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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.

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 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.

The impact of adjuvant sequential chemoradiotherapy (CRT) on survival in resected pancreatic ductal adenocarcinoma (PDAC) remains unclear and warrants further investigation. NCDB patients with R0/R1 resected PDAC who received adjuvant chemotherapy without CRT or followed by CRT per RTOG-0848 protocol were included. Cox regression for 5-year overall survival (OS) was performed and used to construct a pathologic nomogram in patients who did not receive CRT. A risk score was calculated and patients were divided into low-risk and high-risk groups. Patients from each risk stratum were matched for the receipt of CRT to assess the added benefit of CRT on survival. The Kaplan–Meier analysis was performed to compare OS. A total of 7146 patients were selected, 1308 (18.3%) received CRT per RTOG-0848. Cox regression concluded grade, T stage, N stage, node yield

The management of Renal cell carcinoma (RCC) patients with liver metastases is challenging. Liver-directed therapy, such as Transarterial radioembolization (TARE), is a reasonable option for these patients; however, its safety and efficacy are not well characterized. This study evaluated the safety and efficacy of TARE in patients with liver-dominant metastatic RCC. This is a retrospective, single-center study. Thirty-eight patients’ medical records were reviewed who underwent TARE between January 1, 2009, and December 31, 2019, in a tertiary cancer center. Two were excluded from further analysis. Thirty-six patients received 51 TARE treatments. Median follow-up time was 18.2 months. Imaging data were evaluated using mRECIST or RECIST 1.1 criteria. Toxicities, treatment responses, liver progression-free survival (LPFS), and median overall survival (OS) were calculated. Univariate and multivariate analyses were conducted to reveal predictors of OS. Median OS from TARE was 19.3 months (95% CI, 22.6–47.4) and from diagnosis of liver metastases was 36.5 months (95% CI: 26.4–49.8). Mild, grade 1 or 2, biochemical toxicity developed in 27 patients (75%). Grade 3–4 toxicity was noted in two patients (5.5%). The objective response rate was 89%; the disease control rate was 94% (21 complete response, 11 partial response, two stable disease, and two progressive disease). Univariate and multivariate analyses showed longer survival in patients who had objective response, lower lung shunt fraction, and better baseline liver function. TARE is safe and effective and led to promising overall survival in patients with liver-dominant metastatic RCC. Level of Evidence: Level 3, retrospective cohort study.

During the past 30 years, radiation treatment techniques have significantly improved, from conventional external-beam radiation therapy, to three-dimensional conformal radiation therapy, to current intensity-modulated radiation therapy, benefiting patients who undergo treatment of pelvic malignancies. Modern treatment options also include proton beam irradiation as well as low and high dose rate brachytherapy. Although the acute adverse effects of these modalities are well documented in clinical trials, less well known are the true incidence and optimal management of those late adverse effects that can occur months to years later. In a population of survivors of cancer that is steadily increasing, with many such patients receiving radiotherapy at some time during their disease course, these late effects can become a considerable management and quality-of-life issue. This review will examine the range of late toxicities that can occur from pelvic radiotherapy and explore strategies to prevent and mitigate them.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation–positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

Background: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACRT). Material and methods: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET. Results: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1–3; 91% accuracy in predicting TRG 0–1 vs. TRG 2–3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores. Conclusion: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACRT. A larger cohort is warranted for further validation.

The increasing complexity of healthcare emphasizes the need for continued physician leadership and leadership training. This study aims to determine baseline attitudes toward the perceptions and utility of a leadership development curriculum (LDC) for radiation oncology (RO) residents. A novel longitudinal LDC was implemented for RO residents at our institution from 2018 to 2019. Prior to the curriculum, current and past residents in our institution's RO residency program were surveyed on their attitudes towards leadership in healthcare, emotional intelligence competencies, and leadership training interests. After the completion of the LDC, a post-curriculum survey was forwarded to current residents. The response rate was 84% (21 of 24) for the baseline survey and 90% (9 of 10) for the post-curriculum survey. Having a leadership training curriculum during residency was rated as extremely useful, with top training interests involving leading clinical teams, effective communication strategies, and conflict management. After the LDC, the residents reported high satisfaction with the curriculum and utilization of leadership training into their daily work. Our LDC demonstrates significant potential to engage trainees and improve their leadership skills at the graduate medical education level.

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.

