Safety and efficacy of stereotactic body proton therapy for high-risk lung tumors.

Purpose: Stereotactic body proton therapy (SBPT) is an emerging treatment strategy for lung tumors that aims to combine the excellent local control benefits of ultra-hypofractionation with the physical advantages of protons, which reduce the integral dose to organs at risk (OARs) compared to photons. To date, however, very little data delivering SBPT in 5 or fewer fractions to lung tumors have been reported. Given that photon stereotactic body radiation therapy can struggle to deliver ablative doses to high-risk tumors (i.e., central/ultra-central location, prior in-field radiation, tumor size >5 cm, or the presence of severe pulmonary comorbidities) while adhering to OAR dose constraints, we hypothesized that SBPT would be an effective alternative for patients with high-risk tumors. Methods and Materials: Twenty-seven high-risk patients with 29 lung tumors treated with SBPT at the New York Proton Center between December 2019 and November 2022 were retrospectively identified. Patients were divided into three major subgroups: early-stage non-small cell lung cancer (NSCLC), locally recurrent NSCLC, and metastatic cancer from lung cancer or other histologies. Patient characteristics were reported using descriptive statistics, actuarial methods were used to quantify disease control rates, and toxicities were scored using CTCAE v 5.0. Results: The most common high-risk indications for SBPT were central/ultra-central tumor location (69.0%), severe COPD (48.1%), reirradiation (44.4%), significant pulmonary fibrosis (22.2%), and large tumor size > 5 cm (18.5%). In total, 96.6% of tumors were fully covered by the prescription dose without compromising target coverage. Three-year actuarial rates of local control for early-stage NSCLC, locally recurrent NSCLC, and metastatic patients were 89%, 100%, and 43%, respectively. Three-year actuarial rates of regional control were 89%, 67%, and 86%. Three-year actuarial rates of distant metastasis-free survival were 79%, 100%, and 0%. Two patients (7.4%), both of whom had clinically significant baseline interstitial lung disease and pre-treatment continuous oxygen demand, experienced grade ≥2 pulmonary toxicity (1 grade 3, 1 grade 5). There were no acute or late grade ≥2 toxicities related to esophagitis, cardiac injury, airway injury, pulmonary fibrosis, bronchopulmonary hemorrhage or brachial plexopathy. Conclusions: In the largest study of proton SBRT reported to date, SBPT has a favorable toxicity profile while being an effective approach for treating most high-risk tumors without requiring dose de-escalation or compromising tumor coverage and warrants further investigation.

Stereotactic body proton therapy for non-small cell lung cancer: Clinical indications and recommendations.

Stereotactic body radiation therapy (SBRT) has emerged as a standard treatment approach for early-stage lung cancer and intrathoracic oligometastatic or oligoprogressive disease. While local control is often excellent with this modality when delivered with photon therapy, toxicities for select patients can be significant. Proton therapy offers a unique opportunity to widen the therapeutic window when treating patients with thoracic malignancies requiring or benefitting from ultra-high doses per fraction. Thoracic proton SBRT may be particularly beneficial in cases requiring dose escalation, for tumors >5 cm, for central or ultra-central tumors, for reirradiation, in patients with interstitial lung diseases, and when combining radiation with immunotherapy. These clinical indications are detailed, along with supporting literature and clinical recommendations. Other considerations, future directions and potential benefits of proton SBRT, including sparing lymphocytes, when delivered as intensity-modulated proton therapy or as FLASH, and for the treatment of locally advanced non-small cell lung cancer or in patients with homologous recombination repair deficiencies, are also discussed.

Local Therapy for Oligoprogressive Disease: A Systematic Review of Prospective Trials.

