Pleasurable and problematic receptive anal intercourse and diseases of the colon, rectum and anus.

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable.

Gender Representation Among Academic US Radiation Oncology Department Chairs: Who are They?

Purpose: Women are underrepresented in academic radiation oncology (RO), particularly in leadership positions. In this study, we sought to better understand the characteristics of individuals who currently serve as academic RO chairpersons at institutions with an associated Accreditation Council for Graduate Medical Education-accredited RO residency training program. Methods and Materials: We created a database of academic RO chairpersons in the United States by using publicly available sources, including residency training program websites, hospital/institutional websites, Doximity, LinkedIn, the American Society for Radiation Oncology (ASTRO) website, the American College of Radiation Oncology website, and the National Plan and Provider Enumeration System National Provider Identifier Registry. We used the χ2 Goodness of Fit test, Mann-Whitney U test, and Fisher exact test via R version 4.1.1 to evaluate for statistical significance among categorical variables, medians, and proportions, respectively. Results: We identified 85 of the 90 chairpersons (94.4%) currently serving at institutions with an Accreditation Council for Graduate Medical Education-accredited RO residency training program, 5 of whom hold interim positions and were thus excluded from further analyses. Of the remaining 80 chairpersons, 9 (11.3%) are women, and 71 (88.8%) are men (P < .01). Seventy-six chairpersons (95.0%) are full professors, and 19 (23.8%) hold dual MD PhD degrees. Thirty-two chairpersons (40.0%) hold an official leadership role in a cancer center affiliated with their current institution (43.7% of men vs 11.1% of women; P = .08). Seventy-three chairpersons (91.3%) secured their current positions a median of 16 years (range, 6-33 years) after completing RO residency. Thirty-five chairpersons (43.8%) were promoted to chair from positions within their current institutions (40.8% of men vs 66.7% of women; P = .17). The majority of chairpersons are ASTRO Fellows (62.5%); notably fewer are ASTRO (5.0%) or American College of Radiation Oncology (2.5%) Gold Medalists. Eight RO residency programs trained more than half of current chairpersons. Conclusion: Significantly more men than women currently serve as RO chairpersons. Future interventions that promote the recruitment, retention, and promotion of talented women in academic RO should be considered.

Esophagogastric Cancer: The Current Role of Radiation Therapy.

Radiation therapy is an effective treatment modality in the management of patients with esophageal cancer regardless of tumor location (proximal, middle, or distal esophagus) or histology (squamous cell vs adenocarcinoma). The addition of neoadjuvant CRT to surgery in patients who are surgical candidates has consistently shown a benefit in terms of locoregional recurrence, pathologic downstaging, and overall survival. For patients who are not surgical candidates, CRT has a role as definitive treatment.

Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy.

Purpose: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and Materials: Data from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric impact associated with treatment shifts was estimated using a machine learning dosimetric model. Results: Of all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. Conclusion: Real-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

Data-driven optimization of version 9 American Joint Committee on Cancer staging system for anal cancer.

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan-Meier methods analyzed 5-year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1-2N1M0, whereas Stage IIIA was redefined as T3N0-1M0. Reevaluation of 5-year survival based on data-informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data-driven optimization approach can be implemented for staging revisions across all disease sites moving forward.

Analysis of Radiation Therapy Quality Assurance in NRG Oncology RTOG 0848.

PURPOSE: NRG/Radiation Therapy Oncology Group 0848 is a 2-step randomized trial to evaluate the benefit of the addition of concurrent fluoropyrimidine and radiation therapy (RT) after adjuvant chemotherapy (second step) for patients with resected pancreatic head adenocarcinoma. Real-time quality assurance (QA) was performed on each patient who underwent RT. This analysis aims to evaluate adherence to protocol-specified contouring and treatment planning and to report the types and frequencies of deviations requiring revisions. METHODS AND MATERIALS: In addition to a web-based contouring atlas, the protocol outlined step-by-step instructions for generating the clinical treatment volume through the creation of specific regions of interest. The planning target volume was a uniform 0.5 cm clinical treatment volume expansion. One of 2 radiation oncology study chairs independently reviewed each plan. Plans with unacceptable deviations were returned for revision and resubmitted until approved. Treatment started after final approval of the RT plan. RESULTS: From 2014 to 2018, 354 patients were enrolled in the second randomization. Of these, 160 patients received RT and were included in the QA analysis. Resubmissions were more common for patients planned with 3-dimensional conformal RT (43%) than with intensity modulated RT (31%). In total, at least 1 resubmission of the treatment plan was required for 33% of patients. Among patients requiring resubmission, most only needed 1 resubmission (87%). The most common reasons for resubmission were unacceptable deviations with respect to the preoperative gross target volume (60.7%) and the pancreaticojejunostomy (47.5%). CONCLUSION: One-third of patients required resubmission to meet protocol compliance criteria, demonstrating the continued need for expending resources on real-time, pretreatment QA in trials evaluating the use of RT, particularly for pancreas cancer. Rigorous QA is critically important for clinical trials involving RT to ensure that the true effect of RT is assessed. Moreover, RT QA serves as an educational process through providing feedback from specialists to practicing radiation oncologists on best practices.

NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer.

The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.

Promoting Women and Historically Excluded Minorities in Medicine as Essential Leaders of Research.

Women and historically excluded minorities are underrepresented in clinical research. At the ASTRO 2021 annual meeting, the authors reviewed several strategies to improve on this issue. Implementation of such strategies should not only improve their visibility but also provide increased opportunities for their advancement and work in clinical research.

Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership.

Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.

Patient Advocates and Researchers as Partners in Cancer Research: A Winning Combination.

Inclusion of advocates as partners in research is now required by numerous international funding agencies. The role of advocates has expanded in recent years to include all areas of research, including basic cancer research, translational research, and clinical trial design and development. The involvement of advocates as partners in cancer research can be challenging for the advocate and for the researchers, but this collaboration is beneficial to all involved. Herein, we will define patient advocacy, explore advocate engagement, and share information on programs that train advocates and researchers to work together as partners.

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy.

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT.

Consensus report of the 2021 National Cancer Institute neuroendocrine tumor clinical trials planning meeting.

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.

Survival outcomes used to generate version 9 American Joint Committee on Cancer staging system for anal cancer.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer.

PURPOSE: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC. METHODS AND MATERIALS: Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire. RESULTS: Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment. CONCLUSIONS: For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.