The gold standard for locoregional esophageal cancer (LEC) treatment includes preoperative chemoradiation and surgical resection, with possible perioperative or adjuvant systemic therapy. With few data associating histologic grade and prognosis in LEC patients receiving neoadjuvant chemoradiation followed by resection, we seek to evaluate this association.Our institutional esophagectomy database between 1999 and 2019 was queried, selecting esophageal adenocarcinoma patients who completed neoadjuvant therapy (NAT), followed by esophagectomy. Propensity-score matching of low- and high-histologic grade groups was performed to assess survival metrics using initial clinical grade (cG) and final pathologic grade (pG). We performed a multivariable logistic regression to study predictors of pathologic complete response as a secondary objective.A total of 518 patients met the inclusion criteria. Kaplan-Meier analysis of the matched dataset showed no difference in initial or 5-year recurrence-free survival or overall survival (OS) between cG1 and cG2 versus cG3 based on original grade. When matched according to pG, cG1-2 had improved median survival parameters compared to cG3, with 5-year OS for cG1-2 of 45% versus 27% (p = 0.001). Higher pG, pathologic N stage, and poor response to NAT are predictors of poor survival.Patients with post-NAT pG1-2 demonstrated improved survival. Integrating histologic grade into postneoadjuvant staging may be warranted.

A nonoperative management strategy, or Watch-and-Wait, following neoadjuvant therapies of locally advanced rectal adenocarcinoma is increasingly considered for select patients. Yet, standardized tumor response assessment to best select and surveil suitable patients remains an unmet clinical challenge. Endoscopic and MRI currently provide the most reliable tumor response estimations. However, resources illustrating variable tumor responses to neoadjuvant therapies remain limited. This pictorial review aims to provide detailed and annotated examples of common endoscopic and MRI findings of rectal cancer treatment response, while also emphasizing their respective diagnostic shortcomings and consequently, the necessity for a multidisciplinary approach to optimally manage these patients.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E– or HER2 amplification–positive disease.

We are presenting a 63-year-old Caucasian male who complained of 2 months of progressive dysphagia. Upper endoscopy discovered a mass in the distal esophagus near the gastroesophageal junction. Biopsy was consistent with adenocarcinoma. Endoscopic ultrasound (EUS) showed extension beyond the muscularis propria, with an enlarged paraesophageal lymph node (T3N1). Initial positron emission tomography (PET)/computed tomography (CT) showed hypermetabolic portocaval lymphadenopathy presumed to be metastatic, but otherwise without distant disease extension. Neoadjuvant treatment included induction FOLFOX followed by 5,600 cGy over 28 fractions in combination with 5-FU and oxaliplatin. Approximately 3.5 weeks after completion, a repeat PET/CT revealed reduced uptake in both the primary esophageal mass and regional lymph nodes. Of note there were several new mass-like foci of hypermetabolism in the liver, specifically the left lobe, concerning for metastatic disease. Image-guided biopsy did not show any identifiable lesions, but sampling was performed based on anatomical landmarks. Pathology revealed benign parenchyma with minimal inflammation and mild reactive regeneration. In light of this, the patient proceeded to undergo definitive resection via robotic Ivor-Lewis esophagectomy with only 1 positive lymph node. Given pleural involvement by the tumor, staging was revised to pT4aN1 with final histology characterized as adenosquamous carcinoma. Postoperative course was fairly uneventful, with a mild exacerbation of his chronic heart failure. The patient was discharged on post-operative day 7, with his feeding tube removed at his 2-week post-operative clinic visit. This scenario is of particular educational value from the standpoint that when the post-treatment PET/CT images are registered to the radiotherapy treatment planning CT and dose, the areas of abnormal uptake in the liver fall within the higher dose regions. Given this and the liver biopsy findings, caution should be exercised before declaring progressive disease following radiotherapy without first reviewing the treatment plan.

BACKGROUND: The incidence of esophageal cancer (EC) is increasing in the USA. Neoadjuvant therapy for locally advanced cancers followed by surgical resection is the standard of care. The most common post-esophagectomy cardiac complication is atrial fibrillation (AF). New-onset postoperative AF can require a prolonged hospital stay and may confer an overall poorer prognosis. In this study, we seek to identify clinical factors associated with postoperative AF. METHODS: Query of an IRB approved database of 1,039 esophagectomies at our institution revealed 677 patients with EC from 1999 to 2017 who underwent esophagectomy after neoadjuvant treatment. Age, treatment location (primary vs. other), gender, neoadjuvant radiation type [2D vs. 3D vs. intensity modulated radiation therapy (IMRT)], radiation dose, surgery type (transthoracic vs. transhiatal vs. three field), smoking history, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), operative time, blood transfusions, fluid management, and length of stay (LOS) were analyzed in relationship to the development of AF. Statistical analysis was performed with SPSS 24. RESULTS: The mean age of the entire cohort was 64.3 (range, 28–86 years), with a Caucasian and male preponderance (White: 94.5%; male: 83.6%). Of the 677 patients, 14.9% (n=101) developed postoperative AF. Increasing age (P

