Social Vulnerability Index and Survivorship after Colorectal Cancer Resection.

BACKGROUND: Race and socioeconomic status incompletely identify patients with colorectal cancer (CRC) at the highest risk for screening, treatment, and mortality disparities. Social vulnerability index (SVI) was designed to delineate neighborhoods requiring greater support after external health stressors, summarizing socioeconomic, household, and transportation barriers by census tract. SVI is implicated in lower cancer center use and increased complications after colectomy, but its influence on long-term prognosis is unknown. Herein, we characterized relationships between SVI and CRC survival. STUDY DESIGN: Patients undergoing resection of stage I to IV CRC from January 2010 to May 2023 within an academic health system were identified. Clinicopathologic characteristics were abstracted using institutional National Cancer Database and NSQIP. Addresses from electronic health records were geocoded to SVI. Overall survival and cancer-specific survival were compared using Kaplan-Meier and Cox proportional hazards methods. RESULTS: A total of 872 patients were identified, comprising 573 (66%) patients with colon tumor and 299 (34%) with rectal tumor. Patients in the top SVI quartile (32%) were more likely to be Black (41% vs 13%, p < 0.001), carry less private insurance (39% vs 48%, p = 0.02), and experience greater comorbidity (American Society of Anesthesiologists physical status III: 86% vs 71%, p < 0.001), without significant differences by acuity, stage, or CRC therapy. In multivariable analysis, high SVI remained associated with higher all-cause (hazard ratio 1.48, 95% CI 1.12 to 1.96, p < 0.01) and cancer-specific survival mortality (hazard ratio 1.71, 95% CI 1.10 to 2.67, p = 0.02). CONCLUSIONS: High SVI was independently associated with poorer prognosis after CRC resection beyond the perioperative period. Acknowledging needs for multi-institutional evaluation and elaborating causal mechanisms, neighborhood-level vulnerability may inform targeted outreach in CRC care.

Tumor size and survival in intrahepatic cholangiocarcinoma treated with surgical resection or ablation.

OBJECTIVES: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA). METHODS: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6-46.2) vs. 28 months (95% CI: 15.9-28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm. CONCLUSION: Although resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity.

Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.

BACKGROUND: Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry. PATIENTS AND METHODS: Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively]. CONCLUSION: Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible.

Primary tumor resection improves survival of gastrointestinal neuroendocrine carcinoma patients with nonresected liver metastases.

BACKGROUND: The role of primary tumor resection (PTR) in the survival of gastrointestinal neuroendocrine carcinoma (GI-NEC) patients with liver metastases only remains poorly defined. Therefore, we investigated the impact of PTR on the survival of GI-NEC patients with nonresected liver metastases. METHODS: GI-NEC patients with a liver-confined metastatic disease diagnosed between 2016 and 2018 were identified in the National Cancer Database. Multiple imputations by chained equations were used to account for missing data, and the inverse probability of treatment weighting (IPTW) method was used to eliminate selection bias. Overall survival (OS) was compared by adjusted Kaplan-Meier curves and log-rank test with IPTW. RESULTS: A total of 767 GI-NEC patients with nonresected liver metastases were identified. Among all patients, 177 (23.1%) received PTR and had a significantly favorable OS before (median: 43.6 months [interquartile range, IQR, 10.3-64.4] vs. 8.8 months [IQR, 2.1-23.1], p < 0.001 in log-rank test) and after (median: 25.7 months [IQR, 10.0-64.4] vs. 9.3 months [IQR, 2.2-26.4], p < 0.001 in IPTW-adjusted log-rank test) the IPTW adjustment. Additionally, this survival advantage persisted in an adjusted Cox model (IPTW adjusted hazard ratio = 0.431, 95% confidence interval: 0.332-0.560; p < 0.001). The improved survival persisted in subgroups stratified by primary tumor site, tumor grade, and N stage, even in the complete cohort (excluding patients with missing data). CONCLUSIONS: PTR led to improved survival for GI-NEC patients with nonresected liver metastases regardless of primary tumor site, tumor grade, and N stage. However, the decision for PTR should be made on an individualized basis following multidisciplinary evaluation.

Retreatment with talimogene laherparepvec for advanced melanoma.

Aim: Talimogene laherparepvec (T-VEC) is a genetically modified oncolytic herpesvirus approved for the treatment of unresectable, locoregionally advanced and recurrent melanoma. There is little relevant literature in the context of retreatment with T-VEC. Materials & methods: We reviewed four patients aged 71-87 years old with stage IIIB-IV melanoma at treatment who were rechallenged with T-VEC after experiencing recurrence of locoregional disease or prior treatment-limiting toxicity. Results: Cessation of initial treatment was due to one of the following reasons: severe adverse event (one case), mixed response (one case) or complete response (two cases). Three males and one female underwent T-VEC retreatment with a mean of 5.5 injection cycles. Three patients experienced a complete response to retreatment, while one experienced disease progression. Conclusion: Intralesional T-VEC may be effective and well-tolerated in patients who have completed prior T-VEC therapy.

Improved overall survival is still observed in patients receiving delayed adjuvant chemotherapy after pancreaticoduodenectomy for pancreatic adenocarcinoma.

