissue Sarcoma: A Report From Children's Oncology Group and NRG Oncology. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Weiss, A. R., Chen, Y. L., Scharschmidt, T. J., Xue, W., Gao, Z., Black, J. O., Choy, E., Davis, J. L., Fanburg-Smith, J. C., Kao, S. C., Kayton, M. L., Kessel, S., Lim, R., Million, L., Okuno, S. H., Ostrenga, A., Parisi, M. T., Pryma, D. A., Randall, R. L., Rosen, M. A., Shulkin, B. L., Terezakis, S., Venkatramani, R., Zambrano, E., Wang, D., Hawkins, D. S., Spunt, S. L. 2023: JCO2300045


    Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.ARST1321 was a phase II study designed to compare the near complete pathologic response rate after preoperative chemoradiation with/without pazopanib in children and adults with intermediate-/high-risk chemotherapy-sensitive body wall/extremity non-Rhabdomyosarcoma Soft Tissue Sarcoma ( identifier: NCT02180867). Enrollment was stopped early following a predetermined interim analysis that found the rate of near complete pathologic response to be significantly greater with the addition of pazopanib. As a planned secondary aim of the study, the outcome data for this cohort were analyzed. Eight-five eligible patients were randomly assigned to receive (regimen A) or not receive (regimen B) pazopanib in combination with ifosfamide and doxorubicin + preoperative radiotherapy followed by primary resection at week 13 and then further chemotherapy at week 25. As of December 31, 2021, at a median survivor follow-up of 3.3 years (range, 0.1-5.8 years), the 3-year event-free survival for all patients in the intent-to-treat analysis was 52.5% (95% CI, 34.8 to 70.2) for regimen A and 50.6% (95% CI, 32 to 69.2) for regimen B (P = .8677, log-rank test); the 3-year overall survival was 75.7% (95% CI, 59.7 to 91.7) for regimen A and 65.4% (95% CI, 48.1 to 82.7) for regimen B (P = .1919, log-rank test). Although the rate of near complete pathologic response was significantly greater with the addition of pazopanib, outcomes were not statistically significantly different between the two regimens.

    View details for DOI 10.1200/JCO.23.00045

    View details for PubMedID 37523624

  • An affordable platform for virtual reality-based patient education in radiation therapy. Practical radiation oncology Schulz, J. B., Dubrowski, P., Blomain, E., Million, L., Qian, Y., Marquez, C., Yu, A. S. 2023


    The goal of this study is to develop and assess the effectiveness of an affordable smartphone-based Virtual Reality (VR) patient education platform with 360-degree videos produced depicting a first-person patient perspective during the radiation therapy (RT) care path to reduce patient anxiety.and Materials Three disease site-specific (breast, pelvis, head and neck) VR-videos were filmed using a 360-degree camera to portray the first-person perspective of a patient's standard RT appointments: including a Computed Tomography (CT) simulation and the first RT treatment session. Instruction is given for possible clinical implementation. Patient participation was divided into two groups: 1) Group-A (n=28) included patients participating before simulation and later after the first treatment, and 2) Group-B (n=33) included patients participating only while undergoing treatment. Patients viewed their disease site-specific video using an inexpensive cardboard VR-viewer and their smartphone, emulating an expensive VR-headset. Surveys were administered assessing patient anxiety, comfort, satisfaction, and knowledge of RT on a 5-point Likert-type scale.Patients in Group-A and Group-B while undergoing treatment both selected their anxiety "decreased a little" in the survey, after watching the VR-video (Group-A, median on a 5-point Likert-type scale, 4 [interquartile range {IQR}, 4-5]; Group-B, 4 [IQR 4-4]). The VR aspect of the videos was especially liked by patients while undergoing treatment, with 96.4% in Group-A and 90.9% in Group-B reporting that the VR aspect of the videos was helpful. All Group-A participants believed that the VR-videos would be beneficial to new patients.Our affordable VR patient education platform effectively immerses a patient in their care path from simulation through initial treatment delivery, reducing anxiety and increasing familiarity with the treatment process.

    View details for DOI 10.1016/j.prro.2023.06.008

    View details for PubMedID 37482182

  • Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology. Journal of surgical oncology Kayton, M. L., Weiss, A. R., Xue, W., Binitie, O., Hayes Dixon, A., Randall, R. L., Sorger, J. I., Hawkins, D. S., Spunt, S. L., Wang, D., Million, L., Terezakis, S., Choy, E., Okuno, S. H., Venkatramani, R., Chen, Y. L., Scharschmidt, T. J. 2023


    The impact upon wound healing of targeted molecular therapies, when incorporated into neoadjuvant therapy of soft tissue sarcoma, is largely unknown. Here, we describe wound complications following addition of pazopanib, a tyrosine kinase inhibitor (TKI), to neoadjuvant radiotherapy (RT) +/- chemotherapy for soft tissue sarcoma.Wound complications were evaluated on dose-finding and randomized arms of ARST1321, a phase II/III study incorporating neoadjuvant RT, +/- pazopanib, +/- ifosfamide/doxorubicin (ID) for sarcoma therapy.Of 85 evaluable patients, 35 (41%) experienced postoperative wound complications. Most (57%) were grade III. Randomization to pazopanib + RT + ID carried a 50% wound complication rate (17/34, with 47% grade III), compared to 22% (5/23) with ID + RT alone. In nonchemotherapy study arms, pazopanib + RT resulted in a 59% wound complication rate versus 25% for those receiving RT alone. Grade III wound complications occurred among 26% (15/58) of all patients receiving pazopanib. Wound complications occurred a median of 35 days postoperatively. Some occurred following diagnostic biopsies and at remote surgical sites.The addition of pazopanib to neoadjuvant chemotherapy and RT resulted in a higher wound complication rate following therapy of soft tissue sarcoma. The rate of grade III complications remained comparable to that reported in contemporary literature.

    View details for DOI 10.1002/jso.27205

    View details for PubMedID 36779385

  • Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy. Practical radiation oncology Baniel, C., Yoo, C. H., Jiang, A., von Eyben, R., Mohler, D. G., Ganjoo, K., Bui, N., Donaldson, S. S., Million, L., Rijn, M. v., Moon Oh, J., Hiniker, S. M. 2022


    PURPOSE: Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis (PVNS). Primary treatment involves surgical resection, however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy.METHODS AND MATERIALS: We performed a retrospective chart review of 30 patients with TGCT from 2003-2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome.RESULTS: With mean follow-up of 82 months (range 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy following radiotherapy. The most common site of disease was the knee (n=22, 73%), followed by the ankle (n=5, 16%) and the hand (n=3, 10%). Seven patients (24%) presented at time of initial diagnosis while 23 (76%) presented with recurrent disease following surgical resection, with an average of 2.6 surgical procedures prior to radiotherapy. Following resection, 18/30 patients (67%) demonstrated residual TGCT by imaging. The median radiotherapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8-2.5 Gy/fractions over 4 weeks. In the assessment of post-treatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy.CONCLUSIONS: Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Post-surgical radiation therapy is a well-tolerated noninvasive treatment that should be considered following maximal cytoreductive resection to prevent disease progression and recurrence.

