Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas.

OBJECTIVES: The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC. RESULTS: Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively. CONCLUSION: The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.

Receipt of Guideline-Concordant Care Does Not Explain Breast Cancer Mortality Disparities by Race in Metropolitan Atlanta.

BACKGROUND: Racial disparities in breast cancer mortality in the United States are well documented. Non-Hispanic Black (NHB) women are more likely to die of their disease than their non-Hispanic White (NHW) counterparts. The disparity is most pronounced among women diagnosed with prognostically favorable tumors, which may result in part from variations in their receipt of guideline care. In this study, we sought to estimate the effect of guideline-concordant care (GCC) on prognosis, and to evaluate whether receipt of GCC modified racial disparities in breast cancer mortality. PATIENTS AND METHODS: Using the Georgia Cancer Registry, we identified 2,784 NHB and 4,262 NHW women diagnosed with a stage I-III first primary breast cancer in the metropolitan Atlanta area, Georgia, between 2010 and 2014. Women were included if they received surgery and information on their breast tumor characteristics was available; all others were excluded. Receipt of recommended therapies (chemotherapy, radiotherapy, endocrine therapy, and anti-HER2 therapy) as indicated was considered GCC. We used Cox proportional hazards models to estimate the impact of receiving GCC on breast cancer mortality overall and by race, with multivariable adjusted hazard ratios (HRs). RESULTS: We found that NHB and NHW women were almost equally likely to receive GCC (65% vs 63%, respectively). Failure to receive GCC was associated with an increase in the hazard of breast cancer mortality (HR, 1.74; 95% CI, 1.37-2.20). However, racial disparities in breast cancer mortality persisted despite whether GCC was received (HRGCC: 2.17 [95% CI, 1.61-2.92]; HRnon-GCC: 1.81 [95% CI, 1.28-2.91] ). CONCLUSIONS: Although receipt of GCC is important for breast cancer outcomes, racial disparities in breast cancer mortality did not diminish with receipt of GCC; differences in mortality between Black and White patients persisted across the strata of GCC.

Perioperative therapy in metastatic colorectal cancer: Pattern of use and survival outcomes.

BACKGROUND: Multimodality therapy of metastatic colorectal cancer (mCRC) is currently considered the standard of care. The aim of this study was to evaluate the impact of perioperative therapy on surgical resection in mCRC. METHODS: The National Cancer Database was analyzed for affected patients between 2004 and 2013. Univariate and multivariate analyses were done to identify factors associated with patient outcomes. Kaplan-Meier analysis and Cox proportional hazards models were used for the association between patient characteristics and survival. RESULTS: About 61,940 patients with mCRC were identified. Mean age = 63.4 years (SD ± 14). About 69% had a colon primary and 32% had only one metastatic site. Only 49% of those who underwent surgery for both primary and metastatic sites received postoperative chemotherapy (p < .001). Negative prognostic factors included no chemotherapy received (hazard ratio [HR], 2.32; 2.27-2.37; p < .001), more than three metastatic sites (HR, 2.28; 2.09-2.48; p < .001), year of diagnosis between 2004 and 2008 (HR, 1.71; 1.15-1.20; p < .001) and colon tumor location with right worse than left-sided (HR, 1.21; 1.19-1.24; p < .001). Five-year overall survival for resection of the primary and metastatic site (28.2%) was higher than for no surgical treatment (4.7%). CONCLUSION: Perioperative therapy was associated with improved survival, following resection of metastatic sites or primary tumor.

Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer.

