Chemotherapy Versus Supportive Care for Unresected Malignant Pleural Mesothelioma

BackgroundManagement options for unresected malignant pleural mesothelioma (MPM) are largely limited to palliative chemotherapy and best supportive care. This study sought to delineate subgroups most likely to benefit from chemotherapy.Patients and MethodsThe National Cancer Database was queried for newly-diagnosed unresected sarcomatoid, biphasic, and/or metastatic (M1) MPM. Statistics included Kaplan-Meier overall survival (OS) analysis with and without propensity matching, landmark Kaplan-Meier analysis to address immortal time bias, and multivariable Cox proportional hazards modeling in all patients as well as within histologic/M-classification-based subcohorts.ResultsOf 4655 patients (48% chemotherapy, 52% best supportive care), 15%, 27%, and 40% had epithelioid, biphasic, and sarcomatoid disease, respectively; 41% had M1 disease. The median OS in the chemotherapy and BSC cohorts was 10.4 versus 4.8 months (P < .001). OS differences persisted following landmark analysis (P = .038) and propensity matching (P < .001). Chemotherapy was associated with higher OS in M1 cases with unknown histology and M1 epithelioid patients (P < .001 for both). For non-epithelioid cases, chemotherapy was associated with higher OS for M0 (P < .001 for sarcomatoid and biphasic) but not M1 (P > .05 for both) disease.ConclusionsChemotherapy may benefit metastatic epithelioid and non-metastatic non-epithelioid MPM to a greater degree than metastatic non-epithelioid disease. Causation, however, is not implied, and careful patient selection in this population cannot be understated.     

Nomogram Predicting Overall Survival Benefit of Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

ObjectivesTo develop and validate a nomogram that predicts overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) vs. observation.Materials and MethodsAdults with biopsy-proven T1-T2N0 NCSLC treated with SABR (30-70 Gy in 1-10 fractions with biologically effective dose ≥100 Gy₁₀) or observation between 2004 and 2015 in the National Cancer Database (NCDB) were identified. Propensity score was used to match SABR and observation cohorts on prognostic demographic and clinicopathologic factors identified by logistic regression. Using backward selection, a multivariable Cox proportional hazard was identified predicting 2- and 5-year OS via a nomogram. Model prediction accuracy was assessed by time-dependent receiver operating characteristic (ROC) curves and integrated area under the ROC curve (AUC) analysis.ResultsA total of 22,073 adults met inclusion criteria and 4418 matched pairs (total n = 8836) were identified for nomogram development. The factors most strongly associated with improved OS on multivariable analysis included younger age (HR 0.82 by decade, P < .001), female sex (HR 0.81, P < .001), lower comorbidity index (HR 0.65 for 0 vs. ≥3, P < .001), smaller tumor size (HR 0.60 for ≤3 cm vs. 5.1-7 cm, P < .001), adenocarcinoma histology (P < .001), and receipt of SABR (P < .001). Interaction between SABR and histology was significantly associated with OS (P = .017). Relative to adenocarcinoma, patients with squamous cell carcinoma who were observed (HR 1.44, 95% CI 1.33-1.56) or treated with SABR (HR 1.24, 95% CI 1.14-1.35) had significantly worse OS. The nomogram demonstrated fair accuracy for predicting OS, with an integrated time-dependent AUC of 0.694 over the entire follow-up period.ConclusionThis nomogram estimates OS at 2 and 5 years based on whether medically inoperable early-stage NSCLC patients receive SABR or elect for observation. Incorporation of other variables not captured within the NCDB may improve the model accuracy.     

The Controlling Nutritional Status Score Is a Significant Independent Predictor of Poor Prognosis in Patients With Malignant Pleural Mesothelioma

