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Item 18F-FDG PET Predicts Hematologic Toxicity in Patients with Locally Advanced Anal Cancer Treated With Chemoradiation(Elsevier, 2019-07-04) David, John M.; Yue, Yong; Blas, Kevin; Hendifar, Andrew; Kabolizadeh, Peyman; Tuli, Richard; Radiation Oncology, School of MedicinePurpose: Hematologic toxicity (HT) during chemoradiation therapy (CRT) for anal cancer can lead to treatment breaks that compromise efficacy. We hypothesized that CRT-induced HT correlates with changes in active bone marrow (ABM) characterized by pre-/post-CRT positron emission tomography (PET)/computed tomography. Methods and materials: Data from 36 patients with anal cancer who were treated with 18F-fluorodeoxyglucose PET/computed tomography scans 2 weeks before and 6 to 16 weeks after CRT were analyzed. Complete blood counts with differential within 2 weeks from, weekly during, and 2 week after treatment were obtained. HT was defined as baseline complete blood count change to nadir and posttreatment recovery. Total bone marrow was segmented into 2 subregions: lumbosacral (LS) pelvis (L5 vertebrae, sacrum, and coccyx) and lower pelvis (LP) (ilium, femoral head/neck, and greater and lesser trochanter). PET ABM was characterized as the volume having standard uptake value (SUV) greater than the mean uptake of unirradiated extrapelvic bone marrow. PET variables of pre-/post-CRT and HT predictors were analyzed by linear regression. Results: Average pelvic ABM was significantly reduced from 52% to 41% in pre- to post-CRT PET scans for all patients (P = .0012). Regional analysis indicated significant post-CRT reduction of LS-ABM (P < .0001) and LP-ABM (P = .006). Linear regression analysis identified post-CRT SUVmean, differential ΔSUVmean, and ΔABM as correlating significantly with pre- and posttreatment HT. ΔWBC linearly correlated with ΔABM of LS and LP pelvis (P = .033 and P = .028, respectively). Dosimetrically, ABM was sensitive to higher radiation doses (>50 Gy) in terms of acute hematologic ΔWBC (P = .021) and ΔANC(P = .028). HT increased with increasing volume of ABM receiving 40 Gy. The results also suggest that ABM V40 Gy ≤ 20% to 25% may significantly reduce the risk of HT. Conclusions: HT was significantly associated with ΔABM in patients with anal cancer who were treated with CRT. LS-ABM was a robust surrogate for evaluating CRT-induced HT. Our results suggest implementation of ABM dosimetric constraints, V40 Gy ≤ 20-25%, may significantly reduce HT and lead to decreased treatment delays associated with clinical outcomes.Item A National Cancer Database analysis of the patterns of care for meningeal melanocytoma(Future Science Group, 2021) Tep, Amanda C.; Kelly, Patrick D.; Scarpelli, Daphne B.; Bergue, Bailey; McClelland, Shearwood, III; Jaboin, Jerry J.; Radiation Oncology, School of MedicineAim: To evaluate demographics, treatment patterns, radiotherapy utilization and patient outcomes in meningeal melanocytomas. Materials & methods: The National Cancer Database was queried for meningeal melanocytomas diagnosed in 2002-2016. The effects of demographic, clinical and treatment variables were determined via Kaplan-Meier log-rank and Cox regression analyses. Results: The median and 5-year overall survival were 57.46 months and 48%, respectively. Patients earning ≥$48K showed improved survival (p = 0.0319). Radiotherapy and chemotherapy were utilized in 37.7 and 9% of patients, respectively. Conclusion: Income significantly affected survival. Surgery remains the mainstay approach. Radiotherapy was delivered in more than one-third of patients but did not impact survival. However, further analyses were limited by poor treatment modality information in the database.Item A real pain in the neck(VM Media Group, 2022-05-19) McClelland, Shearwood, III.; Mitin, Timur; Radiation Oncology, School of MedicineItem Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice(Springer Nature, 2020-12-10) Levy, Karen; Natarajan, Suchitra; Wang, Jinghui; Chow, Stephanie; Eggold, Joshua T.; Loo, Phoebe E.; Manjappa, Rakesh; Melemenidis, Stavros; Lartey, Frederick M.; Schüler, Emil; Skinner, Lawrie; Rafat, Marjan; Ko, Ryan; Kim, Anna; Al-Rawi, Duaa H.; von Eyben, Rie; Dorigo, Oliver; Casey, Kerriann M.; Graves, Edward E.; Bush, Karl; Yu, Amy S.; Koong, Albert C.; Maxim, Peter G.; Loo, Billy W., Jr.; Rankin, Erinn B.; Radiation Oncology, School of MedicineRadiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.Item ACR Appropriateness Criteria® Hodgkin Lymphoma-Favorable Prognosis Stage I and II(Wolters Kluwer, 2016-12-01) Dhakal, Sughosh; Advani, Ranjana; Ballas, Leslie K.; Dabaja, Bouthaina S.; Flowers, Christopher R.; Ha, Chul S.