NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024.

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.

A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer. Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital. All patients were age ≥18 years, Eastern Cooperative Oncology Group 0-1 and with histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum. Median follow-up was 61.9 months. All patients received concurrent pelvic external beam RT (50.4 Gy in 28 fractions), YIV-906 (taken orally 800 mg twice daily on days 1-4 of RT each week), and oral capecitabine delivered in a neo-adjuvant fashion, followed by definitive surgery. Toxicity was assessed weekly during radiation and until acute symptoms resolved and then at 28 days, 4 months, 7 months and 10 months. Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of surgery, 4 patients (16.7%) had a complete or near-complete response. At a median follow-up of 61.9 months, the mean overall survival (OS) of our patient cohort was 74.9 months [95% confidence interval (CI): 67.3-82.5]. The estimated 5-year OS was 82.0%. We observed 0% acute grade 4 toxicities, and only two cases of acute grade 3 diarrhea (8.3%). Conclusions: The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers.

Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection. Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival. Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023. Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator. Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07). Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer.

Background: For patients with operable locally advanced esophageal carcinoma (LA-EC), we hypothesized that pre-operative induction chemotherapy followed by chemoradiotherapy (IC-CRT) would improve progression-free survival (PFS) and overall survival (OS) when compared to chemoradiotherapy (CRT). Methods: This was a single institution retrospective cohort study including patients with LA-EC who received preoperative-intent IC-CRT vs. CRT between 2013-2019. The Kaplan-Meier method was used to estimate OS and PFS. Cox proportional hazards regression was used to assess for variables associated with survival. The impact of treatment group on pathologic response was assessed by chi-square. Results: Ninty-five patients were included for analysis (IC-CRT n=59; CRT n=36) and the median follow-up was 37.7 months (IQR: 16.8-56.1). There was no difference in median PFS or OS for IC-CRT or CRT, 22 months (95% CI: 12-59) vs. 32 months (95% CI: 10-57) (P=0.64) and 39 months (95% CI: 23-not reached) vs. 56.5 months (95% CI: 38-not reached) (P=0.36), respectively. Amongst the subset of patients with adenocarcinoma histology, there was no difference in median PFS or OS, nor was there when analyses were further restricted to those who received ≥3 cycles of induction 5-fluorouracil and platinum, or for those who underwent esophagectomy. Pathologic complete response occurred in 45% vs. 29% (P=0.24) and N-stage regression occurred in 72% vs. 58% (P=0.28) of patients in the IC-CRT and CRT cohorts, respectively. Distant metastasis occurred in 44% of patients in each treatment cohort. Conclusions: For patients with LA-EC, preoperative-intent IC-CRT was not associated with improved PFS or OS when compared with CRT.

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.

Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer.

Purpose: O6-methylguanine DNA methyltransferase (MGMT)-silenced tumors reveal sensitivity to temozolomide (TMZ), which may be enhanced by PARP inhibitors. Approximately 40% of colorectal cancer has MGMT silencing and we aimed to measure antitumoral and immunomodulatory effects from TMZ and olaparib in colorectal cancer. Experimental Design: Patients with advanced colorectal cancer were screened for MGMT promoter hypermethylation using methylation-specific PCR of archival tumor. Eligible patients received TMZ 75 mg/m2 days 1-7 with olaparib 150 mg twice daily every 21 days. Pretreatment tumor biopsies were collected for whole-exome sequencing (WES), and multiplex quantitative immunofluorescence (QIF) of MGMT protein expression and immune markers. Results: MGMT promoter hypermethylation was detected in 18/51 (35%) patients, 9 received study treatment with no objective responses, 5/9 had stable disease (SD) and 4/9 had progressive disease as best response. Three patients had clinical benefit: carcinoembryonic antigen reduction, radiographic tumor regression, and prolonged SD. MGMT expression by multiplex QIF revealed prominent tumor MGMT protein from 6/9 patients without benefit, while MGMT protein was lower in 3/9 with benefit. Moreover, benefitting patients had higher baseline CD8+ tumor-infiltrating lymphocytes. WES revealed 8/9 patients with MAP kinase variants (7 KRAS and 1 ERBB2). Flow cytometry identified peripheral expansion of effector T cells. Conclusions: Our results indicate discordance between MGMT promoter hypermethylation and MGMT protein expression. Antitumor activity seen in patients with low MGMT protein expression, supports MGMT protein as a predictor of alkylator sensitivity. Increased CD8+ TILs and peripheral activated T cells, suggest a role for immunostimulatory combinations. Significance: TMZ and PARP inhibitors synergize in vitro and in vivo in tumors with MGMT silencing. Up to 40% of colorectal cancer is MGMT promoter hypermethylated, and we investigated whether TMZ and olaparib are effective in this population. We also measured MGMT by QIF and observed efficacy only in patients with low MGMT, suggesting quantitative MGMT biomarkers more accurately predict benefit to alkylator combinations.

