Dr. Rahimy is a radiation oncologist who treats patients with brain, spine, and gastrointestinal tumors. She received her medical training at Yale, followed by a residency in radiation oncology at Stanford. She is a clinical assistant professor with the Stanford School of Medicine Department of Radiation Oncology.

Dr. Rahimy specializes in treating several types of cancer, including brain tumors, such as glioma and glioblastoma, spine tumors, metastatic disease, and gastrointestinal cancer, such as rectal cancer and pancreatic cancer. She is credentialed for CyberKnife Radiosurgery. She is also actively involved in radiation oncology research and clinical trials. Her interests include improving patient and resident education and enhancing patient quality of life and survivorship. Dr. Rahimy’s research has been published in a variety of journals. She is also the current radiation oncology medical student clerkship director.

Clinical Focus

  • Radiation Oncology
  • CyberKnife Radiosurgery
  • Brain and spine tumors
  • Metastatic disease
  • Gastrointestinal tumors

Academic Appointments

Administrative Appointments

  • Associate Program Director, Stanford Radiation Oncology Residency Program (2023 - Present)
  • Director, Radiation Oncology Medical Student Clerkship (2022 - Present)

Professional Education

  • Board Certification: American Board of Radiology, Radiation Oncology (2023)
  • Internship: Scripps Mercy Hospital San Diego (2018) CA
  • Residency: Stanford University Radiation Oncology Residency (2022) CA
  • Medical Education: Yale School Of Medicine (2017) CT

All Publications

  • Where Does Auto-Segmentation for Brain Metastases Radiosurgery Stand Today? Bioengineering (Basel, Switzerland) Kim, M., Wang, J. Y., Lu, W., Jiang, H., Stojadinovic, S., Wardak, Z., Dan, T., Timmerman, R., Wang, L., Chuang, C., Szalkowski, G., Liu, L., Pollom, E., Rahimy, E., Soltys, S., Chen, M., Gu, X. 2024; 11 (5)


    Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It not only alleviates the clinician's manual workload and improves clinical workflow efficiency but also ensures treatment safety, ultimately improving patient care. Recent strides in machine learning, particularly in deep learning (DL), have revolutionized medical image segmentation, achieving state-of-the-art results. This review aims to analyze auto-segmentation strategies, characterize the utilized data, and assess the performance of cutting-edge BM segmentation methodologies. Additionally, we delve into the challenges confronting BM segmentation and share insights gleaned from our algorithmic and clinical implementation experiences.

    View details for DOI 10.3390/bioengineering11050454

    View details for PubMedID 38790322

  • Treatment of Trigeminal Neuralgia Secondary to Petroclival Meningioma Using Microsurgical Resection, Microvascular Decompression, and Stereotactic Radiosurgery: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Park, D. J., Kumar, K. K., Marianayagam, N. J., Yener, U., Rahimy, E., Hancock, S., Meola, A., Chang, S. D. 2024; 26 (1): 107-108

    View details for DOI 10.1227/ons.0000000000000927

    View details for PubMedID 38099694

  • ASO Visual Abstract: Patterns of Recurrence after Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation. Annals of surgical oncology Hui, C., Ewongwo, A., Lau, B., Fisher, G., Delitto, D., Poultsides, G., Ho, Q. A., Rahimy, E., Pollom, E., Chang, D. T., Vitzthum, L. K. 2023

    View details for DOI 10.1245/s10434-023-14475-3

    View details for PubMedID 37875741

  • Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation. Annals of surgical oncology Hui, C., Ewongwo, A., Lau, B., Fisher, G., Delitto, D., Poultsides, G., Ho, Q., Rahimy, E., Pollom, E., Chang, D. T., Vitzthum, L. K. 2023


    BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy.PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence.RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR.CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

    View details for DOI 10.1245/s10434-023-14350-1

    View details for PubMedID 37755563

  • Performance Analysis of a Radiation Oncology Educational Podcast. Journal of the American College of Radiology : JACR Wu, T. C., No, H. J., Rahimy, E., Kishan, A. U., Steinberg, M. L., Raldow, A. C., Beadle, B. M. 2023


    Asynchronous podcast education is a popular supplementary tool with up to 88% of medical residents reporting its use. Radiation Oncology podcasts remain scarce. We analyze the early performance, listenership, and engagement of the first education-specific Radiation Oncology medical podcast.Episode data and listener demographics were gathered from Spotify and Apple Podcasts. Episodes were case based, categorized by disease subsite, and reviewed by a board-certified radiation oncologist. Listenership was defined by the number of plays per day (ppd) on unique devices, averaged up to 60 days from publication. Episode engagement was defined as a percentage of plays on unique devices playing >40% of an episode within a single session. Quantitative endpoints included episode engagement and listenership. Pearson's correlation coefficient calculations were used for analysis.From July 2022 to March 2023, twenty total episodes had 13,078 total plays over 227 days. Median episode length was 13.8 minutes (range 9.2-20.1). Listener demographics included 54.4% male, 44.0% female, 1.3% not specified, and 0.3% non-binary, ranging from ages 18-22 (1%), 23-27 (13%), 28-34 (58%), 35-44 (22%), 45-59 (4%), and 60+ (2%) years. Episodes were played in 53 countries, with the most plays in North America (71.5%), followed by Asia (10.2%), Europe (8.2%), Oceania (8.0%), Africa (1.5%), and South America (0.5%). There was a 585.2% increase in listenership since initiation with median growth of 46.0% per month. Median listenership and engagement were 11.3 ppd (IQR, 10.3-13.8 ppd) and 81.4% (IQR, 72.0-84.2%) for all episodes, respectively. A significant negative relationship between episode length and engagement was observed (r(20) = -0.51, P=0.02). There were no statistically significant relationship between ppd and episode length (r(20) = -0.19, P=0.42).The significant rise in listenership, high episode engagement, and large international audience supports a previously unmet need in Radiation Oncology medical education that may be supplemented by podcasts.

