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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.

Highlights • Complete resection is a potentially curative treatment for pancreatic cancer. • This report studies neoadjuvant chemotherapy with or without radiation. • The addition of radiation was associated with improved complete resection rates. • The addition of radiation was associated with improved pathologic down staging., Purpose Margin-negative (R0) resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Pre-operative multi-agent chemotherapy alone (MAC) or MAC followed by pre-operative radiotherapy (MAC + RT) may be used to improve resectability and potentially survival. However, the optimal pre-operative regimen is unknown. Methods Patients with non-metastatic PDAC from 2006 to 2016 who received pre-operative MAC or MAC + RT before oncologic resection were identified in the National Cancer Database. Univariable and multivariable (MVA) associates with R0 resection were identified with logistic regression, and survival was analyzed secondarily with the Kaplan Meier method and Cox regression analysis. Results 4,599 patients were identified (MAC: 3,109, MAC + RT: 1,490). Compared to those receiving MAC, patients receiving MAC + RT were more likely to have cT3-4 disease (76% vs 64%, p

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.

Stereotactic radiosurgery and stereotactic body radiation therapy (SBRT) have led to a resurgence of the use of radiotherapy in the management of advanced renal cell carcinoma (RCC). These techniques provide excellent local control and palliation of metastatic sites of disease with minimal toxicity. Additionally, SBRT to the primary tumor may be efficacious and well tolerated in select patients that are not surgical candidates. Emerging data suggest that SBRT may potentiate the immune response, and current and future study will evaluate if SBRT can improve survival outcomes in patients with metastatic RCC.

Approximately 8,300 new cases of anal carcinoma will be diagnosed in the United States in 2019. Anal squamous cell carcinoma (SCC) accounts for about 70% of all anal cancers. As cancer prevention and treatments have evolved over time, medical management of human immunodeficiency virus has improved, and sexual behaviors have changed, anal carcinoma incidence rates (IRs) may have also changed.The 9 oldest Surveillance, Epidemiology, and End Results registries were used to identify and determine IR of carcinoma in situ (CIS) and invasive SCC for 9757 patients below 65 years diagnosed with anal SCC/CIS from 1973 to 2014. Joinpoint regression models identified time points at which incidence trends changed.The incidence of CIS decreased since 2010 (age-adjusted IR annual percent change [APC]: -5.65, 95% CI: -10.0 to -1.1), especially for men (APC: -8.30, 95% CI: -12.6 to -3.8). In contrast, the incidence of SCC increased since 2007 (APC: 2.59, 95% CI: 0.1-5.2). During 2010-2014, men were more likely to present with CIS (incidence rate ratio [IRR]: 3.234, 95% CI: 3.000-3.489) but less likely to present with localized (IRR: 0.827, 95% CI: 0.754-0.906), regional (IRR: 0.603, 95% CI: 0.537-0.676), and distant SCC (IRR: 0.751, 95% CI: 0.615-0.915) compared with women.The previously observed rise in anal SCC/CIS incidence slowed in 2010, largely due to a decline in CIS rates. Patients were more likely to present with CIS than SCC at any stage. Future studies are necessary to determine if this decline in CIS precedes a decline in invasive SCC.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin’s lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Objective The objective of this study was to examine patterns of care and outcomes of female cancer patients treated for sexual and menopausal symptoms following pelvic radiotherapy (PRT) at our institution's multidisciplinary Sexuality, Intimacy, and Menopause (SIMS) Program. Materials and methods We performed a retrospective review of 69 female patients who received PRT for gynecologic or gastrointestinal malignancies and were referred for SIMS Program intervention. Indications for referral and treatment patterns were summarized. Preintervention and postintervention, patients were screened at follow-up visits, and symptoms were recorded. Statistics were performed using Stata 13.1. Results Cancer types included cervical (53.6%), endometrial (31.9%), anorectal (5.8%), and vulvar/vaginal (8.7%). The median age was 48 years (interquartile range: 38 to 58 y). Patients were educated on vaginal lubricants, moisturizers, and dilator therapy both before and after PRT. Reasons for SIMS referral included persistent menopausal symptoms (50.7%), dyspareunia (40.6%), vaginal dryness (37.7%), decreased libido (17.4%), intimacy concerns (17.4%), and/or physical examination alterations (27.5%). SIMS interventions included vaginal estrogen (77.3%), nonhormonal climacteric interventions (53%), systemic hormone therapy (31.8%), dehydroepiandrosterone (4.6%), testosterone cream (4.6%), and/or psychological pharmacotherapy or counseling (13.6%). With a median follow-up of 36 months (interquartile range: 18 to 58 mo), sexual symptoms improved or were stable in 83.6%, while menopausal symptoms improved or were stable in 80.5%. Conclusions This study highlights the importance of multidisciplinary care in improving the sexual and menopausal symptoms of women after PRT. Future work examining the impact of intervention timing with respect to PRT and measures of patient satisfaction is warranted.