Utilization and Outcomes of Radiation in Stage IV Esophageal Cancer.

Introduction: For patients with stage IV esophageal cancer, esophageal radiation may be used selectively for local control and palliation. We aimed to understand patterns of radiation administration among patients with stage IV esophageal cancer and any potential survival associations. Methods: In this retrospective cohort study, the National Cancer Database was queried for patients with metastatic stage IV esophageal cancer diagnosed between 2016 and 2019. Patterns of radiation use were identified. Survival was determined through Kaplan-Meier analysis of propensity score-matched pairs of patients who did and did not receive radiotherapy and time-to-event models. Results: Overall, 12,088 patients with stage IV esophageal cancer were identified, including 32.7% who received esophageal radiation. The median age was 65 (interquartile range [IQR]: 58-73) years, and 82.6% were male. Among the irradiated patients, the median total radiation dose was 35 (IQR: 30-50) Gy administered in a median of 14 (IQR: 10-25) fractions given in 22 (IQR: 14-39) days. Overall, esophageal radiation was not associated with better survival (log-rank p = 0.41). When stratified by radiation dose, a survival advantage (over no radiation) was found in the 1144 patients (29% of the irradiated patients) who received 45 to 59.9 Gy (time ratio = 1.28, 95% confidence interval: 1.20-1.37, p < 0.001) and the 88 patients (2.2%) who received 60 to 80 Gy (time ratio = 1.37, 95% confidence interval: 1.11-1.69, p = 0.003). Conclusions: One-third of the patients with metastatic stage IV esophageal cancer in the National Cancer Database received esophageal radiation. Most received a radiation dose that, although consistent with palliative regimens, was not associated with a survival advantage. Further study is warranted to understand the indications for radiation in stage IV esophageal cancer and potentially reevaluate the most appropriate radiation dose for palliation.

Multiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer.

BACKGROUND AND PURPOSE: Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC. METHODS: Patients diagnosed with nonmetastatic PDAC between 2012 and 2017 and who received preoperative MAC or MAC+RT were identified in the National Cancer Database. Variables associated with R0 and overall survival were identified with logistic regression and Cox analysis (P<0.05). RESULTS: A total of 5273 patients were identified (MAC: 3900, MAC+CRT: 955, MAC+SBRT: 418). The median RT dose/fraction (fx) in the MAC+CRT and MAC+SBRT cohorts was 50.4 Gy/28 fx and 33 Gy/5 fx. Patients receiving MAC+CRT versus MAC+SBRT had similar rates of ypT3-T4 disease (54% vs. 58%, P=0.187), R0 (87% vs. 84%, P=0.168), and pathologic complete response (pathologic complete response; 6% vs. 4%, P=0.052), however, MAC+CRT was associated with less regional lymphatic disease (ypN+: 28% vs. 41%, P<0.001). The median overall survival of patients receiving MAC+CRT versus MAC+SBRT was 24.6 versus 29.5 months (P=0.045). CONCLUSIONS: For patients with resected PDAC, MAC+CRT, and MAC+SBRT had similar rates of R0 and pathologic complete response, although MAC+CRT was associated with lower ypN+. Prospective evaluation of neoadjuvant RT regimens with attention to radiation therapy design is warranted.

