Nicholas Trakul, MD, PhD

All Publications

• Detection of Recurrence After Thoracic Stereotactic Ablative Radiotherapy Using FDG-PET-CT. Clinical lung cancer Sodji, Q. H., Harris, J. P., Quon, A., Modlin, L. A., Lau, B., Jiang, A., Trakul, N., Maxim, P. G., Diehn, M., Loo, B. W., Hiniker, S. M. 2022

  Abstract

  INTRODUCTION/BACKGROUND: Differentiating local recurrence (LR) from post-treatment changes following stereotactic ablative radiotherapy (SABR) for thoracic tumors is challenging. We sought to evaluate the performance of FDG-PET-CT in distinguishing recurrence from post-radiation changes in patients with stage I-II non-small cell lung cancer (NSCLC) treated with SABR.MATERIALS AND METHODS: We performed a retrospective review of patients with stage I-II NSCLC treated with SABR and subsequently followed with surveillance FDG-PET-CT scans from 2004 to 2014. The radiology reports were coded as 0 or 1 if minimally or substantially concerning for LR, respectively, and correlated with outcome. Prognostic factors for false-positive FDG-PET-CT were assessed using logistic regression models.RESULTS: We identified 145 patients meeting inclusion criteria for the retrospective analysis. Amongst the 39 (26.9%) patients with FDG-PET-CT scans concerning for LR 3 to 24 months after treatment, 14 were confirmed to have LR. Thus, the positive predictive value (PPV) of FDG-PET-CT in identifying LR was 36% (14/39). Factors associated with a false-positive scan included concerning FDG-PET-CT at the earliest post-treatment time point (3 months) (odds ratio 0.67, P= .04) and older age (odds ratio 2.3, P= .02).CONCLUSION: Our analysis indicates that the PPV of a concerning FDG-PET-CT after SABR for early-stage NSCLC is relatively low, especially at early post-treatment timepoints, but accuracy is improving over time with institutional experience.

  View details for DOI 10.1016/j.cllc.2022.01.006

  View details for PubMedID 35246393

• 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

  Abstract

  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

• Challenges in the re-irradiation of locally advanced head and neck cancers: outcomes and toxicities JOURNAL OF RADIATION ONCOLOGY Phuong, C., Pham, A., Batth, S. S., Tsao-Wei, D., Schechter, N., Jennelle, R. L., Trakul, N., Garsa, A. 2019; 8 (3): 259–66

  View details for DOI 10.1007/s13566-019-00394-y

  View details for Web of Science ID 000504749200002

• The use of texture-based radiomics CT analysis to predict outcomes in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy. The British journal of radiology Starkov, P., Aguilera, T. A., Golden, D. I., Shultz, D. B., Trakul, N., Maxim, P. G., Le, Q., Loo, B. W., Diehn, M., Depeursinge, A., Rubin, D. L. 2018: 20180228

  Abstract

  OBJECTIVE:: Stereotactic ablative radiotherapy (SABR) is being increasingly used as a non-invasive treatment for early-stage non-small cell lung cancer (NSCLC). A non-invasive method to estimate treatment outcomes in these patients would be valuable, especially since access to tissue specimens is often difficult in these cases.METHODS:: We developed a method to predict survival following SABR in NSCLC patients using analysis of quantitative image features on pre-treatment CT images. We developed a Cox Lasso model based on two-dimensional Riesz wavelet quantitative texture features on CT scans with the goal of separating patients based on survival.RESULTS:: The median log-rank p-value for 1000 cross-validations was 0.030. Our model was able to separate patients based upon predicted survival. When we added tumor size into the model, the p-value lost its significance, demonstrating that tumor size is not a key feature in the model but rather decreases significance likely due to the relatively small number of events in the dataset. Furthermore, running the model using Riesz features extracted either from the solid component of the tumor or from the ground glass opacity (GGO) component of the tumor maintained statistical significance. However, the p-value improved when combining features from the solid and the GGO components, demonstrating that there are important data that can be extracted from the entire tumor.CONCLUSIONS:: The model predicting patient survival following SABR in NSCLC may be useful in future studies by enabling prediction of survival-based outcomes using radiomics features in CT images.ADVANCES IN KNOWLEDGE:: Quantitative image features from NSCLC nodules on CT images have been found to significantly separate patient populations based on overall survival (p = 0.04). In the long term, a non-invasive method to estimate treatment outcomes in patients undergoing SABR would be valuable, especially since access to tissue specimens is often difficult in these cases.

