Browsing by Author "Radiation Oncology, School of Medicine"
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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 breast cancer classification and immune landscape analysis based on cancer stem-cell-related risk panel(Springer Nature, 2023-12-08) Hu, Haihong; Zou, Mingxiang; Hu, Hongjuan; Hu, Zecheng; Jiang, Lingxiang; Escobar, David; Zhu, Hongxia; Zhan, Wendi; Yan, Ting; Zhang, Taolan; Radiation Oncology, School of MedicineThis study sought to identify molecular subtypes of breast cancer (BC) and develop a breast cancer stem cells (BCSCs)-related gene risk score for predicting prognosis and assessing the potential for immunotherapy. Unsupervised clustering based on prognostic BCSC genes was used to determine BC molecular subtypes. Core genes of BC subtypes identified by non-negative matrix factorization algorithm (NMF) were screened using weighted gene co-expression network analysis (WGCNA). A risk model based on prognostic BCSC genes was constructed using machine learning as well as LASSO regression and multivariate Cox regression. The tumor microenvironment and immune infiltration were analyzed using ESTIMATE and CIBERSORT, respectively. A CD79A+CD24-PANCK+-BCSC subpopulation was identified and its spatial relationship with microenvironmental immune response state was evaluated by multiplexed quantitative immunofluorescence (QIF) and TissueFAXS Cytometry. We identified two distinct molecular subtypes, with Cluster 1 displaying better prognosis and enhanced immune response. The constructed risk model involving ten BCSC genes could effectively stratify patients into subgroups with different survival, immune cell abundance, and response to immunotherapy. In subsequent QIF validation involving 267 patients, we demonstrated the existence of CD79A+CD24-PANCK+-BCSC in BC tissues and revealed that this BCSC subtype located close to exhausted CD8+FOXP3+ T cells. Furthermore, both the densities of CD79A+CD24-PANCK+-BCSCs and CD8+FOXP3+T cells were positively correlated with poor survival. These findings highlight the importance of BCSCs in prognosis and reshaping the immune microenvironment, which may provide an option to improve outcomes for patients.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 Retrospective Versus Prospective Peer Review in a Multisite Academic Radiation Department(Elsevier, 2023-08-09) Shiue, Kevin R.; Agrawal, Namita; Rhome, Ryan M.; DesRosiers, Colleen M.; Hutchins, Karen M.; Zellars, Richard C.; Watson, Gordon A.; Holmes, Jordan A.; Radiation Oncology, School of MedicinePurpose: Our multisite academic radiation department reviewed our experience with transitioning from weekly primarily retrospective to daily primarily prospective peer review to improve plan quality and decrease the rate of plan revisions after treatment start. Methods and materials: This study was an institutional review board-approved prospective comparison of radiation treatment plan review outcomes of plans reviewed weekly (majority within 1 week after treatment start) versus plans reviewed daily (majority before treatment start, except brachytherapy, frame-based radiosurgery, and some emergent plans). Deviations were based on peer comments and considered major if plan revisions were recommended before the next fraction and minor if modifications were suggested but not required. Categorical variables were compared using χ2 distribution tests of independence; means were compared using independent t tests. Results: In all, 798 patients with 1124 plans were reviewed: 611 plans weekly and 513 plans daily. Overall, 76 deviations (6.8%) were noted. Rates of any deviation were increased in the daily era (8.6% vs 5.2%; P = .026), with higher rates of major deviations in the daily era (4.1% vs 1.6%; P = .012). Median working days between initial simulation and treatment was the same across eras (8 days). Deviations led to a plan revision at a higher rate in the daily era (84.1% vs 31.3%; P < .001). Conclusions: Daily prospective peer review is feasible in a multisite academic setting. Daily peer review with emphasis on prospective plan evaluation increased constructive plan feedback, plan revisions, and plan revisions being implemented before treatment start.