Background Randomized controlled trials (RCTs) are the gold standard for evidence-based practice, but their development and implementation is resource intensive. We aimed to describe modern RCTs in gastrointestinal (GI) cancer and identify predictors of successful accrual and publication. Materials and Methods ClinicalTrials.gov was queried for phase III GI cancer RCTs opened between 2010 and 2019 and divided into two cohorts: past and recruiting. Past trials were analyzed for predictors of successful accrual and the subset with ≥3 years follow-up were analyzed for predictors of publication. Univariate and multivariable (MVA) logistic regression were used to identify covariates associated with complete accrual and publication status. Results A total of 533 GI RCTs were opened from 2010 to 2019, 244 of which are still recruiting. In the “past” trials cohort (235/533) MVA, Asian continent of enrollment was a predictor for successful accrual, whereas trials with prolonged enrollment (duration longer than median of 960 days) trended to failed accrual. Predictors for publication on MVA included international enrollment and accrual completion. Sponsorship was not associated with accrual or publication. Notably, 33% of past trials remain unpublished, and 60% of trials that were closed early remain unpublished. Conclusion Accrual rate and the primary continent of enrollment drive both trial completion and publication in GI oncology. Accrual must be streamlined to enhance the impact of RCTs on clinical management. A large portion of trials remain unpublished, underscoring the need to encourage dissemination of all trials to, at a minimum, inform future trial design. Implications for Practice Two-thirds of gastrointestinal (GI) oncology phase III randomized controlled trials successfully accrue; however, one third of these trials are unpublished and more than half of trials that close early are unpublished. The strongest predictors for publication are successful accrual and international collaborations. Initiatives to optimize the trial enrollment process need to be explored to maximize the potential for trials to engender progress in clinical practice. Moreover, this study identified a significant publication bias in the realm of GI oncology, and the field should promote reporting of all trials in order to better inform future trial questions and design.

OBJECTIVES In the 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) era, the benefit of surgery versus definitive radiation for borderline resectable (BR) and locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC) is not well defined. Our primary objective was to identify the survival impact of surgery for BR and LA unresectable PDAC treated with induction FOLFIRINOX. METHODS We performed a single-center retrospective review of BR and LA PDAC treated with FOLFIRINOX from 2010 to 2018. The overall survival of surgery and consolidative radiotherapy was estimated in the Kaplan-Meier method and compared via the log-rank test. Subgroup analyses were conducted for BR and LA patients. RESULTS We identified 101 BR and LA PDAC patients treated with induction FOLFIRINOX (41 surgeries and 60 consolidative radiotherapies). Surgery patients were 68.3% (28/41) BR and 31.7% (13/41) LA, whereas consolidative radiotherapy patients were 30% (18/60) BR and 70% (42/60) LA. The R0 resection rate was 100%, and 46.3% (19/41) received preoperative radiation. Median overall survival of surgery versus consolidative radiotherapy was 42.3 versus 19.6 months, respectively (P < 0.001). On multivariate analysis, surgery associated with improved survival. CONCLUSIONS Surgery after induction FOLFIRINOX is feasible and has a clinically meaningful survival benefit in BR and LA PDAC.

