Radiation Oncology Publications

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https://hdl.handle.net/20.500.14038/222

ABOUT THIS COLLECTION

The Department of Radiation Oncology provides radiation medicine to the region's oncology patients and serves as the academic infrastructure for radiation science at UMass Chan Medical School. The Department is one of the largest in New England, providing state-of the-art clinical treatment service to cancer patients in Worcester County. This collection showcases journal articles and other publications produced by faculty and researchers of the Department of Radiation Oncology.

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Prognostic Factors in Limited-Stage Small Cell Lung Cancer: A Secondary Analysis of CALGB 30610-RTOG 0538
(2024-10-01) Farris, Michael K; Mix, Michael D; Wang, Xiaofei; Jaszewski, Brandy; Foster, Nathan; Masters, Gregory A; Laurie, Fran; Smith, Koren; Razavian, Niema B; Alden, Ryan S; Komaki, Ritsuko; Stinchcombe, Thomas E; Bradley, Jeffrey D; Vokes, Everett E; Bogart, Jeffrey; Radiation Oncology
Importance: The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design. Objective: To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC. Design, setting, and participants: This post hoc secondary analysis of a randomized clinical trial included 638 adults with LS-SCLC treated at 186 unique treatment sites with at least 1 accrual for all patients from March 15, 2008, to December 1, 2019; 313 patients were randomized to receive RT twice daily to a dosage of 45 Gy for 3 weeks and 325 to receive RT once daily to a dosage of 70 Gy for 7 weeks. Data were locked February 28, 2022, and analyzed from November 28, 2022, to June 4, 2024. Interventions: Twice-daily RT or once-daily RT. Main outcomes and measures: Multivariable Cox proportional hazards models evaluated the association of treatment groups and other risk factors with progression-free survival (PFS) and overall survival (OS). Patient-specific factors included age, sex, and Eastern Cooperative Oncology Group performance status. Disease-related factors included tumor, nodal, and overall cancer stages. Treatment-related factors included type of chemotherapy, timing of concurrent RT, RT technique, and prophylactic cranial irradiation. Social factors included marital status and treatment center accrual volume. Results: Among 507 patients (260 [51.3%] female and 247 [48.7%] male; mean [SD] age, 62.6 [7.9] years) included in the multivariate survival analysis, with a median follow-up of 4.7 (IQR, 3.7-7.1) years, female sex was associated with improved OS (hazard ratio [HR], 0.73 [95% CI, 0.58-0.91]; P = .006), while being 70 years or older was associated with decreased OS (HR, 1.50 [95% CI, 1.14-1.98]; P = .004). Neither age nor sex was associated with PFS. When compared with those with N1 disease, OS and PFS were worse in patients with N2 (HRs, 1.64 [95% CI, 1.19-2.26]; P = .002 and 1.36 [95% CI, 1.02-1.81]; P = .04, respectively) and N3 (HRs, 2.03 [95% CI, 1.40-2.93]; P < .001 and 1.63 [95% CI, 1.17-2.26]; P = .004) disease. Compared with stage II cancer, OS was worse for stage IIIA (HR, 1.65 [95% CI, 1.17-2.31]; P = .004) and stage IIIB (HR, 1.94 [95% CI, 1.34-2.83]; P < .001). Compared with high-volume accrual centers, treatment at low- or middle-volume accrual centers was associated with worse PFS (HRs, 1.94 [95% CI, 1.33-2.82; P < .001] and 1.44 [95% CI, 1.15-1.82; P = .002], respectively) and worse OS (HRs, 1.55 [95% CI, 1.03-2.32; P = .03] and 1.33 [95% CI, 1.04-1.70; P = .02], respectively). Conclusions and relevance: This secondary analysis of the CALGB 30610-RTOG 0538 randomized clinical trial of patients with LS-SCLC found associations between female sex or being younger than 70 years and improved overall survival and between advanced nodal stage or treatment at low- or middle-volume accrual centers and worse outcomes. These findings suggest that stratification by nodal stage, clinical stage, and age should be considered in future randomized trials. Trial registration: ClinicalTrials.gov Identifier: NCT00632853.
