Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

INTRODUCTION: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). METHODS: The National Cancer Database was queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. RESULTS: A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%; odds ratio [OR]: 0.59; p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18; 95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95% CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). CONCLUSION: Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.

The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy.

BACKGROUND: The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS: The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS: After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION: Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.

Impact of Mediating and Confounding Variables on the Volume-Outcome Association in the Treatment of Pancreatic Cancer.

BACKGROUND: High-volume centers (HVC), academic centers (AC), and longer travel distances (TD) have been associated with improved outcomes for patients undergoing surgery for pancreatic adenocarcinoma (PAC). Effects of mediating variables on these associations remain undefined. The purpose of this study is to examine the direct effects of hospital volume, facility type, and travel distance on overall survival (OS) in patients undergoing surgery for PAC and characterize the indirect effects of patient-, disease-, and treatment-related mediating variables. PATIENTS AND METHODS: Using the National Cancer Database, patients with non-metastatic PAC who underwent resection were stratified by annual hospital volume (< 11, 11-19, and ≥ 20 cases/year), facility type (AC versus non-AC), and TD (≥ 40 versus < 40 miles). Associations with survival were evaluated using multiple regression models. Effects of mediating variables were assessed using mediation analysis. RESULTS: In total, 19,636 patients were included. Treatment at HVC or AC was associated with lower risk of death [hazard ratio (HR) 0.90, confidence interval (CI) 0.88-0.92; HR 0.89, CI 0.86-0.91, respectively]. TD did not impact OS. Patient-, disease-, and treatment-related variables explained 25.5% and 41.8% of the survival benefit attained from treatment at HVC and AC, reducing the survival benefit directly attributable to each variable to 4.9% and 6.4%, respectively. CONCLUSIONS: Treatment of PAC at HVC and AC was associated with improved OS, but the magnitude of this benefit was less when mediating variables were considered. From a healthcare utilization and cost-resource perspective, further research is needed to identify patients who would benefit most from selective referral to HVC or AC.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

BACKGROUND: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS: Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS: Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.

Minimally invasive versus open distal pancreatectomy: a matched analysis using ACS-NSQIP.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) is gaining popularity due to improved perioperative outcomes over open distal pancreatectomy (ODP). The purpose of this study is to compare outcomes of MIDP and ODP using patients within a nationwide cohort. METHODS: The American College of Surgeons' National Quality Improvement Program (2014-2018) was used to evaluate incidence of post-operative pancreatic fistula (POPF) as well as 30-day composite major morbidity for patients undergoing MIDP vs. ODP. Matching was performed with a Mahalanobis-distance model for demographic characteristics, preoperative risk factors, and benign versus malignant pathology. Outcomes were assessed via weighted multiple logistic regression. RESULTS: A total of 3940 patients underwent distal pancreatectomy (1978 MIDP, 1962 ODP). After matching, 2985 patients were included (1978 MIDP, 1007 ODP). The rates of major morbidity (8.65% MIDP vs. 9.76% ODP, p = 0.37) were similar between groups. The MIDP group was found to have significantly decreased length of stay (5.6 vs. 7 days, p ≤ 0.001), but greater rates (12.54% MIDP vs. 9.35% ODP, p = 0.02) of post-operative fistula. CONCLUSIONS: When matched for baseline patient characteristics, MIDP was associated with shorter length of hospitalization with similar rates of morbidity compared to ODP. However, MIDP was associated with significantly increased rates of POPF. Further studies are needed to investigate this difference in POPF rate, and determine how to optimize MIDP surgical technique to reduce this risk.

SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

Downstaging of Pancreatic Adenocarcinoma With Either Neoadjuvant Chemotherapy or Chemoradiotherapy Improves Survival.