BACKGROUND: The prognostic impact of DNA mismatch repair (MMR) status remains controversial in patients with stage III colon cancer who are treated with adjuvant chemotherapy (AC). The aim of this study was to evaluate the survival outcome of AC in deficient mismatch repair (dMMR)/microsatellite instable (MSI) stage III CC. METHODS: Patients with pathological stage III CC between 2010 and 2013 were identified from the National Cancer Database using International Classification of Diseases for Oncology (3rd Edition) morphology and topography codes 8140, 8480, and C18.0-18.8. Patients with pathologic stage T3N2, T4N1, or T4N were considered high risk; patients with stage T3N1 were considered low risk. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazards models were used to identify the association between AC and overall survival (OS). RESULTS: A total of 9226 patients with pathological stage III CC were identified, of which 2384 (25.8%) were MSI-high (MSI-H) and met the inclusion criteria of the final analysis. MSI-low (MSI-L) patients (n = 6842) were excluded. There was a preponderance of women (55.0% [n = 1311]), and 76.6% (n = 1825) of patients were non-Hispanic white. The median age was 65 years (range, 19-90 years). The primary sites were the cecum (29.7% [n = 707]), ascending colon (26.0% [n = 620]), sigmoid colon (17.2% [n = 410]), and transverse colon (10.8% [n = 257]). The most common tumor grade was moderately differentiated (n = 50.4% [1202]), followed by poorly differentiated (34.1% [n = 813]) and well differentiated (5.1% [n = 121]). High-risk pathologic stage III CC (T4N1, TxN2) constituted 51.0% (n = 1215) of the study population. High-risk stage III was associated with worse OS compared with low-risk stage III on univariate (P < .001) analysis and displayed a similar trend on multivariable analysis, without a statistically significant difference. Multiagent AC was associated with improved OS compared with no treatment on univariate (P < .001) and multivariable (P < .001) analysis. When stratified by risk status, multiagent AC was associated with improved OS compared with no treatment for high-risk (P < .001) and low-risk (P < .001) stage III disease. CONCLUSION: Adjuvant chemotherapy is associated with better OS in stage III dMMR/MSI-H CC. An enhanced benefit was shown for high-risk stage III disease.

Optimal timing of chemoradiotherapy after surgical resection of glioblastoma: Stratification by validated prognostic classification.

BACKGROUND: Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system. METHODS: Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed. RESULTS: In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P < .03). The detriment to early initiation was consistent across each RPA class subgroup. CONCLUSIONS: The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5 weeks did not negatively affect outcomes, whereas early initiation before 3 weeks may be detrimental.

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy.

BACKGROUND: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database. METHODS: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM). RESULTS: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups. CONCLUSIONS: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers.

Clinicopathological features and survival outcomes of rare histologic variants of gallbladder cancer.

BACKGROUND: Adenocarcinoma (AC) is the most common histological type in gallbladder carcinoma (GBC). Squamous cell carcinoma (SCC), adenosquamous carcinoma (ASC), and papillary carcinoma (PC) are rare histologic variants of GBC. METHODS: Patients with AC, SCC, ASC, and PC of the gallbladder between 2004 and 2013 were identified from the National Cancer Database. Univariate and multivariate analyses were performed, and Kaplan-Meier curves were used to compare overall survival (OS) based on histological subtype. RESULTS: A total of 5956 patients ≥18 years of age were included in the final analysis. Most patients (n = 5398; 90.6%) had AC compared with variant histologies. PC (n = 227; 3.8%) was the most common variant, followed by ASC (n = 216; 3.6%) and SCC (n = 115; 1.9%); 70.3% were female and 78.9% Caucasian. The median age was 70 (range, 25-90) years. Surgical resection was performed in 77.7% of AC, 53.0% of SCC, 88.9% of ASC, and 96.9% of PC (P < .001). Systemic therapy after surgery was administered in 25.1% of AC, 18.3% of SCC, 35.7% of ASC, and 19.4% of PC (P = .001). In multivariate analysis, multiagent chemotherapy was associated with improved OS in all histologies except for SCC and PC (p < .001), and adjuvant systemic therapy was associated with improved OS in ASC and AC (P < .001). CONCLUSION: Survival differs between the gallbladder variants. Except for SCC, GBC variants underwent surgical resection more often than AC. Adjuvant systemic therapy was associated with improved OS in ASC and AC.

High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study.