    View details for DOI 10.1016/j.prro.2022.11.004

    View details for PubMedID 36460182

  • Lymph node metastases in paediatric and young adult patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): Findings from Children's Oncology Group (COG) study ARST0332. European journal of cancer (Oxford, England : 1990) Alvarez, E., He, J., Spunt, S. L., Hayes-Jordan, A., Kao, S. C., Parham, D. M., Million, L., Weiss, A. R., Barkauskas, D. A. 2022; 180: 89-98


    PURPOSE: The aim of this paper is to better define the clinical features and outcomes of young patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) with regional and distant lymph node (LN) metastases treated in a standardised fashion, we analysed LN involvement in COG study ARST0332, which evaluated a risk-based treatment strategy for young patients with all stages of NRSTS.PATIENTS AND METHODS: Patients <30 years old with newly diagnosed NRSTS and LN metastases enrolled on ARST0332 were studied. Regional LN sampling was required for those with epithelioid sarcoma, clear cell sarcomaor clinically/radiographically enlarged LNs. Tumour features and extent of pre-enrolment resection determined treatment, including chemotherapy, radiotherapy, and delayed surgery. Recommendations for LN metastases included LN dissection at the time of primary tumour resection and dose-adapted radiotherapy based on extent of LN resection.RESULTS: Twenty of 529 eligible and evaluable ARST0332 patients with NRSTS had LN metastases; epithelioid sarcoma had the highest incidence (18%, 5 of 28). Pre-treatment imaging identified LN enlargement in 19 of 20 patients; 1 had no pre-treatment LN imaging. At 6.9 years median follow-up for surviving patients, 5-year overall survival was 85.7% (95% CI: 33.4%, 97.9%) for seven patients with isolated LN metastases and 15.4% (95% CI: 2.5%, 38.8%) for 13 patients with additional extranodal metastases. LN recurrence occurred in only one patient without LNs sampled at initial diagnosis.CONCLUSION: LN metastases occur in about 4% of paediatric/young adult NRSTS, are limited to a few histologic subtypes, and are rare in patients who did not have clinical or imaging evidence of lymphadenopathy, suggesting that biopsies of non-enlarged LNs are not necessary to identify occult involvement. Patients with isolated LN metastases have high 5-year overall survival (85%) and should be treated with curative intent.CLINICALTRIALS: GOV REGISTRY NO: NCT00346164.

    View details for DOI 10.1016/j.ejca.2022.11.014

    View details for PubMedID 36566574

  • Outcomes following preoperative chemoradiation plus /- pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): A report from Children's Oncology Group (COG) and NRG Oncology. Weiss, A. R., Chen, Y., Scharschmidt, T., Xue, W., Gao, Z., Black, J. O., Fanburg-Smith, J., Zambrano, E., Choy, E., Davis, J. L., Kayton, M., Million, L., Okuno, S. H., Ostrenga, A., Randall, R., Terezakis, S., Venkatramani, R., Wang, D., Hawkins, D. S., Spunt, S. L. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • CT-less electron radiotherapy simulation and planning with a consumer 3D camera. Journal of applied clinical medical physics Skinner, L., Knopp, R., Wang, Y., Dubrowski, P., Bush, K. K., Limmer, A., Trakul, N., Million, L., Marquez, C. M., Yu, A. S. 2021


    PURPOSE: Electron radiation therapy dose distributions are affected by irregular body surface contours. This study investigates the feasibility of three-dimensional (3D) cameras to substitute for the treatment planning computerized tomography (CT) scan by capturing the body surfaces to be treated for accurate electron beam dosimetry.METHODS: Dosimetry was compared for six electron beam treatments to the nose, toe, eye, and scalp using full CT scan, CT scan with Hounsfield Unit (HU) overridden to water (mimic 3D camera cases), and flat-phantom techniques. Radiation dose was prescribed to a depth on the central axis per physician's order, and the monitor units (MUs) were calculated. The 3D camera spatial accuracy was evaluated by comparing the 3D surface of a head phantom captured by a 3D camera and that generated with the CT scan in the treatment planning system. A clinical case is presented, and MUs were calculated using the 3D camera body contour with HU overridden to water.RESULTS: Across six cases the average change in MUs between the full CT and the 3Dwater (CT scan with HU overridden to water) calculations was 1.3% with a standard deviation of 1.0%. The corresponding hotspots had a mean difference of 0.4% and a standard deviation of 1.9%. The 3D camera captured surface of a head phantom was found to have a 0.59mm standard deviation from the surface derived from the CT scan. In-vivo dose measurements (213±8cGy) agreed with the 3D-camera planned dose of 209±6cGy, compared to 192±6cGy for the flat-phantom calculation (same MUs).CONCLUSIONS: Electron beam dosimetry is affected by irregular body surfaces. 3D cameras can capture irregular body contours which allow accurate dosimetry of electron beam treatment as an alternative to costly CT scans with no extra exposure to radiation. Tools and workflow for clinical implementation are provided.

    View details for DOI 10.1002/acm2.13283

    View details for PubMedID 34042253

  • Non-rhabdomyosarcoma soft-tissue sarcoma. Pediatric blood & cancer Milgrom, S. A., Million, L., Mandeville, H., Safwat, A., Ermoian, R. P., Terezakis, S. 2021; 68 Suppl 2: e28279


    Non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS) comprise 4% of childhood cancers and consist of numerous histologic subtypes. Prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability. Complete surgical resection is critical for the best oncologic outcomes and is prioritized in treatment algorithms. The use of radiation therapy (RT) and chemotherapy is based upon factors such as resectability, histologic grade, tumor size, and stage. North American and European trials are defining a risk-based approach to NRSTS to limit treatment-related toxicity and to maximize therapeutic efficacy. In this paper, we summarize the current roles of surgery, RT, and chemotherapy in NRSTS and describe ongoing research that is advancing the care of NRSTS patients.

    View details for DOI 10.1002/pbc.28279

    View details for PubMedID 33818885

  • Uterine Leiomyosarcoma with FN1-Anaplastic Lymphoma Kinase Fusion Responsive to Alectinib and Lorlatinib. Case reports in oncology Testa, S., Million, L., Longacre, T., Bui, N. 2021; 14 (2): 812-819


    Uterine leiomyosarcoma (LMS) is a rare malignant neoplasm of the female genital tract poorly responsive to conventional chemotherapy and radiotherapy, with an overall poor prognosis. Pazopanib is at the moment the only FDA-approved targeted molecular therapy for uterine LMS, given the exceedingly rare occurrence of actionable genetic mutations in this type of cancer. Here, we describe the first reported case of metastatic uterine LMS with an FN1-anaplastic lymphoma kinase (ALK) fusion mutation occurring in a 63-year-old woman with a history of uterine leiomyomas. The patient progressed on several lines of therapy, including conventional chemotherapy, pazopanib, and the first-generation ALK inhibitor crizotinib. Interestingly, the patient showed a remarkable 16-month response to second generation ALK inhibitors alectinib and lorlatinib. This case demonstrates that ALK inhibitors can be an effective therapeutic strategy for patients with ALK fusion-positive uterine LMS that has progressed on conventional chemotherapy.

    View details for DOI 10.1159/000516758

    View details for PubMedID 34248545

  • Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group Int J Radiat Oncol Biol Phys Million, L., et al 2021; 110 (3): 821-830
  • Surgical management of extremity rhabdomyosarcoma: A consensus opinion from the Children's Oncology Group, the European Pediatric Soft-Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. Pediatric blood & cancer Morris, C. D., Tunn, P., Rodeberg, D. A., Terwisscha van Scheltinga, S., Binitie, O., Godzinski, J., Dall'Igna, P., Million, L., Hawkins, D. S., Koscielniak, E., Bisogno, G., Rogers, T. N. 2020: e28608


    The treatment of extremity rhabdomyosarcoma remains a challenge due to several adverse prognostic factors frequently associated with this tumor site. The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group Soft-Tissue Sarcoma Committee, the European Pediatric Soft-Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. The INSTRuCT surgical committee developed an internationally applicable consensus opinion document for the surgical treatment of extremity rhabdomyosarcoma. This document addresses surgical management, including biopsy, nodal staging, timing of therapy, resection and reexcision, reconstruction, and surgical approach at relapse.