IntroductionMalignant pleural mesothelioma (MPM) is a devastating neoplasm; however, some patients exhibit a good response to chemotherapy or multidisciplinary therapy, including surgery and chemotherapy. It is therefore important to discover the factors that can be used to select patients who will benefit from such treatment. Although the Controlling Nutritional Status (CONUT) score has been used to predict the prognosis in other types of malignancy, its utility in patients with MPM is unknown. The aim of this study was to clarify the clinical significance of the CONUT in patients with MPM.MethodsThe data of 83 patients, who were treated with surgery, chemotherapy, or multidisciplinary therapy, were analyzed in the present study. A cut-off CONUT score of 2 was used to classify all of the patients into low or high CONUT groups.ResultsFifty-two of the 83 patients were classified into the low CONUT group. A high CONUT score was significantly correlated with chemotherapy alone (P = .011). The high CONUT group had significantly poorer overall survival (OS) (P < .001) and disease- or progression-free survival (DFS/PFS) (P < .001). The clinical stage and the CONUT score were found to be independent predictive factors for the OS: clinical stage, I/II and III/IV; P = .001 and CONUT score, ≥ 3 and ≤ 2; P = .011, respectively. The clinical stage and the CONUT score were also independent predictive factors for DFS/PFS: clinical stage, I/II and III/IV; P = .006 and CONUT score, ≥ 3 and ≤ 2; P = .013, respectively.ConclusionsThe CONUT score was an independent predictor of a poor prognosis in the patients with MPM. This score provides useful information for selecting patients who will benefit from the treatment.     

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma

BackgroundThe optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC.Materials and MethodsThe NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as “early” RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as “late” RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS.ResultsA total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53).ConclusionThese data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC.     

Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival

Introduction

For the 3 histologic subtypes of malignant pleural mesothelioma (MPM)—epithelioid, sarcomatoid, and biphasic—the magnitude of benefit with surgical management remains underdefined.

A Reappraisal of the Comparative Effectiveness of Lumpectomy Versus Mastectomy on Breast Cancer Survival: A Propensity Score–Matched Update From the National Cancer Data Base (NCDB)

BackgroundRecent observational studies are concerning because they document rising mastectomy rates coinciding with more than a dozen reports that lumpectomy has better overall survival (OS) than mastectomy. Our aim was to determine if there were differences in OS of matched breast cancer patients undergoing lumpectomy versus mastectomy in the National Cancer Database (NCDB).Patients and MethodsA retrospective cohort of patients with stage I-III breast cancer in the NCDB (2004-2013) was identified. Propensity score matching (PSM), Kaplan-Meier, and multivariate Cox proportional hazards models were used to examine OS by type of surgery.ResultsOf 845,136 patients, 464,052 (54.9%) underwent lumpectomy and 381,084 (45.1%) underwent mastectomy. After PSM, the hazard ratio (HR) and confidence interval (CI) for OS in all patients comparing lumpectomy with mastectomy was 1.02 (CI, 1.00-1.04; P = .002). In patients with stage I, II, and III, they were HR 1.27 (CI, 1.23-1.36; P < .001), HR 0.98 (CI, 0.95-1.01; P = .21), and HR 0.83 (CI, 0.80-0.86; P < .001), respectively. In subgroup analyses of all patients by estrogen receptor (ER) status, they were HR 1.05 (CI, 1.03-1.07; P < .001) and HR 1.00 (CI, 0.96-1.03; P = .65) in ER+ and ER− patients.ConclusionIn our primary model of all stage I-III matched patients, using the most recent NCDB data and the largest observational sample size to date, the OS after mastectomy was not inferior to lumpectomy. This finding can be reassuring to patients and providers. In subgroup analyses, the association between type of surgery and OS differed by cancer stage and hormone receptor status.     

The Effects of Time to Treatment Initiation for Patients With Non–small-cell Lung Cancer in the United States