    View details for DOI 10.1016/j.jacr.2023.06.026

    View details for PubMedID 37516159

  • Lessons and Opportunities for Biomarker-Driven Radiation Personalization in Head and Neck Cancer. Seminars in radiation oncology Rahimy, E., Gensheimer, M. F., Beadle, B., Le, Q. T. 2023; 33 (3): 336-347


    Head and neck cancer is notoriously challenging to treat in part because it constitutes an anatomically and biologically diverse group of cancers with heterogeneous prognoses. While treatment can be associated with significant late toxicities, recurrence is often difficult to salvage with poor survival rates and functional morbidity.1,2 Thus, achieving tumor control and cure at the initial diagnosis is the highest priority. Given the differing outcome expectations (even within a specific sub-site like oropharyngeal carcinoma), there has been growing interest in personalizing treatment: de-escalation in selected cancers to decrease the risk of late toxicity without compromising oncologic outcomes, and intensification for more aggressive cancers to improve oncologic outcomes without causing undue toxicity. This risk stratification is increasingly accomplished using biomarkers, which can represent molecular, clinicopathologic, and/or radiologic data. In this review, we will focus on biomarker-driven radiotherapy dose personalization with emphasis on oropharyngeal and nasopharyngeal carcinoma. This radiation personalization is largely performed on the population level by identifying patients with good prognosis via traditional clinicopathologic factors, although there are emerging studies supporting inter-tumor and intra-tumor level personalization via imaging and molecular biomarkers.

    View details for DOI 10.1016/j.semradonc.2023.03.013

    View details for PubMedID 37331788

  • Radiation Oncology Virtual Education Rotation (ROVER) 2.0 for Residents: Implementation and Outcomes. Journal of cancer education : the official journal of the American Association for Cancer Education Sandhu, N. K., Rahimy, E., Hutten, R., Shukla, U., Rajkumar-Calkins, A., Miller, J. A., Von Eyben, R., Deig, C. R., Obeid, J., Jimenez, R. B., Fields, E. C., Pollom, E. L., Kahn, J. M. 2022


    The COVID-19 pandemic catalyzed the integration of a virtual education curriculum to support radiation oncologists in training. We report outcomes from Radiation Oncology Virtual Education Rotation (ROVER) 2.0, a supplementary virtual educational curriculum created for radiation oncology residents globally. A prospective cohort of residents completed surveys before and after the live virtual webinar sessions (pre- and post-surveys, respectively). Live sessions were structured as complex gray-zone cases across various core disease sites. Resident demographics and responses were summarized using means, standard deviations, and proportions. Nine ROVER sessions were held from October 2020 to June 2021. A total of 1487 registered residents completed the pre-survey, of which 786 attended the live case discussion and 223 completed post-surveys. A total of 479 unique radiation oncology residents (of which 95, n=19.8%, were international attendees) from 147 institutions (national, n=81, 55.1%; international, n=66, 44.9%) participated in the sessions. There was similar participation across post-graduate year (PGY) 2 through 5 (range n=86 to n=105). Of the 122 unique resident post-surveys, nearly all reported learning through the virtual structure as "very easy" or "easy" (97.5%, n=119). A majority rated the ROVER 2.0 educational sessions to be "valuable or "very valuable" (99.2%, n=121), and the panelists-attendee interaction as "appropriate" (97.5%, n=119). Virtual live didactics aimed at radiation oncology residents are feasible. These results suggest that the adoption of the ROVER 2.0 curricula may help improve radiation oncology resident education.

    View details for DOI 10.1007/s13187-022-02216-1

    View details for PubMedID 36083458

  • Post-operative Stereotactic Radiosurgery of Malignant Melanotic Schwannoma. Cureus Hall, J. C., Chang, S. D., Wilson, T. J., Ganjoo, K. N., Toland, A., Vogel, H., Pollom, E. L., Rahimy, E. 2022; 14 (3): e22849


    Melanotic schwannoma is an extremely rare schwannoma variant with malignant potential, demonstrating high local and distant recurrence. Given the paucity of data, recommended treatment with localized disease is radical resection, with the unclear benefit of adjuvant therapy.We present a case of an 18-year-old female with no past medical history or genetic syndromeswho underwent margin-positive resection of an S1 nerve root melanotic schwannoma followed by adjuvant stereotactic radiosurgery (SRS). SRS was delivered without acute or late toxicity by 2.5 years post-treatment. She remains without evidence of recurrent disease, although longer follow-up is needed given the risk of late recurrence. Our case adds to the limited literature documenting the efficacy of adjuvant radiotherapy in melanotic schwannoma and is the first to describe the successful use of SRS for this rare disease.

    View details for DOI 10.7759/cureus.22849

    View details for PubMedID 35399431

  • Evaluating dosimetric parameters predictive of hematologic toxicity in cervical cancer patients undergoing definitive pelvic chemoradiotherapy. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] Rahimy, E., von Eyben, R., Lewis, J., Hristov, D., Kidd, E. 1800


    PURPOSE: We performed aretrospective study of cervical cancer pelvic radiotherapy plans to explore dosimetric parameters predictive of hematologic toxicity (HT), with specific interest in evaluating metabolic parameters and identifying the best predictive model.METHODS: Active marrow was retroactively contoured as pelvic bone with SUV >mean on 18F-FDG-PET. "Highly active" marrow was contoured as the hottest 10-14% volume of active marrow. Pelvic bone contour was segmented into lumbosacral, iliac crest, and lower pelvis. Predictors of HT were evaluated using logistic regression and repeated measures modeling.RESULTS: One hundred women were evaluated from 2009 to 2020. The plurality/majority had stage IIIC1 disease (38%) and underwent IMRT (88%) with pelvic field alone (72%). The majority received weekly cisplatin (78%), and 82% completed at least five cycles. The most common HT was leukopenia (grade2+: 68%). Predictors of grade2+ and3+ HT were baseline WBC (p <0.001), and 10-and 20-Gy dosimetric parameters to the active marrow, highly active marrow, and pelvic bone. The best predictive model of leukocyte trajectory included baseline WBC (p <0.001), highly active marrow V20 (p <0.001), and interactions of baseline WBC with time (p <0.001) and highly active marrow V20 (p <0.001), such that those with low baseline WBC experienced the greatest impact of highly active marrow V20.CONCLUSION: Baseline WBC was highly predictive of HT; dosimetric predictors included dose to the active marrow, highly active marrow, and pelvic bone, with the greatest impact from V20 to the highly active marrow, particularly in women with low baseline WBC. Future studies should consider incorporating baseline WBC and limiting dose to the most highly active marrow.