Pancreatic cancer is characterized by a high rate of metastatic spread and overall poor prognosis. Yet 30% of patients have progressive local disease at the time of death, and local progression can cause significant morbidity. Approximately 30-40% of patients present with locally advanced pancreatic cancer (LAPC) that is not surgically resectable, and the optimal treatment for these patients continues to evolve. The role of radiation in the management of LAPC is an area of controversy, and the recent LAP07 randomized trial reported no survival benefit of radiation following gemcitabine plus or minus erlotinib. However, the efficacy of modern systemic regimens has improved since the design of the LAP07 study, and radiation therapy may be of greater benefit in the context of more effective systemic therapy. Advances in radiation delivery including the increasing use of stereotactic body radiation therapy (SBRT) have the potential to improve outcomes through dose escalation and better treatment tolerability. In addition, the combination of radiation therapy and immune therapy is an area of promising research. These advances suggest that radiation therapy will continue to play an integral role in the management of LAPC.

Background: Adjuvant therapy for gastric adenocarcinoma has shown a survival advantage, though it may be underutilized. The purpose of this study is to examine how infrequently adjuvant therapy is administered with curative intent gastrectomy for node positive gastric cancer and the long-term effects to patients. Methods: The National Cancer Database was queried from 2006–2013 for patients with node positive gastric adenocarcinoma undergoing a potentially curative gastrectomy. Overall survival was compared between patients who received adjuvant chemotherapy or chemoradiation and those who did not. Results: Of 2,565 patients, 793 (30.9%) patients did not receive any adjuvant chemotherapy or radiation therapy, while 147 (5.7%) received peri-operative chemotherapy and 723 (28.2%) received post-operative chemoradiation. From 2006–2013, the percentage of patients receiving peri-operative chemotherapy rose from 1.1% to 9.9%, while those receiving post-operative chemoradiation decreased from 39.7% to 21.6%. The adjusted restricted mean survival time over 5 years for no adjuvant therapy was 27.7 months, peri-operative chemotherapy was 39.6 months, and post-operative chemoradiation was 37.7 months (P Conclusions: Approximately one third of patients treated for node positive gastric cancer undergo surgical resection without adjuvant therapy. This is associated with poorer survival, highlighting the need for improvement in multimodality care and cancer outcomes.

Background Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care. Methods The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared. Results A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P

Purpose/Objective(s) Following curative resection for pancreatic ductal adenocarcinoma (PDAC), there are high rates of local recurrence. The optimal treatment of patients with isolated local recurrence (ILR) – recurrence in the abdomen without distant metastases – is not known. This study evaluated stereotactic body radiation therapy (SBRT) as a treatment option for ILR. Materials/Methods A multi-institutional retrospective analysis was performed on patients with ILR of PDAC following oncologic surgical resection treated with SBRT. Patient demographics, tumor and prior treatment characteristics, details of recurrence, SBRT treatment design and dosimetry, and patient follow-up and toxicity data were recorded from the medical record. Progression and overall survival estimates were calculated using cumulative incidence and Kaplan-Meier models, respectively. Results Between January 2010 and December 2020, 34 patients (17 males and 17 females, median age 69 years) were treated at five institutions in the United States. At the time of initial resection, most patients had T3 tumors (71%) and involved lymph nodes (71%). 31 of 34 (91%) patients underwent a Whipple procedure and 3 (9%) had a distal pancreatectomy. The R0 resection rate was 68%. 29% and 85% received neoadjuvant or adjuvant chemotherapy, respectively; and 12% and 27% had prior neoadjuvant or adjuvant radiation courses around the time of initial surgical resection. Median time to ILR was 18.7mos. The most common location of recurrence was in the pancreatic remnant or near the superior mesenteric artery. All patients underwent 5-fraction photon (28 patients) or proton (6 patients) SBRT to a median dose of 3500cGy (range 3000-4000cGy) with a median BED of 5950cGy (α/β = 10). Median follow-up after SBRT was 3.05 years. The 1-year and 2-year cumulative incidence of cancer progression were 72% (95% CI 56-93%) and 92% (95% CI 76-100%). Distant metastasis was the most common site of first recurrence (15 of 23 recurrences, 65%). 6 patients (25%) had local failure as site of first recurrence. Prior radiation was not associated with increased risk of progression after SBRT (HR 1.31 95% CI 0.56-3.07, P = 0.54). 1-year and 2-year overall survival was 64% (95% CI 49-84%) and 40% (95% CI 25-64%), with a median survival of 1.2 years from time of SBRT. Four patients (12%) developed grade 3 toxicities within one year after completion of SBRT. There were no grade 4-5 toxicities. Conclusion For treatment of PDAC ILR after surgical resection, SBRT was well tolerated and offered high rates of local tumor control with low treatment-related toxicity.