    View details for DOI 10.1002/pbc.28608

    View details for PubMedID 32776456

  • Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood advances Weng, W. K., Arai, S. n., Rezvani, A. n., Johnston, L. n., Lowsky, R. n., Miklos, D. n., Shizuru, J. n., Muffly, L. n., Meyer, E. n., Negrin, R. S., Wang, E. n., Almazan, T. n., Million, L. n., Khodadoust, M. n., Li, S. n., Hoppe, R. T., Kim, Y. H. 2020; 4 (18): 4474–82


    The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at as #NCT00896493.

    View details for DOI 10.1182/bloodadvances.2020001627

    View details for PubMedID 32941647

  • Deep Functional and Molecular Characterization of a High-Risk Undifferentiated Pleomorphic Sarcoma. Sarcoma Berlow, N. E., Grasso, C. S., Quist, M. J., Cheng, M., Gandour-Edwards, R., Hernandez, B. S., Michalek, J. E., Ryan, C., Spellman, P., Pal, R., Million, L. S., Renneker, M., Keller, C. 2020; 2020: 6312480


    Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic, ex vivo live cell chemosensitivity testing, a patient-derived xenograft model, and immunoscoring. Her therapeutic choices were also diverse, including neoadjuvant chemotherapy, radiation therapy, and surgeries. Adjuvant and recurrence strategies included off-label and natural medicines, several immunotherapies, and N-of-1 approaches. Identified treatment options, especially those validated during the in vivo study, were not introduced into the course of clinical treatment but did provide plausible treatment regimens based on FDA-approved clinical agents.

    View details for DOI 10.1155/2020/6312480

    View details for PubMedID 32565715

  • Alveolar rhabdomyosarcoma with regional nodal involvement: Results of a combined analysis from two cooperative groups. Pediatric blood & cancer Gallego, S. n., Chi, Y. Y., De Salvo, G. L., Li, M. n., Merks, J. H., Rodeberg, D. A., van Scheltinga, S. T., Mascarenhas, L. n., Orbach, D. n., Jenney, M. n., Million, L. n., Minard-Colin, V. n., Wolden, S. n., Zanetti, I. n., Parham, D. M., Mandeville, H. n., Venkatramani, R. n., Bisogno, G. n., Hawkins, D. S. 2020: e28832


    Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG).We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). Local treatment was similar in both protocols.The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [CI]: 39-59) and 44% (95% CI: 30-58), and overall survival (OS), 51% (95% CI: 41-61) and 53.6% (95% CI: 40-68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative.The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.

    View details for DOI 10.1002/pbc.28832

    View details for PubMedID 33245207

  • Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. The Lancet. Oncology Weiss, A. R., Chen, Y. L., Scharschmidt, T. J., Chi, Y. Y., Tian, J. n., Black, J. O., Davis, J. L., Fanburg-Smith, J. C., Zambrano, E. n., Anderson, J. n., Arens, R. n., Binitie, O. n., Choy, E. n., Davis, J. W., Hayes-Jordan, A. n., Kao, S. C., Kayton, M. L., Kessel, S. n., Lim, R. n., Meyer, W. H., Million, L. n., Okuno, S. H., Ostrenga, A. n., Parisi, M. T., Pryma, D. A., Randall, R. L., Rosen, M. A., Schlapkohl, M. n., Shulkin, B. L., Smith, E. A., Sorger, J. I., Terezakis, S. n., Hawkins, D. S., Spunt, S. L., Wang, D. n. 2020


    Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone.In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and <18 years) from 57 hospitals in the USA and Canada with unresected, newly diagnosed trunk or extremity chemotherapy-sensitive soft tissue sarcoma, which were larger than 5 cm in diameter and of intermediate or high grade. Eligible patients had Lansky (if aged ≤16 years) or Karnofsky (if aged >16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m2 per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m2 per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients <18 years 350 mg/m2 once daily; if patients ≥18 years 600 mg once daily) or not (control group), with pazopanib not given immediately before or after surgery at week 13. The study projected 100 randomly assigned patients were needed to show an improvement in the number of participants with a 90% or higher pathological response at week 13 from 40% to 60%. Analysis was done per protocol. This study has completed accrual and is registered with, NCT02180867.Between July 7, 2014, and Oct 1, 2018, 81 eligible patients were enrolled and randomly assigned to the pazopanib group (n=42) or the control group (n=39). At the planned second interim analysis with 42 evaluable patients and a median follow-up of 0·8 years (IQR 0·3-1·6) in the pazopanib group and 1 year (0·3-1·6) in the control group, the number of patients with a 90% pathological response or higher was 14 (58%) of 24 patients in the pazopanib group and four (22%) of 18 patients in the control group, with a between-group difference in the number of 90% or higher pathological response of 36·1% (83·8% CI 16·5-55·8). On the basis of an interim analysis significance level of 0·081 (overall one-sided significance level of 0·20, power of 0·80, and O'Brien-Fleming-type cumulative error spending function), the 83·8% CI for response difference was between 16·5% and 55·8% and thus excluded 0. The improvement in pathological response rate with the addition of pazopanib crossed the predetermined boundary and enrolment was stopped. The most common grade 3-4 adverse events were leukopenia (16 [43%] of 37 patients), neutropenia (15 [41%]), and febrile neutropenia (15 [41%]) in the pazopanib group, and neutropenia (three [9%] of 35 patients) and febrile neutropenia (three [9%]) in the control group. 22 (59%) of 37 patients in the pazopanib group had a pazopanib-related serious adverse event. Paediatric and adult patients had a similar number of grade 3 and 4 toxicity. There were seven deaths (three in the pazopanib group and four in the control group), none of which were treatment related.In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up.National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation.

    View details for DOI 10.1016/S1470-2045(20)30325-9

    View details for PubMedID 32702309

  • A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. The Lancet. Oncology Spunt, S. L., Million, L., Chi, Y., Anderson, J., Tian, J., Hibbitts, E., Coffin, C., McCarville, M. B., Randall, R. L., Parham, D. M., Black, J. O., Kao, S. C., Hayes-Jordan, A., Wolden, S., Laurie, F., Speights, R., Kawashima, E., Skapek, S. X., Meyer, W., Pappo, A. S., Hawkins, D. S. 2019


