Adaptive radiation therapy is a feedback process by which imaging information acquired over the course of treatment, such as changes in patient anatomy, can be used to reoptimize the treatment plan, with the end goal of improving target coverage and reducing treatment toxicity. This review describes different types of adaptive radiation therapy and their clinical implementation with a focus on CT-guided online adaptive radiation therapy. Depending on local anatomic changes and clinical context, different anatomic sites and/or disease stages and presentations benefit from different adaptation strategies. Online adaptive radiation therapy, where images acquired in-room before each fraction are used to adjust the treatment plan while the patient remains on the treatment table, has emerged to address unpredictable anatomic changes between treatment fractions. Online treatment adaptation places unique pressures on the radiation therapy workflow, requiring high-quality daily imaging and rapid recontouring, replanning, plan review, and quality assurance. Generating a new plan with every fraction is resource intensive and time sensitive, emphasizing the need for workflow efficiency and clinical resource allocation. Cone-beam CT is widely used for image-guided radiation therapy, so implementing cone-beam CT-guided online adaptive radiation therapy can be easily integrated into the radiation therapy workflow and potentially allow for rapid imaging and replanning. The major challenge of this approach is the reduced image quality due to poor resolution, scatter, and artifacts. Keywords: Adaptive Radiation Therapy, Cone-Beam CT, Organs at Risk, Oncology © RSNA, 2023.

The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about this disease. However, as recent treatment options and an increasing rate of diagnoses are made worldwide, awareness is growing. In the United States alone, 9,090 individuals were expected to be diagnosed with anal cancer in 2021. The US annual incidence of squamous cell carcinoma of the anus continues to increase by 2.7% yearly, whereas the mortality rate increases by 3.1%. The main risk factor for anal cancer is a human papillomavirus infection; those with chronic immunosuppression are also at risk. Patients with HIV are 19 times more likely to develop anal cancer compared with the general population. In this review, we have provided an overview of the carcinoma of the anal canal, the role of screening, advancements in radiation therapy, and current trials investigating acute and chronic treatment–related toxicities. This article is a comprehensive approach to presenting the existing data in an effort to encourage continuous international interest in anal cancer.

Breast cancer subtype, determined by expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2, is predictive for prognosis. The importance of subtype to locoregional recurrence (LRR) following neoadjuvant chemotherapy (NAC) is unknown, particularly after adjuvant radiotherapy (RT). We retrospectively identified 160-breast cancer patients registered at Columbia University Medical Center from 1999 to 2012 treated with NAC, surgery and adjuvant RT. Patients were grouped by receptor status: hormone receptor positive (HR+) [(ER or PR+)/HER2−; n = 75], HER2+ (n = 46), or triple-negative (TNBC) [ER (−) PR (−) HER2 (−); n = 36]. The median follow-up was 28 months. 92.0% received an anthracycline-taxane based NAC and 80.4% of HER2+ patients received trastuzumab. All underwent surgical resection followed by RT. 15.6% had a pathologic complete response (pCR): 26% of HER2+, 5% of HR+, and 25% of TN. The actuarial rate of DM was 13.8% for the entire cohort, with equivalent rates by subtypes in non-pCR patients. The overall rate of LRR was 8%. However, the LRR rate was significantly higher for TNBC patients (22.2%) than HER2+ (5.6%) (p = 0.025) or HR+ (3.0%) (p = 0.037) in non-pCR group. In the pCR group, two patients had recurrence; one LRR and one a DM, both had TNBC. All LRR occurred in or near the radiation field. TNBC patients with < pCR to NAC have a significantly higher LRR rate as compared to other subtypes even with surgery and adjuvant RT. Our data support a need to further intensify local therapy in TNBC patients.

Purpose: While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated. Experimental Design: We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy. Results: We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT [70% {95% confidence interval (CI), 64%–77%} vs. 81% (95% CI, 78%–85%); P < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77–3.14)]. uMGMT was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55–73%) vs. 80% (95% CI, 76%–84%); P < 0.001; aHR, 2.61 (95% CI, 1.89–3.60)] but not in patients who did not receive chemotherapy [P = 0.38; HR, 1.31 (95% CI, 0.71–2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy. Conclusions: Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.

With recent advances in imaging modalities and radiation therapy, stereotactic body radiotherapy (SBRT) has allowed for the delivery of high doses of radiation with accuracy and precision. As such, SBRT has generated favorable results in the treatment of several cancers. Although the role of radiation has been controversial for the treatment of pancreatic ductal adenocarcinoma (PDAC) due to rather lackluster results in clinical trials, SBRT may offer improved outcomes, enhance the quality of life, and aid in palliative care settings for PDAC patients. This review delineates the role of SBRT in the treatment of PDAC, presents the defining principles of radiation biology and the radiation oncology work flow, and discusses the prospects of new treatment regimens involving tumor immunology and radiation therapy.

Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses. This is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto). All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95 %, PTV_2500 V9 5%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. 21 patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 105 fractions. Average total time was 29 min and 16 s (16:36-49:40) and average active physician time was 19:41 min (9:25-39:34). All fractions were treated with adapted plans. 97 % of adapted plans met PTV_4000 V95.0 % >95.0 % coverage goal and 100 % of adapted plans met OAR dose constraints. Median follow up was 6.6 months. Only 1 patient experienced acute grade 3+ toxicity directly attributable to radiation. Only 1 patient experienced late grade 3+ toxicity directly attributable to radiation. Daily CT-based OART was associated with significantly reduced dose OARs while achieving superior PTV coverage. Given the relatively quick total treatment time, radiation delivery was generally well tolerated and easily incorporated into the clinic workflow. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.