BackgroundThe purpose of this study was to determine the effects of time from diagnosis to treatment (TTI) on survival in patients with nonmetastatic non–small-cell lung cancer (NSCLC).Materials and MethodsThe National Cancer Database was queried for patients with stages 1 to 3 NSCLC between 2004 and 2013. Patients with missing survival status/time, unknown TTI, or receipt of palliative therapy were excluded. Multivariable Cox proportional hazards modeling, logistic regression, and recursive partitioning analysis were performed to determine associated variables and survival outcomes.ResultsAltogether, 1,393,232 patients met inclusion criteria. The median follow-up was 36 months. The median TTI increased between 2004 and 2013 from 35 to 39 days (P < .001). On multivariable Cox proportional hazards modeling, TTI groups 31 to 60 days, 61 to 90 days, and > 90 days were independently related to poorer overall survival (OS) compared with TTI 1 to 30 days (hazard ratio, 1.04, 1.10, and 1.14; 95% confidence interval [CI], 1.02-1.06, 1.07-1.12, and 1.11-1.17, respectively; P < .001 for all). Recursive partitioning analysis revealed that TTI of ≤ 45 days was the most optimal threshold for survival (P < .001); patients with TTI ≤ 45 days had a median OS of 70.2 months (95% CI, 69.3-71.1 months) versus 61.5 months (95% CI, 60.5-62.4) (P < .001). There were significant disparities by age, race, ethnicity, and income for delayed (> 45 days) TTI (P < .001 for all). Subgroup analysis revealed that stage 1 and 2 patients with TTI > 45 days had a higher risk of mortality compared with TTI ≤ 45 days (hazard ratio, 1.15 and 1.05; 95% CI, 1.12-1.17 and 1.01-1.09, respectively) (P < .001).ConclusionsIncreased TTI is independently associated with poorer survival in non-metastatic NSCLC. TTI ≤ 45 days is a clinically targetable time frame associated with improved outcomes and ought to be considered for patients with lung cancer undergoing definitive therapy.     

Incidence,Clinical Features,and Outcomes of Langerhans Cell Sarcoma in the United States

BackgroundLimited knowledge exists on the incidence, treatment patterns, and long-term outcomes of Langerhans cell sarcoma (LCS) in the United States.Patients and MethodsWe performed a retrospective study of LCS patients diagnosed between 2001 and 2014 using the Surveillance, Epidemiology, and End Results (SEER) and National Cancer Data Base (NCDB) databases. Incidence was calculated from SEER, and treatment patterns and outcomes were calculated from NCDB.ResultsA total of 25 and 52 cases of LCS were reported to SEER and NCDB, respectively. The overall incidence of the disease was 0.2 per 10,000,000 and did not differ by race (P = .56) or sex (P = .33). The median age at diagnosis was 62 (range, 19-90) years. Of the 52 patients from NCDB, 20 (39%) received chemotherapy as first-line therapy, 24 (46%) received surgery, and 15 (29%) received radiotherapy. The 1-year overall survival (OS) rate was 62%, and the median OS was 19 months. After censoring the patients with bone marrow and reticuloendothelial system involvement, no significant difference in OS was noted between the patients who were managed with or without surgery (P = .75). Postsurgical radiation or chemotherapy were not associated with improvement in median OS (P = .25). Patients who were managed with radiotherapy had a better OS compared to those who received no radiotherapy (P = .03).ConclusionThis dual-national registry study shows that LCS is extremely rare and has a poor prognosis. Radiotherapy may offer a survival advantage to patients with locoregional disease without bone marrow and reticuloendothelial system involvement.     

Three Decades of Malignant Pleural Mesothelioma: An Academic Center Experience

BackgroundMalignant pleural mesothelioma (MPM) remains a challenging disease to manage. In the past few decades, extrapleural pneumonectomy (EPP), pemetrexed-based chemotherapy, and indwelling pleural catheters were introduced to MPM care with variable levels of efficacy and evidence.Patients and MethodsThis was a retrospective review of patients diagnosed with MPM between January 1991 and March 2019. The primary outcome was overall survival (OS). Data were examined by decade to assess trends in MPM demographics, management, and OS. A subgroup analysis was then conducted to examine the impact of EPP, pemetrexed, and indwelling pleural catheters on OS.ResultsThe study included 337 patients; 309 patients had died at last follow-up (91.7%). Median age at diagnosis and the proportion of female patients increased from 65.8 years (interquartile range [IQR], 57.1-73.7) and 11.6% female from 1991 to 1999 to 75 years (IQR, 68.1-80.6) and 20.5% female from 2010 to 2019. Median OS was largely unchanged in the three study periods: 9.0 months (95% confidence interval [CI], 6.9-12.7) in the 1991-1999 cohort, 9.3 months (95% CI, 7.6-13.2) in the 2000-2009 cohort, and 10.1 months (95% CI, 7.9-13.6) in the 2010-2019 cohort. Controlling for a number of demographic and prognostic factors, EPP (hazard ratio [HR] = 0.50; 95% CI, 0.3-0.9; P = .02), pemetrexed-based chemotherapy (HR = 0.59; 95% CI, 0.40-0.87; P = .007), and indwelling pleural catheters (HR = 0.3; 95% CI, 0.13-0.71; P = .006) were each associated with improvements in OS.ConclusionDespite the small incremental improvements in survival shown by the three interventions we examined, prognosis remains guarded for MPM patients. Better modalities of management are needed.     