PURPOSE/OBJECTIVE(S) Across training programs, resident evaluations are based on the Accreditation Council for Graduate Medical Education's (ACGME) Six Core Competencies: practice-based learning and improvement (PBLI), patient care (PC), systems-based practice (SBP), medical knowledge (MK), interpersonal communication skills (ICS), and professionalism (PR). With few studies on resident assessment within radiation oncology (RO), we analyze characteristics of the existing assessment methods. We also analyze factors involved in the evaluations of faculty by residents. We hypothesize that both faculty and resident evaluations vary significantly in length and criteria used. MATERIALS/METHODS Twelve academic RO residency programs provided evaluation forms: faculty resident evaluation (FRE), n = 12, and resident faculty evaluation (RFE), n = 11. Data on the frequency and types of questions were collected. Questions were coded into 9 categories for RFE: teaching skills, patient care, personal qualities (approachability, responsiveness, demeanor and attitude), result of rotation (assessing the degree to which faculty increased knowledge, desire to learn and independent inquiry by end of rotation), knowledge, mentoring skills, learning climate, research, and communication. Analysis-of-variance (ANOVA) was used to determine differences between institutions and between categories. RESULTS Across all institutions, FRE was based on the Six Core Competencies with an average of 19 questions (standard deviation (SD) 11, range 5-47) in total. PR had the most questions (mean 3.7, SD 2.9) followed by PC (mean 3.3, SD 2.8). SBP and PBLI had the fewest questions. ANOVA did not show significant variation in the number of questions between the categories (F = 0.78, P = 0.6). There was a significant difference in the mean number of questions used for assessing the competencies across institutions (F = 6.6, P < 0.01). RFE varied in length, formatting, and content of evaluations across institutions (F = 7.8, P < 0.01). Teaching and personal qualities were evaluated the most with 9/11 institutions posing ≥1 question about these factors. The mean +/- SD for RFE questions per category was personal quality 4.3 +/- 3.1, teaching skills 3.9 +/- 2.0, communication 3.7 +/- 3.0, result of rotation 3.7 +/- 2.1, knowledge 3.5 +/- 2.6, patient care 2.7 +/- 1.5, mentoring skills 2.7 +/- 1.5, learning climate 2.0 +/- 0.6, research 2.0 +/- 1.0. CONCLUSION FRE is primarily based on ACGME core competencies for RO. However, RFE varies by institution. Standardized criteria should be developed for RFE to obtain feedback that can be used to improve residency programs. This study is part of a larger project collecting resident and faculty perspectives with the goal to ultimately develop consensus FRE and RFE recommendations.

Purpose/objective(s) Following presentation of the CALGB 80803 trial, which demonstrated notably high pathologic complete response (pCR) rates with induction FOLFOX followed by chemoradiotherapy (CRT), our institution more routinely incorporated induction chemotherapy (IC) into the management of LA-EC patients. However, improvements in progression-free (PFS) or overall survival (OS) with this regimen compared to pre-operative CRT alone have not yet been shown. We hypothesized IC-CRT would lead to an improvement in OS and PFS when compared to CRT. Materials/methods Patients with operable LA-EC were eligible for analysis if they received CRT between 2013-2019. The cohort was stratified into two groups, IC-CRT vs. CRT. The Kaplan-Meier method was used to estimate OS and PFS. The cumulative incidences of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. The impact of treatment group on pathologic response and surgical outcomes were assessed by Chi-square. Results 95 patients were included for analysis (IC-CRT n = 58; CRT n = 37). Baseline characteristics included median Karnofsky Performance Status 80, median weight loss 5% (IQR 0-9%), with the majority being adenocarcinoma histology (81%), T3-T4 (60%), N+ (79%), located in the distal esophagus or gastroesophageal junction (89%). Patients receiving IC-CRT were more likely to have been treated after 2016 (64% vs 38%, P = 0.021). IC was most commonly FOLFOX (74%) for a median of 3 (IQR 1-3) cycles. CRT was delivered to a median dose of 50 Gy in 25-28 fractions. Surgery was attempted in 60% and 68% of the IC-CRT and CRT cohorts, respectively. Median follow-up was 26 months. ICRT and CRT were associated with similar 2-year OS (66% [95% CI 51-78%] vs 70% [95% CI 52-83%]) and PFS (47% [95% CI 33-59%] vs 48% [95% CI 30-63%]). In the adenocarcinoma subset (n = 77), 2-year OS was 69% (95% CI 52-81%) in the IC-CRT cohort vs 61% (95% CI 40-77%) with CRT. 2-year PFS was 46% (95% CI 31-60%) and 38% (95% CI 20-56%), respectively. IC-CRT was not associated with an OS or PFS benefit among any patient subgroup. Recurrence rates were similar between the cohorts (47%) and first recurrence was most commonly DM (61% IC-CRT vs 65% CRT). Patients receiving IC-CRT compared to CRT had numeric but not statistically significant improvement in pCR (45% vs 29%, P = 0.24) and N-stage regression (72% vs 58%, P = 0.28). There was no difference in the rate of R0 resection, hospitalization, surgical complications, or treatment-related death with use of IC-CRT. Conclusion IC-CRT was not associated with improved OS or PFS in this small and perhaps underpowered cohort study. Further investigations are needed to explore the impact of IC-CRT on quality of life, symptom burden, and to see if meaningful trends develop with time.