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.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

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.

Benefits of a Multidisciplinary Women's Sexual Health Clinic in the Management of Sexual and Menopausal Symptoms After Pelvic Radiotherapy.

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.

Publication Bias in Gastrointestinal Oncology Trials Performed over the Past Decade.

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.

Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis.

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 < 0.001) and cN + disease (33% vs 29%, p = 0.010), but were less likely to have ypT3-4 disease (59% vs 74%, p < 0.001) and ypN + disease (32% vs 55%, p < 0.001) and more likely to have a pathologic complete response (5% vs 2%, p < 0.001) and R0 resection (86% vs 80%, p < 0.001). On MVA, MAC + RT (OR 1.58, 95% CI 1.33-1.89, p < 0.001), evaluation at an academic center (OR 1.33, 95% CI 1.14-1.56, p < 0.001), and female sex (OR 1.43, 95% CI 1.23-1.67, p < 0.001) were associated with higher odds of R0 resection, while cT3-4 disease (OR 0.81, 95% CI 0.68-0.96, p = 0.013) was associated with lower odds of R0 resection. CONCLUSION: For patients with localized PDAC who receive pre-operative MAC, the addition of pre-operative RT was associated with improved rates of R0 resection and pathologic response.

Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System.

BACKGROUND: FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GN) are established first line therapies for metastatic pancreatic cancer (MPC). There are, however, no randomized controlled trials comparing FFX and GN in the first line setting and real-world data on their comparative effectiveness is limited. We aimed to evaluate the outcomes of patients with MPC who were treated with first line FFX and GN and to further characterize dose modifications, discontinuation rates due to treatment toxicity, and rates of hospitalizations while on treatment. METHODS: We manually abstracted data from the electronic medical records (EMR) system at Yale Smilow Hospital and Smilow Cancer Hospital Care Centers for patients with MPC treated with at least one cycle of first line FFX or GN from January 2011 to April 2019. Patients who received prior neoadjuvant or adjuvant FFX or GN and adjuvant gemcitabine less than 6 months prior to metastatic recurrence were excluded. The median time to treatment discontinuation (TTD) and overall survival (OS) were determined using Kaplan-Meier method. RESULTS: We identified 363 patients for analysis; 269 (74%) patients were treated with FFX and 94 (26%) with GN. Median TTD was 4.8 (IQR, 2.3-8.0) months in the FFX group compared to 3.4 (IQR, 1.3-5.7) months in the GN group (P=0.0037). Median OS was 11.3 (95% CI: 10.7-12.9) months in the FFX group and 7.0 (95% CI: 6.0-8.7) months in the GN group (P<0.001). Initial dose modifications occurred in 264 (98%) and 86 (91%) of FFX and GN treated patients, respectively (P=0.001). While on treatment, 56 (60%) of GN-treated patients had at least one hospitalization vs. 110 (41%) in the FFX-group (P=0.002). Treatment was discontinued due to chemotherapy toxicity in 26 (10%) and 14 (15%) among the FFX and GN cohorts, respectively (P=0.275). CONCLUSIONS: Patients treated with first line FFX had increased survival and TTD compared to patients treated with GN despite increased dose modifications and similar rates of treatment discontinuation due to treatment-related toxicity. GN-treated patients were older and more likely to be hospitalized while on treatment. Further study evaluating comparative effectiveness between these two regimens is warranted.

A Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer.

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.

Radiation Therapy for Patients with Advanced Renal Cell Carcinoma.

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.

An Update to Changing Patterns of Anal Carcinoma in the United States.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.