BACKGROUND: Neoadjuvant chemotherapy (NAC) or chemoradiation (NAC+XRT) is incorporated into the treatment of localized pancreatic adenocarcinoma (PDAC), often with the goal of downstaging before resection. However, the effect of downstaging on overall survival, particularly the differential effects of NAC and NAC+XRT, remains undefined. This study examined the impact of downstaging from NAC and NAC+XRT on overall survival. METHODS: The National Cancer Data Base (NCDB) was queried from 2006 to 2015 for patients with non-metastatic PDAC who received NAC or NAC+XRT. Rates of overall and nodal downstaging, and pathologic complete response (pCR) were assessed. Predictors of downstaging were evaluated using multivariable logistic regression. Overall survival (OS) was assessed with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: The study enrolled 2475 patients (975 NAC and 1500 NAC+XRT patients). Compared with NAC, NAC+XRT was associated with higher rates of overall downstaging (38.3 % vs 23.6 %; p ≤ 0.001), nodal downstaging (16.0 % vs 7.8 %; p ≤ 0.001), and pCR (1.7 % vs 0.7 %; p = 0.041). Receipt of NAC+XRT was independently predictive of overall (odds ratio [OR] 2.28; p < 0.001) and nodal (OR 3.09; p < 0.001) downstaging. Downstaging by either method was associated with improved 5-year OS (30.5 vs 25.2 months; p ≤ 0.001). Downstaging with NAC was associated with an 8-month increase in median OS (33.7 vs 25.6 months; p = 0.005), and downstaging by NAC+XRT was associated with a 5-month increase in median OS (30.0 vs 25.0 months; p = 0.008). Cox regression showed an association of overall downstaging with an 18 % reduction in the risk of death (hazard ratio [HR] 0.82; 95 % confidence interval, 0.71-0.95; p = 0.01) CONCLUSION: Downstaging after neoadjuvant therapies improves survival. The addition of radiation therapy may increase the rate of downstaging without affecting overall oncologic outcomes.

Prognostic Role of Lymph Node Sampling in Adolescent and Young Adults With Fibrolamellar Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is rare among adolescent and young adult (AYA) patients, and resection or transplant remains the only curative therapy. The role of lymph node (LN) sampling is not well-defined. The aim of this study was to describe practice patterns, as well as investigate the impact of LN sampling on survival outcomes in this population. MATERIALS AND METHODS: A retrospective cohort study using the 2004-2018 National Cancer Database (NCDB) was performed. Patients ≤21 y old with nonmetastatic HCC who underwent liver resection or transplant were evaluated. Clinical features of patients who underwent LN sampling were compared to those who did not, and univariable and multivariable logistic regression was performed to evaluate independent predictive factors of node positivity. Survival analysis was performed using Kaplan-Meier methods and Cox Proportional Hazard Survival Regression. RESULTS: A total of 262 AYA patients with HCC were identified, of whom 137 (52%) underwent LN sampling, 44 patients had positive nodes, 40 (95%) of them had tumors >5 cm; 87 (64%) of patients with sampled nodes had fibrolamellar carcinoma (FLC), which was an independent risk factor for predicting positive nodes (P = 0.001). There was no difference in overall survival between patients who underwent LN sampling and those who did not; however, 5-y overall survival for node-positive patients was 40% versus 79% for node-negative patients (P < 0.0001). CONCLUSIONS: In AYA patients with HCC, LN sampling was not associated with an independent survival benefit. However, FLC was an independent risk factor for LN positivity, suggesting a role for routine LN sampling in these patients.

Preoperative Risk Prediction for Pancreatectomy: A Comparative Analysis of Three Scoring Systems.