PURPOSE: The successes of local therapy for oligometastatic cancers cannot be extrapolated to oligoprogressive disease (OPD) because they are distinct clinical entities. Given the limited prospective data on OPD to date, summative analyses are urgently needed. METHODS AND MATERIALS: Inclusion criteria for this Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review were as follows. First, only prospective data were included. Second, progression had to have occurred on active/ongoing systemic therapy. Third, the number of progressing areas of disease had to be explicitly listed and ≤5 in number. Fourth, all progressing sites had to undergo local therapy (radiation therapy [RT] /surgery/nonradiation ablative procedures). RESULTS: Eight trials met criteria (summing 290 patients), the vast majority of which used stereotactic RT as the local modality (most commonly, 19-20 Gy in 1 fraction, 27-33 Gy in 3 fractions, or 35-50 Gy in 5 fractions). A study on non-small cell lung cancer (NSCLC) demonstrated that stereotactic RT improved progression-free survival (PFS) and overall survival compared with historical values with systemic therapy alone. Two additional studies on epidermal growth factor receptor mutated (EGFRm) NSCLC also showed acceptable PFS with local therapy, particularly in patients who oligoprogressed on osimertinib. The only randomized trial analyzed herein showed that local therapy improved PFS for NSCLC but not breast cancer. Two trials in castration-resistant prostate cancer illustrated that a substantial proportion of patients did not require any changes in hormonal therapy or delayed the need to change systemic therapies. Lastly, 2 trials of renal cell carcinoma showed high (90%-100%) local control and median PFS of 9 months, and potentially a prolonged time to change systemic therapy. Lastly, from all patients in all trials, local therapy was tolerated well, with only 7 instances of grade 3+ toxicities. CONCLUSIONS: Based on the limited data, local therapy for oligoprogression is safe and yields encouraging short-term preliminary outcomes, but trials with larger sample sizes and longer follow-up are required for more robust conclusions.

DNA-PK Inhibition and Radiation Promote Antitumoral Immunity through RNA Polymerase III in Pancreatic Cancer.

Targeting the DNA damage response in combination with radiation enhances type I interferon (T1IFN)-driven innate immune signaling. It is not understood, however, whether DNA-dependent protein kinase (DNA-PK), the kinase critical for repairing the majority of radiation-induced DNA double-strand breaks in cancer cells, is immunomodulatory. We show that combining radiation with DNA-PK inhibition increases cytosolic double-stranded DNA and tumoral T1IFN signaling in a cyclic GMP-AMP synthase (cGAS)- and stimulator of interferon genes (STING)-independent, but an RNA polymerase III (POL III), retinoic acid-inducible gene I (RIG-I), and antiviral-signaling protein (MAVS)-dependent manner. Although DNA-PK inhibition and radiation also promote programmed death-ligand 1 (PD-L1) expression, the use of anti-PD-L1 in combination with radiation and DNA-PK inhibitor potentiates antitumor immunity in pancreatic cancer models. Our findings demonstrate a novel mechanism for the antitumoral immune effects of DNA-PK inhibitor and radiation that leads to increased sensitivity to anti-PD-L1 in poorly immunogenic pancreatic cancers. IMPLICATIONS: Our work nominates a novel therapeutic strategy as well as its cellular mechanisms pertinent for future clinical trials combining M3814, radiation, and anti-PD-L1 antibody in patients with pancreatic cancer.

The Fistula Risk Score Catalog: Toward Precision Medicine for Pancreatic Fistula After Pancreatoduodenectomy.

OBJECTIVE: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. BACKGROUND: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes. METHODS: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches. RESULTS: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33). CONCLUSION: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.

Extended Experience with a Dynamic, Data-Driven Selective Drain Management Protocol in Pancreaticoduodenectomy: Progressive Risk Stratification for Better Practice.