  View details for PubMedID 30457885

• Challenges in the Re-Irradiation of Locally Advanced Head and Neck Cancers: Outcomes and Toxicity from a Single Institution Phuong, C., Pham, A., Batth, S., Tsao-Wei, D., Garsa, A. A., Schechter, N., Jennelle, R. L., Trakul, N. ELSEVIER SCIENCE INC. 2018: E32

  View details for Web of Science ID 000432447200076

• Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR). Radiotherapy and oncology Chaudhuri, A. A., Binkley, M. S., Rigdon, J., Carter, J. N., Aggarwal, S., Dudley, S. A., Qian, Y., Kumar, K. A., Hara, W. Y., Gensheimer, M., Nair, V. S., Maxim, P. G., Shultz, D. B., Bush, K., Trakul, N., Le, Q., Diehn, M., Loo, B. W., Guo, H. H. 2016; 119 (3): 454-460

  Abstract

  To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR).We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade ⩾ 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake.Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001).Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.

  View details for DOI 10.1016/j.radonc.2016.05.007

  View details for PubMedID 27267049

• Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Trakul, N., Jacobs, L. R., von Eyben, R., Quynh-Thu Le, Q. T., Maxim, P. G., Loo, B. W., Shultz, D. B., Diehn, M. 2015; 92 (5): 1044-1052

  Abstract

  Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes.We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses.We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED10) of <100 Gy versus BED10 of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed.SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

  View details for DOI 10.1016/j.ijrobp.2015.04.004

  View details for Web of Science ID 000357900600024

  View details for PubMedID 26025776

• Stereotactic ablative radiotherapy (SABR) for treatment of central and ultra-central lung tumors LUNG CANCER Chaudhuri, A. A., Tang, C., Binkley, M. S., Jin, M., Wynne, J. F., von Eyben, R., Hara, W. Y., Trakul, N., Loo, B. W., Diehn, M. 2015; 89 (1): 50-56

  Abstract

  Treatment of central and ultra-central lung tumors with stereotactic ablative radiotherapy (SABR) remains controversial due to risks of treatment-related toxicities compared with peripheral tumors. Here we report our institution's experience in treating central and ultra-central lung tumor patients with SABR.We retrospectively reviewed outcomes in 68 patients with single lung tumors, 34 central and 34 peripheral, all treated with SABR consisting of 50 Gy in 4-5 fractions. Tumor centrality was defined per the RTOG 0813 protocol. We defined "ultra-central" tumors as those with GTV directly abutting the central airway.Median follow-up time was 18.4 months and median overall survival was 38.1 months. Two-year overall survival was similar between ultra-central, central, and peripheral NSCLC (80.0% vs. 63.2% vs. 86.6%, P=0.62), as was 2-year local failure (0% vs. 10.0% vs. 16.3%, P=0.64). Toxicity rates were low and comparable between the three groups, with only two cases of grade 3 toxicity (chest wall pain), and one case of grade 4 toxicity (pneumonitis) observed. Patients with ultra-central tumors experienced no symptomatic toxicities over a median follow-up time of 23.6 months. Dosimetric analysis revealed that RTOG 0813 central airway dose constraints were frequently not achieved in central tumor treatment plans, but this did not correlate with increased toxicity rate.Patients with central and ultra-central lung tumors treated with SABR (50 Gy in 4-5 fractions) experienced few toxicities and good outcomes, similar to patients with peripheral lung tumors.

  View details for DOI 10.1016/j.lungcan.2015.04.014

  View details for Web of Science ID 000356546300010

  View details for PubMedID 25997421

• Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

  Abstract

  Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema.We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3).27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, -0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, -3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r(2)=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r(2)=0.47, P<.0001).We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.