Background The optimal treatment for early-stage esophageal cancer with positive surgical margins after an upfront esophagectomy is not well-defined. This study investigates the effect of post-operative radiotherapy (PORT) on overall survival (OS) in clinical stage I-II patients with positive margins. Methods We identified patients diagnosed between 2004 and 2012 with clinical stage I-II esophageal carcinoma from the National Cancer Data Base (NCDB) who underwent an upfront esophagectomy. For those patients with positive margins, administration of PORT was recorded, and OS was compared by the Kaplan-Meier estimator and log-rank test. Multivariable Cox regression analysis was performed to identify variables associated with improved survival. Results Among the 3,490 patients identified, 209 (5.8%) had positive margins. One hundred forty-two (67.9%) patients did not receive PORT while 67 (32.1%) did receive PORT. Compared to those receiving PORT, patients who did not receive PORT were significantly older (68.5 vs. 64.0 years, P=0.003), more likely to have pN0 disease (50.7% vs. 35.4%, P=0.026), and less likely to receive postoperative chemotherapy (21.1% vs. 86.6%, P

Background The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. Methods We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Results Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Conclusions Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results.

Early detection of pancreatic cancer is challenging because cancer-specific symptoms occur only at an advanced stage, and a reliable screening tool to identify high-risk patients is lacking. To address this challenge, an artificial neural network (ANN) was developed, trained, and tested using the health data of 800,114 respondents captured in the National Health Interview Survey (NHIS) and Pancreatic, Lung, Colorectal, and Ovarian cancer (PLCO) datasets, together containing 898 patients diagnosed with pancreatic cancer. Prediction of pancreatic cancer risk was assessed at an individual level by incorporating 18 features into the neural network. The established ANN model achieved a sensitivity of 87.3 and 80.7%, a specificity of 80.8 and 80.7%, and an area under the receiver operating characteristic curve of 0.86 and 0.85 for the training and testing cohorts, respectively. These results indicate that our ANN can be used to predict pancreatic cancer risk with high discriminatory power and may provide a novel approach to identify patients at higher risk for pancreatic cancer who may benefit from more tailored screening and intervention.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Background: Induction FOLFIRINOX is increasingly used for borderline resectable (BR) and locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC), but the benefit of surgery versus consolidative radiation in the FOLFIRINOX era is not well defined. Single institution experiences have included FOLFIRINOX with gemcitabine-based chemotherapy, lack a uniform comparator group to surgery, or are limited to surgical patients after FOLFIRINOX. No prospective clinical trials have assessed surgery versus radiation. Therefore, our primary objective was to identify the long-term survival impact of surgery versus radiation for BR and LA unresectable PDAC treated with induction FOLFIRINOX. Methods: We performed a single center retrospective review of BR and LA PDAC treated with FOLFIRINOX from 2010 - 2018. Patients were divided into two cohorts based on receipt of surgery versus consolidative radiotherapy. Findings: We identified 101 BR and LA PDAC patients treated with induction FOLFIRINOX; 40 underwent surgery and 61 received consolidative radiotherapy. The surgery group was 28/40 (70%) BR and 12/40 (30%) LA, while consolidative radiotherapy was 18/61 (30%) BR and 43/61 (70%) LA. The R0 resection rate was 100% for surgery and 18/40 (45%) received radiation prior to surgery. Median overall survival (OS) for surgery was 42·3 months (95% CI 24·6 - not reached) compared to a median OS of 19·6 months (95% CI 16·3 - 24·6) with consolidative radiotherapy(p = 0·0001). On multivariate analysis, surgery was associated with improved OS (HR 0·35, 95% CI 0·17 - 0·71, p=0·004). Interpretation: Surgery after induction FOLFIRINOX is feasible and has a clinically meaningful survival benefit in BR and LA PDAC compared to induction FOLFIRINOX followed by consolidative radiotherapy. Funding Statement: This research was not supported by any funding. Declaration of Interests: The authors declare no conflicts of interest relevant to this manuscript. Ethics Approval Statement: This study was approved by the Yale University institutional review board.