BACKGROUND: High-grade neuroendocrine carcinomas are rare in the gastrointestinal tract. However, treatment patterns and outcomes have not been well described. SUBJECTS, MATERIALS, AND METHODS: The National Cancer Database was analyzed. The primary objective was to describe the clinical outcomes and identify prognostic factors. Univariate and multivariate analyses were done to identify factors associated with patient outcome. RESULTS: A total of 1,861 patients were identified between 2004 and 2013. The mean age was 63 years (standard deviation ±13). The majority of the patients (78.1%) were non-Hispanic whites. The most common primary sites were pancreas (pancreatic neuroendocrine tumor [PNET] = 19.4%), large intestine (18.1%), esophagus (17.8%), and rectum (15.5%). Stage at presentation was I (6.6%), II (10.5%), III (18%) and IV (64.6%). Only 1.6% of the patients had brain metastases. Surgical resection was the primary therapy in 27.9%, and their median overall survival (OS) was 13.3 months. Patients treated with palliative chemotherapy had a median OS of 11.2 months, compared with 1.7 months for untreated patients. The median OS for high-grade PNET was 6 months, compared with 9.9 months for other high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC). On univariable analysis, age < 65 years (hazard ratio [HR] 0.72; 0.66-0.8; p < .001) and treatment at an academic center (HR 0.88; 0.79-0.99; p < .034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center. CONCLUSION: This is the largest series of HG GI NEC. Most patients present with metastatic disease, and overall survival remains poor. Treatment at an academic center, younger age, and use of chemotherapy were associated with improved survival. Multiagent chemotherapy was found to be associated with superior survival compared with single-agent chemotherapy, which was superior to no chemotherapy. Temporal sequences of chemotherapy, surgery, and radiation administration were not found to be associated with survival differences on multivariable analysis. IMPLICATIONS FOR PRACTICE: Management of patients with high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC) is based on experience with small-cell lung cancer. In this retrospective review, most patients had advanced disease and pancreatic primary had worse outcomes. Treatment at an academic center, younger age, and use of chemotherapy are associated with improved survival. Patients with early-stage disease treated with resection alone had inferior outcomes compared with patients who received neoadjuvant or adjuvant therapy, suggesting that micrometastases contribute to poor surgical outcomes. The relatively high proportion of positive surgical margin favors downstaging with neoadjuvant therapy to improve resection and lower the risk of systemic recurrence.

Racial Disparities, Outcomes, and Surgical Utilization among Hispanics with Esophageal Cancer: A Surveillance, Epidemiology, and End Results Program Database Analysis.

BACKGROUND: Hispanic patients with esophageal cancer (EC) have racially disparate survival outcomes compared with white patients. OBJECTIVES: We explored the impact on survival of racial differences in socioeconomic factors, tumor characteristics, and rates of surgical utilization in patients with EC. METHOD: Using the SEER (Surveillance, Epidemiology, and End Results) registry, we identified 22,531 cases of EC in Hispanic and white patients between the ages of 18 and 65 years in 2003-2014. Of these, 6,250 cases had locoregional EC. Patients were categorized according to age, gender, education, tumor grade, histology, primary tumor site, and surgical status. Postdiagnosis survival was examined over time and compared by race and stratified by surgical status. RESULTS: Compared with whites, Hispanics with EC had significantly higher unadjusted mortality (hazard ratio [HR] 1.11; 95% confidence interval [CI] 1.06-1.17; p < 0.001) as did Hispanics with locoregional EC (HR 1.15; 95% CI 1.03-1.29; p = 0.01). In the multivariate analysis, several socioeconomic and tumor factors were found to be independently associated with survival by race, including county of residence income and prevalence of smoking, tumor grade, stage, and primary site, and surgical utilization. After adjusting for demographic and tumor characteristics, surgical utilization in patients with locoregional EC had a significant interaction with race on overall mortality (p = 0.01). Hispanics with locoregional EC were significantly less likely to receive surgery than whites (46 vs. 60%; p < 0.001) and not receiving surgery was associated with a significantly lower overall survival (HR 2.84; 95% CI 2.65-3.04; p < 0.001). CONCLUSIONS: A lower rate of surgery among Hispanics with potentially resectable esophageal cancer was associated with a decreased survival rate when compared to whites, even when adjusting for relevant socioeconomic and tumor factors. These data support the need to better address patient barriers to surgical treatment and the systemic biases present in medical care.