Phase I Trial of Cisplatin,Pemetrexed, and Imatinib Mesylate in Chemonaive Patients With Unresectable Malignant Pleural Mesothelioma

BackgroundWe conducted a phase I trial of cisplatin/pemetrexed/imatinib mesylate, an oral platelet-derived growth factor receptor (PDGFR) inhibitor, in chemonaive patients with malignant pleural mesothelioma (MPM).MethodsA standard 3 + 3 dose-escalating trial was used with the end points of maximum tolerated dose (MTD), response rate, survival, safety/toxicity, and tumor PDGFR levels.ResultsSeventeen patients with MPM were enrolled. The most common (any grade) side effects were nausea, fatigue, hypomagnesemia, and anemia. The MTD was established at dose level 3 (imatinib 600 mg) with a dose-limiting toxicity (DLT) of nausea and vomiting. The median progression-free survival (PFS) was 7.9 months and the median overall survival (OS) was 8.8 months. Patients with a sarcomatoid subtype had worse PFS (P = .01) and OS (P = .009), whereas they had a better Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 predicted for improved OS (P = .001) and PFS (P = .013). The 6 patients who completed all 6 treatment cycles had better OS (P = .006); the median PFS was 9.6 months and the OS was 22.4 months. In the translational studies, 14 patients had adequate tumor tissue that could be assessed for immunohistochemical (IHC) analysis and fluorescence in situ hybridization (FISH). Patients with higher than median p-PDGFRα IHC expression had a better OS (P = .013). When assessed as a continuous variable, higher p-PDGFRα in tumor cells correlated with an improved OS (P = .045). None of the other 4 IHC biomarkers were predictive or prognostic for survival. Twelve patients had successful PDGFRB FISH results, but none met the criteria of ≥ 4 copies of the PDGFRB gene; thus a correlation with clinical outcomes could not be done.ConclusionThe cisplatin/pemetrexed/imatinib mesylate combination had clinical benefit in some patients with MPM but was not well tolerated. Further investigation into alternative antiangiogenic agents, including PDGFRα inhibitors, is warranted.     

Preoperative Elevation of C-Reactive Protein Is a Predictor for Adverse Oncologic Survival Outcomes for Renal Cell Carcinoma: Analysis from the International Marker Consortium Renal Cancer (INMARC)

BackgroundWe sought to analyze the usefulness of pretreatment C-reactive protein (CRP) as a predictor of survival and oncological outcomes in patients with renal cell carcinoma (RCC).MethodsRetrospective international analysis of patients with RCC with pretreatment CRP values from 2006 to 2017. A CRP of more than >5 mg/L was deemed elevated. The cohort was subdivided into 2 groups for analysis (normal CRP ≤5 mg/L; elevated CRP >5). Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Kaplan–Meier analyses (KMA) and multivariable analyses (MVA) were used to delineate survival outcomes and their predictors.ResultsWe analyzed 2445 patients (1641 male/804 female; normal CRP 1056/elevated CRP 1389; mean follow-up 36 months). Patients with elevated CRP had a higher incidence of hypertension (P = .001), higher body mass index (P < .001), and larger tumor size (6.0 cm vs 3.9 cm; P < .001). MVA for RFS demonstrated elevated CRP (hazard ratio [HR], 1.85; P = .005), tumor size (HR, 1.1; P < .001), and high tumor grade (HR, 3.1; P < .001) to be independent risk factors. For normal vs elevated CRP, KMA for RFS of stages 1–4 RCC revealed a 5-year RFS of 93% vs 88% (P = .001), 95% vs 83% (P = .163), 84% vs 62% (P = .001), and 58% vs 60% (P = .513), respectively. KMA MA KMA for OS of stages 1–4 RCC revealed a 5-year OS of 98% vs 81% (P = .001), 94% vs 80% (P = .103), 94% vs 65% (P = .001), and 99% vs 38% (P < .001), respectively.ConclusionsPretreatment CRP was an independent predictor of RFS and OS in an international multicenter cohort of patients with RCC.     