    View details for DOI 10.1007/s00066-021-01885-z

    View details for PubMedID 35059758

  • Phase II Trial Evaluating Efficacy of a Fitbit Program for Improving the Health of Endometrial Cancer Survivors Rahimy, E., Usoz, M., von Eyben, R., Fujimoto, D., Watanabe, D., Karam, A., Jairam-Thodla, A., Mills, M., Dorigo, O., Diver, E., Teng, N., English, D., Kidd, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S13
  • Stereotactic Radiotherapy for Recurrent Post- Transplant Primary Central Nervous System Lymphoma CUREUS Benitez, C. M., Rahimy, E., Panjwani, N., Maeda, L. S., Soltys, S. G. 2021; 13 (7)
  • #TrendingNow: Instagram versus Twitter Activity Among Radiation Oncology Patients and Providers. Practical radiation oncology Rahimy, E., Sandhu, N. K., Giao, D. M., Pollom, E. L. 2021


    PURPOSE: We aimed to evaluate recent Instagram and Twitter posts to identify the primary disseminators of information related to radiation therapy on social media (healthcare professionals versus patients), to characterize their influencer status, and to characterize the content of this information.METHODS: Using two commercial hashtag analytics platforms, 1,000 of the most recent eligible posts from each platform were evaluated for content, tone, and engagement, as well as user (poster) characteristics. Inclusion criteria were as follows: unique posts, written in English, relevant to human cancer treatment, and contains one of 11 predetermined hashtags (#radiation, #radiotherapy, #radiationtherapy, #radiationoncology, #radonc, #radiationtherapist #radiationtreatment, #medphys, #cyberknife, #radiosurgery, #protontherapy).RESULTS: Users of radiation oncology content on Instagram were primarily patients/caregivers (47%), specifically adult patients (94%) with breast cancer (53%). Patient/caregiver content was focused on patient experience (79%), with approximately half specific to radiation therapy (51%), and most patient/caregiver posts demonstrated a positive tone (86%). In contrast, Twitter content was dominated by health care professionals (53%), specifically within radiation oncology (90% of unique users). Health care professional content was focused on colleague education/research dissemination (53%), with a high proportion of posts specific to radiation therapy (95%).CONCLUSIONS: Given the disproportionate number of patients versus radiation oncology professionals active on Instagram versus Twitter, and the lack of radiation therapy-specific content on Instagram, there may be an opportunity to improve patient outreach and education by promoting presence of radiation oncologists within Instagram.

    View details for DOI 10.1016/j.prro.2021.06.008

    View details for PubMedID 34233217

  • Technical report: 3D-printed patient-specific scalp shield for hair preservation in total skin electron beam therapy. Technical innovations & patient support in radiation oncology Rahimy, E., Skinner, L., Kim, Y. H., Hoppe, R. T. 2021; 18: 12-15


    Techniques for non-lead scalp-shielding in total skin therapy are lacking.3D-printing is a promising technique for patient-specific conformal shielding.We present a case of effective scalp shielding with 3D-printing.

    View details for DOI 10.1016/j.tipsro.2021.03.002

    View details for PubMedID 33997322

  • Phase I/II Dose-Escalation Trial of 3-Fraction Stereotactic Radiosurgery for Resection Cavities From Large Brain Metastases: Health-related Quality of Life Outcomes. American journal of clinical oncology Rahimy, E., Dudley, S. A., von Eyben, R., Pollom, E. L., Seiger, K., Modlin, L., Wynne, J., Fujimoto, D., Jacobs, L. R., Chang, S. D., Gibbs, I. C., Hancock, S. L., Adler, J. R., Li, G., Choi, C. Y., Soltys, S. G. 2021; 44 (11): 588-595


    We investigated differences in quality of life (QoL) in patients enrolled on a phase I/II dose-escalation study of 3-fraction resection cavity stereotactic radiosurgery (SRS) for large brain metastases.Eligible patients had 1 to 4 brain metastases, one of which was a resection cavity 4.2 to 33.5 cm3. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires core-30 (QLQ-30) and brain cancer specific module (QLQ-BN20) were obtained before SRS and at each follow-up. Nine scales were analyzed (global health status; physical, social, and emotional functioning; motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty). QoL was assessed with mixed effects models. Differences ≥10 points with q-value (adjusted P-value to account for multiplicity of testing) <0.10 were considered significant.Between 2009 and 2014, 50 enrolled patients completed 277 QoL questionnaires. Median questionnaire follow-up was 11.8 months. After SRS, insomnia demonstrated significant improvement (q=0.032, -17.7 points at 15 mo post-SRS), and future uncertainty demonstrated significant worsening (q=0.018, +9.9 points at 15 mo post-SRS). Following intracranial progression and salvage SRS, there were no significant QoL changes. The impact of salvage whole brain radiotherapy could not be assessed because of limited data (n=4 patients). In the 28% of patients that had adverse radiation effect, QoL had significant worsening in 3 metrics (physical functioning, q=0.024, emotional functioning q=0.001, and future uncertainty, q=0.004).For patients treated with 3-fraction SRS for large brain metastasis cavities, 8 of 9 QoL metrics were unchanged or improved after initial SRS. Intracranial tumor progression and salvage SRS did not impact QoL. Adverse radiation effect may be associated with at least short-term QoL impairments, but requires further investigation.