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Metzger, Monika L.; Plastaras, John P.; Roberts, Kenneth B.; Shapiro, Ronald; Smith, Sonali M.; Terezakis, Stephanie A.; Winkfield, Karen M.; Younes, Anas; Constine, Louis S.; Expert Panel on Radiation Oncology–Lymphoma; Radiation Oncology, School of MedicineThis topic addresses the treatment of newly diagnosed patients with favorable prognosis stage I and II Hodgkin lymphoma. In most cases, combined modality therapy (chemotherapy followed by involved site radiation therapy) constitutes the current standard of care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the appropriate use of combined modality therapy for favorable prognosis stage I and II Hodgkin lymphoma. Increasing information about the late effects of treatment has led to attempts to decrease toxicity by using less chemotherapy (decreased duration and/or intensity or different agents) and less radiation therapy (reduced volume and/or dose) while maintaining excellent efficacy.Item ACR Appropriateness Criteria® Recurrent Hodgkin Lymphoma(Elsevier, 2016-12-15) Winkfield, Karen M.; Advani, Ranjana H.; Ballas, Leslie K.; Dabaja, Bouthaina S.; Dhakal, Sughosh; Flowers, Christopher R.; Ha, Chul Soo; Hoppe, Bradford S.; Mansur, David B.; Mendenhall, Nancy P.; Metzger, Monika L.; Plastaras, John P.; Roberts, Kenneth B.; Shapiro, Ronald; Smith, Sonali M.; Terezakis, Stephanie A.; Younes, Anas; Constine, Louis S.; Radiation Oncology, School of MedicineThis topic addresses the management of recurrent Hodgkin lymphoma. While autologous stem cell transplantation may be appropriate for select cases of recurrent disease following comprehensive combined-modality therapy, other options exist for patients treated with lower-dose therapy for early-stage disease. Additionally, innovative targeted therapies provide newer salvage options to consider. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decisionmaking associated with the management of recurrent Hodgkin lymphoma.Item Adjuvant vs. salvage radiation therapy in men with high-risk features after radical prostatectomy: Survey of North American genitourinary expert radiation oncologists(Canadian Urological Association, 2019-05) McClelland, Shearwood; Sandler, Kiri A.; Degnin, Catherine; Chen, Yiyi; Mitin, Timur; Radiation Oncology, School of MedicineINTRODUCTION: The management of patients with high-risk features after radical prostatectomy (RP) is controversial. Level 1 evidence demonstrates that adjuvant radiation therapy (RT) improves survival compared to no treatment; however, it may overtreat up to 30% of patients, as randomized clinical trials (RCTs) using salvage RT on observation arms failed to reveal a survival advantage of adjuvant RT. We, therefore, sought to determine the current view of adjuvant vs. salvage RT among North American genitourinary (GU) radiation oncology experts. METHODS: A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding adjuvant vs. salvage RT for this patient population. Treatment recommendations were correlated with practice patterns using Fisher's exact test. RESULTS: Forty-two of 88 radiation oncologists completed the survey; 23 (54.8%) recommended adjuvant RT and 19 (45.2%) recommended salvage RT. Recommendation of active surveillance for Gleason 3+4 disease was a significant predictor of salvage RT recommendation (p=0.034), and monthly patient volume approached significance for recommendation of adjuvant over salvage RT; those seeing <15 patients/month trended towards recommending adjuvant over salvage RT (p=0.062). No other demographic factors approached significance. CONCLUSIONS: There is dramatic polarization among North American GU experts regarding optimal management of patients with high-risk features after RP. Ongoing RCTs will determine whether adjuvant RT improves survival over salvage RT. Until then, the almost 50/50 division seen from this analysis should encourage practicing clinicians to discuss the ambiguity with their patients.Item Analysis of pre-residency research productivity, dual degree status, and gender distribution of underrepresented minorities among a current United States radiation oncology junior resident class(Elsevier, 2019-04-05) McClelland, Shearwood, III; Woodhouse, Kristina D.; Jaboin, Jerry J.; Zellars, Richard C.; Radiation Oncology, School of MedicineBackground: Among the most