Outcomes After Stereotactic Body Radiation for Hepatocellular Carcinoma in Patients With Child-Pugh A Versus Child-Pugh B/C Cirrhosis
(2024-11-04) Diamond, Brett H; Banson, Kara; Ayash, Jonathan; Lee, Peter; Shukla, Utkarsh C; Jones, Gavin; Rava, Paul; Fitzgerald, Thomas J; Sioshansi, Shirin; Radiation Oncology
Purpose: For patients with hepatocellular carcinoma (HCC), stereotactic body radiation therapy (SBRT) has emerged as a locoregional treatment. Our purpose was to report outcomes in patients with HCC with Child-Pugh A (CP A) versus Child-Pugh B or C (CP B/C) liver dysfunction treated with SBRT. Methods and materials: A retrospective analysis of 80 patients with HCC, with a total of 94 tumors treated with SBRT, was conducted at a single institution. Outcomes were compared between patients with CP A (n = 51) and CP B/C (n = 29) liver dysfunction. Outcomes of interest included local control, overall survival (OS), and toxicity. Results: Median tumor size was 3.2 cm. There were 59 tumors included in the CP A cohort and 35 tumors in the CP B/C cohort. Median radiation dose was 50 Gy in 5 fractions for the CP A cohort and 40 Gy in 5 fractions for the CP B/C cohort. The rates of pathologic complete response were similar between the 2 groups at 63% for the CP A group and 61% for the CP B/C group. The estimated 1-year local control rates were similar between the 2 groups at 93% for the CP A group and 91% for the CP B/C group (P = .59). The 1-year OS for the CP A group was 85%, whereas the 1-year OS for the CP B/C group was 61% (P = .19). There was a 5.9% rate of grade 3+ toxicity in the CP A group and a 20.7% rate of grade 3+ toxicity in the CPB/C group. Conclusions: Our findings suggest that SBRT is feasible and effective in patients with both CP A and CP B/C liver dysfunction with similar rates of local control and pathologic complete response despite lower radiation doses in the CP B/C cohort. In patients with more advanced CP B/C cirrhosis, toxicities were higher and must be weighed against possible treatment benefits. Further studies characterizing the optimal role of SBRT in patients with advanced cirrhosis are warranted.
SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma
(2024-09-17) Elaimy, Ameer L; El-Derany, Marwa O; James, Jadyn; Wang, Zhuwen; Pearson, Ashley N; Holcomb, Erin A; Huber, Amanda K; Gijón, Miguel A; Bell, Hannah N; Sanghvi, Viraj R; Frankel, Timothy L; Su, Grace L; Tapper, Elliot B; Tai, Andrew W; Ramnath, Nithya; Centonze, Christopher P; Dobrosotskaya, Irina; Moeller, Julie A; Bryant, Alex K; Elliott, David A; Choi, Enid; Evans, Joseph R; Cuneo, Kyle C; FitzGerald, Thomas J; Wahl, Daniel R; Morgan, Meredith A; Chang, Daniel T; Wicha, Max S; Lawrence, Theodore S; Shah, Yatrik M; Green, Michael D; Radiation Oncology
End stage liver disease is marked by portal hypertension, systemic elevations in ammonia, and development of hepatocellular carcinoma (HCC). While these clinical consequences of cirrhosis are well described, it remains poorly understood whether hepatic insufficiency and the accompanying elevations in ammonia contribute to HCC carcinogenesis. Using preclinical models, we discovered that ammonia entered the cell through the transporter SLC4A11 and served as a nitrogen source for amino acid and nucleotide biosynthesis. Elevated ammonia promoted cancer stem cell properties in vitro and tumor initiation in vivo. Enhancing ammonia clearance reduced HCC stemness and tumor growth. In patients, elevations in serum ammonia were associated with an increased incidence of HCC. Taken together, this study forms the foundation for clinical investigations using ammonia lowering agents as potential therapies to mitigate HCC incidence and aggressiveness.