    View details for DOI 10.1097/COC.0000000000000868

    View details for PubMedID 34670228

  • Telemedicine in Radiation Oncology: Is It Here to Stay? Impacts on Patient Care and Resident Education. International journal of radiation oncology, biology, physics Gutkin, P. M., Prionas, N. D., Minneci, M. O., Allen, E. 3., Balazy, K. E., Rahimy, E., Chang, D. T., Horst, K. C. 2020; 108 (2): 416–20


    PURPOSE: Telemedicine was rapidly and ubiquitously adopted during the COVID-19 pandemic. However, there are growing discussions as to its role postpandemic.METHODS AND MATERIALS: We surveyed patients, radiation oncology (RO) attendings, and RO residents to assess their experience with telemedicine. Surveys addressed quality of patient care and utility of telemedicine for teaching and learning core competencies. Satisfaction was rated on a 6-point Likert-type scale. The quality of teaching and learning was graded on a 5-point Likert-type scale, with overall scores calculated by the average rating of each core competency required by the Accreditation Council for Graduate Medical Education (range, 1-5).RESULTS: Responses were collected from 56 patients, 12 RO attendings, and 13 RO residents. Patient feedback was collected at 17 new-patient, 22 on-treatment, and 17 follow-up video visits. Overall, 88% of patients were satisfied with virtual visits. A lower proportion of on-treatment patients rated their virtual visit as "very satisfactory" (68.2% vs 76.5% for new patients and 82.4% for follow-ups). Only 5.9% of the new patients and none of the follow-up patients were dissatisfied, and 27% of on-treatment patients were dissatisfied. The large majority of patients (88%) indicated that they would continue to use virtual visits as long as a physical examination was not needed. Overall scores for medical training were 4.1 out of 5 (range, 2.8-5.0) by RO residents and 3.2 (range, 2.0-4.0) by RO attendings. All residents and 92% of attendings indicated they would use telemedicine again; however, most indicated that telemedicine is best for follow-up visits.CONCLUSIONS: Telemedicine is a convenient means of delivering care to patients, with some limitations demonstrated for on-treatment patients. The majority of both patients and providers are interested in using telemedicine again, and it will likely continue to supplement patient care.

    View details for DOI 10.1016/j.ijrobp.2020.06.047

    View details for PubMedID 32890524

  • Outcomes and Tolerability of Definitive and Preoperative Chemoradiation in Elderly Patients With Esophageal Cancer: A Retrospective Institutional Review. Advances in radiation oncology Rahimy, E. n., Koong, A. n., Toesca, D. n., White, M. N., Panjwani, N. n., Fisher, G. n., Chang, D. n., Pollom, E. n. 2020; 5 (6): 1188–96


    Our purpose was to report outcomes of elderly patients who underwent definitive treatment involving radiation therapy for esophageal cancer at our institution.We performed a retrospective review of patients aged ≥75 years with esophageal cancer treated with definitive radiation therapy (≥45 Gy) at our institution from 1997 to 2019. Acute and late Radiation Therapy Oncology Group grade 3+ toxicities were recorded. Survival was estimated using the Kaplan-Meier method.Of the 89 patients included, median age was 80 and 78% were male. Median adjusted Charlson Comorbidity Index and Karnofsky Performance Status were 5 (3-12) and 80 (50-100), respectively. The majority of cancers were adenocarcinoma (58%), distal (67%), and stage III (62%). Fifty-eight percent underwent definitive chemoradiotherapy, and one-third underwent preoperative intent chemoradiotherapy. Median prescribed dose was 50 Gy (45-66 Gy), and intensity modulated radiation therapy was used in 76%. Eighty-five percent completed the radiation therapy course. Among these, 20% had radiation therapy breaks. For those receiving concurrent chemotherapy, 37% had a dose reduction and 39.5% had a break/cycle reduction. Acute grade 3+ toxicity was 22%, with 2% grade 5 toxicity. Twenty-one of the 29 patients (72%) treated with preoperative intent underwent surgery. There were no deaths 90 days postoperatively. For patients who underwent surgery, 1- and 2-year overall survival were 95% and 84%. For those who did not undergo surgery, 1- and 2-year overall survival were 70% and 52%.There is a role for aggressive radiation therapy in well-selected elderly patients with esophageal cancer. However, optimization of supportive care, chemotherapy regimens, radiation therapy dose/fractionation, and surgical indications are needed to reduce toxicity.

    View details for DOI 10.1016/j.adro.2020.05.001

    View details for PubMedID 33305080

    View details for PubMedCentralID PMC7718494

  • Successful Use of Frameless Stereotactic Radiosurgery for Treatment of Recurrent Brain Metastases in an 18 Month Old Child. The International journal of neuroscience Rahimy, E., Chuang, C., Spunt, S. L., Mahaney, K., Donaldson, S. S., Gibbs, I. C., Soltys, S. G., Pollom, E., Hiniker, S. M. 2019: 1–6


    There are very few reported cases of stereotactic radiosurgery delivered in children under 3 years of age. We report an 18 month old boy with metastatic recurrence of undifferentiated round cell sarcoma to the brain which was treated with chemotherapy, resection, and robotic frameless stereotactic radiosurgery (SRS). Frameless SRS was delivered without technical difficulties, acute adverse events, or clinical sequelae 1.5 months post-radiation. Longer term follow-up will be needed to evaluate local tumor control and effects on neurocognitive development, endocrine function, and growth. This report adds to the literature of the few reported cases of successfully attempted SRS in very young children.