competitive medical subspecialties, representation of underrepresented minorities (African-American race and/or Hispanic ethnicity) among resident trainees has historically been low compared to their United States Census general population representation. Research productivity and dual degree status may impact residency applicant competitiveness. To date, such an analysis has yet to be performed in Radiation Oncology. Methods: A list of radiation oncology residents from the graduating class of 2022 was obtained through internet searches. Demographics included were gender and dual degree status. Research productivity was calculated using the number of pre-residency peer-reviewed publications (PRP). Fisher's exact test was used for statistical analysis. Results: Of the 179 residents evaluated from the 2022 class, eleven (6.1%) were underrepresented minorities. Compared to the remainder of the class, underrepresented minorities had a lower proportion of men (63.6% versus 69.3%), a higher proportion of dual degrees (45.5% versus 28.6%), and a lower proportion of MD-PhD degrees (9.1% versus 17.2%). Underrepresented minorities had a higher proportion of residents with at least two PRP (72.7% versus 57.1%) and a lower proportion of residents with no PRP (18.2% versus 24.4%). None of these differences reached statistical significance (p > 0.05). Conclusion: Underrepresented minorities were comparable to the remainder of their Radiation Oncology resident class regarding gender distribution, dual degrees status, and likelihood of having at least two peer-reviewed publications cited in PubMed during the calendar year of residency application. Further studies will be needed to determine how these findings translate into future scholarly activity and post-graduate career choice.Item Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department(Elsevier, 2021-11) McClelland, Shearwood III; Amy Achiko, Flora; Bartlett, Gregory K.; Watson, Gordon A.; Holmes, Jordan A.; Rhome, Ryan M.; DesRosiers, Colleen M.; Hutchins, Karen M.; Shiue, Kevin; Agrawal, Namita; Radiation Oncology, School of MedicinePurpose In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. Methods and Materials Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. Results In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. Conclusions Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.Item Augmentation of the anticancer activity of CYT997 in human prostate cancer by inhibiting Src activity(Springer Nature, 2017-06-12) Teng, Yong; Cai, Yafei; Pi, Wenhu; Gao, Lixia; Shay, Chloe; Radiation Oncology, School of MedicineBACKGROUND: Abnormalities of tubulin polymerization and microtubule assembly are often seen in cancer, which make them very suitable targets for the development of therapeutic approach against rapidly dividing and aggressive cancer cells. CYT997 is a novel microtubule-disrupting agent with anticancer activity in multiple cancer types including prostate cancer. However, the molecular mechanisms of action of CYT997 in prostate cancer have not been well characterized. METHODS: Src knockdown cells were achieved by lentiviral-mediated interference. The drug effects on cell proliferation were measured by MTS. The drug effects on cell viability and death were determined by Cell Titer-Glo® Luminescent cell viability kit and flow cytometry with Zombie Aqua™ staining. The drug effects on apoptosis were assessed by Cell Death Detection Elisa kit and Western blot with a cleaved PARP antibody. The drug effects on cell invasion were examined by Matrigel-coated Boyden chambers. Oxidative stress was detected by DCFH-DA staining and electrochemical biosensor. Mouse models generated by subcutaneous or intracardiac injection were used to investigate the in vivo drug efficacy in tumor growth and metastasis. RESULTS: CYT997 effectively inhibited proliferation, survival, and invasion of prostate cancer cells via blocking multiple oncogenic signaling cascades but not the Src pathway. Inhibition of Src expression by small hairpin RNA or inactivation of Src by dasatinib increased the CYT997-induced cytotoxicity of in vitro. Moreover, the combination of dasatinib and CYT997 exhibited a superior inhibitory effect on tumor growth and metastasis compared with either of the drugs alone. CONCLUSION: Our findings demonstrate that blockage of Src augments the anticancer effect of CYT997 on prostate cancer and suggest that co-treatment of dasatinib and CYT997 may represent an effective therapeutic regimen for limiting prostate cancer.