    BACKGROUND: Tumour grade, tumour size, resection potential, and extent of disease affect outcome in paediatric non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS), but no risk stratification systems exist and the standard of care is poorly defined. We developed a risk stratification system from known prognostic factors and assessed it in the context of risk-adapted therapy for young patients with NRSTS.METHODS: In this prospective study, eligible patients enrolled in 159 hospitals in three countries were younger than 30 years, had a Lansky (patients ≤16 years) or Karnofsky (patients >16 years) performance status score of at least 50, and a new diagnosis of a WHO (2002 criteria) intermediate (rarely metastasising) or malignant soft-tissue tumour (apart from tumour types eligible for other Children's Oncology Group studies and tumours for which the therapy in this trial was deemed inappropriate), malignant peripheral nerve sheath tumour, non-metastatic and grossly resected dermatofibrosarcoma protuberans, undifferentiated embryonal sarcoma of the liver, or unclassified malignant soft-tissue sarcoma. Each patient was assigned to one of three risk groups and one of four treatment groups. Risk groups were: low (non-metastatic R0 or R1 low-grade, or ≤5 cm R1 high-grade tumour); intermediate (non-metastatic R0 or R1 >5 cm high-grade, or unresected tumour of any size or grade); or high (metastatic tumour). The treatment groups were surgery alone, radiotherapy (55·8 Gy), chemoradiotherapy (chemotherapy and 55·8 Gy radiotherapy), and neoadjuvant chemoradiotherapy (chemotherapy and 45 Gy radiotherapy, then surgery and radiotherapy boost based on margins with continued chemotherapy). Chemotherapy included six cycles of ifosfamide 3 g/m2 per dose intravenously on days 1-3 and five cycles of doxorubicin 37·5 mg/m2 per dose intravenously on days 1-2 every 3 weeks with sequence adjusted on the basis of timing of surgery or radiotherapy. The primary outcomes were event-free survival, overall survival, and the pattern of treatment failure. Analysis was done per protocol. This study has been completed and is registered with, NCT00346164.FINDINGS: Between Feb 5, 2007, and Feb 10, 2012, 550 eligible patients were enrolled, of whom 21 were treated in the incorrect group and excluded from this analysis. 529 evaluable patients were included in the analysis: low-risk (n=222), intermediate-risk (n=227), high-risk (n=80); surgery alone (n=205), radiotherapy (n=17), chemoradiotherapy (n=111), and neoadjuvant chemoradiotherapy (n=196). At a median follow-up of 6·5 years (IQR 4·9-7·9), 5-year event-free survival and overall survival were: 88·9% (95% CI 84·0-93·8) and 96·2% (93·2-99·2) in the low-risk group; 65·0% (58·2-71·8) and 79·2% (73·4-85·0) in the intermediate-risk group; and 21·2% (11·4-31·1) and 35·5% (23·6-47·4) in the high-risk group, respectively. Risk group predicted event-free survival and overall survival (p<0·0001). No deaths from toxic events during treatment were reported. Nine patients had unexpected grade 4 adverse events (chemoradiotherapy group, n=2; neoadjuvant chemoradiotherapy group, n=7), including three wound complications that required surgery (all in the neoadjuvant chemoradiotherapy group).INTERPRETATION: Pre-treatment clinical features can be used to effectively define treatment failure risk and to stratify young patients with NRSTS for risk-adapted therapy. Most low-risk patients can be cured without adjuvant therapy, thereby avoiding known long-term treatment complications. Survival remains suboptimal for intermediate-risk and high-risk patients and novel therapies are needed.FUNDING: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation, American Lebanese Syrian Associated Charities.

    View details for DOI 10.1016/S1470-2045(19)30672-2

    View details for PubMedID 31786124

  • Preoperative chemoradiation plus /- pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): A report from Children's Oncology Group (COG) and NRG Oncology. Weiss, A. R., Chi, Y., Chen, Y., Choy, E., Davis, J. L., Fanburg-Smith, J., Hawkins, D. S., Kayton, M., Million, L., Okuno, S. H., Ostrenga, A., Randall, R., Scharschmidt, T., Sorger, J., Spunt, S. L., Tian, J., Terezakis, S., Wang, D., Zambrano, E., Black, J. O. AMER SOC CLINICAL ONCOLOGY. 2019
  • Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials EUROPEAN JOURNAL OF CANCER Spunt, S. L., Francotte, N., De Salvo, G., Chi, Y., Zanetti, I., Hayes-Jordan, A., Kao, S. C., Orbach, D., Brennan, B., Weiss, A. R., van Noesel, M. M., Million, L., Alaggio, R., Parham, D. M., Kelsey, A., Randall, R., McCarville, M., Bisogno, G., Hawkins, D. S., Ferrari, A. 2019; 112: 98–106
  • Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials. European journal of cancer (Oxford, England : 1990) Spunt, S. L., Francotte, N., De Salvo, G. L., Chi, Y., Zanetti, I., Hayes-Jordan, A., Kao, S. C., Orbach, D., Brennan, B., Weiss, A. R., van Noesel, M. M., Million, L., Alaggio, R., Parham, D. M., Kelsey, A., Randall, R. L., McCarville, M. B., Bisogno, G., Hawkins, D. S., Ferrari, A. 2019; 112: 98–106


    BACKGROUND: Data on the clinical features, optimal treatmentand outcomes of paediatric patients with epithelioid sarcoma (ES) are limited and mostly retrospective.METHODS: A subset analysis of ES patients<30 years of age enrolled on two international prospective clinical trials conducted between 7/2005 and 11/2015 was performed. Risk-adapted therapy was based on tumour diameter, histologic grade, extent of surgeryand presence/absence of metastasesand included surgery±radiotherapy for all patients with the addition of ifosfamide/doxorubicin chemotherapy for intermediate-/high-risk patients. Response to therapy, event-free and overall survivaland pattern and predictors of treatment failure were evaluated.RESULTS: Sixty-three ES patients (median age 13.1 years, 52% male) were eligible. Clinical features included the following: 68% extremity, median tumour diameter 3.5cm, 56% high histologic grade, 14% nodal metastases, 14% distant metastases. Thirty-four low-risk patients underwent surgery (n=30) or surgery/radiotherapy (n=4); 16 intermediate-risk and 13 high-risk patients received chemotherapy±surgery±radiotherapy. Partial response was observed in 11/22 (50%) patients receiving neoadjuvant therapy. Events were local recurrence (n=10) and distant recurrence (n=15); estimated 5-year survival was 86.4%, 63.5%and 0%, respectively, for low-, intermediate-and high-risk patients. Locoregional nodal involvement, invasive tumour, high gradeand lesser extent of resection predicted event-free survival in patients without metastases.CONCLUSIONS: Most low-risk ES patients who have undergone an adequate resection fare well without adjuvant therapy. Large tumour size, high histologic grade, tumour invasiveness, inadequate tumour resectionand metastatic disease predict poorer outcomes in higher risk ES patients, for whom more effective therapies are needed.CLINICAL TRIAL REGISTRATION: COG ARST0332: Identifier NCT00346164, EpSSG NRSTS 2005: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.

    View details for PubMedID 30954717

  • Moody D. Wharam Jr, MD, FACR, FASTRO, July 22, 1941-August 10, 2018. International journal of radiation oncology, biology, physics Jabbour, S. K., Timmerman, R. D., Raben, D., DeWeese, T. L., Donaldson, S. S., Thomas, P., Laurie, F., Bishop-Jodoin, M., Tarbell, N., Wolden, S., Halperin, E., Constine, L. S., Haas-Kogan, D., Marcus, K., Freeman, C., Terezakis, S., Million, L., Smith, M. A., Mendenhall, N. P., Marcus, R. B., Cherlow, J., Kalapurakal, J., Breneman, J., Yock, T., MacDonald, S., Laack, N., Donahue, B., Indelicato, D., Michalski, J., Perkins, S., Kachnic, L., Esiashvilli, N., Roberts, K. B., FitzGerald, T. J. 2019; 103 (5): 1026–30

    View details for PubMedID 30900552

  • Pediatric Soft Tissue and Bone Sarcomas in Tanzania: Epidemiology and Clinical Features JOURNAL OF GLOBAL ONCOLOGY Siwillis, E., Dharse, N. J., Scanlan, T., Ngoma, M., Abraham, Z., Kahiu, J. N., Million, L. 2019; 5
  • Pediatric Soft Tissue and Bone Sarcomas in Tanzania: Epidemiology and Clinical Features. Journal of global oncology Siwillis, E. M., Dharse, N. J., Scanlan, T., Ngoma, M., Abraham, Z. S., Kahiu, J. W., Million, L. 2019: 1–6