Background Gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ) are molecularly diverse. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. This qualitative study describes the distinct genomic alterations in GCs and GEJs stratified by TP53 mutation status. Patients and Methods Tumor DNA sequencing results of 324 genes from 3741 patients with GC and GEJ were obtained from Foundation Medicine. Association between gene mutation frequency and TP53 mutation status was examined using Fisher’s exact test. Functional gene groupings representing molecular pathways suggested to be differentially mutated in TP53 wild-type (TP53WT) and TP53 mutant (TP53MUT) tumors were identified. The association of the frequency of tumors containing a gene mutation in the molecular pathways of interest and TP53 mutation status was assessed using Fisher’s exact test with a P-value of Results TP53 mutations were noted in 61.6% of 2946 GCs and 81.4% of 795 GEJs (P < .001). Forty-nine genes had statistically different mutation frequencies in TP53WT vs. TP53MUT patients. TP53WT tumors more likely had mutations related to DNA mismatch repair, homologous recombination repair, DNA and histone methylation, Wnt/B-catenin, PI3K/Akt/mTOR, and chromatin remodeling complexes. TP53MUT tumors more likely had mutations related to fibroblast growth factor, epidermal growth factor receptor, other receptor tyrosine kinases, and cyclin and cyclin-dependent kinases. Conclusion The mutational profiles of GCs and GEJs varied according to TP53 mutation status. These mutational differences can be used when designing future studies assessing the predictive ability of TP53 mutation status when targeting differentially affected molecular pathways.

Purpose: Our purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease. Methods and Materials: This retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors. Results: Median overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%. Conclusions: The treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases.

The standard of care for locally advanced rectal cancer (clinical T3/4N0 or T any N+) has evolved from upfront surgery followed by postoperative adjuvant therapy to a paradigm delivering neoadjuvant chemoradiation (CRT). More recently, the sequence of therapies has been re-examined, delivering all treatment (CRT and chemotherapy) in a total neoadjuvant approach. Subgroups of patients with locally advanced or earlier stage disease may achieve a clinical complete response (cCR), allowing highly selected patients to defer or avoid major pelvic surgery, managed by a rectal-preserving non-operative management (NOM) strategy. In rare instances, early and severe toxicity may occur during CRT which can be associated with genetic alterations that disrupt DNA damage response pathways. In this case report, we highlight the clinical course of a patient with T2N0 rectal cancer who declined APR and subsequently experienced early toxicity during treatment, ultimately discovered to be a carrier for Fanconi anemia after broad panel testing for hereditary cancer. Summary Acute toxicities secondary to pelvic radiotherapy are common, however, most are not treatment-limiting. In rare instances, radiotherapy can induce acute and severe toxicities which may be attributed to genetic alterations. Pathogenic genetic variants in DNA damage response genes can be associated with radiation-induced toxicity. Herein, we describe a patient with rectal cancer receiving pelvic irradiation with significant early toxicity subsequently confirmed to have a heterozygous Fanconi anemia mutation in the FANCD2 gene.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

Objective: Gastrostomy tubes (g-tubes) have been used with caution prior to esophageal resection due to the risks of inoculation metastasis and of injury to the gastric conduit used for reconstruct...

A radiation oncologist’s recognition of the typical course of anticipated side effects during pancreatic stereotactic body radiation therapy (SBRT) is important. Given the excellent rates of toleration, development of unanticipated pain calls for prompt evaluation. In this article, we report the case of a 51-year-old male with locally advanced pancreatic cancer experiencing focal right upper quadrant abdominal pain during pancreatic SBRT caused by rapid tumor in-growth through an open metal stent. With a variety of stents choices available, radiation oncologists need to recognize the potential for stent malfunction and occlusion to prevent a delay in SBRT delivery and the possibility for secondary infection.

OBJECTIVE We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). SUMMARY OF BACKGROUND DATA The optimal neoadjuvant therapy regimen for resectable GA is not defined. METHODS Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. RESULTS Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20-70) in the CT group and 113mo (95%CI: 75-151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30-77) versus 120mo (95%CI: 101-138); p = 0.015. CONCLUSIONS In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.Level of Evidence: Level III.