BACKGROUND: Intraoperative drain use for pancreaticoduodenectomy has been practiced in an unconditional, binary manner (placement/no placement). Alternatively, dynamic drain management has been introduced, incorporating the Fistula Risk Score (FRS) and drain fluid amylase (DFA) analysis, to mitigate clinically relevant postoperative pancreatic fistula (CR-POPF). STUDY DESIGN: An extended experience with dynamic drain management was used at a single institution for 400 consecutive pancreaticoduodenectomies (2014 to 2019). This protocol consists of the following: drains omitted for negligible/low-risk FRS (0 to 2) and drains placed for moderate/high-risk FRS (3 to 10) with early (postoperative day [POD] 3) removal if POD1 DFA ≤5,000 U/L. Adherence to this protocol was prospectively annotated and outcomes were retrospectively analyzed. RESULTS: The overall CR-POPF rate was 8.7%, with none occurring in the negligible/low-risk cases. Moderate/high-risk patients manifested an 11.9% CR-POPF rate (n = 35 of 293), which was lower on-protocol (9.5% vs 21%; p = 0.014). After drain placement, POD1 DFA ≥5,000 U/L was a better predictor of CR-POPF than FRS (odds ratio 14.7; 95% CI, 4.3 to 50.3). For POD1 DFA ≤5,000 U/L, early drain removal was associated with fewer CR-POPFs (2.8% vs 23.5%; p < 0.001), and substantiated by multivariable analysis (odds ratio 0.09; 95% CI, 0.03 to 0.28). Surgeon adherence was inversely related to CR-POPF rate (R = 0.846). CONCLUSIONS: This extended experience validates a dynamic drain management protocol, providing a model for better drain management and individualized patient care after pancreaticoduodenectomy. This study confirms that drains can be safely omitted from negligible/low-risk patients, and moderate/high-risk patients benefit from early drain removal.

Decoding Grade B Pancreatic Fistula: A Clinical and Economical Analysis and Subclassification Proposal.

OBJECTIVE: The aim of this study was to describe characteristics and management approaches for grade B pancreatic fistula (B-POPF) and investigate whether it segregates into distinct subclasses. BACKGROUND: The 2016 ISGPS refined definition of B-POPF is predicated on various postoperative management approaches, ranging from prolonged drainage to interventional procedures, but the spectrum of clinical severity within this entity is yet undefined. METHODS: Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to identify B-POPFs and their treatment strategies. Subclassification of B-POPFs into 3 classes was modeled after the Fistula Accordion Severity Grading System (B1: prolonged drainage only; B2: pharmacologic management; B3: interventional procedures). Clinical and economic outcomes, unique from the ISGPS definition qualifiers, were analyzed across subclasses. RESULTS: B-POPF developed in 320 of 1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage occurred in 79 patients (24.7%), always in combination with other strategies. Management of B-POPFs was widely heterogeneous with a median of 2 approaches/patient (range 1 to 6) and 38 various strategy combinations used. Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and were associated with progressively worse clinical and economic outcomes. These results were confirmed by multivariable analysis adjusted for clinical and operative factors. Notably, distribution of the B-POPF subclasses was influenced by institution and type of resection (P < 0.001), while clinical/demographic predictors proved elusive. CONCLUSION: B-POPF is a heterogeneous entity, where 3 distinct subclasses with increasing clinical and economic burden can be identified. This classification framework has potential implications for accurate reporting, comparative research, and performance evaluation.

Risk Factors and Mitigation Strategies for Pancreatic Fistula After Distal Pancreatectomy: Analysis of 2026 Resections From the International, Multi-institutional Distal Pancreatectomy Study Group.

OBJECTIVE: To identify a clinical fistula risk score following distal pancreatectomy. BACKGROUND: Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. METHODS: This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. RESULTS: CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001). CONCLUSIONS: From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation.

OBJECTIVE: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. BACKGROUND: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. METHODS: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables. RESULTS: In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts. CONCLUSION: A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

The Beneficial Effects of Minimizing Blood Loss in Pancreatoduodenectomy.