748 Background: Cytoreductive nephrectomy (CN) for patients (pts) with metastatic renal cell carcinoma (mRCC) improved overall survival (OS) in the interferon (IFN) era, but the benefit of CN in the immune checkpoint inhibitor (ICI) era is unknown. Methods: We identified pts with mRCC receiving immunotherapy (IT) from 2004-2015 in the National Cancer Database (NCDB). Pts with partial nephrectomy or ablation were excluded. The ICI era was defined as 2013-2015 based on a high-profile publication in 2012 demonstrating efficacy of ICI in mRCC and the IFN era was defined as 2004-2005 due to FDA approval of sorafenib in 12/2005. Pts receiving CN with TKI were excluded, as prior NCDB study showed an OS benefit to CN in contrast to the results of the CARMENA trial. Univariable (UVA) and multivariable (MVA) associates with OS during each era were identified using Cox regression analysis including age, sex, race, income, insurance, treatment facility type, treatment location, clinical T stage (cT), clinical N stage (cN), histology, Fuhrman grade (FG), other metastectomy, and CN. Results: There was a 65% decline in mRCC pts receiving IT from 2005 to 2006 (end of the IFN era), which remained low (11% rise from 2006-2012) until a 93% rise from 2012 to 2013 (start of the ICI era). 128 of 422 (30.3%) pts in the IFN era received CN compared to 218 of 526 (41.4%) patients in the ICI era, p

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.

Metastatic melanoma often involves the brain. Radiotherapy is an important treatment of melanoma brain metastases, although melanoma radiosensitivity is considered heterogeneous. Thus, identifying subsets with differential radiosensitivity is essential.Patients with metastatic melanoma were identified in a prospective stereotactic radiosurgery (SRS) database. Tumor were tested for alterations in B-RAF, N-RAS, and c-KIT. Standardized imaging following SRS was reviewed for recurrence. Differences in local and distant failure were determined using modified Cox proportional hazards models.102 patients and 1,028 brain metastases were included. N-RAS mutated patients were significantly less likely to develop local recurrence after SRS than wild type patients (HR 0.17, 95% CI 0.04-0.72, p=0.017). B-RAF and c-KIT mutations were not associated with altered rates of local recurrence. Lower local recurrence rates for N-RAS mutated tumors persisted on multivariate analysis (HR 0.18, 95% CI 0.04-0.84p=0.029).N-RAS mutation is associated with improved local control following SRS. Local recurrence is more common in wild type patients and those with B-RAF or c-KIT mutations. Further research is needed to validate these findings and integrate into practice.

