The role of rectal magnetic resonance imaging in accurate localization and designation of colorectal cancer for optimal management: Case study.

Colorectal cancer, developing from malignant transformation of the distal gut epithelium, is the second leading cause of cancer death in the United States. We present a gentleman in his 60s who was diagnosed with colorectal cancer during a routine screening colonoscopy with no evidence of distant metastasis on subsequent staging with positron emission tomography and computed tomography (PET-CT). The outside rectal MR (magnetic resonance) imaging report localized a mass to the upper rectum. Review of the MRI at an institutional, Multidisciplinary Tumor Board designated the tumor as "rectosigmoid," straddling the rectosigmoid junction at the level of the "sigmoid take-off" (STO) or alternatively at the level of the last sigmoid artery take-off (SAT) at the origin of the superior rectal artery. The anatomic differentiation between upper rectal and lower sigmoid colon cancers carries clinical importance which is highlighted in this case report and brief literature review. Optimal anatomic localization of colorectal cancers helps direct the clinical team to tailor an individualized patient care plan.

Radiation Oncology Resident Education: Is Change Needed?

Leading successful change efforts first requires assessment of the "before change" environment and culture. At our institution, the radiation oncology (RO) residents follow a longitudinal didactic learning program consisting of weekly 1-h lectures, case conferences, and journal clubs. The resident didactic education series format has not changed since its inception over 10 years ago. We evaluated the perceptions of current residents and faculty about the effectiveness of the curriculum in its present form. Two parallel surveys were designed, one each for residents and attendings, to assess current attitudes regarding the effectiveness and need for change in the RO residency curriculum, specifically the traditional didactic lectures, the journal club sessions, and the case conferences. We also investigated perceived levels of engagement among residents and faculty, whether self-assessments would be useful to increase material retention, and how often the content of didactic lectures is updated. Surveys were distributed individually to each resident (N = 10) and attending (N = 24) either in-person or via Zoom. Following completion of the survey, respondents were informally interviewed about their perspectives on the curriculum's strengths and weaknesses. Compared to 46% of attendings, 80% of RO residents believed that the curriculum should be changed. Twenty percent of residents felt that the traditional didactic lectures were effective in preparing them to manage patients in the clinic, compared to 74% of attendings. Similarly, 10% of residents felt that the journal club sessions were effective vs. 42% of attendings. Finally, 40% of residents felt that the case conferences were effective vs. 67% of attendings. Overall, most respondents (56%) favored change in the curriculum. Our results suggest that the perceptions of the residents did not align with those of the attending physicians with respect to the effectiveness of the curriculum and the need for change. The discrepancies between resident and faculty views highlight the importance of a dedicated change management effort to mitigate this gap. Based on this project, we plan to propose recommended changes in structure to the residency program directors. Main changes would be to increase the interactive nature of the course material, incorporate more ways to increase faculty engagement, and consider self-assessment questions to promote retention. Once we get approval from the residency program leadership, we will follow Kotter's "Eight steps to transforming your organization" to ensure the highest potential for faculty to accept the expectations of a new curriculum.

Novel Virtual Reality App for Training Patients on MRI-guided Radiation Therapy.

Purpose: Patients receiving respiratory gated magnetic resonance imaging-guided radiation therapy (MRIgRT) for abdominal targets must hold their breath for ≥25 seconds at a time. Virtual reality (VR) has shown promise for improving patient education and experience for diagnostic MRI scan acquisition. We aimed to develop and pilot-test the first VR app to educate, train, and reduce anxiety and discomfort in patients preparing to receive MRIgRT. Methods and Materials: A multidisciplinary team iteratively developed a new VR app with patient input. The app begins with minigames to help orient patients to using the VR device and to train patients on breath-holding. Next, app users are introduced to the MRI linear accelerator vault and practice breath-holding during MRIgRT. In this quality improvement project, clinic personnel and MRIgRT-eligible patients with pancreatic cancer tested the VR app for feasibility, acceptability, and potential efficacy for training patients on using breath-holding during MRIgRT. Results: The new VR app experience was tested by 19 patients and 67 clinic personnel. The experience was completed on average in 18.6 minutes (SD = 5.4) by patients and in 14.9 (SD = 3.5) minutes by clinic personnel. Patients reported the app was "extremely helpful" (58%) or "very helpful" (32%) for learning breath-holding used in MRIgRT and "extremely helpful" (28%) or "very helpful (50%) for reducing anxiety. Patients and clinic personnel also provided qualitative feedback on improving future versions of the VR app. Conclusion: The VR app was feasible and acceptable for training patients on breath-holding for MRIgRT. Patients eligible for MRIgRT for pancreatic cancer and clinic personnel reported on future improvements to the app to enhance its usability and efficacy.