    View details for DOI 10.1080/00207454.2019.1655015

    View details for PubMedID 31401906

  • Quality at the American Society for Radiation Oncology Annual Meeting: Gender Balance Among Invited Speakers and Associations with Panel Success INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rahimy, E., Jagsi, R., Park, H. S., Moran, J. M., Cervino, L., Albert, A., Lee, A., Evans, S. 2019; 104 (5): 987–96
  • Patient-Reported Outcomes and Cosmesis in a Feasibility Study of 4-Dimensional Simulated Image Guided Accelerated Partial Breast Irradiation PRACTICAL RADIATION ONCOLOGY Rahimy, E., Weidhaas, J., Wei, W., Lannin, D., Horowitz, N., Higgins, S., Wilson, L. D., Knowlton, C., Moran, M. S., Young, M., Killelea, B., Chagpar, A., Yeboa, D., Zelterman, D., Evans, S. 2019; 9 (3): E257–E265


    Three-dimensional conformal accelerated partial breast irradiation (APBI) is a treatment option for well selected women with breast cancer, despite reports of adverse cosmetic outcome with this technique. Dose-volume relationships may be responsible for this poor cosmesis. We aimed to determine the feasibility of limiting the exposure of nontarget breast tissue to radiation through smaller planning target volumes achieved through daily image guidance and 4-dimensional computed tomography simulation.Eligibility criteria included the following: women, age ≥50 years, Karnofsky performance status score ≥70, stage 0 and I breast cancer treated with breast-conserving surgery, margins clear by ≥2 mm, pathologic tumor size ≤2 cm, and 4-dimensional computed tomography with planning target volumes of 0.2 cm rather than the standard 1.0 cm. A dose of 3850 cGy was prescribed in 10 fractions. The study was considered successful if ≥50% of enrollees met dosimetric constraints on the breast (V50 < 45% and V100 < 23.5%).The study achieved its primary endpoint of feasibility of reducing the nontarget breast dose with a breast median of V50 = 31% and V100 = 11%. There were no recurrences and no toxicity grade >3. At baseline, fair/poor cosmesis was low (2.2%). By year 3, adverse cosmesis post-APBI had increased by 13.2% (to 15.4%). Patient decisional satisfaction was reached completely in 84.2% of patients.This study demonstrated that with 4-dimensional simulated APBI that uses stringent dosimetric constraints and image guidance radiation therapy, it is possible to obtain acceptable cosmetic outcomes. We report no locoregional recurrences in 3 years and no toxicity grade >3. The observed decline in cosmesis was acceptable compared with that of prior published studies, and patient satisfaction with APBI was excellent.

    View details for PubMedID 30796975

  • Mentorship in Radiation Oncology: Role of Gender Diversity in Abstract Presenting and Senior Author Dyads on Subsequent High-Impact Publications. Advances in radiation oncology Lee, A. n., Albert, A. n., Griffith, K. n., Evans, S. n., Rahimy, E. n., Park, H. S., Cervino, L. I., Moran, J. M., Jagsi, R. n. 2019; 5 (2): 292–96


    To generate insights regarding the role of gender in research mentorship, we analyzed characteristics of abstracts selected for oral and poster discussion presentations at the American Society for Radiation Oncology annual meeting and subsequent high-impact publications.Clinical radiation oncology abstracts selected for oral and poster discussion presentations at the American Society for Radiation Oncology annual meetings in 2014 and 2015 were reviewed. A multivariable logistic regression model evaluated factors associated with subsequent higher-impact publications among abstracts that led to manuscript publications. The primary independent variable was the presenting-senior (last) author gender dyad (divided into 4 groups based on gender of presenting and senior authors, respectively; eg, "MF" indicates male presenting and female senior). Dyads were classified as MF, FM, MM, or FF.Data were derived from 390 oral and 142 poster discussions. Presenting and senior author pairings were MM for 286 (53.8%), FF for 67 (12.6%), MF for 84 (15.8%), and FM for 94 (17.7%) abstracts. Overall, 403 abstracts led to subsequent publications, of which 52.1% (210) were in a higher-impact journal. Eventual publication in a higher-impact journal was significantly associated with senior author H-index (odds ratio [OR] 3.30 for H ≥ 41 vs < 17; group P = .007), grant support for the study (OR 2.09 for funded vs not, P = .0261), and with the presenting and senior author gender pairing (group P = .0107). Specifically, FM pairings (OR 2.48; 95% confidence interval, 1.32-4.66) and MF pairings (OR 2.38; 95% confidence interval, 1.19-4.77) had higher odds of high-impact publication than MM pairings, whereas there was no significant difference in this outcome between FF and MM pairings.Although unmeasured confounding remains possible, MF and FM dyads of presenting and senior authors were more likely than MM dyads to obtain journal publication in a higher-impact journal. Institutions and the profession should support the development and maintenance of respectful, collaborative cross-gender mentorship.

    View details for DOI 10.1016/j.adro.2019.10.005

    View details for PubMedID 32280830

    View details for PubMedCentralID PMC7136636

  • Radiation dose and cardiac risk in breast cancer treatment: An analysis of modern radiation therapy including community settings PRACTICAL RADIATION ONCOLOGY Hong, J. C., Rahimy, E., Gross, C. P., Shafman, T., Hu, X., Yu, J. B., Ross, R., Finkelstein, S. E., Dosoretz, A., Park, H. S., Soulos, P. R., Evans, S. B. 2018; 8 (3): E79-E86