    PURPOSE: Pediatric sarcomas represent an important group of childhood tumors that require treatment at Muhimbili National Hospital (MNH), the largest pediatric oncology center in Tanzania. Treatment is often adapted from established childhood protocols validated in clinical trials from the United States and the United Kingdom. There are no studies describing the types of pediatric sarcomas most commonly seen in Tanzania to understand similarities and disparities with other countries and which sarcomas to prioritize in adapting treatment protocols. The objective of this study was to establish a baseline of the epidemiologic and clinical features of pediatric sarcomas diagnosed at MNH.METHODS: Information was collected on clinical and tumor features of all children seen at MNH pediatric oncology unit between 2011 and 2016 with a confirmed histologic diagnosis of either bone or soft tissue sarcoma (STS).RESULTS: A total of 135 cases were analyzed; 89 (66%) were STS and 46 (34%) were bone sarcomas. There was a slight female predominance (n = 69; 51%), and the mean age (SD) of patients was 6.3 (5.1) years. Greater than 90% (n = 123) of the cases presented with a painless swelling. The commonest STS, accounting for almost three-fourths of the cases (n = 66) was rhabdomyosarcoma (RMS), with embryonal subtype being the most common RMS (n = 49; 74%). Osteosarcoma was the most common bone sarcoma, accounting for greater than 80% (n = 40) of the cases. Ewing sarcoma accounted for less than 15% (n = 6). Most of the patients presented with stage IV disease (n = 57; 87%) and lung was the commonest metastatic site.CONCLUSION: To our knowledge, this report is the first study documenting the epidemiologic and clinical features of pediatric sarcomas in a modern Tanzanian pediatric hospital. Embryonal RMS and osteosarcomas should be prioritized for adapting treatment protocols from other countries.

    View details for PubMedID 30917068

  • The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2019; 42 (2): 166–71
  • Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332. International journal of radiation oncology, biology, physics Rao, A. D., Chen, Q., Million, L., Spunt, S. L., Fitzgerald, T. J., Hu, C., Rao, S. S., Laurie, F., Kessel, S., Morano, K., Ladra, M. M., Terezakis, S. A. 2019; 103 (1): 38–44


    PURPOSE: For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique.METHODS AND MATERIALS: Of 550 eligible patients <30years of age, 200 were enrolled in arm D of ARST0332 and received neoadjuvant ifosfamide/doxorubicin, then chemoradiotherapy (45Gy and ifosfamide) and surgery followed by postoperative RT if gross or microscopic positive surgical margins. One-hundred thirteen patients had extremity nonrhabdomyosarcoma soft-tissue sarcomas, of which 56 patients had preoperative RT plans for digital review. The doses to the target volume, skin (surface to 5mm depth), adjacent joint, and extremity diameter were analyzed with respect to RT technique.RESULTS: Thirty-eight patients (65%) received 3-dimensional conformal RT (3D-CRT) and 18 (32%) received intensity modulated RT (IMRT). There was no difference in clinical target volume (CTV) size between groups (P=.920); however, IMRT plans had improved CTV coverage to 100% of the prescription dose compared with 3D-CRT plans (median CTV coverage, 92.7% vs 98.6%; P=.011). In patients without target overlap with the skin, IMRT use was associated with reduced percent volume of skin receiving 45Gy or more (V45Gy) compared with 3D-CRT (median, 1.6% vs 6.3%, respectively; P=.005). IMRT was also associated with reduced V45Gy to the adjacent joint compared with 3D-CRT (median, 1.1% vs 13.2%; P=.018).CONCLUSIONS: Preoperative IMRT may improve CTV coverage and reduce the volume of skin and adjacent joint treated to high doses. Future studies should assess whetherthese dosimetric findings produce differences in clinical and toxicity outcomes.

    View details for PubMedID 30213752

  • Outcomes for pediatric patients with osteosarcoma treated with palliative radiotherapy. Pediatric blood & cancer Chen, E. L., Yoo, C. H., Gutkin, P. M., Merriott, D. J., Avedian, R. S., Steffner, R. J., Spunt, S. L., Pribnow, A. K., Million, L. n., Donaldson, S. S., Hiniker, S. M. 2019: e27967


    Few studies have addressed the efficacy of palliative radiotherapy (RT) for pediatric osteosarcoma (OS), a disease generally considered to be radioresistant. We describe symptom relief, local control, and toxicity associated with palliative RT among children with OS.Patients diagnosed with OS at age 18 and under and treated with RT for palliation of symptomatic metastases or local recurrence at the primary site from 1997 to 2017 were included. We retrospectively reviewed details of RT, symptom improvement, local control, survival, and toxicity.Thirty-two courses of palliative RT were given to 20 patients with symptomatic metastatic and/or locally recurrent primary disease. The median equivalent dose in 2 Gy fractions (EQD2) was 40.0 Gy (range, 20.0-60.4). The median number of fractions per course was 15 (range, 5-39). Symptom improvement occurred in 24 (75%) courses of RT at a median time of 15.5 days (range, 3-43). In nine courses (37.5%), symptoms recurred after a median duration of symptom relief of 140 days (range, 1-882). Higher EQD2 correlated with longer duration of response (r = 0.39, P = 0.0003). Imaging revealed local failure in 3 of 14 courses followed with surveillance imaging studies (21.4%). The median time to progression was 12.9 months (range, 4.4-21.8). The median follow-up time following the first course of palliative RT was 17.5 months (range, 1.74-102.24), and median time to overall survival was 19.4 months. Toxicity was mild, with grade 2 toxicity occurring in one course (3.1%).RT is an effective method of symptom palliation for patients with recurrent or metastatic OS, with higher delivered dose correlating with longer symptom relief and with little associated toxicity.

    View details for DOI 10.1002/pbc.27967

    View details for PubMedID 31407520

  • Larry Emanuel Kun, March 10, 1946-May 27, 2018. International journal of radiation oncology, biology, physics FitzGerald, T. J., Donaldson, S. S., Wharam, M., Laurie, F., Bishop-Jodoin, M., Moni, J., Tarbell, N., Shulkin, B., McCarville, E., Merchant, T., Krasin, M., Wolden, S., Halperin, E., Constine, L. S., Haas-Kogan, D., Marcus, K., Freeman, C., Wilson, J. F., Hoppe, R., Cox, J., Terezakis, S., Million, L., Smith, M. A., Mendenhall, N. P., Marcus, R. B., Cherlow, J., Kalapurakal, J., Breneman, J., Yock, T., MacDonald, S., Laack, N., Donahue, B., Indelicato, D., Michalski, J., Perkins, S., Kachnic, L., Choy, H., Braunstein, S., Esiashvilli, N., Roberts, K. B. 2019; 103 (1): 8–14

    View details for PubMedID 30563668

  • The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University. American journal of clinical oncology Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2018


    BACKGROUND: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.METHODS: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.RESULTS: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).CONCLUSIONS: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

    View details for PubMedID 30557163

  • Evaluating Barriers and Opportunities in Delivering High-Quality Oncology Care in a Resource-Limited Setting Using a Comprehensive Needs Assessment Tool. Journal of global oncology Nwachukwu, C. R., Mudasiru, O., Million, L., Sheth, S., Qamoos, H., Onah, J. O., Okemini, A., Rhodes, M., Barry, M., Banjo, A. A., Habeebu, M., Olasinde, T. A., Bhatt, A. S. 2018: 1–9


    PURPOSE: Despite recognition of both the growing cancer burden in low- and middle-income countries and the disproportionately high mortality rates in these settings, delivery of high-quality cancer care remains a challenge. The disparities in cancer care outcomes for many geographic regions result from barriers that are likely complex and understudied. This study describes the development and use of a streamlined needs assessment questionnaire (NAQ) to understand the barriers to providing quality cancer care, identifies areas for improvement, and formulates recommendations for implementation.METHODS: Using a comprehensive NAQ, in-depth interviews were conducted with 17 hospital staff involved in cancer care at two teaching hospitals in Nigeria. Data were analyzed using content analysis and organized into a framework with preset codes and emergent codes, where applicable.RESULTS: Data from the interviews were organized into six broad themes: staff, stuff, system, space, lack of palliative care, and provider bias, with key barriers within themes including: financial, infrastructural, lack of awareness, limited human capacity resources, lack of palliative care, and provider perspective on patient-related barriers to cancer care. Specific solutions based on ability to reasonably implement were subcategorized into short-, medium-, and long-term goals.CONCLUSION: This study provides a framework for a streamlined initial needs assessment and a unique discussion on the barriers to high-quality oncology care that are prevalent in resource-constrained settings. We report the feasibility of collecting and organizing data using a streamlined NAQ and provide a thorough and in-depth understanding of the challenges in this setting. Knowledge gained from the assessments will inform steps to improve oncology cancer in these settings.