Support Through Remote Observation and Nutrition Guidance (STRONG), a digital health intervention to reduce malnutrition among pancreatic cancer patients: A study protocol for a pilot randomized controlled trial.

Background: Malnutrition is a common and distressing condition among pancreatic cancer patients. Fewer than a quarter of pancreatic cancer patients receive medical nutrition therapy (MNT), important for improving nutritional status, weight maintenance, quality of life and survival. System, provider, and patient level barriers limit access to MNT. We propose to examine the feasibility of a 12-week multi-level, digital health intervention designed to expand MNT access among pancreatic cancer patients. Methods: Individuals with advanced pancreatic cancer starting chemotherapy (N = 80) will be 1:1 randomized to the intervention or usual care. The Support Through Remote Observation and Nutrition Guidance (STRONG) intervention includes system-level (e.g., routine malnutrition and screening), provider-level (e.g., dietitian training and web-based dashboard), and patient-level strategies (e.g., individualized nutrition plan, self-monitoring of dietary intake via Fitbit, ongoing goal monitoring and feedback). Individuals receiving usual care will be referred to dietitians based on their oncologists' discretion. Study assessments will be completed at baseline, 4-, 8-, 12-, and 16-weeks. Results: Primary outcomes will be feasibility (e.g., recruitment, retention, assessment completion) and acceptability. We will collect additional implementation outcomes, such as intervention adherence, perceived usability, and feedback on intervention quality via an exit interview. We will collect preliminary data on outcomes that may be associated with the intervention including malnutrition, quality of life, treatment outcomes, and survival. Conclusion: This study will advance our knowledge on the feasibility of a digital health intervention to reduce malnutrition among individuals with advanced pancreatic cancer. Trial registration: NCT05675059, registered on December 9, 2022.

Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design.

Ablative doses of stereotactic body radiotherapy (SBRT) may improve pancreatic cancer outcomes but may carry greater potential for gastrointestinal toxicity. Rucosopasem, an investigational selective dismutase mimetic that converts superoxide to hydrogen peroxide, can potentially increase tumor control of SBRT without compromising safety. GRECO-2 is a phase II, multicenter, randomized, double-blind, placebo-controlled trial of rucosopasem in combination with SBRT in locally advanced or borderline resectable pancreatic cancer. Patients will be randomized to rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT fraction (5 × 10 Gy). The primary end point is overall survival. Secondary end points include progression-free survival, locoregional control, time to metastasis, surgical resection rate, best overall response, in-field local response and acute and long-term toxicity.

The use of high doses of radiation delivered directly to tumors (stereotactic body radiation therapy [SBRT]) may improve survival compared with lower doses of radiation in patients with pancreatic cancer, but it may increase side effects. Rucosopasem, an investigational new drug being developed, can potentially improve the ability of SBRT to treat tumors without decreasing safety. In a previous study, median overall survival was improved when patients were treated with SBRT plus avasopasem, a drug that works the same way as rucosopasem. GRECO-2 is a clinical trial of rucosopasem used in combination with SBRT for treatment of localized pancreatic cancer. Patients will be randomly selected to receive either rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT treatment. The main result being studied is overall survival. Additional results include amount of time before tumors start to grow, how often patients get tumors surgically removed, best overall response and long-term safety. Clinical Trial Registration: NCT04698915 (ClinicalTrials.gov).