OBJECTIVE: The aim of this study was to elucidate the impact of intraoperative blood loss on outcomes following pancreatoduodenectomy (PD). BACKGROUND: The negative impact of intraoperative blood loss on outcomes in PD has long been suspected but not well characterized, particularly those factors that may be within surgeons' control. METHODS: From 2001 to 2015, 5323 PDs were performed by 62 surgeons from 17 institutions. Estimated blood loss (EBL) was discretized (0 to 300, 301 to 750, 751 to 1300, and >1300 mL) using optimal scaling methodology. Multivariable regression, adjusted for patient, surgeon, and institutional variables, was used to identify associations between EBL and perioperative outcomes. Factors associated with both increased and decreased EBL were elucidated. The relative impact of surgeon-modifiable contributors was estimated through beta coefficient standardization. RESULTS: The median EBL of the series was 400 mL [interquartile range (IQR) 250 to 600]. Intra-, post-, and perioperative transfusion rates were 15.8%, 24.8%, and 37.2%, respectively. Progressive EBL zones correlated with intra- but not postoperative transfusion in a dose-dependent fashion (P < 0.001), with a key threshold of 750 mL EBL (8.14% vs 40.9%; P < 0.001). Increasing blood loss significantly correlated with poor perioperative outcomes. Factors associated with increased EBL were trans-anastomotic stent placement, neoadjuvant chemotherapy, pancreaticogastrostomy reconstruction, multiorgan or vascular resection, and elevated operative time, of which 38.7% of the relative impact was "potentially modifiable" by the surgeon. Conversely, female sex, small duct, soft gland, minimally invasive approach, pylorus-preservation, biological sealant use, and institutional volume (≥67/year) were associated with decreased EBL, of which 13.6% was potentially under the surgeon's influence. CONCLUSION: Minimizing blood loss contributes to fewer intraoperative transfusions and better perioperative outcomes for PD. Improvements might be achieved by targeting modifiable factors that influence EBL.

Taking Theory to Practice: Quality Improvement for Pancreaticoduodenectomy and Development and Integration of the Fistula Risk Score.

BACKGROUND: Improvements in surgical outcomes are predicated on recognizing effective practices with subsequent adaptation. It is unknown whether risk assessment for pancreatic fistula (clinically relevant postoperative pancreatic fistula [CR-POPF]) after pancreaticoduodenectomy (PD) translates to improved patient outcomes at the practice level. STUDY DESIGN: A prospectively collected, single-surgeon career experience (2003 to 2018) of 455 consecutive pancreatectomies (303 PDs and 152 distal pancreatectomies) was examined. Analysis occurred during 4 eras of practice: learning curve for PD (n = 50); development of the Fistula Risk Score (n = 48); reactive, data-driven adjustments of anastomotic stent use (n = 94); and omission of prophylactic octreotide with adoption of selective drainage (n = 111). Observed to expected ratios of CR-POPF were calculated using a multi-institutional derivation set (5,379 PDs). RESULTS: After adjustment for increasing fistula risk across the 4 eras (p = 0.016), the risk-adjusted CR-POPF rate declined significantly (observed to expected ratio 1.42→1.28→1.01→0.30; p < 0.001). Literature-driven changes in fistula mitigation strategies likewise led to reductions in the overall complication burden (Postoperative Morbidity Index: 0.20→0.24→0.25→0.15; p = 0.015) and resource use (therapeutic antibiotics: p = 0.019; hospital readmission: p = 0.006; postoperative transfusion: p = 0.007). In contrast, the CR-POPF rate after distal pancreatectomy, for which no validated risk-adjustment process exists, did not vary (approximately 12%; p = 0.878). CONCLUSIONS: Patient outcomes for PD can be optimized by risk-adjusted evaluation and deliberate modification of practice.

Effect of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small-Cell Lung Cancer: A Propensity Score-Matched Analysis.