    View details for PubMedID 30532992

  • The impact of postoperative therapy on primary cardiac sarcoma. The Journal of thoracic and cardiovascular surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018; 156 (6): 2194-2203


    Primary cardiac sarcomas (PCS) are extremely rare, portend a very poor prognosis, and have limited outcomes data to direct management. This study evaluated the impact of postoperative chemotherapy and/or radiotherapy on survival for PCS.A retrospective chart review was conducted of 12 patients diagnosed with and who underwent resection for PCS at a single institution between 2000 and 2016. Data were collected on patient/tumor characteristics and analyzed with respect to treatment and outcome using Kaplan-Meier methods.Median age was 43 (range 21-73 years) with a 50:50 male-to-female ratio. The most common subtype was angiosarcoma (42%), and 25% presented with distant metastases (DMs). The initial treatment modality for all patients was surgery, with 58% having macroscopically positive (R2) margins. In total, 75% received postoperative chemotherapy and/or radiotherapy. Median progression-free survival (PFS) was 5.9 months, and median overall survival (OS) was 12.0 months. Achieving negative or microscopically positive margins (R0/R1) as compared with R2 resection significantly improved PFS (12.6 vs 2.7 months, P = .008) and OS (21.8 vs 7.2 months, P = .006). DM at presentation demonstrated a significantly shorter OS (7.0 vs 16.9 months, P = .04) and PFS (0.7 vs 7.9 months, P = .003) compared with localized disease. Patients given postoperative therapy had longer OS compared with surgery only, but this difference was not statistically significant (15.5 vs 2.6 months, P = .12).Gross total surgical resection can significantly improve PFS and OS in PCS, but DM at diagnosis is an extremely poor prognostic sign. Postoperative therapy should be considered, although this study was likely underpowered to demonstrate a statistically significant benefit.

    View details for DOI 10.1016/j.jtcvs.2018.04.127

    View details for PubMedID 30454911

  • Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Hawkins, D. S., Chi, Y., Anderson, J. R., Tian, J., Arndt, C. A., Bomgaars, L., Donaldson, S. S., Hayes-Jordan, A., Mascarenhas, L., McCarville, M. B., McCune, J. S., McCowage, G., Million, L., Morris, C. D., Parham, D. M., Rodeberg, D. A., Rudzinski, E. R., Shnorhavorian, M., Spunt, S. L., Skapek, S. X., Teot, L. A., Wolden, S., Yock, T. I., Meyer, W. H. 2018: JCO2018779694


    Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided alpha-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.

    View details for PubMedID 30091945

  • The Impact of Post-Operative Therapy on Primary Cardiac Sarcoma The Journal of Thoracic and Cardiovascular Surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018
  • NCCN Guidelines (R) Insights Bone Cancer, Version 2.2017 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Biermann, J. S., Chow, W., Reed, D. R., Lucas, D., Adkins, D. R., Agulnik, M., Benjamin, R. S., Brigman, B., Budd, G. T., Curry, W. T., Didwania, A., Fabbri, N., Hornicek, F. J., Kuechle, J. B., Lindskog, D., Mayerson, J., McGarry, S. V., Million, L., Morris, C. D., Movva, S., O'Donnell, R. J., Randall, R. L., Rose, P., Santana, V. M., Satcher, R. L., Schwartz, H., Siegel, H. J., Thornton, K., Villalobos, V., Bergman, M. A., Scavone, J. L. 2017; 15 (2): 155-167
  • A Robust and Affordable Table Indexing Approach for Multi-isocenter Dosimetrically Matched Fields. Cureus Yu, A. n., Fahimian, B. n., Million, L. n., Hsu, A. n. 2017; 9 (5): e1270


    Purpose  Radiotherapy treatment planning of extended volume typically necessitates the utilization of multiple field isocenters and abutting dosimetrically matched fields in order to enable coverage beyond the field size limits. A common example includes total lymphoid irradiation (TLI) treatments, which are conventionally planned using dosimetric matching of the mantle, para-aortic/spleen, and pelvic fields. Due to the large irradiated volume and system limitations, such as field size and couch extension, a combination of couch shifts and sliding of patients are necessary to be correctly executed for accurate delivery of the plan. However, shifting of patients presents a substantial safety issue and has been shown to be prone to errors ranging from minor deviations to geometrical misses warranting a medical event. To address this complex setup and mitigate the safety issues relating to delivery, a practical technique for couch indexing of TLI treatments has been developed and evaluated through a retrospective analysis of couch position. Methods The indexing technique is based on the modification of the commonly available slide board to enable indexing of the patient position. Modifications include notching to enable coupling with indexing bars, and the addition of a headrest used to fixate the head of the patient relative to the slide board. For the clinical setup, a Varian Exact Couch(TM) (Varian Medical Systems, Inc, Palo Alto, CA) was utilized. Two groups of patients were treated: 20 patients with table indexing and 10 patients without. The standard deviations (SDs) of the couch positions in longitudinal, lateral, and vertical directions through the entire treatment cycle for each patient were calculated and differences in both groups were analyzed with Student's t-test. Results The longitudinal direction showed the largest improvement. In the non-indexed group, the positioning SD ranged from 2.0 to 7.9 cm. With the indexing device, the positioning SD was reduced to a range of 0.4 to 1.3 cm (p < 0.05 with 95% confidence level). The lateral positioning was slightly improved (p < 0.05 with 95% confidence level), while no improvement was observed in the vertical direction. Conclusions The conventional matched field TLI treatment is error-prone to geometrical setup error. The feasibility of full indexing TLI treatments was validated and shown to result in a significant reduction of positioning and shifting errors.

    View details for PubMedID 28652953

  • Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839


    Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

    View details for PubMedID 28761389

  • Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience. International journal of radiation oncology, biology, physics Million, L., Yi, E. J., Wu, F., von Eyben, R., Campbell, B. A., Dabaja, B., Tsang, R. W., Ng, A., Wilson, L. D., Ricardi, U., Kirova, Y., Hoppe, R. T. 2016; 95 (5): 1454-1459


    To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome.The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide.Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease.Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

    View details for DOI 10.1016/j.ijrobp.2016.03.023

    View details for PubMedID 27315663

  • The Parotid Gland is an Underrecognized Organ at Risk for Craniospinal Irradiation TECHNOLOGY IN CANCER RESEARCH & TREATMENT King, M. T., Modlin, L., Million, L., Donaldson, S. S., Gibbs, I. C., Choi, C. Y., Soltys, S. G. 2016; 15 (3): 472-479