Neuropilin-2 expressing cells in breast cancer are S-nitrosylation hubs that mitigate radiation-induced oxidative stress
(2024-10-01) Kumar, Ayush; Goel, Hira; Wisniewski, Christi; Wang, Tao; Geng, Yansong; Wang, Mengdie; Goel, Shivam; Hu, Kai; Li, Rui; Zhu, Lihua Julie; Clark, Jennifer L; Ferreira, Lindsay M; Brehm, Michael A; FitzGerald, Thomas J; Mercurio, Arthur M; Molecular, Cell and Cancer Biology; Pathology; Program in Molecular Medicine; Radiation Oncology
The high rate of recurrence after radiation therapy in triple-negative breast cancer (TNBC) indicates that novel approaches and targets are needed to enhance radiosensitivity. Here, we report that neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor (VEGF) that is enriched on sub-populations of TNBC cells with stem cell properties, is an effective therapeutic target for sensitizing TNBC to radiotherapy. Specifically, VEGF/NRP2 signaling induces nitric oxide synthase 2 (NOS2) transcription by a mechanism dependent on Gli1. NRP2-expressing tumor cells serve as a hub to produce nitric oxide (NO), an autocrine and paracrine signaling metabolite, which promotes cysteine-nitrosylation of Kelch-like ECH-asssociated protein 1 (KEAP1) and, consequently, nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated transcription of antioxidant response genes. Inhibiting VEGF binding to NRP2, using a humanized monoclonal antibody (mAb), results in NFE2L2 degradation via KEAP1 rendering cell lines and organoids vulnerable to irradiation. Importantly, treatment of patient-derived xenografts with the NRP2 mAb and radiation resulted in significant tumor necrosis and regression compared to radiation alone. Together, these findings reveal a targetable mechanism of radioresistance and they support the use of NRP2 mAb as an effective radiosensitizer in TNBC.
Report of the Medical Image De-Identification (MIDI) Task Group - Best Practices and Recommendations [preprint]
(2023-04-01) Clunie, David A; Flanders, Adam; Taylor, Adam; Erickson, Brad; Bialecki, Brian; Brundage, David; Gutman, David; Prior, Fred; Seibert, J Anthony; Perry, John; Gichoya, Judy Wawira; Kirby, Justin; Andriole, Katherine; Geneslaw, Luke; Moore, Steve; FitzGerald, Thomas J; Tellis, Wyatt; Xiao, Ying; Farahani, Keyvan; Luo, James; Rosenthal, Alex; Kandarpa, Kris; Rosen, Rebecca; Goetz, Kerry; Babcock, Debra; Xu, Ben; Hsiao, John; Radiation Oncology
This report addresses the technical aspects of de-identification of medical images of human subjects and biospecimens, such that re-identification risk of ethical, moral, and legal concern is sufficiently reduced to allow unrestricted public sharing for any purpose, regardless of the jurisdiction of the source and distribution sites. All medical images, regardless of the mode of acquisition, are considered, though the primary emphasis is on those with accompanying data elements, especially those encoded in formats in which the data elements are embedded, particularly Digital Imaging and Communications in Medicine (DICOM). These images include image-like objects such as Segmentations, Parametric Maps, and Radiotherapy (RT) Dose objects. The scope also includes related non-image objects, such as RT Structure Sets, Plans and Dose Volume Histograms, Structured Reports, and Presentation States. Only de-identification of publicly released data is considered, and alternative approaches to privacy preservation, such as federated learning for artificial intelligence (AI) model development, are out of scope, as are issues of privacy leakage from AI model sharing. Only technical issues of public sharing are addressed.
Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas
(2024-03-15) Tchelebi, Leila T; Segovia, Diana; Smith, Koren; Shi, Qian; FitzGerald, Thomas J; Chuong, Michael D; Zemla, Tyler J; O'Reilly, Eileen M; Meyerhardt, Jeffrey A; Koay, Eugene J; Lowenstein, Jessica; Shergill, Ardaman; Katz, Matthew H G; Herman, Joseph M; Radiation Oncology
Purpose: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered. Methods and materials: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, or 3) based on adequacy. A score of 1 indicated no deviation, 2 indicated minor deviation, and 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score. Results: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic and 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets and 4 for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT and 7 (17.9%) with hypofractionated RT. Five cases (13%) required revision before treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2, and 11 (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded. Conclusions: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. Although clinical outcomes did not appear to have been affected, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.
Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A Comprehensive PENTEC Review
(2023-09-29) Casey, Dana L; Vogelius, Ivan R; Brodin, N Patrik; Roberts, Kenneth B; Avanzo, Michele; Moni, Janaki; Owens, Constance; Ronckers, Cécile M; Constine, Louis S; Bentzen, Soren M; Olch, Arthur; Radiation Oncology
Purpose: A Pediatric Normal Tissue Effects in the Clinic (PENTEC) analysis of published investigations of central nervous system (CNS) subsequent neoplasms (SNs), subsequent sarcomas, and subsequent lung cancers in childhood cancer survivors who received radiation therapy (RT) was performed to estimate the effect of RT dose on the risk of SNs and the modification of this risk by host and treatment factors. Methods and materials: A systematic literature review was performed to identify data published from 1975 to 2022 on SNs after prior RT in childhood cancer survivors. After abstract review, usable quantitative and qualitative data were extracted from 83 studies for CNS SNs, 118 for subsequent sarcomas, and 10 for lung SNs with 4 additional studies (3 for CNS SNs and 1 for lung SNs) later added. The incidences of SNs, RT dose, age, sex, primary cancer diagnosis, chemotherapy exposure, and latent time from primary diagnosis to SNs were extracted to assess the factors influencing risk for SNs. The excess relative ratio (ERR) for developing SNs as a function of dose was analyzed using inverse-variance weighted linear regression, and the ERR/Gy was estimated. Excess absolute risks were also calculated. Results: The ERR/Gy for subsequent meningiomas was estimated at 0.44 (95% CI, 0.19-0.68); for malignant CNS neoplasms, 0.15 (95% CI, 0.11-0.18); for sarcomas, 0.045 (95% CI, 0.023-0.067); and for lung cancer, 0.068 (95% CI, 0.03-0.11). Younger age at time of primary diagnosis was associated with higher risk of subsequent meningioma and sarcoma, whereas no significant effect was observed for age at exposure for risk of malignant CNS neoplasm, and insufficient data were available regarding age for lung cancer. Females had a higher risk of subsequent meningioma (odds ratio, 1.46; 95% CI, 1.22-1.76; P < .0001) relative to males, whereas no statistically significant sex difference was seen in risk of malignant CNS neoplasms, sarcoma SNs, or lung SNs. There was an association between chemotherapy receipt (specifically alkylating agents and anthracyclines) and subsequent sarcoma risk, whereas there was no clear association between specific chemotherapeutic agents and risk of CNS SNs and lung SNs. Conclusions: This PENTEC systematic review shows a significant radiation dose-response relationship for CNS SNs, sarcomas, and lung SNs. Given the linear dose response, improved conformality around the target volume that limits the high dose volume might be a promising strategy for reducing the risk of SNs after RT. Other host- and treatment-related factors such as age and chemotherapy play a significant contributory role in the development of SNs and should be considered when estimating the risk of SNs after RT among childhood cancer survivors.
Stereotactic body radiation therapy for metastatic non-small cell lung cancer: a versatile treatment, repurposed
(2022-07-01) Shen, James L; Ko, Eric C; Morningside Graduate School of Biomedical Sciences; Radiation Oncology; T.H. Chan School of Medicine; James L Shen
Comment on: Lester-Coll NH, Skelly J, Vacek PM, et al. Trends and costs of stereotactic body radiation therapy in metastatic non-small cell lung cancer. J Thorac Dis 2022;14:2579-90.
The Importance of Quality Assurance in Radiation Oncology Clinical Trials
(2023-10-01) FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Laurie, Fran; Iandoli, Matthew; Smith, Koren; Ulin, Kenneth; Ding, Linda; Moni, Janaki; Cicchetti, M Giulia; Knopp, Michael; Kry, Stephen; Xiao, Ying; Rosen, Mark; Prior, Fred; Saltz, Joel; Michalski, Jeff; Radiation Oncology
Clinical trials have been the center of progress in modern medicine. In oncology, we are fortunate to have a structure in place through the National Clinical Trials Network (NCTN). The NCTN provides the infrastructure and a forum for scientific discussion to develop clinical concepts for trial design. The NCTN also provides a network group structure to administer trials for successful trial management and outcome analyses. There are many important aspects to trial design and conduct. Modern trials need to ensure appropriate trial conduct and secure data management processes. Of equal importance is the quality assurance of a clinical trial. If progress is to be made in oncology clinical medicine, investigators and patient care providers of service need to feel secure that trial data is complete, accurate, and well-controlled in order to be confident in trial analysis and move trial outcome results into daily practice. As our technology has matured, so has our need to apply technology in a uniform manner for appropriate interpretation of trial outcomes. In this article, we review the importance of quality assurance in clinical trials involving radiation therapy. We will include important aspects of institution and investigator credentialing for participation as well as ongoing processes to ensure that each trial is being managed in a compliant manner. We will provide examples of the importance of complete datasets to ensure study interpretation. We will describe how successful strategies for quality assurance in the past will support new initiatives moving forward.