BACKGROUND The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness. METHODS Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base. Overall survival (OS) was compared for CT and CRT groups with Cox regression and propensity score matching. Subset analyses by clinicopathologic characteristics were performed. RESULTS This study identified 6165 patients treated with CT (n = 2334 or 38%) or CRT (n = 3831 or 62%). Most were classified as pT3 (72%), pN1 (67%), and status-post R0 resection (84%). For CRT patients, the median radiotherapy dose was 50.4 Gy. Compared with CT, CRT was associated with improved OS in a univariate analysis (median, 20.0 vs 22.3 months; at 5 years, 16.5% vs 19.6%; P

Aggressive local therapy for patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC) has traditionally not been pursued due to high rates of distant progression. We describe a 62-year-old male initially presenting with resectable PDAC who underwent the Whipple procedure but developed multiple liver metastases within two months of starting adjuvant gemcitabine. Oxaliplatin was added to the regimen and complete resolution of the liver lesions resulted. He remained disease-free for five years until re-staging revealed a small lung nodule. This was resected and confirmed to be metastatic PDAC. After additional adjuvant gemcitabine, the patient remained free of recurrence for 12 years after diagnosis of metastatic disease and ultimately passed away from complications of ascending cholangitis associated with stricture at the biliary-enteric anastomosis site. He had no evidence of disease recurrence at the time of death. Next-generation sequencing of the tumor was unrevealing, showing only an activating mutation of KRAS and a deleterious mutation of tumor protein p53 (TP53). Our case suggests that while the prognosis for metastatic PDAC is poor, the population is nonetheless heterogeneous. Prognostic biomarkers are needed for the identification of patients for whom aggressive local treatment of oligometastatic PDAC may be warranted.

437 Background: Induction FFX for PC deemed either BR or LA at diagnosis provides an opportunity to downstage pts with the aim of an R0 surgery. The addition of RT after induction FFX may further downstage. However, there is a paucity of data regarding long-term survival for BR and LA patients successfully downstaged and resected. We performed a retrospective review of BR and LA PC treated with induction FFX +/- RT followed by surgery or consolidative RT at the Yale Cancer Center (YCC) to assess survival in these two cohorts. Methods: Clinical data was abstracted for pts with BR or LA PC who had surgery or received consolidative RT without surgery after induction FFX +/- RT at the YCC from 2010-2018. Surgical pts were re-reviewed by a radiologist to assess vascular involvement (BR vs. LA) using NCCN criteria. PFS and OS for surgery and consolidative RT were analyzed by the Kaplan-Meier method. Survival was compared via the log rank test. Results: 102 pts met inclusion criteria (BR=47, LA=55), 41 pts had surgery [BR=29/47 (62%) LA=12/55 (22%)] and 61 pts had consolidative RT [(BR= 18/47 (38%), LA= 43/55 (78%)] after induction FFX. 18 surgery pts received RT prior to resection and all surgery pts had R0 resection. Median follow up was 25 mo (range 5 – 97). Median PFS with surgery was 22 mo (95% CI 15 – 59) vs 14 mo (95% CI 10.9 – 20.1) with consolidative RT (p

Purpose: Non–small cell lung cancer (NSCLC) includes a spectrum of radiosensitive and radioresistant tumors. However, little is known about the molecular determinants of cellular radiation responses. We examined clinical outcomes after gamma knife radiotherapy for NSCLC intracranial metastases to evaluate the use of this model for determining radiosensitive tumor genotypes. Experimental Design: Between 2005 and 2012, 239 patients with NSCLC were enrolled in a prospective gamma knife data repository. Molecular pathology regarding EGF receptor (EGFR), ALK, and KRAS mutation status was available for 81 patients. Local and distant brain control was determined for 79 patients with 469 brain metastases. Modified Cox proportional hazards models were established to evaluate local control for treated lesions after serial gamma knife treatments. Results: In total, 11% of patients developed in-field recurrence. No patients with metastases from tumors with EGFR mutations (0/164 lesions) or EML4-ALK translocations (0/61 lesions) recurred in-field. In contrast, 19% of patients without these mutations and 18% of patients with KRAS mutations recurred in-field (10/139 and 3/105 lesions, respectively). Rates of distant brain recurrence did not significantly differ across tumor genotypes. The predicted median in-field local control was significantly longer for EGFR-mutant and ALK-translocated tumors compared with other patients with NSCLC (P < 0.001), whereas distant brain recurrence time was equivalent (P = 0.97). On multivariate analysis, EGFR mutation, ALK translocation, and metastasis size were independent predictors for superior local control after gamma knife treatment. Conclusions: This study suggests that EGFR kinase domain mutations and EML4-ALK translocations are radiosensitive NSCLC genotypes, and proposes a novel model to identify radiosensitive subtypes of NSCLC. Clin Cancer Res; 19(19); 5523–32. ©2013 AACR.

