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Background: Image-guided radiation therapy (IGRT) is dependent on the presence of fiducial markers for target localization and tracking. EUS-guided placement of fiducial markers with a 19-gauge needle has been reported. However, the size and stiffness of the 19-gauge needle may compromise the safety and ease of fiducial placement. Objective: The aim of this study was to evaluate the safety and feasibility of EUS-guided placement of thin flexible gold coil fiducials by using a 22-gauge needle. Design: Retrospective study. Setting: Memorial Sloan-Kettering Cancer Center, between December 2008 and November 2009. Patients: A total of 30 patients with GI malignancies of the mediastinum and upper abdomen who were to undergo IGRT. Interventions: EUS evaluation with a curvilinear-array echoendoscope was performed. The target lesion was identified, a 22-gauge needle preloaded with a gold coil fiducial was inserted into the lesion, and the fiducial was deployed under EUS guidance. Main Outcome Measurements: Technical success was defined as the ability to place fiducials in the desired location. Immediate and delayed complications were also noted. Results: A total of 69 fiducials were placed in 12 different sites in the mediastinum and upper abdomen. Technical success was achieved in 29 out of 30 cases (97%). No intraprocedural complications were encountered. One patient developed a fever and abnormal liver function tests 12 hours after fiducial placement. Limitations: Retrospective design, small case series. Conclusions: EUS-guided placement of thin flexible gold coil fiducials by using a 22-gauge needle is both safe and feasible for upper GI malignancies. [ABSTRACT FROM AUTHOR]

Accumulating evidence has implicated Helicobacter pylori, an established cause of chronic gastritis and peptic ulcer, in the etiology of gastric cancer. Control of this infection would reduce the occurrence of chronic gastritis and peptic ulcer and might substantially lower the risk of stomach cancer as well. The public health impact of this infectious agent warrants efforts to identify preventive measures. This paper reviews the evidence linking H. pylori infection to gastric cancer and evaluates the potential for control in high-risk populations. Current obstacles to H. pylori control are discussed, including the link to poor socioeconomic conditions, difficulty in identifying incident cases, lack of natural immunity to reinfection, limited effectiveness of antibiotic therapy in high-prevalence populations, and incomplete knowledge regarding the reservoir of infection, mode of transmission, host susceptibility factors, and the potential for developing an effective vaccine. Worthwhile avenues of research include studies designed to identify modifiable risk factors for acquisition of the infection, modifiable host factors that may increase resistance to chronic infection, more effective antibiotic therapies, and effective vaccines.

Abstract The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Abstract Purpose To assess the quality of life in curatively treated patients with rectal cancer in a prospectively collected cohort. Methods Patients with stage I-III rectal cancer who were treated curatively in a single institution were accrued prospectively. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29). Quality of life among different treatment modalities and between stoma and nonstoma patients was evaluated in all patients. Results A total of 154 patients were assessed. The median time of completion for the questionnaires was 10 months after all the treatments. For patients with different treatment modalities, faecal incontinence and diarrhea were significantly higher in radiation group (p = 0.002 and p = 0.001, respectively), and no difference in male or female sexual function was found between radiation group and non-radiation group. For stoma and nonstoma patients, the QLQ-CR29 module found the symptoms of Defaecation and Embarrassment with Bowel Movement were more prominent in stoma patients, while no difference was detected in scales QLQ-C30 module. Conclusions Our study provided additional information in evaluating QoL of Chinese rectal cancer patients with currently widely used QoL questionnaires. As a supplement to the QLQ-C30, EORTC QLQ-CR29 is a useful questionnaire in evaluating curatively treated patients with rectal cancer. Bowel dysfunction (diarrhea and faecal incontinence) was still the major problem compromising QoL in patients with either pre- or postoperative chemoradiotherapy.

Abstract Two persistent myths in epidemiology are that we can use a list of "causal criteria" to provide an algorithmic approach to inferring causation and that a modern "counterfactual model" can assist in the same endeavor. We argue that these are neither criteria nor a model, but that lists of causal considerations and formalizations of the counterfactual definition of causation are nevertheless useful tools for promoting scientific thinking. They set us on the path to the common sense of scientific inquiry, including testing hypotheses (really putting them to a test, not just calculating simplistic statistics), responding to the Duhem-Quine problem, and avoiding many common errors. Austin Bradford Hill's famous considerations are thus both over-interpreted by those who would use them as criteria and under-appreciated by those who dismiss them as flawed. Similarly, formalizations of counterfactuals are under-appreciated as lessons in basic scientific thinking. The need for lessons in scientific common sense is great in epidemiology, which is taught largely as an engineering discipline and practiced largely as technical tasks, making attention to core principles of scientific inquiry woefully rare.