AAPM task group report 302: Surface-guided radiotherapy
(2022-03-15) Al-Hallaq, Hania A; Cerviño, Laura; Gutierrez, Alonso N; Havnen-Smith, Amanda; Higgins, Susan A; Kügele, Malin; Padilla, Laura; Pawlicki, Todd; Remmes, Nicholas; Smith, Koren; Tang, Xiaoli; Tomé, Wolfgang A; Radiation Oncology
The clinical use of surface imaging has increased dramatically, with demonstrated utility for initial patient positioning, real-time motion monitoring, and beam gating in a variety of anatomical sites. The Therapy Physics Subcommittee and the Imaging for Treatment Verification Working Group of the American Association of Physicists in Medicine commissioned Task Group 302 to review the current clinical uses of surface imaging and emerging clinical applications. The specific charge of this task group was to provide technical guidelines for clinical indications of use for general positioning, breast deep-inspiration breath hold treatment, and frameless stereotactic radiosurgery. Additionally, the task group was charged with providing commissioning and on-going quality assurance (QA) requirements for surface-guided radiation therapy (SGRT) as part of a comprehensive QA program including risk assessment. Workflow considerations for other anatomic sites and for computed tomography simulation, including motion management, are also discussed. Finally, developing clinical applications, such as stereotactic body radiotherapy (SBRT) or proton radiotherapy, are presented. The recommendations made in this report, which are summarized at the end of the report, are applicable to all video-based SGRT systems available at the time of writing.
Editorial: Rising stars in radiation oncology 2022
(2023-06-21) FitzGerald, Thomas J; Radiation Oncology
As patient care has matured and become increasingly complex, the fundamental skill set for the modern radiation oncologist has evolved as well. The initial generation of radiation oncologists trained in the United States and North America were taught by highly skilled mentors with expertise in surface anatomy and fluoroscopy with radiation fields designed by common understanding of the pattern of disease spread. Our first-generation mentors were critical thought leaders in applying management tools available at that time to trainees. This generation of radiation oncologists applied their expertise with the tools of the day; however, as our technology has evolved, the modern radiation oncologist requires skills commensurate with rapid technology changes. As we evolve and mature as thought leaders in the oncology practice of today, the skills required for the modern radiation oncologist both in clinical care and in basic science evolve and reach a new level of performance to match expectations of our colleagues and patients.
Children's Oncology Group's 2023 blueprint for research: Radiation oncology
(2023-07-24) Kalapurakal, John A; Wolden, Suzanne L; Haas-Kogan, Daphne; Laack, Nadia N; Hua, Chia-Ho; Paulino, Arnold C; Hill-Kayser, Christine E; Hoppe, Bradford S; FitzGerald, Thomas J; Radiation Oncology
Radiation oncology is an integral part of the multidisciplinary team caring for children with cancer. The primary goal of our committee is to enable the delivery of the safest dose of radiation therapy (RT) with the maximal potential for cure, and to minimize toxicity in children by delivering lower doses to normal tissues using advanced technologies like intensity-modulated RT (IMRT) and proton therapy. We provide mentorship for y ators and are actively involved in educating the global radiation oncology community. We are leaders in the effort to discover novel radiosensitizers, radioprotectors, and advanced RT technologies that could help improve outcomes of children with cancer.