INTRODUCTION: Pancreatectomy is associated with high morbidity and mortality. Therefore, patient selection and risk prediction is paramount. In this study, three validated perioperative risk scoring systems were compared among patients undergoing pancreatectomy to identify the most clinically useful model. MATERIALS AND METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried for pancreatectomy patients. Three models were evaluated: National Surgical Quality Improvement Program Universal Risk Calculator (URC), Model for End-Stage Liver Disease (MELD), and Modified Frailty Index-5 Factor (mFI-5). Outcomes were 30-d mortality and complications. Predictive performance of the models was compared using area under the receiver operating characteristic curve (AUC) and Brier scores. RESULTS: Twenty two thousand one hundred twenty three pancreatectomy patients were identified. The 30-d mortality rate was 1.4% (n = 319). Complications occurred in 6020 cases (27.2%). AUC (95% CI) for 30-d mortality were 0.70 (0.67-0.73), 0.63 (0.60-0.67), and 0.60 (0.57-0.63) for URC, MELD, and mFI-5, respectively, with Brier score of 0.014 for all three models. AUC (95% confidence interval) for any complication was 0.59 (0.58-0.59) for URC, 0.53 (0.52-0.54) for MELD, and 0.53 (0.52-0.54) for mFI-5, with Brier scores 0.193 (URC), 0.200 (MELD), and 0.197 (mFI-5). For individual complications, URC was more predictive than MELD or mFI-5. CONCLUSIONS: Of the validated preoperative risk scoring systems, URC was most predictive of both complications and 30-d mortality. None of the models performed better than fair to good. The lack of predictive accuracy of currently existing models highlights the need for development of improved perioperative risk models.

Disparities in Amputation Rates for Non-metastatic Extremity Soft Tissue Sarcomas and the Impact on Survival.

BACKGROUND: There are no definitive recommendations guiding amputation use in extremity soft tissue sarcomas (STSs). This study explores disparities in amputation rates and survival in patients with non-metastatic adult-type extremity STSs. METHODS: Patients with non-metastatic adult-type extremity STSs were identified from the 1998-2012 National Cancer Database. Factors affecting amputation were examined across all ages and separately in adults (> 40 years), adolescent/young adults (AYA: ages 15-39), and children (age < 15). Impact on 10-year overall survival (OS) was explored. RESULTS: Of 15,886 patients, 4.65% had an amputation. AYAs had the most amputations (6.4%) compared to children (5.9%) and adults (4.2%) (p < 0.001). Patients with public insurance (OR 1.3, CI 1.08-1.58) and from central states (OR 1.5, CI 1.2-1.86) were more likely to undergo amputation, whereas those from high income brackets (OR 0.8, CI 0.62-0.94) and treated at community cancer centers were less likely (OR 0.7, CI 0.62-0.90). Amputation was an independent risk factor for death at 10 years, with the greatest impact in AYAs compared to older adults (HR 1.7, p < 0.001). Treatment in eastern or central states, lower income, lack of private insurance, and comorbidities were all associated with decreased OS (all p < 0.05). Female gender (HR 0.8, CI 0.78-0.89) and high-volume centers (HR 0.8, CI 0.74-0.94) were associated with improved OS. CONCLUSIONS: Although amputations for extremity STSs are rare, disparities exist across age groups, insurance and geography when it comes to the use of amputation in patients with extremity STSs. Moreover, having an amputation is an independent risk factor for death, with the greatest impact in AYAs.

Adjuvant Chemotherapy in Resectable Gallbladder Cancer is Underutilized Despite Benefits in Node-Positive Patients.

BACKGROUND: Adjuvant chemotherapy (AC) is recommended following surgical resection of gallbladder cancer regardless of stage. However, stage-specific benefits of AC in gallbladder cancer are unclear. PATIENTS AND METHODS: Patients with resected pathologic stage I-III gallbladder cancer were identified using the 2006-2015 National Cancer Database. Utilization trends, predictors of use, and impact of AC on overall survival (OS) were determined. RESULTS: A total of 5656 patients were included. Use of AC increased from 9.9% in 2006 to 24.2% in 2015 (OR 2.91; 95% CI 2.06-4.09; p < 0.001). However, only 17.5% of patients overall and only 32.4% of node-positive (stage IIIb) patients received AC. Patients receiving AC were younger and had fewer comorbidities, shorter hospitalizations, more advanced disease, and more margin-positive resections (all p < 0.01). Higher pathologic T stage and positive nodal status represented the greatest independent predictors of receipt of AC. While AC demonstrated no OS advantage for stage I patients (p = 0.83), AC was associated with improved OS among stage II patients (p = 0.003), though this impact was not independently associated with improved OS on multivariable analysis. AC was independently associated with improved OS among stage IIIb patients, with a 30% reduction in risk of death (HR 0.70; 95% CI 0.58-0.83; p < 0.001). Younger age, fewer comorbidities, and shorter hospitalization all predicted receipt of AC among stage IIIb patients (all p < 0.05). CONCLUSIONS: Systemic therapy remains underprescribed, in particular among patients that would seem to benefit most. Adjuvant chemotherapy likely improves survival in node-positive gallbladder cancer, but its utility in the treatment of node-negative disease has not been demonstrated.