Combination of Platelet-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio as a New Promising Prognostic Factor in Upper Tract Urothelial Carcinoma With Large Tumor Sizes > 3 cm

PurposeThe purpose of this study was to evaluate the prognostic values of pathological tumor size and preoperative blood-based inflammation biomarkers, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in upper tract urothelial carcinoma (UTUC).Materials and MethodsFrom 2007 to 2017, retrospective data of 449 patients with UTUC who underwent radical nephroureterectomy were assessed. Use of Kaplan-Meier and univariable/multivariable analyses evaluated the effect of preoperative blood-based inflammation biomarkers on overall (OS), cancer-specific (CSS), and progression-free survival (PFS) in pathological tumor sizes > and ≤3 cm.ResultsKaplan-Meier analyses showed that high-level NLR, PLR, or MLR had significantly shorter OS, CSS, and PFS for tumor sizes >3 cm (all P < .05), but not for ≤3 cm. For UTUCs with tumor sizes >3 cm, multivariable analyses showed simultaneously high-level PLR and MLR to be independent predicators of poor OS, CSS, and PFS (all P < .05). Moreover, receiver operating characteristic (ROC) analyses revealed that the predictive accuracy of the combination of PLR and MLR for OS, CSS, and PFS with the area under the ROC curve of 0.836, 0.871, and 0.806, respectively, in tumor sizes >3 cm (all P < .001).ConclusionsOur study demonstrated that a high-level PLR and MLR can serve as an independent predicator of worse outcomes in UTUCs with tumor sizes >3 cm. This combination can clinically help enhance the prognostic discrimination of UTUCs with tumor sizes >3 cm and further may guide physicians in selecting patients for postoperatively systemic chemotherapy.     

Overall Survival After Treatment of Localized Prostate Cancer With Proton Beam Therapy,External-Beam Photon Therapy,or Brachytherapy

BackgroundThere are few comparative outcomes data regarding the therapeutic delivery of proton beam therapy (PBT) versus the more widely used photon-based external-beam radiation (EBRT) and brachytherapy (BT). We evaluated the impact of PBT on overall survival (OS) compared to EBRT or BT on patients with localized prostate cancer.Patients and MethodsThe National Cancer Data Base (NCDB) was queried for 2004-2015. Men with clinical stage T1-3, N0, M0 prostate cancer treated with radiation, without surgery or chemotherapy, were included. OS, the primary clinical outcome, was fit by Cox proportional hazard model. Propensity score matching was implemented for covariate balance.ResultsThere were 276,880 eligible patients with a median follow-up of 80.9 months. A total of 4900 (1.8%) received PBT, while 158,111 (57.1%) received EBRT and 113,869 (41.1%) BT. Compared to EBRT and BT, PBT patients were younger and were less likely to be in the high-risk group. On multivariable analysis, compared to PBT, men had worse OS after EBRT (adjusted hazard ratio [HR] = 1.72; 95% confidence interval [CI], 1.51-1.96) or BT (adjusted HR = 1.38; 95% CI, 1.21-1.58). After propensity score matching, the OS benefit of PBT remained significant compared to EBRT (HR = 1.64; 95% CI, 1.32-2.04) but not BT (adjusted HR = 1.18; 95% CI, 0.93-1.48). The improvement in OS with PBT was most prominent in men ≤ 65 years old with low-risk disease compared to other subgroups (interaction P < .001).ConclusionIn this national data set, PBT was associated with a significant OS benefit compared to EBRT, and with outcomes similar to BT. These results remain to be validated by ongoing prospective trials.     

Response to chemotherapy is predictive in relation to longer overall survival in an individual patient combined-analysis with pleural mesothelioma