  View details for DOI 10.1016/j.ijrobp.2014.05.025

  View details for Web of Science ID 000341456500029

• Lung volume reduction after stereotactic ablative radiation therapy of lung tumors: potential application to emphysema. International journal of radiation oncology, biology, physics Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

  Abstract

  Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema.We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3).27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, -0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, -3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r(2)=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r(2)=0.47, P<.0001).We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.

  View details for DOI 10.1016/j.ijrobp.2014.05.025

  View details for PubMedID 25015205

• Imaging Features Associated With Disease Progression After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer CLINICAL LUNG CANCER Shultz, D. B., Trakul, N., Abelson, J. A., Murphy, J. D., Maxim, P. G., Quynh-Thu Le, Q. T., Loo, B. W., Diehn, M. 2014; 15 (4): 294-301

  Abstract

  The aim of this study was to identify imaging-based predictors of progression in patients treated with SABR for stage I NSCLC.Between March 2003 and December 2012, 117 patients with stage I NSCLC meeting our study criteria were treated with SABR at Stanford University. Median follow-up was 17 months (range, 3-74 months) for all patients and 19 months for living patients (range, 3-74 months). Tumors were classified according to whether or not they contacted the pleura adjacent to the chest wall or mediastinum (MP), according to their maximum dimension based on computed tomography scans, and, for 102 patients who had archived pretreatment fluorine-18 fluorodeoxyglucose positron-emission tomography scans, according to SUVmax.Ten patients (9%) developed local progression, 17 (15%) developed regional progression, and 19 (16%) developed distant metastasis. Two-year freedom from local progression, freedom from regional progression, and freedom from distant metastasis (FFDM) were 88%, 83%, and 83%, respectively. Overall survival was 70% at 2 years. FFDM was significantly associated with MP contact, maximum tumor dimension, and SUVmax, and these variables could be combined into an exploratory prognostic index that identified patients at highest risk for developing metastases.In our cohort, noninvasive, imaging-based features were associated with distant progression after SABR for early stage NSCLC. If validated, our prognostic index could allow identification of patients who might benefit from systemic therapy after SABR.

  View details for DOI 10.1016/j.cllc.2013.12.011

  View details for Web of Science ID 000338412800007

• Imaging features associated with disease progression after stereotactic ablative radiotherapy for stage I non-small-cell lung cancer. Clinical lung cancer Shultz, D. B., Trakul, N., Abelson, J. A., Murphy, J. D., Maxim, P. G., Le, Q., Loo, B. W., Diehn, M. 2014; 15 (4): 294-301 e3

  Abstract

  The aim of this study was to identify imaging-based predictors of progression in patients treated with SABR for stage I NSCLC.Between March 2003 and December 2012, 117 patients with stage I NSCLC meeting our study criteria were treated with SABR at Stanford University. Median follow-up was 17 months (range, 3-74 months) for all patients and 19 months for living patients (range, 3-74 months). Tumors were classified according to whether or not they contacted the pleura adjacent to the chest wall or mediastinum (MP), according to their maximum dimension based on computed tomography scans, and, for 102 patients who had archived pretreatment fluorine-18 fluorodeoxyglucose positron-emission tomography scans, according to SUVmax.Ten patients (9%) developed local progression, 17 (15%) developed regional progression, and 19 (16%) developed distant metastasis. Two-year freedom from local progression, freedom from regional progression, and freedom from distant metastasis (FFDM) were 88%, 83%, and 83%, respectively. Overall survival was 70% at 2 years. FFDM was significantly associated with MP contact, maximum tumor dimension, and SUVmax, and these variables could be combined into an exploratory prognostic index that identified patients at highest risk for developing metastases.In our cohort, noninvasive, imaging-based features were associated with distant progression after SABR for early stage NSCLC. If validated, our prognostic index could allow identification of patients who might benefit from systemic therapy after SABR.