Abstract Background Africa is in an orphan-care crisis. In Zimbabwe, where one-fourth of adults are HIV-positive and one-fifth of children are orphans, AIDS and economic decline are straining society's ability to care for orphans within their extended families. Lack of stable care is putting thousands of children at heightened risk of malnourishment, emotional underdevelopment, illiteracy, poverty, sexual exploitation, and HIV infection, endangering the future health of the society they are expected to sustain. Methods To explore barriers and possible incentives to orphan care, a quantitative cross-sectional survey in rural eastern Zimbabwe asked 371 adults caring for children, including 212 caring for double orphans, about their well-being, needs, resources, and perceptions and experiences of orphan care. Results Survey responses indicate that: 1) foster caregivers are disproportionately female, older, poor, and without a spouse; 2) 98% of non-foster caregivers are willing to foster orphans, many from outside their kinship network; 3) poverty is the primary barrier to fostering; 4) financial, physical, and emotional stress levels are high among current and potential fosterers; 5) financial need may be greatest in single-orphan AIDS-impoverished households; and 6) struggling families lack external support. Conclusion Incentives for sustainable orphan care should focus on financial assistance, starting with free schooling, and development of community mechanisms to identify and support children in need, to evaluate and strengthen families' capacity to provide orphan care, and to initiate and support placement outside the family when necessary.

Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Dose-escalated radiotherapy is increasingly used in the treatment of pancreatic cancer, however approaches to target delineation vary widely. We present the first North American cooperative group consensus contouring atlas for dose-escalated pancreatic cancer radiotherapy., Materials/methods: An expert international panel comprising 15 radiation oncologists, 2 surgeons and 1 radiologist were recruited. Participants used MimCloud software to contour high and low risk clinical target volumes (CTV) on three pancreatic cancer cases: a borderline resectable head tumor, a locally advanced head tumor, and a medically inoperable tail tumor. Simultaneous truth and performance level estimation (STAPLE) volumes were created, and contours were analyzed using Dice similarity coefficients., Results: The contoured gross tumor volume (GTV) for the borderline head, locally advanced head, and unresectable tail tumor cases were 156.7, 58.2 and 9.0 cc, respectively, and the Dice similarity coefficients (SD) for the high- and low-risk CTV ranged from 0.45 to 0.82. Consensus volumes were agreed upon by authors. High-risk CTVs comprised the tumor plus abutting vessels. Low-risk CTVs started superiorly at (tail tumors) or 1 cm above (head tumors) the celiac takeoff and extended inferiorly to the superior mesenteric artery (SMA) at the level of the first jejunal takeoff. For head, neck, and proximal body tumors, the lateral volume encompassed the entire pancreas head and 5-10 mm around the celiac, superior mesenteric artery (SMA), superior mesenteric vein (SMV), including the common hepatic artery and medial portal vein, consistent with a "Triangle" volume-based approach. For distal body and tail tumors, the entire tail was included, along with the splenic vessels and the takeoffs of celiac artery., Conclusion: Through multidisciplinary collaboration, we created consensus contouring guidelines for dose-escalated pancreatic cancer radiotherapy. These volumes include not only gross disease, but also routine elective coverage, and can be used to standardize practice for future trials seeking to define the role of dose escalated radiotherapy in pancreatic cancer., (Copyright © 2024. Published by Elsevier Inc.)

The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions., Competing Interests: Disclosures Christopher H. Crane receives consulting fees from Trisalis and honoraria from Elekta and has stock options in Oncternal. Karyn A. Goodman serves on the advisory board of RenovoRx and leadership in the NCI GI Steering Committee. Percy Lee receives consulting fees from Varian, ViewRay, AstraZeneca, Genentech, Johnson & Johnson, RTOG Foundation, honoraria from Varian, ViewRay, AstraZeneca, and travel support from Radiosurgery Society; serves on the advisory board for Genentech, ViewRay, AstraZeneca, Roche, and leadership of Radiosurgery Society, ASTRO. Michael D. Chuong receives grants, consulting fees, honoraria, and travel support from ViewRay, and serves on the advisory board of ViewRay., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. Springer Nature Limited.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2023 American Cancer Society.)