Multi-institutional experience of MR-guided stereotactic body radiation therapy for adrenal gland metastases.

Purpose: While dose escalation is associated with improved local control (LC) for adrenal gland metastases (AGMs), the proximity of gastrointestinal (GI) organs-at-risk (OARs) limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The advantages of magnetic resonance-guided SBRT (MRgSBRT), including tumor tracking and online plan adaptation, facilitate safe dose escalation. Methods: This is a multi-institutional review of 57 consecutive patients who received MRgSBRT on a 0.35-T MR linac to 61 AGMs from 2019 to 2021. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and LC, and the Cox proportional hazards model was utilized for univariate analysis (UVA). Results: Median follow up from MRgSBRT was 16.4 months (range [R]: 1.1-39 months). Median age was 67 years (R: 28-84 years). Primary histologies included non-small cell lung cancer (N = 38), renal cell carcinoma (N = 6), and melanoma (N = 5), amongst others. The median maximum diameter was 2.7 cm (R: 0.6-7.6 cm), and most AGMs were left-sided (N = 32). The median dose was 50 Gy (R: 30-60 Gy) in 5-10 fractions with a median BED10 of 100 Gy (R: 48-132 Gy). 45 cases (74 %) required adaptation for at least 1 fraction (median: 4 fractions, R: 0-10). Left-sided AGMs required adaptation in at least 1 fraction more frequently than right-sided AGMs (88 % vs 59 %, p = 0.018). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N = 1) and 40 Gy in 5 fractions (N = 2). One-year LC, PFS, and OS were 92 %, 52 %, and 78 %, respectively. On UVA, melanoma histology predicted for inferior 1-year LC (80 % vs 93 %, p = 0.012). There were no instances of grade 3+ toxicity. Conclusions: We demonstrate that MRgSBRT achieves favorable early LC and no grade 3 + toxicity despite prescribing a median BED10 of 100 Gy to targets near GI OARs.

Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma.

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. METHODS: We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. RESULTS: From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. CONCLUSION: There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma. METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six academic sites in the USA. Eligible patients were randomly assigned (1:1), with block randomisation (block sizes of 6-12) with a maximum of 24 patients per group, to receive daily avasopasem (90 mg) or placebo intravenously directly before (ie, within 180 min) SBRT (50, 55, or 60 Gy in five fractions, adaptively assigned in real time by Bayesian estimates of 90-day safety and efficacy). Patients and physicians were masked to treatment group allocation, but not to SBRT dose. The primary objective was to find the optimal dose of SBRT with avasopasem or placebo as determined by the late onset EffTox method. All analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT03340974, and is complete. FINDINGS: Between Jan 25, 2018, and April 29, 2020, 47 patients were screened, of whom 42 were enrolled (median age was 71 years [IQR 63-75], 23 [55%] were male, 19 [45%] were female, 37 [88%] were White, three [7%] were Black, and one [2%] each were unknown or other races) and randomly assigned to avasopasem (n=24) or placebo (n=18); the placebo group was terminated early after failing to meet prespecified efficacy parameters. At data cutoff (June 28, 2021), the avasopasem group satisfied boundaries for both efficacy and toxicity. Late onset EffTox efficacy response was observed in 16 (89%) of 18 patients at 50 Gy and six (100%) of six patients at 55 Gy in the avasopasem group, and was observed in three (50%) of six patients at 50 Gy and nine (75%) of 12 patients at 55 Gy in the placebo group, and the Bayesian model recommended 50 Gy or 55 Gy in five fractions with avasopasem for further study. Serious adverse events of any cause were reported in three (17%) of 18 patients in the placebo group and six (25%) of 24 in the avasopasem group. In the placebo group, grade 3 adverse events within 90 days of SBRT were abdominal pain, acute cholangitis, pyrexia, increased blood lactic acid, and increased lipase (one [6%] each); no grade 4 events occurred. In the avasopasem group, grade 3-4 adverse events within 90 days of SBRT were acute kidney injury, increased blood alkaline phosphatase, haematoma, colitis, gastric obstruction, lung infection, abdominal abscess, post-surgical atrial fibrillation, and pneumonia leading to respiratory failure (one [4%] each).There were no treatment-related deaths but one late death in the avasopasem group due to sepsis in the setting of duodenal obstruction after off-study treatment was reported as potentially related to SBRT. INTERPRETATION: SBRT that uses 50 or 55 Gy in five fractions can be considered for patients with localised pancreatic ductal adenocarcinoma. The addition of avasopasem might further enhance disease outcomes. A larger phase 2 trial (GRECO-2, NCT04698915) is underway to validate these results. FUNDING: Galera Therapeutics.