Rates, Predictors, and Outcomes of Portal Lymphadenectomy for Resectable Gallbladder Cancer.

INTRODUCTION: Lymphadenectomy (LND) is recommended following surgical resection of ≥ T1b gallbladder cancer (GBC). However, frequency and stage-specific survival benefits of LND remain unclear. PATIENTS AND METHODS: The National Cancer Database (NCDB; 2006-15) was queried for resected pathologic stage I-III GBC. LND performance, predictors of receiving LND, and LND association with overall survival (OS) were assessed. RESULTS: Of 2302 total patients, 1343 (58.3%) underwent LND. Patients who underwent LND were younger and more frequently had private health insurance, a negative surgical margin, higher pathologic T stage, and received adjuvant chemotherapy (all p < 0.001). LND rates were highest at academic centers (70.1%) relative to all other facility types (p < 0.001). LND was independently associated with improved OS [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.44-0.61]. LND was associated with improved OS for pT1b, pT2, and pT3 patients (all p < 0.05) on univariate analysis. LND was independently associated with improved OS in pT2 (HR 0.44, CI 0.35-0.56) and pT3 (HR 0.54, CI 0.43-0.69) patients. CONCLUSIONS: LND is associated with a 48% reduction in risk of death in patients with resectable non-metastatic GBC, with greatest impact in pT2-3 patients. Patients without LND have similar OS to patients with node-positive disease, highlighting the importance of LND. Underutilization of LND likely results in undertreatment of patients with undiagnosed nodal disease, which may contribute to unfavorable oncologic outcomes.

Impact of Hepatic Metastasectomy in the Multimodal Treatment of Metastatic Breast Cancer.

BACKGROUND: Surgical management of hepatic metastases in patients with stage IV breast cancer remains controversial. The purpose of this study was to examine the impact of hepatic metastasectomy on long-term outcomes. METHODS: The 2004-2015 National Cancer Database was queried for all patients diagnosed with stage IV breast cancer with metastases isolated to the liver. Patient demographics, disease-, treatment- and outcome-related data were analyzed. RESULTS: Of 2,895 patients, only 90 (3.1%) underwent hepatic resection. Compared to patients who did not undergo metastasectomy, patients treated with metastasectomy tended to be younger (52 ± 12.7 versus 59.2 ± 14.6; P < 0.001) and have private insurance (74.4% versus 45.3%; P < 0.001). Independent predictors of metastasectomy included younger age (OR 0.98; CI 0.96-0.99; P = 0.01), lobular carcinoma (OR 2.26; CI 1.06-4.82; P = 0.03), and prior surgery of the primary site (partial mastectomy (OR 6.96; CI 3.47-13.95; P < 0.001) or total mastectomy (OR 5.74; CI 3.06-10.76; P < 0.001)). Compared to no metastasectomy, hepatic metastasectomy was independently associated with a 37% reduction in the risk of death (HR 0.63; CI 0.44-0.91; P = 0.01). CONCLUSIONS: Stage IV breast cancer with metastases to the liver is rare and few patients undergo hepatic resection. However, in this select patient population, hepatic metastasectomy was associated with a significant survival advantage when included in the multimodal treatment of synchronous stage IV breast cancer.

Examining Perioperative Risk Associated with Simultaneous Resection of Primary Neuroendocrine Tumors and Synchronous Hepatic Metastases.