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.

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 χ 2 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., Competing Interests: Kristin Hsieh is the 2023 American Society for Radiation Oncology AstraZeneca Radiation Oncology Research Training Fellow. Karyn A. Goodman participates in Viewray Data Safety Monitoring Board, RenovoRx Advisory Board, and Philips Advisory Board; and she is a cochair of National Cancer Institute Gastrointestinal Steering Committee. The remaining authors declare that they have no conflict of interest., (© 2024 The Author(s).)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: BLJ and MM report grants from Varian Medical Systems during the conduct of the study, outside of the submitted work. In addition, BLJ and MM have a patent, Automated Tracking of Fiducial Marker Clusters in X-ray Images, US Provisional Patent Application 62/368,870., (© 2023 The Author(s).)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Heart doses have been shown to be predictive of cardiac toxicity and overall survival (OS) for esophageal cancer patients. There is potential for functional imaging to provide valuable cardiac information. The purpose of this study was to evaluate the cardiac metabolic dose-response using 18 F-deoxyglucose (FDG)-PET and to assess whether standard uptake value (SUV) changes in the heart were predictive of OS., Methods: Fifty-one patients with esophageal cancer treated with radiation who underwent pre- and post-treatment FDG-PET scans were retrospectively evaluated. Pre- and post-treatment PET-scans were rigidly registered to the planning CT for each patient. Pre-treatment to post-treatment absolute mean SUV (SUVmean) changes in the heart were calculated to assess dose-response. A dose-response curve was generated by binning each voxel in the heart into 10 Gy dose-bins and analyzing the SUVmean changes in each dose-bin. Multivariate cox proportional hazard models were used to assess whether pre-to-post treatment cardiac SUVmean changes predicted for OS., Results: The cardiac dose-response curve demonstrated a trend of increasing cardiac SUV changes as a function of dose with an average increase of 0.044 SUV for every 10 Gy dose bin. In multivariate analysis, disease stage and SUVmean change in the heart were predictive (p < 0.05) for OS., Conclusions: Changes in pre- to post-treatment cardiac SUV were predictive of OS with patients having a higher pre- to post-treatment cardiac SUV change surviving longer., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

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., (© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

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., (Copyright © 2023. Published by Elsevier Inc.)

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.)., (Copyright © 2023 Massachusetts Medical Society.)

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., Competing Interests: Shilpen Patel reports being American Society for Radiation Oncology (ASTRO) Sexual and Gender Minorities co-chair, ASTRO delegate to the AMA, and AMA Reference Committee F Member. Dayssy A. Diaz reports American Society of Clinical Oncology speaker honoraria, support to attend ASTRO meeting. Sue S. Yom reports grants from Genentech, Bristol-Myers Squibb, Merck, BioMimetix, and from EMD Serono, and personal fees from UpToDate and Springer, outside the submitted work. Karyn A. Goodman reports being a member of the Viewray SMART Trial data safety and monitoring board, RenovoRx Advisory Board, Philips Health Care co-chair, and the National Cancer Institute Gastrointestinal Steering Committee. Parul N. Barry reports receiving Varian Speaker honoraria, American College of Radiation Oncology (ACRO) New Practitioner Grant, support for attending ACRO and ASTRO annual meetings and board meetings, being an Elsevier Pathways Consultant, ACRO Board of Chancellors member, and on the UPMC Hillman Cancer Center data safety and monitoring board., (© 2023 The Author(s).)

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.

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.