  View details for DOI 10.1016/j.cllc.2013.12.011

  View details for PubMedID 24594400

• Vagal and recurrent laryngeal neuropathy following stereotactic ablative radiation therapy in the chest. Practical radiation oncology Shultz, D. B., Trakul, N., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 4 (4): 272-278

  Abstract

  To identify clinical and dosimetric factors associated with vagus nerve (VN) and recurrent laryngeal nerve (RecLN) injury following stereotactic ablative radiation therapy (SABR) in the chest.We examined the clinical courses and SABR plans of 67 patients treated for T1 or T2 non-small cell lung cancer of the upper right or left lung, including 2 who developed vocal cord paresis (VCP) following treatment. After developing a contouring atlas for the VN and RecLN in the thorax, dose to those structures was retrospectively determined for each patient, and we identified 12 patients whose treatment imparted significant dose to either nerve and who were assessable for more than 12 months follow-up. Biologically effective doses using linear-quadratic (LQ) and linear quadratic-linear (LQ-L) modeling were correlated with VN and RecLN toxicity.Of 12 patients, 2 developed VCP. The first underwent repeat SABR and received a cumulative single fraction equivalent dose (alpha/beta = 3; SFED3) of 37.4 or 64.5 Gy to the VN and 13.7 or 15.3 Gy to the RecLN (by LQ or LQ-L modeling, respectively). This was the highest VN dose and fifth highest RecLN dose in the cohort. The second had rheumatoid arthritis and connective tissue disease and received a SFED3 of 16 Gy to the VN and 19.5 Gy to the RecLN (by both LQ and LQ-L modeling). This was in the upper tertile of VN and RecLN doses for the cohort.Following SABR for non-small cell lung cancer, VCP was associated with high cumulative dose to the VN in 1 patient and a moderately high dose to the VN and RecLN in another patient with rheumatoid arthritis and connective tissue disease. Particularly in the setting of reirradiation or connective tissue disease, potential toxicity to the VN or RecLN should be considered.

  View details for DOI 10.1016/j.prro.2013.08.005

  View details for PubMedID 25012837

• Stereotactic Body Radiotherapy in the Treatment of Pancreatic Cancer SEMINARS IN RADIATION ONCOLOGY Trakul, N., Koong, A. C., Chang, D. T. 2014; 24 (2): 140-147

  Abstract

  Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effectiveness, and further investigation is currently underway. Here, we review the technology behind SBRT for pancreatic malignancy and its future direction in the overall management of pancreatic cancer.

  View details for DOI 10.1016/j.semradonc.2013.11.008

  View details for Web of Science ID 000333435300010

• Stereotactic body radiotherapy in the treatment of pancreatic cancer. Seminars in radiation oncology Trakul, N., Koong, A. C., Chang, D. T. 2014; 24 (2): 140-147

  Abstract

  Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effectiveness, and further investigation is currently underway. Here, we review the technology behind SBRT for pancreatic malignancy and its future direction in the overall management of pancreatic cancer.

  View details for DOI 10.1016/j.semradonc.2013.11.008

  View details for PubMedID 24635871

• Early-stage non-small cell lung cancer: surgery, stereotactic radiosurgery, and individualized adjuvant therapy. Seminars in oncology Padda, S. K., Burt, B. M., Trakul, N., Wakelee, H. A. 2014; 41 (1): 40-56

  Abstract

  Despite cures in early stage (IA-IIB) non-small cell lung cancer (NSCLC), the 5-year survival rate is only 36%-73%. Surgical resection via lobectomy is the treatment of choice in early-stage NSCLC, with the goal being complete anatomic resection of the tumor and mediastinal lymph node evaluation. Newer technologies, including the minimally invasive thoracoscopic approach and the many techniques available to stage the mediastinum, have introduced advantages over traditional approaches in achieving this goal. The advent of stereotactic ablative radiotherapy (SABR) has changed how we treat those patients who cannot undergo surgery secondary to comorbidities or patient preference. SABR allows for precise radiation delivery in a short course and at high doses. Adjuvant cisplatin-based chemotherapy is the standard of care for completely resected high-risk stage IB and stage II NSCLC based on a ~5% improvement in 5-year overall survival. The concept of customized adjuvant chemotherapy is emerging, and we will explore the potential value of targeting tumor mutations with available drugs (ie, epidermal growth factor receptor [EGFR] mutations with erlotinib), a strategy that for the moment should be restricted to clinical trials.