Quality improvements in radiation oncology clinical trials
(2023-01-26) Smith, Koren; Ulin, Kenneth; Knopp, Michael; Kry, Stephan; Xiao, Ying; Rosen, Mark; Michalski, Jeff; Iandoli, Matthew; Laurie, Fran; Quigley, Jean; Reifler, Heather; Santiago, Juan; Briggs, Kathleen; Kirby, Shawn; Schmitter, Kate; Prior, Fred; Saltz, Joel; Sharma, Ashish; Bishop-Jodoin, Maryann; Moni, Janaki; Cicchetti, M Giulia; FitzGerald, Thomas J; Radiation Oncology
Clinical trials have become the primary mechanism to validate process improvements in oncology clinical practice. Over the past two decades there have been considerable process improvements in the practice of radiation oncology within the structure of a modern department using advanced technology for patient care. Treatment planning is accomplished with volume definition including fusion of multiple series of diagnostic images into volumetric planning studies to optimize the definition of tumor and define the relationship of tumor to normal tissue. Daily treatment is validated by multiple tools of image guidance. Computer planning has been optimized and supported by the increasing use of artificial intelligence in treatment planning. Informatics technology has improved, and departments have become geographically transparent integrated through informatics bridges creating an economy of scale for the planning and execution of advanced technology radiation therapy. This serves to provide consistency in department habits and improve quality of patient care. Improvements in normal tissue sparing have further improved tolerance of treatment and allowed radiation oncologists to increase both daily and total dose to target. Radiation oncologists need to define a priori dose volume constraints to normal tissue as well as define how image guidance will be applied to each radiation treatment. These process improvements have enhanced the utility of radiation therapy in patient care and have made radiation therapy an attractive option for care in multiple primary disease settings. In this chapter we review how these changes have been applied to clinical practice and incorporated into clinical trials. We will discuss how the changes in clinical practice have improved the quality of clinical trials in radiation therapy. We will also identify what gaps remain and need to be addressed to offer further improvements in radiation oncology clinical trials and patient care.
Definitive Radiation Therapy for Medically Inoperable Endometrial Carcinoma
(2022-10-25) Shen, James L; O'Connor, Kevin W; Moni, Janaki; Zweizig, Susan; FitzGerald, Thomas J; Ko, Eric C; Obstetrics and Gynecology; Radiation Oncology; Morningside Graduate School of Biomedical Sciences; T.H. Chan School of Medicine
Purpose: Upfront radiation therapy consisting of brachytherapy with or without external beam radiation therapy is considered standard of care for patients with endometrial carcinoma who are unable to undergo surgical intervention. This study evaluated the cancer-free survival (CFS), cancer-specific survival (CSS), and overall survival (OS) of patients with endometrial carcinoma managed with definitive-intent radiation therapy. Methods and materials: This was a single-institution retrospective analysis of medically inoperable patients with biopsy-proven endometrial carcinoma managed with up-front, definitive radiation therapy at UMass Memorial Medical Center between May 2010 and October 2021. A total of 55 cases were included for analysis. Patients were stratified as having low-risk endometrial carcinoma (LREC; uterine-confined grade 1-2 endometrioid adenocarcinoma) or high-risk endometrial carcinoma (HREC; stage III/IV and/or grade 3 endometrioid carcinoma, or any stage serous or clear cell carcinoma or carcinosarcoma). The CFS, CSS, OS, and grade ≥3 toxic effects were reported for patients with LREC and HREC. Results: The median age was 66 years (range, 42-86 years), and the median follow-up was 44 months (range, 4-135 months). Twelve patients (22%) were diagnosed with HREC. Six patients (11%) were treated with high-dose-rate brachytherapy alone and 49 patients (89%) were treated with high-dose-rate brachytherapy and external beam radiation therapy. Twelve patients (22%) were treated with radiation and chemotherapy. The 2-year CFS was 82% for patients with LREC and 80% for patients with HREC (log rank P = .0654). The 2-year CSS was 100% for both LREC and HREC patients. The 2-year OS was 92% for LREC and 80% for HREC (log P = .0064). There were no acute grade ≥3 toxic effects. There were 3 late grade ≥3 toxic effects owing to endometrial bleeding and gastrointestinal adverse effects. Conclusions: For medically inoperable patients with endometrial carcinoma, up-front radiation therapy provided excellent CFS, CSS, and OS. The CSS and OS were higher in patients with LREC than in those with HREC. Toxic effects were limited in both cohorts.
