Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma

BackgroundEarly progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.Patients and MethodsWe performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.ResultsWe included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.ConclusionAmong patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.     

Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study

BackgroundThe Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.Methods1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.ResultsOverall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111–1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034–1.358, P = 0.007).ConclusionsPatients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.     

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis

PurposeThere is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.Patients and methodsData of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.ResultsOf the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.ConclusionTumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.     

A population-based study on incidence,treatment, and survival in ampullary cancer in the Netherlands

IntroductionAmpullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016.MethodsPatients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease.ResultsIn total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989–1995 to 0.68 per 100,000in 2010–2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989–1995 to 63.9% in 2010–2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9–22.8) in 1989–1995 to 29.1% (26.0–31.2) in 2010–2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6–5.0) to 5.9 months (4.7–7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients.ConclusionBoth incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy.     

Liver resection is justified for multinodular hepatocellular carcinoma in selected patients with cirrhosis: A multicenter analysis of 1,066 patients

BackgroundThe role of liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) remains unclear, especially among patients with severe underlying liver disease. We sought to evaluate surgical outcomes among patients with cirrhosis and multinodular HCC undergoing liver resection.MethodsUsing a multicenter database, outcomes among cirrhotic patients who underwent curative-intent resection of HCC were examined stratified according to the presence or absence of multinodular disease. Perioperative mortality and morbidity, as well as overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups.ResultsAmong 1066 cirrhotic patients, 906 (85.0%) had single- or double-nodular HCC (the non-multinodular group), while 160 (15.0%) had multinodular HCC (the multinodular group). There were no differences in postoperative 30-day mortality and morbidity among non-multinodular versus multinodular patients (1.8% vs. 1.9%, P = 0.923, and 36.0% vs. 39.4%, P = 0.411, respectively). In contrast, 5-year OS and RFS of multinodular patients were worse compared with non-multinodular patients (34.6% vs. 58.2%, and 24.7% vs. 44.5%, both P < 0.001). On multivariable analyses, tumor numbers ≥5, total tumor diameter ≥8 cm and microvascular invasion were independent risk factors for decreased OS and RFS after resection of multinodular HCC in cirrhotic patients.ConclusionsLiver resection can be safely performed for multinodular HCC in the setting of cirrhosis with an overall 5-year survival of 34.6%. Tumor number ≥5, total tumor diameter ≥8 cm and microvascular invasion were independently associated with decreased OS and RFS after resection in cirrhotic patients with multinodular HCC.     

The Dynamics of Financial Toxicity in Multiple Myeloma

Introduction/BackgroundPeople with multiple myeloma are at risk for financial toxicity due to the high cost of treatment and prolonged treatment duration. However, little data exist regarding financial toxicity among people with myeloma.Patients and MethodsIn this study, a cohort of 135 patients were recruited from an ongoing observational trial to complete the Comprehensive Score for financial Toxicity (COST). Participants were sent follow-up surveys at 3, 6, and 12 months.ResultsThe median age was 68 years; the majority were non-Hispanic whites (88%), male (63%), held a college degree (61%), and had left the workforce (70%). The median time from myeloma diagnosis was 28 months. The median COST score was 27; 48% of participants had a score below 27 and considered to have financial toxicity. The only characteristic associated with financial toxicity was a college degree. After controlling for other covariates, those with a college education were 69% less likely to have financial toxicity. Of the 108 participants who completed a follow-up survey, 34% reported changes in their financial toxicity status at a subsequent time point. Transitioning from not having financial toxicity to having financial toxicity was more common than the reverse.ConclusionBecause financial toxicity is a dynamic process, which patients are experiencing it at any given time is difficult to predict. Focusing the research agenda on improved detection and intervention may be warranted.     