Induction Fluorouracil-Based Chemotherapy and PET-Adapted Consolidation Chemoradiation with Esophagectomy for High-Risk Gastroesophageal Adenocarcinoma.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal adenocarcinoma. Induction chemotherapy with a tailored approach to chemoradiation based on metabolic response to therapy on PET was explored as an alternative strategy in the CALGB 80803 trial. We sought to describe real-world institutional experience implementing this approach outside of a clinical trial. Methods: Patients who were treated with induction fluorouracil-leucovorin-oxaliplatin (FOLFOX) or fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) with tailored chemoradiation based on PET response and subsequent esophagectomy were identified from a prospectively maintained database. Primary outcomes were pathologic complete response (pCR) and overall survival (OS) following completion of all therapy. Results: There were 35 patients who completed induction chemotherapy, chemoradiation, and esophagectomy. Thirty-three completed restaging PET following induction chemotherapy with metabolic response seen in 76% (n = 25/33). The pCR rate was 31% (n = 11/35) and the ypN0 rate was 71% (n = 25/35). Among the patients who demonstrated metabolic response to induction FOLFOX/FLOT and subsequently continued fluorouracil-based chemoradiation, the pCR rate was 39% (n = 9/23). The rate of pathologically negative lymph nodes in this group was high (n = 19/23, 83%) with 100% R0 resection rate (n = 23/23). With the median follow-up of 43 months, the median OS was not reached for this group and was significantly longer than the OS for the remainder of the cohort (p = 0.027, p = 0.046 adjusted for clinical stage). Conclusions: Induction FOLFOX/FLOT chemotherapy with evaluation of sensitivity via metabolic response and tailored chemoradiation seems to lead to high pCR and ypN0 rates in high-risk patients with adenocarcinoma of the esophagus and GE junction. This approach in clinical practice seems to recapitulate encouraging results in clinical trials.

Neoadjuvant chemotherapy and stereotactic body radiation therapy for borderline resectable pancreas adenocarcinoma: influence of vascular margin status and type of chemotherapy.

BACKGROUND: The influence of chemotherapy type and vascular margin status after sequential chemotherapy and stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer (BRPC) is unknown. METHODS: A retrospective review was performed on BRPC patients treated with chemotherapy and 5-fraction SBRT from 2009 to 2021. Surgical outcomes and SBRT-related toxicity were reported. Clinical outcomes were estimated by Kaplan-Meier with log rank comparisons. RESULTS: A total of 303 patients received neoadjuvant chemotherapy and SBRT to a median dose of 40 Gy prescribed to the tumor-vessel interface and median dose of 32.4 Gyto 95% of the gross tumor volume. One hundred and sixty-nine patients (56%) were resected and benefited from improved median OS (41.1 vs 15.5 months, P < 0.001). Close/positive vascular margins were not associated with worse OS or FFLRF. Type of neoadjuvant chemotherapy did not influence OS for resected patients, but FOLFIRINOX was associated with improved median OS in unresected patients (18.2 vs 13.1 months, P = 0.001). CONCLUSION: For BRPC, the effect of a positive or close vascular margin may be mitigated by neoadjuvant therapy. Shorter duration neoadjuvant chemotherapy as well as the optimal biological effective dose of radiotherapy should be prospectively explored.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma-A Prospective Feasibility Study.