  View details for DOI 10.1053/j.seminoncol.2013.12.011

  View details for PubMedID 24565580

• Clinical impact of dose overestimation by effective path length calculation in stereotactic ablative radiation therapy of lung tumors. Practical radiation oncology Liu, M. B., Eclov, N. C., Trakul, N., Murphy, J., Diehn, M., Le, Q., Dieterich, S., Maxim, P. G., Loo, B. W. 2013; 3 (4): 294-300

  Abstract

  To determine the clinical impact of calculated dose differences between effective path length (EPL) and Monte Carlo (MC) algorithms in stereotactic ablative radiation therapy (SABR) of lung tumors.We retrospectively analyzed the treatment plans and clinical outcomes of 77 consecutive patients treated with SABR for 82 lung tumors between 2003 and 2009 at our institution. Sixty treatments were originally planned using EPL, and 22 using MC. All plans were recalculated for the same beam specifications using MC and EPL, respectively. The doses covering 95%, 50%, and 5% (D95, D50, D5, respectively) of the target volumes were compared between EPL and MC (assumed to be the actual delivered dose), both as physical dose and biologically effective dose. Time to local recurrence was correlated with dose by Cox regression analysis. The relationship between tumor control probability (TCP) and biologically effective dose was determined via logistic regression and used to estimate the TCP decrements due to prescribing by EPL calculations.EPL overestimated dose compared with MC in all tumor dose-volume histogram parameters in all plans. The difference was >10% of the MC D95 to the planning target volume and gross tumor volume in 60 of 82 (73%) and 52 of 82 plans (63%), respectively. Local recurrence occurred in 13 of 82 tumors. Controlling for gross tumor volume, higher physical and biologically effective planning target volume D95 correlated significantly with local control (P = .007 and P = .045, respectively). Compared with MC, prescribing based on EPL translated to a median TCP decrement of 4.3% (range, 1.2%-37%) and a >5% decrement in 46% of tumors.Clinical follow-up for local lung tumor control in a sizable cohort of patients treated with SABR demonstrates that EPL overestimates dose by amounts that substantially decrease TCP in a large proportion. EPL algorithms should be avoided for lung tumor SABR.

  View details for DOI 10.1016/j.prro.2012.09.003

  View details for PubMedID 24674401

• Metabolic imaging metrics correlate with survival in early stage lung cancer treated with stereotactic ablative radiotherapy LUNG CANCER Abelson, J. A., Murphy, J. D., Trakul, N., Bazan, J. G., Maxim, P. G., Graves, E. E., Quon, A., Quynh-Thu Le, Q. T., Diehn, M., Loo, B. W. 2012; 78 (3): 219-224

  Abstract

  To test whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging metrics correlate with outcomes in patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR).Fifty-four patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR PET within 6 months. We analyzed maximum standardized uptake value (SUV(max)) and metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7, and 10). Endpoints included primary tumor control (PTC), progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). We performed Kaplan-Meier, competing risk, and Cox proportional hazards survival analyses.Patients received 25-60 Gy in 1 to 5 fractions. Median follow-up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83, 87 and 94%, respectively. Pre-treatment SUV(max) (p=0.014), MTV(7) (p=0.0077), and MTV(10) (p=0.0039) correlated significantly with OS. In the low-MTV(7)vs. high-MTV(7) sub-groups, 1-year estimated OS was 100 vs. 78% (p=0.0077) and CSS was 100 vs. 88% (p=0.082).In this hypothesis-generating study we identified multiple pre-treatment PET-CT metrics as potential predictors of OS and CSS in patients with NSCLC treated with SABR. These could aid risk-stratification and treatment individualization if validated prospectively.

  View details for DOI 10.1016/j.lungcan.2012.08.016

  View details for Web of Science ID 000311881400008

• Metabolic imaging metrics correlate with survival in early stage lung cancer treated with stereotactic ablative radiotherapy. Lung cancer Abelson, J. A., Murphy, J. D., Trakul, N., Bazan, J. G., Maxim, P. G., Graves, E. E., Quon, A., Le, Q., Diehn, M., Loo, B. W. 2012; 78 (3): 219-224