Although the number of gastrointestinal (GI) cancer survivors is projected to increase in the coming years, there are currently no survivorship care models that address the specific and growing needs of this population. Current survivorship care models were evaluated to assess their suitability for GI cancer survivors. A survivorship care model based on foundational wellness principles is under development to address the specific needs of GI cancer survivors. This model delivers a cohesive and collaborative care continuum for survivors of different GI malignancies. Oncology providers in GI departments and internal medicine providers in survivorship programs are positioned to provide a comprehensive approach for the care of patients treated with curative intent. Survivorship care is introduced at the conclusion of active treatment in the form of an Onco-wellness consultation, an in-person or telemedicine comprehensive care plan creation and review by our Survivorship Program. Personalized care plan including long term and late effects of treatment, nutrition, physical activity and rehabilitation recommendations, prevention of secondary malignancies and psychosocial needs are reviewed. As patients transition from active treatment to survivorship within the GI Program, the GI Advance Practice Professionals (APPs) are well-positioned to deliver comprehensive survivorship care specific to the GI patient’s needs while integrating recommendations and principles from the Onco-wellness consultation. With projected shortages of both oncology and primary care physicians, such an APP-based model has the potential to bridge gaps in the survivorship care continuum and mutually benefit patients and physicians.

Pelvic radiation therapy is an integral component in the treatment of various gastrointestinal, gynecologic, and genitourinary cancers. As survival rates from these malignancies improve, the prevalence of toxicity secondary to pelvic radiation has increased. Gastrointestinal toxicities are the most common complications and greatly impact quality of life. Toxicities can present in acute or late stages; although symptoms may be similar during both, the management may differ. Acute toxicities represent an inflammatory reaction in response to the radiation exposure, whereas late toxicities may arise as a result of small vessel disease, ischemia, and fibrosis. Currently, there are no large clinical trials and only limited guidelines on the management of late gastrointestinal radiation toxicities. Therapy is generally approached in a stepwise manner from medical to endoscopic to surgical methods. Several endoscopic therapies, such as the treatment of radiation proctitis with argon plasma coagulation and dilation of radiation bowel strictures, may prevent the need for surgical intervention, which may be associated with high morbidity and mortality. Given that late toxicities can occur years after radiation therapy, they are often difficult to recognize and diagnose. Successful management of late toxicities requires recognition, an understanding of the underlying pathophysiology, and a multidisciplinary approach. More dedicated research could clarify the prevalence of gastrointestinal pelvic radiation toxicities, permit a better understanding of the efficacy and safety profile of current therapies, and allow for the development of novel therapeutic approaches.

TPS4175 Background: While systemic treatment of PC has improved, rates of surgical resection - considered optimum treatment - remain low. Patients with un-resectable or borderline PC still have poor outcomes, with both toxicity and disease progression during induction chemotherapy limiting the number eligible for surgery. SBRT practice to enhance margin negative resection or to provide local control, if inoperable after neoadjuvant therapy, has shifted to higher dose delivery (Mellon 2015, Colbert 2018), but timing and appropriate patient selection are under constant debate. SBRT delivery over 50Gy exhibits superior cell killing compared to conventionally fractionated RT but carries potential GI toxicity risk (Zhong 2017). GC4711 is a selective superoxide dismutase mimetic that converts superoxide to hydrogen peroxide. As radiation response modifiers, dismutase mimetics have the potential to increase tumor control without compromising radiation safety (Sishc, AACR 2019). GC4711 consistently augmented tumor control by SBRT in PC experimental xenograft mouse models. In a pilot phase 1/2 trial (GC4419-101), subjects with locally advanced PC were randomized to receive SBRT plus either the selective dismutase mimetic GC4419 or placebo. This pilot trial has demonstrated acceptable safety with SBRT (5 × 10-11Gy), as well as apparent improvements in survival, surgical resection, locoregional control, and time to distant metastases. Altogether, these data support the hypothesis that GC4711 may improve tumor outcomes and the benefit-risk ratio of 5-fraction SBRT delivering 50Gy by improving efficacy without increasing GI-toxicity. Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine the effect on overall survival of adding GC4711 to SBRT following 4 months of chemotherapy in subjects with un-resectable or borderline non-metastatic PC. Approximately 160 subjects will be enrolled at over 20 sites to receive GC4711 100 mg or placebo IV given as IV infusion over 15 min, prior to each of 5 SBRT fractions of 10Gy). Subjects judged operable will be explored within 8 weeks after SBRT. All subjects will complete 2 additional months of adjuvant chemotherapy. Primary end point is overall survival and secondary endpoints address resection rates, local and distant disease progression, and safety, while exploratory studies include ctDNA, tumor exome/transcriptome sequencing, and immune profiling, patient-reported symptoms (PRO-CTCAE), CA19.9 normalization, and radiomics. Colbert L, Rebueno N, Moningi S et al Advances in Radiation Oncology (2018) 3, 693-700 Mellon EA, Hoffe SE, Springett GM, et al Acta Oncologica, 2015;54:7 Zhong J, Patel K, Switchenko J, et al. Cancer. 2017 Sep 15;123(18):3486-3493. Sishc BJ, Saha D, Story MD. AACR PADC 2019 C52. Clinical trial information: NCT04698915.