    Adjuvant radiation therapy (RT) for breast cancer improves outcomes, but prior studies have documented substantive cardiac dose and cardiac risk. We assessed the mean heart dose (MHD) of RT and estimated the risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for breast cancer in contemporary (predominantly) community practice.We identified women with left-sided breast cancer receiving adjuvant RT between 2012 and 2014 from 94 centers across 16 states. We used bivariate analyses and multivariable linear regression to assess associations between RT techniques and MHD. Excess RT-related cardiac risk by age 80 was estimated for women diagnosed at age 60 using the previously reported relationship between MHD and cardiac risk.Among 1161 women, 77.3% were treated in community practice and with breast conservation (77.8%). The most common techniques were free-breathing (92.2%), supine (94.8%), and fixed gantry intensity modulated RT (FG-IMRT; 46.9%). The median MHD was 2.76 Gy (interquartile range, 1.47-5.03). In multivariable analyses, the predicted median MHD with deep inspiration breath hold was 2.41 Gy compared with 3.86 Gy with free-breathing (P < .001). Three-dimensional conformal RT (3D-CRT) was associated with a lower predicted median MHD (2.78 Gy) than FG-IMRT (4.02 Gy) or rotational IMRT, 6.60 Gy, P < .001). For 60-year-old women with the median MHD of the study population (2.76 Gy) and no cardiovascular risk factors, the 20-year predicted excess risk of death from ischemic heart disease attributable to radiation was 3.5 excess events/1000 patients, in contrast to estimates of 8 events/1000 from prior analyses. The predicted risk of cardiac events varied based on radiation technique, with 4 excess events/1000 with 3D-CRT, 5 excess events/1000 with FG-IMRT, and 8 excess events/1000 with rotational IMRT.MHD varies substantially across patients and is influenced by technique in predominantly community settings. Overall risk of cardiac toxicity is modest.

    View details for DOI 10.1016/j.prro.2017.07.005

    View details for Web of Science ID 000432348600001

    View details for PubMedID 28888675

  • Increased Number of Beam Angles Is Associated With Higher Cardiac Dose in Adjuvant Fixed Gantry Intensity Modulated Radiation Therapy of Left-Sided Breast Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rahimy, E., Hong, J. C., Gross, C. P., Hu, X., Soulos, P. R., Shafman, T., Connor, H. J., Ross, R., Yu, J. B., Dosoretz, A., Evans, S. B. 2017; 99 (5): 1137-1145


    To analyze the relationship between angle number and mean heart dose (MHD) in adjuvant fixed gantry intensity modulated radiation therapy (FG-IMRT) treatment of left-sided breast cancer as is currently practiced in the community.We performed a retrospective, multi-institutional review of women with left-sided breast cancer receiving adjuvant FG-IMRT between 2012 and 2014, encompassing 85 centers in 15 states. Bivariate and multivariate regression analyses were done to identify factors associated with MHD. Long-term cardiac risk was estimated according to a previously published model.Of the 538 women included, 284 had >2 gantry angle treatment plans (multi-angle), and 254 had 2 gantry angle (standard) plans. Median MHD was higher in patients with multi-angle plans compared with standard (median 475 vs 203 cGy). Number of gantry angles was significantly associated with MHD, with multi-angle plans independently increasing MHD by 229 cGy. Absolute risk of acute coronary events 20 years after treatment was estimated as 7 excess events per 1000 women for standard plans, compared with 12 excess events for multi-angle plans.Fixed gantry IMRT breast treatment plans with >2 gantry angles were associated with increased MHD, which translated to an increased cardiac risk. Clinicians should account for this potential drawback in treatment technique when assessing overall plan quality.

    View details for DOI 10.1016/j.ijrobp.2017.06.2451

    View details for Web of Science ID 000416919400020

    View details for PubMedID 28864402

  • Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy JOURNAL OF INFECTIOUS DISEASES Rahimy, E., Li, F., Hagberg, L., Fuchs, D., Robertson, K., Meyerhoff, D. J., Zetterberg, H., Price, R. W., Gisslen, M., Spudich, S. 2017; 215 (7): 1132-1140


    We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART).The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance.The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance.The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection.

    View details for DOI 10.1093/infdis/jix013

    View details for Web of Science ID 000401987400018

    View details for PubMedID 28368497

    View details for PubMedCentralID PMC5426376

  • AGENTS UNDER STUDY ANTI-VEGF: USE IN OPHTHALMOLOGY Rahimy, E., Rahimy, E., Joseph, A., Duker, J. S., Liang, M. C. 2017: 29-45
  • RNA-seq analysis identifies key long non-coding RNAs connected to the pathogenesis of alcohol-associated head and neck squamous cell carcinoma ONCOLOGY LETTERS Yu, V., Singh, P., Rahimy, E., Zheng, H., Kuo, S. Z., Kim, E., Wang-Rodriguez, J., Ongkeko, W. M. 2016; 12 (4): 2846-2853


    Alcohol consumption has been implicated in the pathogenesis of head and neck squamous cell carcinoma (HNSCC), although its mechanism is poorly understood. Recent advances in the identification and understanding of long non-coding RNAs (lncRNAs) have indicated that these molecules have a profound effect on numerous biological processes, including tumorigenesis and oncogenesis. The present authors hypothesize that alcohol-mediated dysregulation of lncRNAs is a key event in HNSCC pathogenesis. An in silico differential expression analysis utilizing RNA sequencing (RNA-seq) data from 34 HNSCC patients, which included alcohol drinkers and non-alcohol drinkers, identified a panel of lncRNAs that were dysregulated due to alcohol consumption. Normal oral keratinocytes were then exposed to ethanol and acetaldehyde to validate the RNA-seq results. Two lncRNAs that were differentially expressed due to alcohol consumption were identified from RNA-seq analysis of the clinical data: lnc-PSD4-1 and lnc-NETO-1. Oral keratinocytes exposed to alcohol and acetaldehyde demonstrated dysregulation of these two lncRNAs, thus validating the results of RNA-seq analysis. In addition, low expression of the lnc-PSD4-1 isoform, lnc-PSD4-1:14, exhibited a strong correlation with high survival rates in a Cox proportional hazards regression model. Therefore, these lncRNAs may play a key role in the early pathogenesis of HNSCC, since they are dysregulated in both clinical data and in vitro experiments mimicking the effects of alcohol use.