    Current craniospinal irradiation (CSI) protocols do not include the parotid gland as an organ at risk, potentially leading to late effects of xerostomia and secondary parotid malignancies. We analyzed the effect of CSI treatment parameters on parotid dose.We retrospectively reviewed 50 consecutive patients treated with CSI to an intracranial dose >26 Gy. Parotid dose was compared to a Radiation Therapy Oncology Group (RTOG) dose constraint (at least 1 parotid with mean dose <26 Gy). The effects of CSI dose (≤24 Gy vs 24 Gy), volumetric-modulated arc therapy (VMAT) versus 3-dimensional (3D) CSI technique, boost dose (≤24 Gy vs 24 Gy), supratentorial versus infratentorial boost location, intensity-modulated radiation therapy (IMRT)-based versus 3D boost technique, supine versus prone position, and age on parotid dose were analyzed using multivariate regression analysis.The RTOG parotid dose constraint was exceeded in 22 (44%) of 50 patients. On multivariate regression analysis, lower CSI dose and VMAT CSI technique were associated with reduced parotid dose for the CSI fields. For the boost fields, lower boost dose and supratentorial boost location were associated with lower parotid dose. All 5 patients who underwent VMAT CSI met dose constraints. Furthermore, for infratentorial lesions with a total (CSI plus boost) dose prescription dose >50 Gy (n = 24), 11 of 16 patients who received low-dose CSI (18-23.4 Gy) were able to meet dose constraints, when compared to only 2 of 8 patients who received high dose CSI (36 Gy).Given the large number of patients exceeding the parotid dose constraint, the parotid gland should be considered an organ at risk. CSI dose de-escalation and IMRT-based CSI techniques may minimize the risk of xerostomia.

    View details for DOI 10.1177/1533034615583406

    View details for Web of Science ID 000375704500008

    View details for PubMedID 25948323

  • Occult Dermal Lymphatic Involvement Is Frequent in Primary Cutaneous Anaplastic Large Cell Lymphoma. American Journal of dermatopathology Gratzinger, D., Million, L., Kim, Y. H. 2015; 37 (10): 767-770


    Primary cutaneous anaplastic large cell lymphoma (pcALCL) is an indolent T-cell lymphoproliferative disorder managed with low-dose radiation therapy, surgery, and/or mild chemotherapy; patients with extensive limb disease (ELD) have a more aggressive clinical course. We have previously demonstrated that histologically apparent vascular involvement in pcALCL is lymphatic. We hypothesized that histologically occult lymphatic involvement may be associated with particular patterns of disease spread that could involve lymphangitic spread including locoregional spread of disease in the form of ELD and extracutaneous spread of disease. We have therefore set out to quantitate the incidence of occult lymphovascular involvement in pcALCL and to assess for an association between lymphovascular involvement and these patterns of disease. We performed immunohistochemistry for the lymphovascular marker D2-40 on skin biopsies from 29 patients with pcALCL followed in the Stanford Cutaneous Lymphoma Clinic. Immunohistochemically evident dermal lymphovascular involvement was found in nearly half of cases examined (48%; 95% confidence interval, 29%-67%). There was a nonsignificant trend toward a higher prevalence of ELD among patients with pcALCL involving dermal lymphatics (7% vs. 29%; p = 0.12). In this small cohort, there was no indication of a significantly more aggressive disease course in patients with lymphatic involvement either in the form of disease-related mortality (one each in the lymphatic and nonlymphatic groups) or in time to extracutaneous involvement.

    View details for DOI 10.1097/DAD.0000000000000377

    View details for PubMedID 26381026

  • Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: Results of a pooled analysis from 3 phase-II clinical trials. Journal of the American Academy of Dermatology Hoppe, R. T., Harrison, C., Tavallaee, M., Bashey, S., Sundram, U., Li, S., Million, L., Dabaja, B., Gangar, P., Duvic, M., Kim, Y. H. 2015; 72 (2): 286-292


    Standard-dose (36-Gy) total skin electron beam therapy (TSEBT) is a highly effective treatment in mycosis fungoides. However, the regimen is time-intensive and may be associated with significant toxicity.We sought to evaluate the efficacy and tolerability associated with low-dose (12-Gy) TSEBT.Data from 3 clinical trials using low-dose (12-Gy) TSEBT were pooled. In all trials, TSEBT-naïve patients with stage IB to IIIA mycosis fungoides were treated with TSEBT (12 Gy, 1 Gy per fraction over 3 weeks). The primary end point was clinical response rate. Secondary end points included time to response and duration of clinical benefit.In all, 33 patients enrolled. Eighteen were male; stages were 22 IB, 2 IIA, 7 IIB, and 2 IIIA. Overall response rate was 88% (29/33), including 9 patients with complete response. Median time to response was 7.6 weeks (3-12.4 weeks). Median duration of clinical benefit was 70.7 weeks (95% confidence interval 41.8-133.8 weeks). Toxicities from TSEBT were mild and reversible.Conclusions are limited because of the small number of patients.Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times during the course of a patient's disease with acceptable toxicity profile.

    View details for DOI 10.1016/j.jaad.2014.10.014

    View details for PubMedID 25476993

  • Successful Treatment with Temozolomide Combined with Chemoradiotherapy and Surgery of a Metastatic Undifferentiated Soft Tissue Sarcoma with Relapse in the Central Nervous System of a Young Adult JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Hsu, C. H., Daldrup-Link, H. E., Yeom, K. W., Donaldson, S. S., Million, L., Hazard, F. K., Rangaswami, A. 2014; 3 (2): 100-103
  • Survival and neurocognitive outcomes after cranial or craniospinal irradiation plus total-body irradiation before stem cell transplantation in pediatric leukemia patients with central nervous system involvement. International journal of radiation oncology, biology, physics Hiniker, S. M., Agarwal, R., Modlin, L. A., Gray, C. C., Harris, J. P., Million, L., Kiamanesh, E. F., Donaldson, S. S. 2014; 89 (1): 67-74


    To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen.Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes.All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college.The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.

    View details for DOI 10.1016/j.ijrobp.2014.01.056

    View details for PubMedID 24725690

  • Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: A report from the Children's Oncology Group PEDIATRIC BLOOD & CANCER Raney, B., Huh, W., Hawkins, D., Hayes-Jordan, A., Million, L., Rodeberg, D., Teot, L., Anderson, J. 2013; 60 (3): 371-376


    We wanted to ascertain patterns of recurrence, re-treatment, and outcome among 188 eligible patients treated for localized orbital sarcoma on IRSG Protocols III/IV, 1984-1997.Retrospective chart review.Twenty-four of 188 patients (12.8%) developed local (n = 22) or distant relapse (n = 2) at 0.057-7.05 years (median, 1.58) after enrollment. Ages at study entry were 0.14-17 years (median, 5 years). Initial tumor operations included biopsy (n = 20) or gross resection with microscopic residual (n = 4). Initial tumor diameters were 0.5-7 cm (median, 3). Pathologic subtypes were embryonal rhabdomyosarcoma (ERMS, n = 19), sarcoma not otherwise specified (n = 2), and alveolar RMS, botryoid ERMS, or undifferentiated sarcoma (n = 1 each). Initial treatment included vincristine/dactinomycin (n = 24) including an alkylator (n = 4) and radiotherapy (RT, n = 21). Twenty patients responded, 14 completely, 6 partially. After recurrence, patients underwent orbital exenteration (n = 10), enucleation (2), tumor excision (3), or biopsy (1); 7 had no operation, and 1 had no data. Post-relapse chemotherapy included combinations of etoposide (n = 14 patients), doxorubicin (14), ifosfamide (12), cyclophosphamide (7), and dacarbazine (n = 1). Six patients received RT, including four previously treated and two not irradiated initially. Two patients died; one at 1.79 years after contralateral brain metastasis followed by local recurrence, and another at 2.49 years after multiple local recurrences. Twenty-two patients (91.7%) survived sarcoma-free for 0.04-17 years (median, 6.9) after relapse, and 18 of 22 (82%) were alive ≥5 years after relapse.Survival following recurrent localized orbital sarcoma appears likely after vigorous re-treatment given with curative intent.