Purpose/objective(s) Magnetic resonance image guided stereotactic body radiotherapy (MRgSBRT) is an advanced technology that may provide radiomic feature changes during treatment of adrenal lesions feasible for adaptation. Materials/methods A prospectively maintained database was retrospectively reviewed for 24 patients with adrenal lesions who underwent MRgSBRT. Histogram features (n = 7, Table 1) were extracted from MRgSBRT images (TRueFISP sequence, 1.5mm/3mm voxel size/slice thickness) from adrenal malignancy patients scanned at simulation (SIM) approximately 14 days before SBRT start, and prior to each of 5 daily fractions (F1-F5) of 8-12 Gy to Gross Tumor Volume (GTV). Tumor ROI was derived by 3mm radial erosion of GTV in 3D. Each scan was divided by median intensity in kidney for image normalization. Significance of changes SIM-F1 and F1-F5 were assessed using two-sided paired t-test. Response to treatment was assessed via follow up CT scan roughly 3 months after MRgSBRT via RECIST v1.1, with overall response rate (ORR) including complete and partial response. Radiomics features were tested for association with clinical variables using the Kruskal-Wallis test. Results Patients had a median age of 67 years (19-80). The majority of adrenal lesions were metastatic sites (88%), while there were 2 patients with primary adrenocortical carcinoma and 1 patient with pheochromocytoma. All patients were treated with MRgSBRT in 5 fractions to a median dose of 50 Gy (40-60). Of 23 evaluable cases, rates of complete response (CR), partial response (PR), and stable disease (SD) were 13%, 35%, and 52%, respectively. Median follow up was 9.7 months (1-22). Significant changes in MRgSBRT of the tumors were observed after treatment (F1-F5, Table 1) with an increase in image signal median and interquartile range (IQR) consistent with radiation response. No signal changes were seen prior to treatment (SIM-F1). Erosion of GTV to remove tissue borders was required to observe the changes F1-F5 (P = 0.08 median,0.67 IQR for full GTV volume). For association to outcome considering varying dose per fraction, signal ratios were calculated between F1 and fraction closest to 40 Gy cumulative dose. There was a significant relationship between IQR ratio and ORR (CR/PR cases: mean 0.94 ± 0.03, SD cases: mean 1.11 ± 0.06, P = 0.011). Conclusion Significant increases in image signal median and IQR were identified in patients with adrenal lesions undergoing MRgSBRT, consistent with radiation response. MRgSBRT radiomic feature changes may allow for better personalization of radiotherapy going forward.

The increasing complexity of healthcare emphasizes the need for continued physician leadership and leadership training. This study aims to determine baseline attitudes toward the perceptions and utility of a leadership development curriculum (LDC) for radiation oncology (RO) residents. A novel longitudinal LDC was implemented for RO residents at our institution from 2018 to 2019. Prior to the curriculum, current and past residents in our institution's RO residency program were surveyed on their attitudes towards leadership in healthcare, emotional intelligence competencies, and leadership training interests. After the completion of the LDC, a post-curriculum survey was forwarded to current residents. The response rate was 84% (21 of 24) for the baseline survey and 90% (9 of 10) for the post-curriculum survey. Having a leadership training curriculum during residency was rated as extremely useful, with top training interests involving leading clinical teams, effective communication strategies, and conflict management. After the LDC, the residents reported high satisfaction with the curriculum and utilization of leadership training into their daily work. Our LDC demonstrates significant potential to engage trainees and improve their leadership skills at the graduate medical education level.

Purpose: Long-term outcomes of successful mentoring relationships have not been fully studied in radiation oncology. This chapter seeks to clarify the best practice approach to provide readers with a roadmap to aid in the navigation of these important relationships.