Purpose: It is well-documented that gender disparities exist in academic radiation oncology departments. The purpose of this study was to analyze gender differences in research productivity during residency among recent graduates of radiation oncology training programs in the United States (US)., Methods and Materials: We used several publicly available sources to create a database of US radiation oncology residents who graduated between 2015 and 2019. We systematically collected gender information from the National Plan and Provider Enumeration System National Provider Identifier Registry and Medicare claims registry. Postresidency employment information was collected using several publicly available sources. PubMed was queried to identify first-author publications of residents. A secondary analysis of metadata including impact factor, number of citations, modified Hirsch index ( h index), and type of publication was performed. A multivariable linear regression was performed to evaluate the effect of gender on research productivity during residency., Results: There were 910 total graduates identified during this period and who were entered into this database, of whom all had available gender information. Female trainees comprised 29.0% (n = 264) of RO residents and had fewer first-author publications and citations, had lower mean modified h index, and were published in journals with lower impact factors. On multivariable linear regression analysis, female gender was independently associated with decreased total number of publications ( P  = .005), mean number of citations ( P < .001), and modified h index ( P  = .001) when controlling for residency size and advanced (PhD or master's) degrees., Conclusions: In the US, female RO trainees had lower research productivity, which was not explained by advanced degrees or residency size. A significant gender gap in trainee research productivity persists, which has known implications in terms of academic achievement, promotions, and career trajectory. Future interventions to improve resident research productivity and mentorship are warranted., (© 2022 The Authors.)

Objective: The objective of this study was to systematically evaluate the data regarding the use of neoadjuvant, perioperative, surgical, and adjuvant treatment options in localized gastric cancer patients and to develop Appropriate Use Criteria recommended by a panel of experts convened by the American Radium Society., Methods: Preferred reporting items for systematic reviews and meta-analyses methodology was used to develop an extensive analysis of peer-reviewed phase 2/2R/3 trials, as well as meta-analyses found within the Ovid Medline database between 2010 and 2020. The expert panel then rated the appropriateness of various treatments in 5 representative clinical scenarios through a well-established consensus methodology (modified Delphi)., Results: For patients with medically operable locally advanced gastric cancer, the strongest recommendation was for perioperative chemotherapy based on high-quality data. Acceptable alternatives included surgery followed by either chemotherapy or concurrent chemoradiotherapy (CRT). For patients with upfront resection of stages I to III gastric cancer (no neoadjuvant therapy), the group strongly recommended adjuvant therapy with either chemotherapy alone or CRT, based on high-quality data. For patients with locally advanced disease who received preoperative chemotherapy without tumor regression, the group strongly recommended postoperative chemotherapy or postoperative CRT. Finally, for medically inoperable gastric cancer patients, there was moderate consensus recommending definitive concurrent CRT., Conclusions: The addition of chemotherapy and/or radiation, either in the neoadjuvant, adjuvant, or perioperative setting, results in improved survival rates for patients compared with surgery alone. For inoperable patients, definitive CRT is a reasonable treatment option, though largely palliative., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Purpose: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited., Methods: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival., Results: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates., Conclusion: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

In the past 40 years, the treatment of locally advanced rectal cancer has evolved with the addition of radiotherapy or chemoradiotherapy and providing (neo)adjuvant systemic chemotherapy to major surgery. However, recent trends have focused on improving our ability to risk-stratify patients and tailoring treatment to achieve the best oncologic outcome while limiting the impact on long-term quality of life. Therefore, there has been increasing interest in pursuing a watch-and-wait approach to achieve organ preservation. Several retro- and prospective studies suggest safety of the watch-and-wait approach, though it is still considered controversial due to limited clinical evidence, concerns about tumor regrowth, and subsequent distant progression. To further reduce treatment, MRI risk stratification, together with patient characteristics and patient preferences, can guide personalized treatment and reserve radiation and chemotherapy for a select patient population. Ultimately, improved options for reassessment during neoadjuvant treatment may allow for more adaptive therapy options based on treatment response. This article provides an overview of some major developments in the multimodal treatment of locally advanced rectal cancer. It reviews some relevant, controversial issues of the watch-and-wait approach and opportunities to personally tailor and reduce treatment. It also reviews the overall neoadjuvant treatment, including total neoadjuvant therapy trials, and how to best optimize for a potential complete response. Finally, it provides an algorithm as an example of how such a personalized, tailored, adaptive, and reduced treatment could look like in the future.