Prostate Cancer: Advances in Radiation Oncology, Molecular Biology, and Future Treatment Strategies
(2022-09-12) Wang, Tao; Lewis, Brian; Ruscetti, Marcus; Mittal, Kriti; Wang, Ming-Jin; Sokoloff, Mitchell H.; Ding, Linda; Bishop-Jodoin, Maryann; FitzGerald, Thomas J; Medicine; Molecular, Cell and Cancer Biology; Radiation Oncology; Urology
Prostate cancer remains an important health problem worldwide affecting one in every six men including members of vulnerable communities. Although successful treatments have been delivered to men affected with the disease resulting in improved patient outcome, process improvements including therapy titration and augmentation are needed to optimize tumor control and limit normal tissue injury from therapy. In this chapter, we describe current management strategies for optimal patient care with radiation therapy and opportunities for improvement of care moving forward with applied science to apply therapy in a strategic manner, potentially improving care and outcome for patients treated for this disease.
Extranodal presentation in limited-stage diffuse large Bcell lymphoma as a prognostic marker in three SWOG trials S0014, S0313 and S1001
(2022-11-01) Stephens, Deborah M; Li, Hongli; Constine, Louis S; FitzGerald, Thomas J; Leonard, John P; Kahl, Brad S; Song, Joo Y; LeBlanc, Michael L; Smith, Sonali M; Persky, Daniel O; Friedberg, Jonathan W; Radiation Oncology
Several recent trials have changed the standard-of-care for patients with limited stage (LS) diffuse large B-cell lymphoma (DLBCL) by minimizing the number of chemoimmunotherapy cycles and/or eliminating the need for radiotherapy without compromising long-term outcomes. However, there may be patient subsets where an abbreviated-treatment approach is insufficient. With this in mind, Bobillo et al., retrospectively reviewed LS DLBCL patients treated at a single institution with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) for four to six cycles with or without radio-therapy. This group reported that an extranodal presentation had shorter progression-free (PFS) and overall survival (OS) compared with nodal presentation. In these patients, consolidative radiotherapy prolonged survival in patients with extranodal disease, especially those with a positive positron emission tomography (PET) scan at the end of chemoimmunotherapy. In response, we analyzed similar patients treated on three consecutive SWOG studies (S0014, S0313, S1001; clinicaltrails gov. Identifier: NCT00005089, NCT00070018, NCT01359592).
Radiation Oncology: Future Vision for Quality Assurance and Data Management in Clinical Trials and Translational Science
(2022-08-10) Ding, Linda; Bradford, Carla; Kuo, I-Lin; Fan, Yankhua; Ulin, Kenneth; Khalifeh, Abdulnasser; Yu, Suhong; Liu, Fenghong; Saleeby, Jonathan; Bushe, Harry; Smith, Koren; Bianciu, Camelia; LaRosa, Salvatore; Prior, Fred; Saltz, Joel; Sharma, Ashish; Smyczynski, Mark S.; Bishop-Jodoin, Maryann; Laurie, Fran; Iandoli, Matthew; Moni, Janaki; Cicchetti, M Giulia; FitzGerald, Thomas J; Radiation Oncology
The future of radiation oncology is exceptionally strong as we are increasingly involved in nearly all oncology disease sites due to extraordinary advances in radiation oncology treatment management platforms and improvements in treatment execution. Due to our technology and consistent accuracy, compressed radiation oncology treatment strategies are becoming more commonplace secondary to our ability to successfully treat tumor targets with increased normal tissue avoidance. In many disease sites including the central nervous system, pulmonary parenchyma, liver, and other areas, our service is redefining the standards of care. Targeting of disease has improved due to advances in tumor imaging and application of integrated imaging datasets into sophisticated planning systems which can optimize volume driven plans created by talented personnel. Treatment times have significantly decreased due to volume driven arc therapy and positioning is secured by real time imaging and optical tracking. Normal tissue exclusion has permitted compressed treatment schedules making treatment more convenient for the patient. These changes require additional study to further optimize care. Because data exchange worldwide have evolved through digital platforms and prisms, images and radiation datasets worldwide can be shared/reviewed on a same day basis using established de-identification and anonymization methods. Data storage post-trial completion can co-exist with digital pathomic and radiomic information in a single database coupled with patient specific outcome information and serve to move our translational science forward with nimble query elements and artificial intelligence to ask better questions of the data we collect and collate. This will be important moving forward to validate our process improvements at an enterprise level and support our science. We have to be thorough and complete in our data acquisition processes, however if we remain disciplined in our data management plan, our field can grow further and become more successful generating new standards of care from validated datasets.