TPS4184 Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks (Zhong 2017). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide (Riley 2006). Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells (Doskey 2016). As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety (El-Mahdy 2020, Sishc 2021). In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Materials/Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial is now enrolling. Clinical trial information: NCT04698915.

Objective To evaluate perioperative and oncologic outcomes in our RAMIE cohort and compare outcomes with contemporary OE controls. Summary of background data RAMIE has emerged as an alternative to traditional open or laparoscopic approaches. Described in all esophagectomy techniques, rapid adoption has been attributed to both enhanced visualization and technical dexterity. Methods We retrospectively reviewed patients who underwent RAMIE for malignancy. Patient characteristics, perioperative outcomes, and survival were evaluated. For perioperative and oncologic outcome comparison, contemporary OE controls were propensity-score matched from NSQIP and NCDB databases. Results We identified 350 patients who underwent RAMIE between 2010 and 2019. Median body mass index was 27.4, 32% demonstrated a Charlson Comorbidity Index ≥4. Nodal disease was identified in 50% of patients and 74% received neoadjuvant chemoradiotherapy. Mean operative time and blood loss were 425 minutes and 232 mL, respectively. Anastomotic leak occurred in 16% of patients, 2% required reoperation. Median LOS was 9 days, and 30-day mortality was 3%. A median of 21 nodes were dissected with 96% achieving an R0 resection. Median survival was 67.4 months. 222 RAMIE were matched 1:1 to the NSQIP OE control. RAMIE demonstrated decreased LOS (9 vs 10 days, P = 0.010) and reoperative rates (2.3 vs 12.2%, P = 0.001), longer operative time (427 vs 311 minutes, P = 0.001), and increased rate of pulmonary embolism (5.4% vs 0.9%, P = 0.007) in comparison to NSQIP cohort. There was no difference in leak rate or mortality. Three hundred forty-three RAMIE were matched to OE cohort from NCDB with no difference in median overall survival (63 vs 53 months; P = 0.130). Conclusion In this largest reported institutional series, we demonstrate that RAMIE can be performed safely with excellent oncologic outcomes and decreased hospital stay when compared to the open approach.

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide, and the incidence is increasing among younger patients. 30% of these malignancies arise in the rectum. Patients with rectal cancer have historically been managed with preoperative radiation, followed by radical surgery, and adjuvant chemotherapy, with permanent colostomies in up to 20% of patients. Beginning in the early 2000s, non-operative management (NOM) of rectal cancer emerged as a viable alternative to radical surgery in select patients. Efforts have been ongoing to optimize neoadjuvant therapy for rectal cancer, thereby increasing the number of patients potentially eligible to forgo radical surgery. Magnetic resonance guided radiotherapy (MRgRT) has recently emerged as a treatment modality capable of intensifying preoperative radiation therapy for rectal cancer patients. This technology may also predict which patients will achieve a complete response to preoperative therapy, thereby allowing for more appropriate selection of patients for NOM. The present work seeks to illustrate the potential role MRgRT could play in personalizing rectal cancer treatment thus expanding the role of NOM in rectal cancer.

Emergence of the COVID-19 crisis has catalyzed rapid paradigm shifts throughout medicine. Even after the initial wave of the virus subsides, a wholesale return to the prior status quo is not prudent. As a specialty that values the proper application of new technology, radiation oncology should strive to be at the forefront of harnessing telehealth as an important tool to further optimize patient care. We remain cognizant that telehealth cannot and should not be a comprehensive replacement for in-person patient visits because it is not a one for one replacement, dependent on the intention of the visit and patient preference. However, we envision the opportunity for the virtual patient “room” where multidisciplinary care may take place from every specialty. How we adapt is not an inevitability, but instead, an opportunity to shape the ideal image of our new normal through the choices that we make. We have made great strides toward genuine multidisciplinary patient-centered care, but the continued use of telehealth and virtual visits can bring us closer to optimally arranging the spokes of the provider team members around the central hub of the patient as we progress down the road through treatment.

Aim: Genomic-based risk stratification to personalize radiation dose in rectal cancer. Patients & methods: We modeled genomic-based radiation dose response using the previously validated radiosensitivity index (RSI) and the clinically actionable genomic-adjusted radiation dose. Results: RSI of rectal cancer ranged from 0.19 to 0.81 in a bimodal distribution. A pathologic complete response rate of 21% was achieved in tumors with an RSI