BackgroundThere is currently no early predictive marker of survival for patients receiving chemotherapy for malignant pleural mesothelioma (MPM). Tumour response may be predictive for overall survival (OS), though this has not been explored. We have thus undertaken a combined-analysis of OS, from a 42 day landmark, of 526 patients receiving systemic therapy for MPM. We also validate published progression-free survival rates (PFSRs) and a progression-free survival (PFS) prognostic-index model.MethodsAnalyses included nine MPM clinical trials incorporating six European Organisation for Research and Treatment of Cancer (EORTC) studies. Analysis of OS from landmark (from day 42 post-treatment) was considered regarding tumour response. PFSR analysis data included six non-EORTC MPM clinical trials. Prognostic index validation was performed on one non-EORTC data-set, with available survival data.ResultsMedian OS, from landmark, of patients with partial response (PR) was 12·8 months, stable disease (SD), 9·4 months and progressive disease (PD), 3·4 months. Both PR and SD were associated with longer OS from landmark compared with disease progression (both p < 0·0001). PFSRs for platinum-based combination therapies were consistent with published significant clinical activity ranges. Effective separation between PFS and OS curves provided a validation of the EORTC prognostic model, based on histology, stage and performance status.ConclusionResponse to chemotherapy is associated with significantly longer OS from landmark in patients with MPM.     

Pulmonary Carcinosarcoma: A Surveillance,Epidemiology, and End Results (SEER) Analysis

IntroductionPulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage.Patients and MethodsSEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods.ResultsA total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months).ConclusionTreatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.     

Small-Cell Carcinoma of the Prostate: Report of Outcomes of Localized Disease Using the National Cancer Database

BackgroundSmall-cell carcinoma of the prostate (SCCP) is a rare but aggressive prostate cancer histology. We studied the reported comparative outcomes of the efficacy of radiotherapy (RT) versus surgery for nonmetastatic SCCP.MethodsThe National Cancer Database (NCDB) was queried for nonmetastatic disease diagnosed from 2004 to 2015 as SCCP (defined as having a component of SCCP) receiving a single definitive local control modality (RT or surgery).ResultsA total of 243 patients were included (177 RT and 66 surgery). A total of 142 patients received chemotherapy (CHT). Mean age was 68 years. One hundred forty patients had adenocarcinoma concurrently with the SCCP while 103 patients had pure histology. For pure histology, multivariable analysis (MVA) showed nonacademic facility, stage 4 disease, and poorly differentiated grade were associated with worse survival. On MVA, receipt of CHT (hazard ratio [HR] = 0.84, P = .644) or receipt of androgen deprivation therapy (HR = 0.88, P = .715) did not affect overall survival. Receipt of RT was nonsignificant compared to surgery (HR = 0.75, P = .475). For mixed histology, MVA showed receipt of CHT and prostate-specific antigen > 20 ng/mL were associated with worse survival. Receipt of androgen deprivation therapy (HR = 1.35, P = .414) did not affect overall survival. Receipt of RT was also nonsignificant compared to surgery (HR = 1.42, P = .344).ConclusionRT and surgery for nonmetastatic SCCP yield comparable options as local therapies.     

Determinants of Survival in Advanced Non–Small-Cell Lung Cancer in the Era of Targeted Therapies

BackgroundMolecular profiling of non–small-cell lung cancer (NSCLC) samples has a profound impact on choice of therapy. However, it is less clear whether EGFR and KRAS mutations are prognostic outside of a trial-based treatment paradigm.MethodsWe performed a retrospective chart review of 513 patients with NSCLC undergoing EGFR and KRAS mutational analysis at the Hospital of the University of Pennsylvania between May 2008 and November 2011. Survival analysis was based on the 376 patients who received systemic treatment, and their survival was determined from the date of initiation of systemic therapy.ResultsThe median overall survival (OS) was 30.8 months (95% confidence interval [CI], 24.7-36.9). Neither EGFR mutational status (P = .09) nor KRAS mutational status (0.69) was associated with OS. Female sex (P < .001), never smoker status (P = .01), better performance status (PS) (P < .001), lower Charlson Comorbidity Index (P < .001), and lower age-weighted index (P < .001) were associated with prolonged survival. The presence of bone metastases (P = .001) and liver metastases (P = .004) was also associated with a shortened survival. In a multivariable regression that adjusted for stage, we demonstrated that male gender (P = .002), worse Eastern Cooperative Oncology Group PS (P = .01), metastases to bone (P = .03), and higher age-weighted comorbidity index (P = .001) were independent prognostic factors for shorter survival. EGFR mutation status was not prognostic (P = .85).ConclusionIn our series, EGFR and KRAS do not function as prognostic determinants for NSCLC.     