    View details for DOI 10.1002/pbc.24289

    View details for Web of Science ID 000313727000005

    View details for PubMedID 22961750

  • Is Tanning Bed Exposure Associated With Aggressive Basal Cell Carcinoma? JOURNAL OF CLINICAL ONCOLOGY Gamba, C. A., Wysong, A., Million, L., Aasi, S., Kim, J., Tang, J. Y. 2012; 30 (32): E333-E336

    View details for DOI 10.1200/JCO.2012.42.1008

    View details for Web of Science ID 000310914800006

    View details for PubMedID 23008324

  • Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Henry, E., Villalobos, V., Million, L., Jensen, K. C., West, R., Ganjoo, K., Lebensohn, A., Ford, J. M., Telli, M. L. 2012; 10 (8): 939-942


    Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

    View details for PubMedID 22878818

  • Resectable pediatric nonrhabdomyosarcoma soft tissue sarcoma: which patients benefit from adjuvant radiation therapy and how much? ISRN oncology Million, L., Donaldson, S. S. 2012; 2012: 341408-?


    It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy.

    View details for DOI 10.5402/2012/341408

    View details for PubMedID 22523704

    View details for PubMedCentralID PMC3316976



    Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control.All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation.Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children.Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.

    View details for DOI 10.1016/j.ijrobp.2010.01.058

    View details for Web of Science ID 000290837100003

    View details for PubMedID 20646841

  • Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma: a report from the children's oncology group. Cancer Rodeberg, D. A., Stoner, J. A., Garcia-Henriquez, N., Randall, R. L., Spunt, S. L., Arndt, C. A., Kao, S., Paidas, C. N., Million, L., Hawkins, D. S. 2010


    BACKGROUND:: The objectives of this study were to compare tumor volume and patient weight versus traditional factors of tumor size (greatest dimension) and patient age and to determine which parameters best discriminated outcome among pediatric patients with intermediate-risk rhabdomyosarcoma (RMS). METHODS:: Complete information was available for 370 patients with nonmetastatic RMS who were enrolled in the Children's Oncology Group (COG) intermediate-risk study D9803 (1999-2005). The Kaplan-Meier method was used to estimate survival distributions. A recursive partitioning model was used to identify prognostic factors that were associated with event-free survival (EFS). Cox proportional hazards regression models were used to estimate the association between patient characteristics and the risk of failure or death. RESULTS:: For all patients with intermediate-risk RMS, a recursive partitioning algorithm for EFS suggested that prognostic groups should be defined optimally by tumor volume (with a transition point at 20 cm(3)), patient weight (with a transition point at 50 kg), and embryonal histology. Tumor volume and patient weight added significant outcome information to the standard prognostic factors, including greatest tumor dimension and patient age (P = .02). The ability to resect the tumor completely was not associated significantly with the size of the patient, and patient weight did not significantly modify the association between tumor volume and EFS after adjustment for standard risk factors (P = .2). CONCLUSIONS:: The factors that had the strongest association with EFS were tumor volume, patient weight, and histology. On the basis of regression modeling, tumor volume and patient weight were superior predictors of outcome compared with greatest tumor dimension and patient age in children with intermediate-risk RMS. The current results indicated that the prognostic performance of tumor volume and patient weight should be assessed in an independent prospective study. Cancer 2011. © 2010 American Cancer Society.

    View details for DOI 10.1002/cncr.25719

    View details for PubMedID 21157950

    View details for PubMedCentralID PMC3117103

  • Early Treatment Failure in Intermediate-Risk Rhabdomyosarcoma: Results From IRS-IV and D9803-A Report From the Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY Minn, A. Y., Lyden, E. R., Anderson, J. R., Million, L., Arndt, C. A., Brown, K., Hawkins, D. S., Donaldson, S. S. 2010; 28 (27): 4228-4232


    The goal of this study was to determine the frequency and clinical features of early treatment failure during induction chemotherapy before protocol radiation therapy for children with intermediate-risk rhabdomyosarcoma (RMS).Patients with intermediate-risk RMS enrolled onto the Intergroup Rhabdomyosarcoma Study-IV and the Children's Oncology Group D9803 study were reviewed for an early treatment failure. Early failure was defined as failure caused by progressive disease, death as a result of progressive disease, or death as a result of other causes occurring fewer than 120 days from study entry. Patients with parameningeal site RMS with high-risk features who received radiation therapy at week 1 were excluded from analysis. Overall survival (OS) was estimated using the Kaplan-Meier method. Fisher's exact test was used to compare differences between groups. Cumulative incidence of progression was estimated.Of 916 patients, 20 (2.2%) were found to have an early disease progression and did not receive planned protocol radiotherapy. Three additional early failures resulted from treatment-related death without progression. Median time to failure was 48 days (range, 7 to 106 days). Nineteen (95%) of the 20 patients experienced progression at their primary site. Five-year OS was 32% (95% CI, 12% to 54%) for patients experiencing an early progression.A small proportion of patients with intermediate-risk RMS suffer an early failure as a result of early progression (2.2%) or treatment-related mortality (0.3%). The majority of patients with early progression had a local failure. Earlier radiotherapy could potentially improve outcome by preventing early local progression.

    View details for DOI 10.1200/JCO.2010.29.0247

    View details for Web of Science ID 000281909700020

    View details for PubMedID 20713850

    View details for PubMedCentralID PMC2953975

  • Undifferentiated High-Grade Pleomorphic Sarcomas in Children: A Clinicopathologic Study of 10 Cases and Review of Literature PEDIATRIC AND DEVELOPMENTAL PATHOLOGY Alaggio, R., Collini, P., Randall, R. L., Barnette, P., Million, L., Coffin, C. M. 2010; 13 (3): 209-217


    Undifferentiated high-grade pleomorphic sarcoma (UHGPS) is a sarcoma of debated nosology affecting adults, with rare cases reported in children. In order to investigate the clinicopathologic and prognostic features of pediatric UHGPS, 10 cases of UHGPS occurring before 18 years (mean age, 8.9 years) were analyzed. All were localized at diagnosis (head, 4; lower extremities, 4; trunk, 2), with a mean diameter of 4.5 cm. Mean follow-up was 6 years. Six patients were in complete remission, 1 after a relapse; 2 died of metastatic disease; 1 was alive with metastasis. Histologically, 8 tumors showed spindle cells with a focal or diffuse storiform pattern; 2 tumors had scattered aggregates of epithelioid cells. Two tumors displayed a prominent epithelioid component. Cellular pleomorphism, high mitotic rate with atypical mitoses, were found in all tumors; necrosis in 6 and vascular invasion in 2. CD68 and desmin were positive in 2 cases each, smooth muscle actin in 4, and S100 in 1. Five tumors in 1st and 1 in 2nd complete remission were superficial; 1 showed a spindle cell morphology with epithelioid foci, 3 had necrosis; 5 were grade 3; and 1 was grade 2. Three metastatic tumors (2 in the dura, 1 in the leg) displayed either a prominent epithelioid morphology (2) or scattered aggregates of epithelioid cells (1), with a myxoid background in 1. All were grade 3 and showed foci of necrosis. In summary, UHGPS is rare in children and frequently located in the head. A more favorable outcome is associated with superficial location. Foci of epithelioid cell may portend an aggressive behavior.

    View details for DOI 10.2350/09-07-0673-OA.1

    View details for Web of Science ID 000280500400006

    View details for PubMedID 20055602