Surgery improves overall and cancer-specific survival of rare urinary cancers; population - based study

Numerous rare urinary tract (UT) cancers lack adequate understanding of survival and therapeutic options, and nearly all responses to systemic therapy are unsatisfactory, yet clinical research is scarce.MethodsBetween 2010 and 2015, a total of (14,622 patients) with uncommon UT cancer (62.5%) in the overall survival (OS) group and (37.5%) in the cancer specific survival (CSS)group were identified in the SEER database. multimodality therapeutic approach on OS and CSS were compared.ResultsIn uncommon UT malignancies, OS outperformed CSS in the locoregional stage (P < 0.05), but not in the distant stage (P = 0.34). Non-performed surgery had poor survival in both OS (HR 1.647; 95% CI (1.461–1.856)) and CSS (HR 1.573; 95% CI (1.399–1.769)) respectively (P < 0.05). There were no significant differences in survival in the CSS group between those who received or did not obtain chemotherapy.ConclusionsThe OS group survives substantially longer than the CSS group in the locoregional stage, but not at the distant stage. While both the OS and CSS groups of the locoregional stage were linked with improved survival after surgery, chemotherapy treatment decreased OS but not CSS in patients with uncommon urological cancers. There were no differences in radiation between the OS and CSS.     

Patterns of Utilization and Outcomes of Autologous Stem Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements

BackgroundPatients with Diffuse Large Bcell Lymphoma (DLBCL) with MYC and BCL2 and/or BCL6 gene rearrangements [double-hit lymphoma/triple-hit lymphoma (DHL/THL)] have poor prognosis in the relapsed/refractory setting.MethodsWe utilized a real-world deidentified database of DLBCL patients and report patterns of therapy utilization in relapsed/refractory DLBCL. We used log-rank test to compare real-world overall survival (rwOS) among DHL and non-DHL subgroups for CAR Tcell therapy or ASCT respectively, stratified for prior lines of therapy.ResultsOf all 7,877 patients with DLBCL, 367 patients had DHL while 6113 had non-DHL. Second line chemotherapy was administered to 147 DHL patients and 1517 non-DHL. 1393 were excluded, including 934 with unknown DHL/THL status. Approximately 47% received salvage intent chemotherapy in the DHL subgroup, of which 19% patients eventually received ASCT, while 34% received salvage intent chemotherapy in the non-DHL/THL group with 32% receiving ASCT. DHL/THL status negatively influenced median rwOS for patients who underwent ASCT in the second-line while it was associated with numerically inferior but without statistically significant rwOS among patients that underwent CAR Tcell therapy on multivariable analysis.ConclusionrwOS of relapsed DHL/THL is inferior to non-DHL/THL. Fewer patients with DHL/THL were able to proceed with ASCT after salvage chemotherapy compared to non-DHL/THL. ASCT as second-line therapy for relapsed DHL/THL had worse rwOS than for non-DHL/THL, consistent with the natural history of DHL/THL. This difference was not seen for CAR Tcell therapy, which combined with promising results from clinical trials, suggests a greater role for CAR T-cell therapy in relapsed/refractory DHL.     

Vinorelbine After Prior Treatment With Eribulin for Advanced Breast Cancer: A Single-Centre Experience Suggesting Cross-Resistance

IntroductionThe tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.Materials and MethodsA retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011. Patient demographics, histopathological features, treatment duration and responses were recorded. The primary endpoint was progression-free survival from date of first vinorelbine for each cohort. Secondary endpoints included radiological response rate, and overall survival (OS).ResultsThirty-five VAE and 103 VWE patients were identified, all female, 71.4% and 78.6% were ER positive/HER2 negative, 8.6% and 6.8% HER2 positive, and 20.0% and 14.6% triple negative for VAE and VWE cohorts, respectively. The median number of lines of chemotherapy lines prior to vinorelbine was 4 (range 2-6) and 2 (range 0-4), respectively. Fifteen VAE patients (42.9%) received ≥1 line of chemotherapy between eribulin and vinorelbine. VAE and WWE Patients received a median of 3 cycles of vinorelbine (range 1-9 and 1-12, respectively). The median progression-free survival for VAE patients was 2.1 months and 2.0 months for VWE patients. No VAE patients were progression-free at 24 weeks, compared to 15.5% of VWE patients. Median OS from commencing vinorelbine was 4.3 months for VAE and 6.4 months for VWE patients.ConclusionVinorelbine was of limited benefit after prior eribulin in our study, suggesting cross-resistance. Even without prior eribulin, only 15% of patients experienced clinical benefit from vinorelbine monotherapy.     

Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial

BackgroundHigh body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients.Patients and methodsPatients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses.ResultsOverall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m² was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS.ConclusionsIn our study, obesity with BMI > 30 kg/m² was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.     

Preoperative hiatal hernia in esophageal adenocarcinoma; does it have an impact on patient outcomes?

BackgroundThe impact of hiatal hernia (HH) on oncologic outcomes of patients with esophageal adenocarcinoma (AC) remains unclear. The aim of this study was to assess the effect of pre-existing HH (≥3 cm) on histologic response after neoadjuvant treatment (NAT), overall (OS) and disease-free survival (DFS).MethodsAll consecutive patients with oncological esophagectomy for AC from 2012 to 2018 in our center were eligible for assessment. Categorical variables were compared with the X² or Fisher's test, continuous ones with the Mann-Whitney-U test, and survival with the Kaplan-Meier and log-rank test.ResultsOverall, 101 patients were included; 33 (32.7%) had a pre-existing HH. There were no baseline differences between HH and non-HH patients. NAT was used in 81.8% HH and 80.9% non-HH patients (p = 0.910), most often chemoradiation (63.6% and 57.4% respectively, p = 0.423). Good response to NAT (TRG 1–2) was observed in 36.4% of HH versus 32.4% of non-HH patients (p = 0.297), whereas R0 resection was achieved in 90.9% versus 94.1% respectively (p = 0.551). Three-year OS was comparable for the two groups (52.4% in HH, 56.5% in non-HH patients, p = 0.765), as was 3-year DFS (32.7% for HH versus 45.6% for non-HH patients, p = 0.283).ConclusionHH ≥ 3 cm are common in patients with esophageal AC, concerning 32.7% of all patients in this series. However, its presence was neither associated with more advanced disease upon diagnosis, worse response to NAT, nor overall and disease-free survival. Therefore, such HH should not be considered as risk factor that negatively affects oncological outcome after multimodal treatment of esophageal AC.     

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis

PurposePortal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED).Patients and methodsFrom a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM).ResultsOf the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001).ConclusionHepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.     

Prognostic factors in patients with oligometastatic breast cancer – A systematic review

AimOligometastatic breast cancer (OMBC) is a disease-entity with potential for long-term remission in selected patients. Those with truly limited metastatic load (rather than occult widespread metastatic disease) may benefit from multimodality treatment including local ablative therapy of distant metastases. In this systematic review, we studied factors associated with long-term survival in patients with OMBC.MethodsEligible studies included patients with OMBC who received a combination of local and systemic therapy as multimodal approach and reported overall survival (OS) or progression-free survival (PFS), or both. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of each included study. Independent prognostic factors for OS and/or PFS are summarized.ResultsOf 1271 screened abstracts, 317 papers were full-text screened and twenty studies were included. Eleven of twenty studies were classified as acceptable quality. Definition of OMBC varied between studies and mostly incorporated the number and/or location of metastases. The 5-year OS ranged between 30 and 79% and 5-year PFS ranged between 25 and 57%. Twelve studies evaluated prognostic factors for OS and/or PFS in multivariable models. A solitary metastasis, >24 months interval between primary tumor and OMBC, no or limited involved axillary lymph nodes at primary diagnosis, and hormone-receptor positivity were associated with better outcome. HER2-positivity was associated with worse outcome, but only few patients received anti-HER2 therapy.ConclusionsOMBC patients with a solitary distant metastasis and >24 months disease-free interval have the best OS and may be optimal candidates to consider a multidisciplinary approach.     