Approach to Stereotactic Body Radiotherapy for the Treatment of Advanced Hepatocellular Carcinoma in Patients with Child-Pugh B-7 Cirrhosis
(2022-11-05) Daniell, Kayla M; Banson, Kara Micah; Diamond, Brett H; Sioshansi, Shirin; Radiation Oncology; T.H. Chan School of Medicine
Patients with hepatocellular carcinoma (HCC) with underlying Child-Pugh B-7 cirrhosis benefit from management from an experienced, multidisciplinary team. In patients with localized disease who meet criteria for liver transplant, establishing care at a liver transplant center is crucial. For those awaiting transplant, local bridge therapies have emerged as a strategy to maintain priority status and eligibility. Multiple liver-directed therapies exist to provide locoregional tumor control. The careful selection of locoregional therapy is a multidisciplinary endeavor that takes into account patient factors including tumor resectability, underlying liver function, performance status, previous treatment, tumor location/size, and vascular anatomy to determine the optimal management strategy. Technological advances in external beam radiation therapy have allowed stereotactic body radiation therapy (SBRT) to emerge in recent years as a versatile and highly effective bridge therapy consisting of typically between 3 and 5 high dose, highly focused, and non-invasive radiation treatments. When treating cirrhotic patients with HCC, preserving liver function is of utmost importance to prevent clinical decline and decompensation. SBRT has been shown to be both safe and effective in carefully selected patients with Child-Pugh B cirrhosis; however, care must be taken to prevent radiation-induced liver disease. This review summarizes the evolving role of SBRT in the treatment of HCC in patients with Child-Pugh B-7 cirrhosis.
A Review of Concurrent Chemo/Radiation, Immunotherapy, Radiation Planning, and Biomarkers for Locally Advanced Non-small Cell Lung Cancer and Their Role in the Development of ECOG-ACRIN EA5181
(2022-06-30) Varlotto, John Michael; Sun, Zhuoxin; Ky, Bonnie; Upshaw, Jenica; FitzGerald, Thomas J; Diehn, Max; Lovly, Christine; Belani, Chandra; Oettel, Kurt; Masters, Gregory; Harkenrider, Matthew; Ross, Helen; Ramalingam, Suresh; Pennell, Nathan A; Radiation Oncology
ECOG-ACRIN EA5181 is a current prospective, randomized trial that is investigating whether the addition of concomitant durvalumab to standard chemo/radiation followed by 1 year of consolidative durvalumab results in an overall survival benefit over standard chemo/radiation alone followed by 1 year of consolidative durvalumab in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC). Because multiple phase I/II trials have shown the relative safety of adding immunotherapy to chemo/radiation and due to the known synergism between chemotherapy and immunotherapy, it is hoped that concomitant durvalumab can reduce the relatively high incidence of local failure (38%-46%) as seen in recent prospective, randomized trials of standard chemo/radiation in this patient population. We will review the history of radiation for LA-NSCLC and discuss the role of induction, concurrent and consolidative chemotherapy as well as the concerns for late cardiac and pulmonary toxicities associated with treatment. Furthermore, we will review the potential role of next generation sequencing, PD-L1, ctDNA and tumor mutation burden and their possible impact on this trial.
Chapter 1. The Head & Neck
(University of Massachusetts Medical School, 2014-12-01) Bogdasarian, Ronald N.; Fusick, Adam J.; Chen, Andrew; Pieters, Richard S.; FitzGerald, Thomas J
This chapter in the Radiology-Based USMLE Board Prepbook provides medical students with an efficient, interactive resource to enhance USMLE National Board Step1 and 2 preparation and mastery. The workbook also aids students in learning clinical interpretation of computed tomography (CT) images of the head and neck. The atlas portion is also published separately as an anatomical reference for students and clinical practitioners. Contents: Three Dimensional: Skeletal System, Muscular System, Vascular System, Digestive and Respiratory Systems, Nervous System, Lymphatic. Two Dimensional: Frontal, Sagittal, Axial (All Structures), Axial (Lymphatic System). Images of Pathology: USMLE Style Questions. Age of Subject: 17 Reviewed by: Richard Gacek, MD, David Goff, MD, Alan Stark, MD, of the University of Massachusetts Medical School; Ozan Toy, BA

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