  Abstract

  To test whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging metrics correlate with outcomes in patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR).Fifty-four patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR PET within 6 months. We analyzed maximum standardized uptake value (SUV(max)) and metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7, and 10). Endpoints included primary tumor control (PTC), progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). We performed Kaplan-Meier, competing risk, and Cox proportional hazards survival analyses.Patients received 25-60 Gy in 1 to 5 fractions. Median follow-up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83, 87 and 94%, respectively. Pre-treatment SUV(max) (p=0.014), MTV(7) (p=0.0077), and MTV(10) (p=0.0039) correlated significantly with OS. In the low-MTV(7)vs. high-MTV(7) sub-groups, 1-year estimated OS was 100 vs. 78% (p=0.0077) and CSS was 100 vs. 88% (p=0.082).In this hypothesis-generating study we identified multiple pre-treatment PET-CT metrics as potential predictors of OS and CSS in patients with NSCLC treated with SABR. These could aid risk-stratification and treatment individualization if validated prospectively.

  View details for DOI 10.1016/j.lungcan.2012.08.016

  View details for PubMedID 23009727

• Stereotactic Ablative Radiotherapy for Reirradiation of Locally Recurrent Lung Tumors JOURNAL OF THORACIC ONCOLOGY Trakul, N., Harris, J. P., Le, Q., Hara, W. Y., Maxim, P. G., Loo, B. W., Diehn, M. 2012; 7 (9): 1462-1465

  Abstract

  Patients with thoracic tumors that recur after irradiation currently have limited therapeutic options. Retreatment using stereotactic ablative radiotherapy (SABR) is appealing for these patients because of its high conformity but has not been studied extensively. Here we report our experience with SABR for lung tumors in previously irradiated regions.We conducted a retrospective study of patients with primary lung cancer or metastatic lung tumors treated with SABR. We identified 17 such tumors in 15 patients and compared their outcomes with those of a cohort of 135 previously unirradiated lung tumors treated with SABR during the same time period.Twelve-month local control (LC) for retreated tumors was 65.5%, compared with 92.1% for tumors receiving SABR as initial treatment. Twelve-month LC was significantly worse for reirradiated tumors in which the time interval between treatments was 16 months or less (46.7%), compared with those with longer intertreatment intervals (87.5%). SABR reirradiation did not lead to significant increases in treatment-related toxicity.SABR for locally recurrent lung tumors arising in previously irradiated fields seems to be feasible and safe for appropriately selected patients. LC of retreated lesions was significantly lower, likely owing to the lower doses used for retreatment. Shorter time to retreatment was associated with increased risk of local failure, suggesting that these tumors may be particularly radioresistant. Our findings suggest that dose escalation may improve LC while maintaining acceptable levels of toxicity for these patients.

  View details for DOI 10.1097/JTO.0b013e31825f22ce

  View details for Web of Science ID 000308073300024

  View details for PubMedID 22895143

• Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Trakul, N., Chang, C. N., Harris, J., Chapman, C., Rao, A., Shen, J., Quinlan-Davidson, S., Filion, E. J., Wakelee, H. A., Colevas, A. D., Whyte, R. I., Dieterich, S., Maxim, P. G., Hristov, D., Tran, P., Quynh-Thu Le, Q. T., Loo, B. W., Diehn, M. 2012; 84 (1): 231-237

  Abstract

  Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy.We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2).The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02).A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  View details for DOI 10.1016/j.ijrobp.2011.10.071

  View details for PubMedID 22381907

• Modern Radiation Therapy Techniques for Pancreatic Cancer GASTROENTEROLOGY CLINICS OF NORTH AMERICA Trakul, N., Koong, A. C., Maxim, P. G., Chang, D. T. 2012; 41 (1): 223-?

  Abstract

  Radiation therapy is a rapidly evolving field, and recent technical advances have spurred an increasing number of new treatments as well as marked improvements in previously existing treatments. Despite a growing body of published evidence demonstrating that radiotherapy for the treatment of pancreatic cancer is improving in efficacy and safety, the ultimate effect on patient outcomes remains to be seen. It is an unfortunate fact that the majority of pancreatic cancer patients will ultimately have metastases and succumb to distant disease. Thus, improvements in local tumor control engendered by these recent advances will have little impact on overall survival without the coincident development of better systemic treatment regimens.

  View details for DOI 10.1016/j.gtc.2011.12.011

  View details for PubMedID 22341260