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study

BackgroundTrifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.MethodsFrom October 2020 to February 2022, patients with metastatic colorectal cancer who failed from 2 or more lines of prior therapy and treated with TAS-102 monotherapy, in combination with bevacizumab or immune checkpoint inhibitors (ICIs) were analyzed. The evaluation indicators were progression free survival (PFS), objective response rate , disease control rate (DCR), overall survival (OS) and drug toxicities.ResultsA total of 70 patients were enrolled. The objective response rate and DCR were 1.4% and 68.6%. The median PFS and OS were 6.0 (95% CI: 4.1-7.9) and 10.0 (95% CI: 8.3-11.7) months. Compared with TAS-102 monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab obtained superior DCR (75.9% vs. 50% vs. 40%, P = .047), PFS (6.3m vs. 3.0 m vs. 3.0 m, P = .041) and OS (12.0 m vs. 6.5 m vs. 6.0m, P = .013). Patients without prior regorafenib or fruquintinib therapy obtained better median PFS (6.3 vs. 4.3 m, P = .031) and OS (NR vs. 9.0 m, P = .036). Other indicators, including age, tumor site, KRAS status and use of fluoropyrimidine as last regimen before TAS-102, did not affect the clinical efficacy of TAS-102. The most frequent adverse events were leukopenia, neutropenia, anemia, fatigue, nausea, and vomiting.ConclusionIn real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.     

Is bile leakage after hepatic resection associated with impaired long-term survival?

BackgroundBile leakage (BL) is a frequent and severe complication following liver surgery. The aim of this study was to evaluate risk factors for BL, related other complications and association with long-term survival.MethodsThis study included all patients undergoing hepatectomy in a single centre from 2005 to 2016. Perioperative risk factors related to BL were identified using univariable and multivariable analysis. Kaplan-Meier method was used for survival analysis.ResultsBL occurred in 48 of 458 patients (11%). BLs were more frequent in patients after major hepatectomy (p = 0.001). Portal vein embolization, bilioenteric-anastomosis, lymphadenectomy, vascular reconstruction and operative time were significant factors for developing BL. Comparing patients with or without BL, BL was more commonly associated with other postoperative complications (p = 0.001), especially acute kidney failure and surgical-site-infections. There was no difference in 90-day-mortality (p = 0.124). The median disease-free survival was comparable (17 vs. 15 months, p = 0.976), also no difference was observed when stratifying for different tumour entities. There was no difference in median overall survival (OS) among malignant disease (35 vs. 47 months, p = 0.200) and in 3-year OS (46% vs. 59%). Multivariate analysis confirmed that postoperative liver failure and major hepatectomy were risk factors for reduced OS (p = 0.010).ConclusionsMany concerns have been raised regarding tumour progression after major complications. In this study, we only found a relevant influence of BL on OS in pCC, whereas no association was seen in other cancer types, indicating that tumour progression might be triggered by BL in cancer types arising from the bile ducts itself.     

Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

IntroductionThis study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.Material and methodsFrom 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.ResultsThe 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3–16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001).ConclusionsNeoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.     

Transverse myocutaneous gracilis flap reconstruction is feasible after pelvic exenteration: 12-year surgical and oncological results

IntroductionPelvic exenteration (PE) is the only curative treatment for certain locally advanced intrapelvic malignancies. PE has high morbidity, and optimal reconstruction of the pelvic floor remains undetermined.Materials and methodsA retrospective chart review was performed at a tertiary university center to assess the surgical and oncological outcomes of 39 PE procedures over a 12-year period. The majority of patients (n = 25) underwent transverse musculocutaneous gracilis (TMG) flap reconstruction for pelvic floor reconstruction.ResultsThe 1- and 5-year overall survival (OS) was 72% (95%CI 58%–86%) and 48% (95%CI 31%–65%), respectively. In multivariate analysis, lymph node metastasis (HR 3.070, p = 0.024) and positive surgical margins (HR 3.928, p = 0.009) were risk factors for OS. In this population, 71.8% of the patients had at least one complication. The complication rate was 65.4% and 84.6% for patients with versus without flap reconstruction, respectively (p = 0.191). The length of stay was longer for patients with a major complication 16,0 ± 5,9 days vs. 29,4 ± 14,8 days, p = 0,001, but complications did not affect OS.ConclusionFor selected patients, PE is a curative option for locally advanced, residual, or recurrent intrapelvic tumors. Pelvic floor and vulvovaginal defects can reliably be reconstructed using TMG flaps. TMG flaps are favored in our institution over abdominal-based flaps because the donor site morbidity is reasonable and TMG does not interfere with enterostomy.