Background: Definitive chemoradiotherapy (CRT) is recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma for all patients with stage I anal canal cancer. Because these patients were not well represented in clinical trials establishing CRT as standard therapy, it is unclear whether NCCN recommendations are being closely followed for stage I disease. This study identified factors that predict for NCCN Guideline-concordant versus NCCN Guideline-discordant care. Methods: Using the National Cancer Data Base, we identified patients diagnosed with anal canal carcinoma from 2004 to 2012 who received concurrent CRT (radiotherapy [RT] 45.0-59.4 Gy with multiagent chemotherapy), RT alone (45.0-59.4 Gy), or surgical procedure alone (local tumor destruction, tumor excision, or abdominoperineal resection). Demographic and clinicopathologic factors were analyzed using the chi-square test and logistic regression modeling. Results: A total of 1,082 patients with histologically confirmed stage I anal cancer were identified, among whom 665 (61.5%) received CRT, 52 (4.8%) received RT alone, and 365 (33.7%) received only a surgical procedure. Primary analyses were restricted to patients receiving CRT or excision alone, as these were most common. Multivariable analysis identified factors independently associated with reduced odds of CRT receipt: low versus intermediate/high tumor grade (adjusted odds ratio [AOR], 0.21; 95% CI, 0.14-0.29; P

Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

This work demonstrates a central role for the retinoblastoma (Rb) family in driving the transcriptional program of induced and replicative senescence. HeLa cervical carcinoma cells rapidly undergo senescence when the human papillomavirus (HPV) type 18 E7 gene in these cells is repressed by the bovine papillomavirus (BPV) E2 protein. This senescence response requires the endogenous Rb pathway but not the p53 pathway. Microarray analysis 6 days after BPV E2 introduction into HeLa cells identified 224 cellular genes induced by E7 repression and 354 repressed genes. Many repressed genes were involved in cell cycle progression, and numerous induced genes encoded lysosomal proteins. These gene expression changes were blocked by constitutive expression of the wild-type HPV16 E7 or adenovirus E1A gene, but not by E7 or E1A mutants defective for Rb binding. Short hairpin RNAs targeting the Rb family also inhibited these gene expression changes and blocked senescence. Therefore, surprisingly, the transcriptional response to BPV E2 expression was entirely dependent on E7 repression and activation of the Rb family, and the BPV E2 protein did not directly affect the expression of cellular genes. Activation of the Rb family repressed E2F-responsive genes and stimulated transcriptional activators, thereby mobilizing multiple signals, such as repression of B-MYB and DEK, that were independently sufficient to induce senescence. There was extensive overlap between the transcriptional profiles of senescent, late-passage primary human fibroblasts and senescent cervical carcinoma cells, suggesting that this Rb family-mediated transcriptional cascade also plays a central role in replicative senescence.

The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness.Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base. Overall survival (OS) was compared for CT and CRT groups with Cox regression and propensity score matching. Subset analyses by clinicopathologic characteristics were performed.This study identified 6165 patients treated with CT (n = 2334 or 38%) or CRT (n = 3831 or 62%). Most were classified as pT3 (72%), pN1 (67%), and status-post R0 resection (84%). For CRT patients, the median radiotherapy dose was 50.4 Gy. Compared with CT, CRT was associated with improved OS in a univariate analysis (median, 20.0 vs 22.3 months; at 5 years, 16.5% vs 19.6%; P .001) and a multivariate analysis (hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.837-0.953; P = .001). CRT remained associated with improved OS after propensity score matching (HR, 0.851; 95% CI, 0.793-0.913; P .001). Subset analyses showed that CRT was associated with improved OS among patients with pT3 (HR, 0.892; 95% CI, 0.828-0.962; P = .003) or pN1 disease (HR, 0.856; 95% CI, 0.793-0.924; P .001) and both R0 resection (HR, 0.901; 95% CI, 0.839-0.969; P = .005) and R1 resection (HR, 0.842; 95% CI, 0.722-0.983; P = .030).CRT was independently associated with improved OS after the resection of pancreatic adenocarcinoma in a large national cohort and particularly among patients with R1 resection and pN1 disease. Well-designed randomized comparisons of CRT and CT are urgently needed.