Association Between Perioperative Chemotherapy and Survival in Men Undergoing Radical Resection for Primary Urethral Urothelial Carcinoma: An Analysis of the National Cancer Database

IntroductionThe treatment landscape in invasive primary carcinoma of the urethra of urothelial histology closely aligns that of locally advanced urothelial carcinoma of the bladder. The survival benefit of perioperative chemotherapy for men undergoing radical surgery for primary urethral urothelial carcinoma (UUC) has not yet been well-elucidated.Patients and MethodsUsing the National Cancer Database (NCDB), we identified men diagnosed with non-metastatic invasive UUC (T2-4 N0-2 M0) from 2004 to 2016 treated with radical extirpative surgery. We compared OS between patients who had received peri-operative neoadjuvant (NAC) or adjuvant (AC) chemotherapy and those who had not using Kaplan-Meier curves and multivariable Cox proportional hazards regression model.ResultsA total of 191 patients met inclusion criteria. 113 patients (59.2%) did not receive chemotherapy, while 39 (20.4%) and 39 (20.4%) received NAC and AC, respectively. Median follow-up was 28.0 months. Upon multivariable analysis, receipt of NAC (HR 0.50, 95% CI 0.28-0.91, P = .02) decreased the risk of all-cause mortality, while receipt of AC (HR 0.76, 95% CI 0.41-1.41) was not significantly associated with an OS benefit, as compared to no chemotherapy.ConclusionOur study is the first to evaluate treatment specific outcomes in male patients with primary carcinoma of the urethra. We observed that neoadjuvant chemotherapy in men with UUC was associated with OS benefit. The utilization of NAC may improve survival, consistent with urothelial carcinoma of the bladder.     

Clinical Outcomes of Small Bowel Adenocarcinoma

BackgroundSmall bowel adenocarcinomas (SBAs) are rare tumors. Management of SBA is extrapolated from colorectal cancer treatments. Recent evidence suggests that the biology and molecular features of SBA differ from colorectal cancer. The aim of this study was to evaluate the management and outcome of SBA patients.Patients and MethodsThe National Cancer Data Base (NCDB) was queried for patients with SBA between 2004 and 2013 using ICD-O-3 histology code 8140/3 and topography codes C17.0, C17.1, C17.2, C17.8, and C17.9. Univariate and multivariate survival analyses were conducted to analyze the association between SBA location and overall survival (OS) stratified by stage. Treatment outcomes of surgery, radiation, and systemic therapy were compared.ResultsA total of 7954 SBA patients were identified; duodenum (D) 4607 (57.9%), jejunum (J) 1241 (15.6%), ileum (I) 857 (10.8%), and unspecified 1249 (15.7%). A total of 53.6% patients were male, and 76.6% white. Median age was 66 years. D mostly presented as stage IV disease (37.6%), J as stage II (34.5%) and IV disease (33.8%), and I as stage II (32.2%) and III (30.3%) disease (P < .001). Grade distribution was similar among D, J, and I; the majority were moderately differentiated (40.8%-55.0%), followed by poorly differentiated (30.9%-35.8%) and well differentiated (6.0%-12.4%) (P < .001). D underwent surgery (50.2%) less often than J (90.8%) and I (94.5%) (P < .001). Adjuvant radiation was provided in 8.5% of D, 2.6% of J, and 2.1% of I (P < .001). Adjuvant chemotherapy was provided in 21.9% of D, 50.2% of J, and 42.0% of I (P < .001). The rate of adjuvant chemotherapy was the highest in patients with stage III SBA, and was as follows: D (43.4%), J (65.4%), and I (63.6%) (P < .001). In univariate and multivariate analyses of all patients, adjuvant chemotherapy was associated with improved OS in stage II-III SBA patients. J had the best 5-year OS rate (42.0%; 95% confidence interval, 38.8-45.1, P < .001), and D had the worst (23.0%; 95% confidence interval, 21.6-24.2, P < .001). In multivariate analysis stratified by stage, chemotherapy was associated with improved OS in patients with stage II-IV SBA.ConclusionMost SBA patients present with stage IV disease. D underwent surgery less often than J and I. Stage II and III D received adjuvant chemotherapy less often compared to stage II and III J and I. Adjuvant chemotherapy was associated with improved OS in patients with stage II-III disease. J had the best 5-year OS rate, and D had the worst.