BACKGROUND: Surgical debulking of primary neuroendocrine tumors (NETs) and hepatic resection of metastatic NET disease may each independently improve overall survival. However, evidence for combined primary site debulking and metastasectomy on survival and impact on short-term perioperative outcomes is limited. METHODS: The 2014-2016 ACS-NSQIP targeted hepatectomy database was queried for all patients undergoing liver resection for metastatic NET. Secondary procedure codes were evaluated for major concurrent operations. Multivariable analysis was performed to determine risk factors for 30-day morbidity and mortality. RESULTS: A total of 472 patients were identified, of whom 153 (32.4%) underwent ≥1 additional concurrent major operation. The most common concurrent procedures were small bowel resection (14.6%), partial colectomy (8.9%), and radical lymphadenectomy (7.4%). Among all patients, overall 30-day mortality and morbidity were 1.5% and 25.6%, respectively. Modifiable and treatment-related factors associated with increased major postoperative morbidity risk included >10% weight loss within six months of surgery (p = 0.05), increasing number of hepatic lesions treated (p = 0.05), and biliary reconstruction (p = 0.001). No major concurrent procedure was associated with increased 30-day morbidity (all p > 0.05). CONCLUSIONS: Approximately one-third of patients with stage IV NET underwent combined hepatic and multi-organ resection. Although modifiable and treatment-related factors predictive of perioperative morbidity were identified, performance of concurrent major procedures did not increase perioperative morbidity. These results support consideration of multi-organ resection in carefully selected patients with metastatic NET.

Pancreatectomy in Stage I pancreas cancer: national underutilization of surgery persists.

BACKGROUND: Pancreatectomy in early pancreas adenocarcinoma has been historically underutilized. This retrospective study examines recent trends in the use of pancreatectomy in clinical Stage I (T1-2N0M0) pancreas cancer. METHODS: Using the 2004-2014 National Cancer Database, patients with clinical Stage I pancreas cancer were identified. Patients who underwent surgery or failed to undergo surgery with no identifiable reason were included in analysis. Chi-square, binary logistic regression, and Kaplan Meier estimate were used to identify risk factors for failure to undergo surgery. RESULTS: 23,365 patients were identified. Pancreatectomy increased from 38.4% in 2004 to 52.3% in 2014 (p < 0.001). 50% (n = 11,922) of patients underwent surgery and 48.0% (n = 11,433) did not, of whom 6.8% had a prohibitive co-morbidity, and 36.1% (n = 8594) had no identifiable reason for the lack of operation. Failure to operate was associated with older age, African American race, residence in lower income and less educated areas, lack of insurance, and treatment at community hospitals (all p < 0.001). 5-year survival was maximized in patients who underwent surgery and chemotherapy at 28.1%. CONCLUSION: While utilization of surgery increased overtime, 36% of patients fail to undergo surgery without an identifiable reason. Future investigation is warranted to explain continuing underuse of surgery in early pancreas cancer.

Colon cancer as a subsequent malignant neoplasm in young adults.

BACKGROUND: The incidence of colon cancer (CC) is rising in younger adults and can occur de novo or in patients previously treated for another cancer. To the authors' knowledge, the impact on survival of CC occurring as a subsequent malignant neoplasm (SMN) has not been described for younger patients, which the authors anticipate to be lower with SMNs than that of primary CC. METHODS: Patients aged <50 years with CC in the 2004 through 2014 National Cancer Data Base were identified. Patients were stratified by primary or subsequent occurrence. The impact of SMN status on overall survival (OS) was evaluated. RESULTS: Of 41,915 patients, 2852 (6.8%) had colon SMNs. More patients with colon SMNs were aged 40 to 49 years compared with patients with primary CC (83% vs 77%; P < .001). Patients with colon SMNs presented with earlier clinical and pathological T, N, and M classifications (all P < .001). Colon SMNs more commonly occurred in the right colon, whereas primary CC was found to have a higher prevalence in the sigmoid colon (P < .001). Patients with colon SMNs more frequently underwent total colectomy (17% vs 5%; P < .001), but received less chemotherapy (53% vs 65%; P < .001). When adjusted for demographic, tumor, and treatment characteristics, SMN status was associated with a 23% decreased OS compared with primary CC (95% CI, 1.14-1.31; P < .001). Chemotherapy offered a 33% improvement in OS (95% CI, 0.56-0.8; P < .001). CONCLUSIONS: Colon SMNs in younger patients present at an earlier stage and are treated more aggressively surgically compared with primary CCs. Patients with SMNs of the colon have decreased survival, although chemotherapy offers a survival advantage. Further investigation is warranted to determine whether these disparities are due to the effects of cancer treatment or differences in tumor biology.