PURPOSE: To evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: This prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. RESULTS: Twenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9-7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0-33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8-31.0 months) versus 10.7 months (95% CI, 8.0-13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7-20.7 months) versus 37.3 months (95% CI, 16.5-58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. CONCLUSIONS: First-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

PURPOSE: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. METHODS: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). RESULTS: A total of 49 patients were evaluated with a median age of 81 years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50 Gy (range, 40-50 Gy) in 5 fractions. 1 Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6 months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. CONCLUSIONS: A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

A Practical Workflow for Magnetic Resonance-Guided Stereotactic Body Radiation Therapy to the Pancreas.

The increased adoption of stereotactic body radiation therapy has allowed for delivery of higher doses, potentially associated with better outcomes but at the risk of higher toxicity. The intimate association of radiosensitive organs at risk (eg, stomach, duodenum, bowel) has historically limited the delivery of ablative doses to the pancreas. The advent of magnetic resonance-guided radiation therapy with improved soft-tissue contrast allows for gated delivery without an internal target volume and online adaptive replanning to maximize the therapeutic ratio. Patient selection requires additional resources, including increased patient on-table time, physician time, and physics support. Within our center's workflow, integrating an educational video at consultation as well as optimizing biofeedback mechanisms have significantly improved the experience for our patients.

Surgical and Pathologic Outcomes of Pancreatic Adenocarcinoma (PA) After Preoperative Ablative Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy (A-SMART).

Purpose: Preoperative radiation therapy (RT) for pancreatic adenocarcinoma reduces positive surgical margin rates, and when delivered to an ablative dose range it may improve local control and overall survival for patients with unresectable disease. Use of stereotactic body RT to achieve a higher biologically effective dose has been limited by toxicity to adjacent radiosensitive structures, but this can be mitigated by stereotactic magnetic resonance image guided adaptive radiation therapy (SMART). Methods and Materials: We describe our single-institution experience of high biologically effective dose SMART before resection of localized pancreatic adenocarcinoma. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (V 5.0). Tumor response was evaluated according to the College of American Pathologists tumor regression grading criteria. Results: We analyzed 26 patients with borderline resectable (80.8%), locally advanced (11.5%), and resectable (7.7%) tumors who received ablative dose SMART (A-SMART) followed by surgical resection. Median age at diagnosis was 68 years (range, 34-86). Most patients received chemotherapy (80.8%) before RT. All patients received A-SMART to a median dose of 50 (range, 40-50) Gy in 5 fractions. Toxicity data were collected prospectively and there were no acute grade 2+ toxicities associated with RT. The median time to resection was 50 days (range, 37-115), and the procedure types included Whipple (69%), distal (23%), or total pancreatectomy (8%). The R0 resection rate was 96% and no perioperative deaths occurred within 90 days. Pathologic response was observed in 88% of cases. The time from RT to surgery was associated with tumor regression grade (P = .0003). The median follow-up after RT was 16.5 months (range, 3.9-26.2). The derived median progression-free survival from RT was 13.2 months. Conclusions: The initial surgical and pathologic outcomes after A-SMART are encouraging. Preoperative A-SMART was associated with low toxicity rates and no surgical or RT-associated mortality. The surgical morbidity was comparable to historic rates after upfront resection. These data also suggest that the time from stereotactic body RT to surgical resection is associated with pathologic response.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Yttrium-90 Radioembolization for Liver-Dominant Metastatic Prostate Cancer: A Case Series.

Transarterial radioembolization (TARE) with yttrium-90 glass microspheres is widely used to treat primary and secondary malignancies in the liver. However, the safety and efficacy of TARE in patients with liver-dominant metastatic castration-resistant prostate cancer (mCRPC) is unknown. A proof-of-concept, retrospective analysis of 7 consecutive patients with liver-dominant mCRPC who were treated with TARE was performed. The median overall survival was 27.2, 32.1, and 108.1 months from the time of TARE, the diagnosis of liver metastases, and initial cancer diagnosis, respectively. The median liver progression-free survival was 7.3 months. No grade 3 or higher adverse effects were noted. TARE was found to be a safe and effective tool for treating patients with liver-dominant mCRPC in this limited cohort.