Competing Interests: William A. HallResearch Funding: ElektaTravel, Accommodations, Expenses: Elekta Laura A. DawsonResearch Funding: Merck Theodore S. HongStock and Other Ownership Interests: PanTher TherapeuticsConsulting or Advisory Role: Merck, Synthetic Biologics, Novocure, SyndaxResearch Funding: Taiho Pharmaceutical, AstraZeneca, IntraOp, Tesaro, Bristol Myers Squibb, Ipsen Manisha PaltaHonoraria: OakstoneConsulting or Advisory Role: Syntactx, VoxelMetrixResearch Funding: Merck, Varian Medical SystemsPatents, Royalties, Other Intellectual Property: UpToDate—Annual royalties for being a section author Joseph M. HermanHonoraria: Sirtex MedicalTravel, Accommodations, Expenses: Varian Medical SystemsOther Relationship: 1440 Foundation Jason B. FlemingLeadership: Bio-Path Holdings, IncConsulting or Advisory Role: Johnson and Johnson, GlycosBio, Moleculin Biotech, Perthera, Covidien LP/Medtronic, PanTher TherapeuticsPatents, Royalties, Other Intellectual Property: US Application No. 15/780,799, based on International Application No. PCT/US2016/065763, titled Polymeric Drug Delivery Systems for Treatment of Disease, by Chun Li et al; In the Name of Board of Regents, The University of Texas System Daniel T. ChangStock and Other Ownership Interests: ViewRayResearch Funding: Varian Medical Systems, Reflexion MedicalOther Relationship: ViewRay Christopher CraneStock and Other Ownership Interests: Oncternal TherapeuticsHonoraria: ElektaConsulting or Advisory Role: TriSalus Life SciencesResearch Funding: Elekta Albert C. KoongStock and Other Ownership Interests: Aravive Parag ParikhStock and Other Ownership Interests: NuvairaHonoraria: ViewRaySpeakers' Bureau: ViewrayResearch Funding: ViewRayTravel, Accommodations, Expenses: IBA Beth EricksonResearch Funding: ElektaTravel, Accommodations, Expenses: Elekta Sarah HoffeStock and Other Ownership Interests: VitalAireHonoraria: UpToDateConsulting or Advisory Role: MerckResearch Funding: Varian Medical Systems, Galera TherapeuticsPatents, Royalties, Other Intellectual Property: I cowrote the bone metastases chapter for UpToDate. They pay royalties/honoraria for that yearlyTravel, Accommodations, Expenses: Varian Medical SystemsOther Relationship: Beyond the White Coat, VitalAireUncompensated Relationships: Galera Therapeutics, ViewRay Karyn A. GoodmanConsulting or Advisory Role: RenovoRx, Roche/Genentech, NovartisNo other potential conflicts of interest were reported.

Background: Neoadjuvant chemotherapy with concurrent radiotherapy (nCRT) is an accepted treatment regimen for patients with potentially curable esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The purpose of this study is to evaluate whether induction chemotherapy (IC) before nCRT is associated with improved pathologic complete response (pCR) and overall survival (OS) when compared with patients who received nCRT alone for esophageal and GEJ adenocarcinoma., Methods: Using the National Cancer Database (NCDB), patients who received nCRT and curative-intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006 to 2015 were included. Chemotherapy and radiation therapy start dates were used to define cohorts who received IC before nCRT (IC + nCRT) versus those who only received concurrent nCRT before surgery. Propensity weighting was conducted to balance patient, disease, and facility covariates between groups., Results: 12,460 patients met inclusion criteria, of whom 11,880 (95%) received nCRT and 580 (5%) received IC + nCRT. Following propensity weighting, OS was significantly improved among patients who received IC + nCRT versus nCRT (HR 0.82; 95% CI 0.74-0.92; p < 0.001) with median OS for the IC + nCRT cohort of 3.38 years versus 2.45 years for nCRT. For patients diagnosed from 2013 to 2015, IC + nCRT was also associated with higher odds of pCR compared with nCRT (OR 1.59; 95% CI 1.14-2.21; p = 0.007)., Conclusion: IC + nCRT was associated with a significant OS benefit as well as higher pCR rate in the more modern patient cohort. These results merit consideration of a sufficiently powered prospective multiinstitutional trial to further evaluate these observed differences., (© 2021. Society of Surgical Oncology.)