INTRODUCTION: Patients with small-cell lung cancer (SCLC) have a high incidence of occult brain metastases and are often treated with prophylactic cranial irradiation (PCI). Despite a small survival advantage in some studies, the role of PCI in extensive stage SCLC remains controversial. We used the National Cancer Database to assess survival of patients with metastatic SCLC treated with PCI. PATIENTS AND METHODS: Metastatic SCLC patients without brain metastases were identified. To minimize treatment selection bias, patients with an overall survival (OS) < 6 months were excluded. Cox regression identified variables associated with OS. Patients were propensity score-matched on factors associated with receipt of PCI or OS. The effect of PCI on OS was examined using Kaplan-Meier estimates. RESULTS: In the overall cohort (n = 4257), treatment with PCI (n = 473) was associated with improved survival (hazard ratio, 0.66; 95% confidence interval, 0.60-0.74; P < .0001). Comparisons of propensity score-matched cohorts revealed a significant survival benefit for patients who received PCI in median OS (13.9 vs. 11.1 months; P < .0001), as well as 1- and 2-year OS (61.2% vs. 44.0% and 19.8% vs. 11.5%, respectively; P < .0001). This survival benefit persisted even after excluding patients who survived < 9 months (median: 15.3 vs. 12.9 months; P < .0001). In multivariable analysis, predictors of receipt of PCI were Caucasian race, younger age, and lower Charlson-Deyo score. CONCLUSION: Using a modern population-based data set, we showed that metastatic SCLC patients treated with PCI have significantly improved OS. This large retrospective study helps address the conflicting prospective data.

Characterization and Optimal Management of High-risk Pancreatic Anastomoses During Pancreatoduodenectomy.

OBJECTIVE: The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. BACKGROUND: The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. METHODS: This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. RESULTS: A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). CONCLUSIONS: The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.

Surgical experience and the practice of pancreatoduodenectomy.

BACKGROUND: Experienced surgeons demonstrate improved pancreatoduodenectomy outcomes, but little is known about what distinguishes their practice. Furthermore, the concept of experience has been variably interpreted in the surgical literature. We investigated how 4 interpretations of experience influence pancreatoduodenectomy management decisions. METHODS: A survey assessing pancreatoduodenectomy practice patterns was distributed by 6 surgical societies. Regression analysis identified behaviors associated with 4 forms of experience: years in practice, surpassing the learning curve (≥50 pancreatoduodenectomies), high annual volume (≥25 pancreatoduodenectomy/year), and high career volume (>200 pancreatoduodenectomy). RESULTS: In the study, 861 surgeons responded, representing 6 continents. Senior surgeons were more likely to use pancreatogastrostomy, dunking/invagination, and external stents (all P < .05). Sixty-five percent of respondents surpassed the learning curve, and these surgeons were more likely to use a 2-layer pancreatic enteric anastomosis, stents, and the Fistula Risk Score (all P < .05). High annual volume surgeons were more likely to use the same reconstruction on every case and autologous tissue patches but less likely to use the Roux limb technique and multiple drains (all P < .05). High career volume surgeons mirrored the behaviors of those surpassing the learning curve except for using the Fistula Risk Score. CONCLUSION: Experience encompasses several components, each of which seems to influence decision making in different ways.

Radiation Treatment Time and Overall Survival in Locally Advanced Non-small Cell Lung Cancer.

PURPOSE: Prolonged radiation treatment (RT) time (RTT) has been associated with worse survival in several malignancies. The present study investigated whether delays during RT are associated with overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: The National Cancer Database was queried for patients with stage III NSCLC who had received definitive concurrent chemotherapy and fractionated RT to standard doses (59.4-70.0 Gy) and fractionation from 2004 to 2013. The RTT was classified as standard or prolonged for each treatment regimen according to the radiation dose and number of fractions. Cox proportional hazards models were used to evaluate the association between the following factors and OS: RTT, RT fractionation, demographic and pathologic factors, and chemotherapeutic agents. RESULTS: Of 14,154 patients, the RTT was prolonged in 6262 (44.2%). Factors associated with prolonged RTT included female sex (odds ratio [OR] 1.21, P<.0001), black race (OR 1.20, P=.001), nonprivate health insurance (OR 1.30, P<.0001), and lower income (<$63,000 annually, OR 1.20, P<.0001). The median OS was significantly worse for patients with prolonged RTT than that for those with standard RTT (18.6 vs 22.7 months, P<.0001). Furthermore, the OS worsened with each cumulative interval of delay (standard RTT vs prolonged 1-2 days, 20.5 months, P=.009; prolonged 3-5 days, 17.9 months, P<.0001; prolonged 6-9 days, 17.7 months, P<.0001; prolonged >9 days, 17.1 months, P<.0001). On multivariable analysis, prolonged RTT was independently associated with inferior OS (hazard ratio 1.21, P<.0001). Prolonged RTT as a continuous variable was also significantly associated with worse OS (hazard ratio 1.001, P=.0007). CONCLUSIONS: Delays during RT appear to negatively affect survival for patients with locally advanced NSCLC. We have detailed the demographic and socioeconomic barriers influencing prolonged RTT as a method to address the health disparities in this regard. Cumulative interruptions of RT should be minimized.