    View details for DOI 10.3892/ol.2016.4972

    View details for Web of Science ID 000385579200094

    View details for PubMedID 27698869

    View details for PubMedCentralID PMC5038566

  • Bilateral Optic Nerve Coloboma and Macular Schisis in Papillorenal Syndrome OPHTHALMOLOGY Rahimy, E., Rahimy, E. 2016; 123 (5): 990

    View details for DOI 10.1016/j.ophtha.2016.02.039

    View details for Web of Science ID 000375942300017

    View details for PubMedID 27107352

  • Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma MOLECULAR CANCER Saad, M. A., Kuo, S. Z., Rahimy, E., Zou, A. E., Korrapati, A., Rahimy, M., Kim, E., Zheng, H., Yu, M., Wang-Rodriguez, J., Ongkeko, W. M. 2015; 14: 181


    Alcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype.Using RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC.From RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934.Alcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC.

    View details for DOI 10.1186/s12943-015-0452-8

    View details for Web of Science ID 000362815600001

    View details for PubMedID 26472042

    View details for PubMedCentralID PMC4608114

  • Parathyroid Hormone Related-Protein Promotes Epithelial-to-Mesenchymal Transition in Prostate Cancer PLOS ONE Ongkeko, W. M., Burton, D., Kiang, A., Abhold, E., Kuo, S. Z., Rahimy, E., Yang, M., Hoffman, R. M., Wang-Rodriguez, J., Deftos, L. J. 2014; 9 (1): e85803


    Parathyroid hormone-related protein (PTHrP) possesses a variety of physiological and developmental functions and is also known to facilitate the progression of many common cancers, notably their skeletal invasion, primarily by increasing bone resorption. The purpose of this study was to determine whether PTHrP could promote epithelial-to-mesenchymal transition (EMT), a process implicated in cancer stem cells that is critically involved in cancer invasion and metastasis. EMT was observed in DU 145 prostate cancer cells stably overexpressing either the 1-141 or 1-173 isoform of PTHrP, where there was upregulation of Snail and vimentin and downregulation of E-cadherin relative to parental DU 145. By contrast, the opposite effect was observed in PC-3 prostate cancer cells where high levels of PTHrP were knocked-down via lentiviral siRNA transduction. Increased tumor progression was observed in PTHrP-overexpressing DU 145 cells while decreased progression was observed in PTHrP-knockdown PC-3 cells. PTHrP-overexpressing DU 145 formed larger tumors when implanted orthoptopically into nude mice and in one case resulted in spinal metastasis, an effect not observed among mice injected with parental DU 145 cells. PTHrP-overexpressing DU 145 cells also caused significant bone destruction when injected into the tibiae of nude mice, while parental DU 145 cells caused little to no destruction of bone. Together, these results suggest that PTHrP may work through EMT to promote an aggressive and metastatic phenotype in prostate cancer, a pathway of importance in cancer stem cells. Thus, continued efforts to elucidate the pathways involved in PTHrP-induced EMT as well as to develop ways to specifically target PTHrP signaling may lead to more effective therapies for prostate cancer.

    View details for DOI 10.1371/journal.pone.0085803

    View details for Web of Science ID 000330283100076

    View details for PubMedID 24465715

    View details for PubMedCentralID PMC3899059

  • Evaluation of Non-Coding RNAs as Potential Targets in Head and Neck Squamous Cell Carcinoma Cancer Stem Cells CURRENT DRUG TARGETS Rahimy, E., Kuo, S. Z., Ongkeko, W. M. 2014; 15 (13): 1247-1260


    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and has not seen improved survival rates over the past few decades. Current treatment plans include surgery, radiation therapy, and chemotherapy, but these are relatively ineffective options for recurrent or metastatic tumors. Therefore, there is a high priority for new therapies that specifically target the resistant HNSCC cancer stem cells (CSCs), a subpopulation responsible for tumor initiation and metastasis. Given their vast effects on gene expression and biological processes, including stem cell capabilities, non-coding RNAs (ncRNAs) have become a promising new repertoire of genes to investigate as potential diagnostic or therapeutic targets. This review presents a comprehensive overview of current investigative studies that can contribute to our understanding of the still tentative link between ncRNA and the biology of HNSCC cancer stem cells. In doing so, we aim to analyze the potential role of stem cell-related ncRNAs in the development of molecularly targeted cancer therapy for HNSCC. Although the majority of updated knowledge on HNSCC and ncRNA focuses heavily on microRNA, we chose to give considerable attention to the promise of other classes of ncRNAs (lncRNA, piRNA, and snoRNA), many of which are not yet well characterized or are yet to be discovered, and thus represent a potentially exciting and untapped pool of molecular targets or biomarkers in HNSCC therapy.

    View details for DOI 10.2174/1389450115666141024113446

    View details for Web of Science ID 000346162900007

    View details for PubMedID 25341422

  • Nicotine Promotes Acquisition of Stem Cell and Epithelial-to-Mesenchymal Properties in Head and Neck Squamous Cell Carcinoma PLOS ONE Yu, M., Kiang, A., Wang-Rodriguez, J., Rahimy, E., Haas, M., Yu, V., Ellies, L. G., Chen, J., Fan, J., Brumund, K. T., Weisman, R. A., Ongkeko, W. M. 2012; 7 (12): e51967


    The ability of nicotine to enhance the malignancy of cancer cells is known; however, the possibility that nicotine could regulate a cancer stem cell phenotype remains to be well-established. In this study we sought to determine whether long-term exposure to nicotine could promote cancer stem cell-like properties in two head and neck squamous cell carcinoma cell lines, UMSCC-10B and HN-1. Nicotine treatment induced epithelial-to-mesenchymal transition (EMT) in both cell lines by repressing E-cadherin expression, and led to the induction of stem cell markers Oct-4, Nanog, CD44 and BMI-1, which was reversed upon ectopic re-expression of E-cadherin. Nicotine-treated cells formed spheres at a higher efficiency than non-treated cells, formed larger tumors when injected into mice, and formed tumors with 4-fold greater efficiency compared to control cells when injected at limiting doses. Consistent with previous literature, nicotine-treated cells demonstrated a greater capacity for survival and also a higher tendency to invade. Comparison of microRNA profiles between nicotine and control cells revealed the upregulation of miR-9, a repressor of E-cadherin, and the downregulation of miR-101, a repressor of EZH2. Taken together, these results suggest that nicotine may play a critical role in the development of tobacco-induced cancers by regulating cancer stem cell characteristics, and that these effects are likely mediated through EMT-promoting, microRNA-mediated pathways. Further characterization of such pathways remains a promising avenue for the understanding and treatment of tobacco-related cancers.