Purpose: To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma., Methods: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy., Results: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached., Conclusion: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%., Competing Interests: Karyn A. GoodmanConsulting or Advisory Role: RenovoRx Tanios Bekaii-SaabConsulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation MedicinePatents, Royalties, Other Intellectual Property: Patent WO/2018/183488 and Patent WO/2019/055687Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, Pancreatic Cancer Action Network Daniel J. BoffaResearch Funding: Epic Sciences Wendy L. FrankelPatents, Royalties, Other Intellectual Property: Patent title: Automated Identification of Tumor Buds. Application No.: 16/230,118. Filing date: December 21, 2018. Publication date: July 4, 2019. Applicant(s): Ohio State Innovation Foundation, Columbus, OH. Inventor(s): Metin Gurcan, Winston-Salem, NC; Wendy Frankel, Columbus, OH; Wei Chen, Columbus, OH; Ahmad Fauzi and Mohammad Faizal, Selangor, MY Anne NoonanConsulting or Advisory Role: Helsinn Healthcare, QED Therapeutics, Exelixis, Eisai Yelena Y. JanjigianStock and Other Ownership Interests: RgenixConsulting or Advisory Role: Pfizer, Merck, Bristol Myers Squibb, Merck Serono, Daiichi Sankyo, Rgenix, Bayer, Imugene, AstraZeneca, Lilly, Zymeworks, Seattle Genetics, Merck Sharpe and Dohme Corp, Michael J. Hennessy Associates, Jounce Therapeutics, Ono PharmaceuticalResearch Funding: Boehringer Ingelheim, Bayer, Roche, Genentech, Rgenix, Bristol Myers Squibb, Merck, LillyOther Relationship: Paradigm, Clinical Care Options, Axis Medical Education, Research to Practice Paul J. ThurmesConsulting or Advisory Role: US OncologyTravel, Accommodations, Expenses: US Oncology Alan P. VenookConsulting or Advisory Role: Merck Sharp & Dohme, Array BioPharmaResearch Funding: Genentech/Roche, Bristol Myers Squibb, AmgenPatents, Royalties, Other Intellectual Property: Royalties from Now-UptoDate for authoring and maintaining two chaptersTravel, Accommodations, Expenses: Genentech, Roche Jeffrey A. MeyerhardtHonoraria: Cota Healthcare, Taiho PharmaceuticalResearch Funding: Boston Biomedical Eileen M. O'ReillyConsulting or Advisory Role: Merck, Agios, AstraZeneca, Bayer, BeiGene, Berry Genomics, Celgene, CytomX Therapeutics, Debiopharm Group, Eisai, Exelixis/Ipsen, Flatiron Health, Incyte, Janssen, LAM Therapeutics, Lilly, Loxo, Genentech/Roche, Minapharma, QED Therapeutics, RedHill Biopharma, Sillajen, SOBI, Yiviva, Autem Medical, Gilead Sciences, Ipsen, Silenseed, TheraBionic, twoXAR, Vector HealthResearch Funding: AstraZeneca/MedImmune, Acta Biologica, Bristol Myers Squibb, Celgene, Genentech, Halozyme, MabVax, Roche, Silenseed David H. IlsonConsulting or Advisory Role: Lilly/ImClone, Roche/Genentech, Bristol Myers Squibb, Pieris Pharmaceuticals, Merck, Bayer, AstraZeneca, Taiho Pharmaceutical, Astellas Pharma, IQvia, MacrogenicsNo other potential conflicts of interest were reported.

The present study aims to monitor longitudinal changes in simulated tumor interstitial fluid pressure (IFP) and velocity (IFV) values using dynamic contrast-enhanced (DCE)-MRI-based computational fluid modeling (CFM) in pancreatic ductal adenocarcinoma (PDAC) patients. Nine PDAC patients underwent MRI, including DCE-MRI, on a 3-Tesla MRI scanner at pre-treatment (TX (0)), after the first fraction of stereotactic body radiotherapy (SBRT, (D1-TX)), and six weeks post-TX (D2-TX). The partial differential equation of IFP formulated from the continuity equation, incorporating the Starling Principle of fluid exchange, Darcy velocity, and volume transfer constant (K trans ), was solved in COMSOL Multiphysics software to generate IFP and IFV maps. Tumor volume (V t ), K trans , IFP, and IFV values were compared (Wilcoxon and Spearman) between the time- points. D2-TX K trans values were significantly different from pre-TX and D1-TX ( p < 0.05). The D1-TX and pre-TX mean IFV values exhibited a borderline significant difference ( p = 0.08). The IFP values varying <3.0% between the three time-points were not significantly different ( p > 0.05). V t and IFP values were strongly positively correlated at pre-TX (ρ = 0.90, p = 0.005), while IFV exhibited a strong negative correlation at D1-TX (ρ = -0.74, p = 0.045). V t , K trans , IFP, and IFV hold promise as imaging biomarkers of early response to therapy in PDAC.