Adjuvant chemotherapy versus chemoradiotherapy in the management of patients with surgically resected duodenal adenocarcinoma: A propensity score-matched analysis of a nationwide clinical oncology database.

BACKGROUND: To the authors' knowledge, optimal adjuvant approaches for resected duodenal adenocarcinoma are not well established. Given the significant risk of locoregional disease recurrence, there may be a subset of patients who demonstrate an improvement in overall survival (OS) from the addition of radiotherapy (chemoradiotherapy [CRT]) to an adjuvant chemotherapy regimen. METHODS: Patients with resected, nonmetastatic duodenal adenocarcinoma who received chemotherapy (694 patients) or CRT (550 patients) were identified in the National Cancer Data Base (1998-2012). Cox regression identified covariates associated with OS. The chemotherapy and CRT cohorts were matched (1:1) by propensity scores based on the likelihood of receiving CRT or the survival hazard from Cox modeling. OS was compared using Kaplan-Meier estimates. RESULTS: CRT was more frequently used for patients who underwent positive-margin surgical resection (15.9% vs 9.1%; P<.001). At a median follow-up of 79.2 months (interquartile range, 52.9-114.9 months), the median OS of the propensity score-matched cohort was 46.7 months (interquartile range, 18.9 months to not reached). No survival advantage was observed for patients who were treated with adjuvant CRT compared with those treated with adjuvant chemotherapy (median OS: 48.9 months vs 43.5 months [HR, 1.04; 95% confidence interval, 0.88-1.22 (P = .669)]). CRT was not found to be associated with a significant improvement in the median OS after positive-margin surgical resection (133 patients; 27.6 months vs 18.5 months [P = .210]) or in the presence of T4 classification (461 patients; 30.6 months vs 30.4 months [P = .844]) inadequate lymph node staging (584 patients; 40.5 months vs 43.2 months [P = .707]), lymph node positivity (647 patients; 38.3 months vs 34.1 months [P = .622]), or poorly differentiated histology (429 patients; 46.6 months vs 35.7 months [P = .434]). CONCLUSIONS: The addition of radiation to adjuvant therapy does not appear to significantly improve survival, even in high-risk cases. Cancer 2017;123:967-76. © 2016 American Cancer Society.

Pancreatic fistula risk for pancreatoduodenectomy: an international survey of surgeon perception.

INTRODUCTION: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a morbid complication following pancreatoduodenectomy (PD). It is unclear how pancreatic surgeons perceive risk for this complication, and the implications thereof. METHODS: A web-based survey was distributed to members of 22 international GI surgical societies. CR-POPF risk factors were categorized as follows: (i) patient factors, (ii) pancreatic gland characteristics, (iii) intraoperative variables, (iv) perioperative mitigation techniques, or (v) institutional features. RESULTS: Surveys were completed by 897 surgeons worldwide. The most commonly cited contributors to CR-POPF risk were gland characteristics (90.7%), while patient and intraoperative factors were selected 71.2 and 69.3% of the time, respectively. Conversely, institutional features (31.7%) and perioperative mitigation techniques (21.3%) were rarely recognized. Eighty percent of surgeons use drain amylase concentration to guide drain removal decision-making; however, only 45.2% of surgeon remove drains early based upon drain amylase values. When evaluating clinical scenarios, surgeons were able to identify both negligible and high risk scenarios but struggled to differentiate between low and moderate CR-POPF risk. CONCLUSION: This international study analyzed how surgeons discern CR-POPF risk for PD. There was considerable variability in surgeons' perceptions of risk, which may have an adverse effect on the clinical use of risk adjustment measures.