Impact of Effective Systemic Therapy on Metastasectomy in Stage IV Melanoma: A Matched-Pair Analysis.

BACKGROUND: Although resection historically played a prominent role in the treatment of metastatic melanoma, recent advances have altered the therapeutic landscape, and potentially the role of surgery. We examined surgical selection and metastasectomy outcomes before and after the onset of the effective drug therapy era. METHODS: Patients with stage IV melanoma were identified and characterized by treatment era (either 1965-2007 or 2008-2015) and by systemic therapy agents. BRAF and/or MEK inhibitors, as well as checkpoint inhibitors, were included as modern agents. Selection factors for metastasectomy were examined by era. A matched-pair analysis of outcomes of surgical and non-surgical patients receiving modern systemic agents was performed. RESULTS: Among 2353 eligible patients, 1065 (45.2%) underwent surgical treatment. Factors associated with selection for metastasectomy in the early era included female sex, no prior stage III disease, single-organ involvement, and M1a (vs. M1c) disease (all p < 0.007). In the current era, the proportion of surgically treated patients increased modestly (54.5% vs. 44.7%, p = 0.02) and age was the only independent selection factor (p < 0.01). Surgery followed by modern therapy in 47 matched pairs was associated with higher 5-year melanoma-specific survival (MSS) versus modern therapy alone (58.8% vs. 38.9%, p = 0.049). Multivariable regression showed single-organ involvement (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.21-0.90, p = 0.02) and first-line surgery (HR 0.47, 95% CI 0.23-0.98, p = 0.04), as well as use of modern agents (HR 0.29, 95% CI 0.21-0.40, p < 0.001), were independently associated with improved MSS. CONCLUSIONS AND RELEVANCE: While modern systemic agents have improved outcomes in stage IV melanoma, metastasectomy remains associated with favorable survival. Resection remains a viable therapeutic approach, possibly worthy of prospective evaluation.

Adjuvant Radiation is Associated with Improved Survival for Select Patients with Non-metastatic Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy for which surgery is the mainstay of treatment and for which adjuvant radiation is infrequently employed; however, small, single-institution series suggest adjuvant radiation may improve outcomes. METHODS: All patients with non-metastatic ACC treated with either surgery alone or surgery followed by adjuvant radiation were identified in the 2004-2013 National Cancer Database. Factors associated with receipt of radiation and the impact of adjuvant radiation on survival were determined by multivariable analysis. RESULTS: Of 1184 patients, 171 (14.4%) received adjuvant radiation. Patient demographics were similar between the two groups, but those receiving radiation were more likely to have had positive margins following surgery (37.4 vs. 14.6%; p < 0.001), evidence of vascular invasion (14.0 vs. 5.1%; p = 0.05), and receive concurrent chemotherapy (57.3 vs. 28.8%; p < 0.001). After adjustment for tumor and other treatment factors, only positive margins following surgery was associated with an increased likelihood of receiving adjuvant radiation (odds ratio 3.84, 95% confidence interval [CI] 1.95-7.56). Radiation therapy did not confer a difference in median overall survival in the general cohort. However, for patients with positive margins, adjuvant radiation was associated with a 40% decreased yearly risk of death after adjustment for concurrent chemotherapy (hazard ratio 0.60, 95% CI 0.40-0.92; p = 0.02). This survival advantage was not evident for other traditional high-risk features. CONCLUSION: Adjuvant radiation appears to decrease the risk of death in ACC patients with positive margins following surgical resection, but only a small percentage are currently receiving radiation. Multidisciplinary treatment with surgery and radiation should be considered for these patients.