Background: Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly., Methods: This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70-74, 75 or more years) and respective treatment outcomes were compared., Results: The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70-74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70-74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70-74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor., Conclusion: The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The role of neoadjuvant stereotactic body radiation therapy (SBRT) in patients with borderline resectable pancreas cancer (BRPC) and locally advanced pancreas cancer (LAPC) remains controversial., Methods: We retrospectively evaluated BRPC and LAPC patients treated at our institution who underwent 2-3 months of chemotherapy followed by SBRT to a dose of 30-33 Gy. Overall survival (OS) and recurrence-free survival (RFS) were estimated and compared by Kaplan-Meier and log-rank methods., Results: We identified 103 (85 BRPC and 18 LAPC) patients treated per our neoadjuvant paradigm between 2011 and 2018, with resectability based on NCCN definitions. Median follow up was 25 months. Of patients completing neoadjuvant therapy, 73 (71%) underwent definitive resection. Seventy-one (97%) patients with definitively resected tumors had R0 resection and 5 (7%) had a complete pathologic response CR to neoadjuvant therapy. The median overall survival (OS) of the cohort was 24 months. Those with a complete or marked pathologic response had significantly better OS than those with a moderate response (41 vs 24 months, p < 0.02) and patients unable to undergo definitive surgery (17 months, p < 0.0003). Six resected patients experienced grade ≥3 surgical complications., Conclusions: Neoadjuvant chemotherapy and SBRT are associated with promising pathologic response rates and R0 resection rates, with acceptable perioperative morbidity., (Copyright © 2020. Published by Elsevier Ltd.)

Cancer is a heterogeneous disease, consisting of a spectrum of disorders ranging from local-only disease to those that are widely metastatic from their onset. The oligometastatic state, in which tumors harbor a limited number of metastases, may be curable in a subset of patients. The early success of surgical resection of hepatic metastases from colorectal cancer led to investigations into metastatectomy of other sites and, more recently, into the use of stereotactic ablative radiotherapy (SABR) for oligometastatic disease. This article reviews the data establishing the role of surgery for managing limited metastatic disease. Further, we review recent experiences using alternative local therapies, such as SABR, for oligometastases. This review also discusses ongoing trials evaluating local therapies for patients with a limited burden of metastatic cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Nurses in the radiation oncology (RO) clinic have a critical role in the management of patients receiving radiation therapy. However, limited data exist regarding the exposure of nurses to RO during training and the current educational needs of practicing RO nurses. This study assesses nurses' prior RO education, participation in national training efforts, and perceived educational needs., Methods and Materials: A web-based survey using a 5-point Likert-type scale was distributed to RO nurses at 3 academic medical centers. Questions focused on prior education experiences, clinical areas of strength/weakness, and perceived value of future educational interventions. Likert-type scores are reported as median (interquartile range), and a Kruskal-Wallis test was conducted to assess for significant differences in responses., Results: The survey response rate was 39 of 54 (72%). Respondents were 90% female and trained at 30 nursing schools in 17 states. Only 5% of nurses reported a curriculum in nursing school with RO content, and nearly all (97%) received their RO education on the job. Forty-one percent of nurses completed the Oncology Nursing Society radiation therapy certificate course, and only 5% completed the American Society for Radiation Oncology nursing module. Nurses felt most confident in the overall management of patients with breast (4 [3-4]), prostate (4 [3-5]), and central nervous system (4 [3-4]) cancers and least confident for lymphoma (3 [2-4]), gynecologic (3 [2-4]), and head and neck cancers (3 [2-4]; P < .01). Nurses rated didactic lectures from physicians (5 [3-5]), shadowing RO residents (4 [3-5]), and working with simulation therapists (4 [3-5]) as valuable components to include in a training curriculum (P = .08)., Conclusions: Nursing school exposure to RO is limited, and only a minority of RO nurses complete RO-specific training or certification available from national organizations. This study identifies several areas of perceived clinical nursing strengths and weaknesses that can be used to inform the design of future RO nursing educational programs., (Copyright © 2021 Elsevier Inc. All rights reserved.)