BACKGROUND: Adjuvant chemotherapy (AC) is associated with improved survival following resection of pancreatic adenocarcinoma but is frequently delayed or deferred due to perioperative complications or patient deconditioning. The aim of this study was to assess impact of delayed AC on overall survival after pancreaticoduodenectomy for pancreatic head adenocarcinoma. METHODS: Patients with stage I-III pancreatic head adenocarcinoma in the 2006-2015 National Cancer Database were grouped by timing of AC (<6-weeks, 6-12-weeks, and 12-24-weeks). Overall survival was compared using Cox proportional hazard models adjusting for patient, tumor, and hospital factors. Subgroup analyses were conducted to assess the impact of comorbidities, readmission or extended hospital stay, and receipt of single- versus multi-agent chemotherapy. RESULTS: Of 13438 patients, 4552 (33.9%) received no AC, 2112 (15.7%) received AC <6-weeks following resection, 5580 (41.5%) within 6-12 weeks, and 1194 (8.9%) within 12-24 weeks. AC was associated with improved overall survival (adjusted hazard ratio [HR] <6-weeks: 0.765, 6-12-weeks: 0.744, and 12-24-weeks: 0.736 (p < 0.001)). This survival advantage persisted for patients with comorbidities, those with postoperative complications, and in those receiving single- or multi-agent regimens. CONCLUSIONS: For patients with stage I-III pancreatic adenocarcinoma, receipt of AC is associated with improved overall survival, even if delayed up to 24-weeks.

Correction to: Sentinel Lymph Node Biopsy and Completion Lymph Node Dissection for Melanoma.

The original version of this article, which published in Current Treatment Options in Oncology, Volume 19, Issue 11, November 2018, contained an error within the Conflict of Interest statements. It was originally stated that "Norma E. Farrow received support from an NIH T32 grant (T32-CA009111."

Efficacy of Talimogene Laherparepvec (T-VEC) Therapy in Patients with In-Transit Melanoma Metastasis Decreases with Increasing Lesion Size.

BACKGROUND: Talimogene laherparepvec (T-VEC) is the first injectable oncolytic viral therapy approved for in-transit melanoma metastasis, with a reported overall response rate (ORR) of 25% and complete response rate (CRR) of 10%. To ascertain the role of patient selection on outcomes in routine practice, we evaluated the impact of patient, lesion, and treatment factors on clinical response. METHODS: Medical records were extracted for patients with recurrent stage IIIB-IV melanoma completing T-VEC at Duke University Medical Center between 1 January 2016 and 1 September 2018. Kaplan-Meier analysis assessed time to response and survival, while logistic regression measured associations of clinicopathologic status, lesion burden, T-VEC dosing, and use of prior and concurrent therapy with ORR and CRR. RESULTS: Of 27 patients, an objective response was observed in 11 (40.7%), including one patient with partial response (3.7%) and 10 with complete response (37.0%). Time to complete response and overall response was a median 22 weeks (95% confidence interval [CI] 2.0-41.9 weeks and 15.8-28.2 weeks, respectively), and median progression-free survival was 17 weeks (95% CI 0-36 weeks). Logistic regression demonstrated each millimeter increase in maximum lesion diameter predicted decreased ORR (odds ratio [OR] 0.866, 95% CI 0.753-0.995; p = 0.04). Stage IV disease (OR 0.04, 95% CI 0.00-0.74; p = 0.031) and programmed death-1 inhibitor treatment (OR 0.06, 95% CI 0.01-0.74; p = 0.028) also predicted reduced clinical response. CONCLUSIONS: This study corroborates recent data suggesting response rates to T-VEC may be higher than reported in clinical trials, arising in part from patient selection. T-VEC lesion diameter was persistently associated with clinical response and is a readily assessed predictor of successful T-VEC therapy.

Sentinel Lymph Node Biopsy and Completion Lymph Node Dissection for Melanoma.

OPINION STATEMENT: This review critically evaluates recent trials which have challenged the practice of completion lymph node dissection (CLND) for melanoma patients diagnosed with regional metastasis by positive sentinel lymph node biopsy (SLNB). Two trials in the last 2 years, DeCOG-SLT and MSLT-II, found no significant differences in melanoma-specific survival between patients, whether they received immediate CLND or observation after positive SLNB, despite decreases in nodal recurrence achieved by dissection. These trials together disfavor routine CLND in most patients after positive SLNB. However, their conclusions are limited by study populations which overall harbored a lower burden of SLN disease. Special attention needs to be given to patients who do have higher risk disease, with SLN tumor burdens exceeding 1 mm in diameter, for whom CLND may remain both prognostic and therapeutic. Current guidelines thus recommend either CLND or careful observation after positive SLNB after appropriate risk stratification of patients. While a decline in CLND is inevitable, treatment of stage III melanoma is witnessing the concurrent rise of effective adjuvant therapies. PD-1 inhibitors such as nivolumab, or combination BRAF/MEK inhibitors for V600E or K mutant melanoma, which were previously available to only trial patients with completely resected stage III disease, are now approved for use in patients with positive SLNB alone. Providers are better equipped than ever to treat clinically occult, regional metastatic disease with SLNB followed by adjuvant therapy for most patients, but should take steps to avoid undertreatment of high-risk patients who may proceed to disease relapse or progression.