    View details for DOI 10.1371/journal.pone.0051967

    View details for Web of Science ID 000313618800041

    View details for PubMedID 23300583

    View details for PubMedCentralID PMC3530520

  • Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt BMC CANCER Kuo, S. Z., Blair, K. J., Rahimy, E., Kiang, A., Abhold, E., Fan, J., Wang-Rodriguez, J., Altuna, X., Ongkeko, W. M. 2012; 12: 556


    Cancer stem cells (CSC) are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells.MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose.In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR.These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and decrease stem cell properties despite activation of both EMT and Akt.

    View details for DOI 10.1186/1471-2407-12-556

    View details for Web of Science ID 000312310200001

    View details for PubMedID 23176396

    View details for PubMedCentralID PMC3522015

  • EGFR Kinase Promotes Acquisition of Stem Cell-Like Properties: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma Stem Cells PLOS ONE Abhold, E. L., Kiang, A., Rahimy, E., Kuo, S. Z., Wang-Rodriguez, J., Lopez, J., Blair, K. J., Yu, M., Haas, M., Brumund, K. T., Altuna, X., Patel, A., Weisman, R. A., Ongkeko, W. M. 2012; 7 (2): e32459


    Members of the EGFR/ErbB family of tyrosine kinases are found to be highly expressed and deregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs) which are believed to be responsible for tumor initiation and maintenance. In this study, we investigated the possible role of EGFR as a regulator of "stemness" in HNSCC cells. Activation of EGFR by the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC cell lines (UMSCC-22B and HN-1) resulted in the induction of CD44, BMI-1, Oct-4, NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased tumorsphere formation, a characteristic ability of cancer stem cells. Conversely, treatment with the EGFR kinase inhibitor, Gefinitib (Iressa), resulted in decreased expression of the aforementioned genes, and loss of tumorsphere-forming ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture derived from a fresh HNSCC tumor, confirming our findings for the cell lines. Additionally, we found that these putative cancer stem cells, when treated with Gefitinib, possessed a lower capacity to invade and became more sensitive to cisplatin-induced death in vitro. These results suggest that EGFR plays critical roles in the survival, maintenance, and function of cancer stem cells. Drugs that target EGFR, perhaps administered in combination with conventional chemotherapy, might be an effective treatment for HNSCC.

    View details for DOI 10.1371/journal.pone.0032459

    View details for Web of Science ID 000302918500093

    View details for PubMedID 22384257

    View details for PubMedCentralID PMC3288103

  • Recombinant human erythropoietin promotes the acquisition of a malignant phenotype in head and neck squamous cell carcinoma cell lines in vitro. BMC research notes Abhold, E., Rahimy, E., Wang-Rodriguez, J., Blair, K. J., Yu, M. A., Brumund, K. T., Weisman, R. A., Ongkeko, W. M. 2011; 4: 553


    BACKGROUND: Recent studies indicate an increase in tumor progression and recurrence in head and neck squamous cell carcinomas (HNSCC) of cancer patients taking recombinant human erythropoietin (rhEpo) for anemia. This study was undertaken to investigate the potential role of rhEpo in invasion, proliferation, and cisplatin-induced cell death in HNSCC cell lines.METHODS: The following experiments were performed with two HNSCC cell lines, UMSCC-10B and UMSCC-22B. Presence of EpoR in both cell lines was determined by western blot and quantitative PCR. Colorimetric MTS assays and clonogenic assays were used to study the effect of rhEpo at pharmacologically relevant doses on cell proliferation. Matrigel invasion assays were performed in order to determine effects of exogenous rhEpo on invasive abilities. Clonogenic assays were also used to study potential cytoprotective effects of rhEpo against cisplatin. Immunoblotting was done to analyze the effect of rhEpo on Akt phosphorylation. Finally, MTS and TUNEL assays were performed to test our hypothesis that Akt activation by PI3K was involved in rhEpo-mediated cisplatin resistance.RESULTS: HNSCC cell lines were shown to express Epo receptor (EpoR). RhEpo increased invasion 1.8-fold in UMSCC-10B and 2.6-fold in UMSCC-22B compared to control. RhEpo at 10 U/ml increased cell proliferation by 41% and 53% in UMSCC-10B and UMSCC-22B, respectively, and colony formation by 1.5-fold and 1.8-fold. UMSCC-10B treated with cisplatin and exposed to rhEpo at 1 and 10 U/ml resulted in a 1.7-fold and 3.0-fold increase in colony number compared to control, respectively. UMSCC-22B treated with cisplatin and rhEpo at 1 or 10 U/ml resulted in ~2.5-fold increase in colony number. A TUNEL assay demonstrated a 30.5% and 76.5% increase in survival in UMSCC-10B and UMSCC-22B cells, respectively, in cisplatin and rhEpo-treated cells compared to cisplatin alone. MTS assay showed similar cytoprotective effects. Western blot revealed increased phosphorylation of Akt upon exposure of HNSCC cell lines to rhEpo. MTS assay and TUNEL analyses implicate Akt as a likely contributor to regulation of rhEpo-mediated cytoprotection.CONCLUSIONS: The results demonstrate that, in HNSCC cells expressing functional EpoR, rhEpo promotes invasion, cell proliferation, and induces resistance to cisplatin, which may contribute to tumor progression.

    View details for DOI 10.1186/1756-0500-4-553

    View details for PubMedID 22188703