Validation of the newly proposed American Joint Committee on Cancer (AJCC) breast cancer prognostic staging group and proposing a new staging system using the National Cancer Database.

BACKGROUND: The eighth edition of AJCC cancer staging manual incorporated biomarker status into the prognostic staging group (PSG). We used data from National Cancer Database (NCDB) to validate and improve the PSG. METHODS: All patients had surgery and at least some systemic treatment (endocrine therapy, chemotherapy or HER2 targeted therapy). Information from 420,520 patients was assessed for potential predictors of overall survival (OS), including age at diagnosis (age), tumor grade (G), hormonal receptor and HER2 status, and presence of lymph vascular invasion (LVI), stratified by stage or sub-stages. Based on the multivariate Cox analyses, we built different point systems to predict OS and evaluated the different point systems by Akaike's information criterion (AIC), Harrell's concordance index (C-index), and Uno's concordance index. RESULTS: Age, G, hormonal receptor and HER2 status, LVI and being TNBC were significantly associated with OS (all P < 0.0001). Three staging systems were correlated with OS: system 1 was the conventional anatomic TNM staging; system 2 included TNM, age, G, hormonal receptor, HER2, and LVI; system 3 included TNM, age, G, TNBC versus non-TNBC, and LVI. System 3 (C-index; 0.7316; AIC: 488138.91) achieved the best balance between predictive performance and goodness-of-fit to the NCDB data as compared to system 2 (C-index: 0.7325; AIC: 498087.73) and system 1 (C-index: 0.716; AIC: 688536.49). CONCLUSIONS: The new PSG is a better staging system than the conventional anatomic TNM system. Grouping breast cancer into TNBC versus non-TNBC may be simpler while retaining similar accuracy as using ER/PR/HER2 status to predict OS.

Downstream Breast Imaging Following Screening Mammography in Medicare Patients with Advanced Cancer: A Population-Based Study.

BACKGROUND: Screening tests are generally not recommended in patients with advanced cancer and limited life expectancy. Nonetheless, screening mammography still occurs and may lead to follow-up testing. OBJECTIVE: We assessed the frequency of downstream breast imaging following screening mammography in patients with advanced colorectal or lung cancer. DESIGN: Population-based study. PARTICIPANTS: The study included continuously enrolled female fee-for-service Medicare beneficiaries ≥65 years of age with advanced colorectal (stage IV) or lung (stage IIIB-IV) cancer reported to a Surveillance, Epidemiology, and End Results (SEER) registry between 2000 and 2011. MAIN MEASURES: We assessed the utilization of diagnostic mammography, breast ultrasound, and breast MRI following screening mammography. Logistic regression models were used to explore independent predictors of utilization of downstream tests while controlling for cancer type and patient sociodemographic and regional characteristics. KEY RESULTS: Among 34,127 women with advanced cancer (23% colorectal; 77% lung cancer; mean age at diagnosis 75 years), 9% (n = 3159) underwent a total of 5750 screening mammograms. Of these, 11% (n = 639) resulted in at least one subsequent diagnostic breast imaging examination within 9 months. Diagnostic mammography was most common (9%; n = 532), followed by ultrasound (6%; n = 334) and MRI (0.2%; n = 14). Diagnostic mammography rates were higher in whites than African Americans (OR, 1.6; p <0.05). Higher ultrasound utilization was associated with more favorable economic status (OR, 1.8; p <0.05). CONCLUSIONS: Among women with advanced colorectal and lung cancer, 9% continued screening mammography, and 11% of these screening studies led to at least one additional downstream test, resulting in costs with little likelihood of meaningful benefit.

Health care disparities among octogenarians and nonagenarians with stage II and III rectal cancer.

BACKGROUND: Octogenarians and nonagenarians with stage II/III rectal adenocarcinomas are underrepresented in the randomized trials that have established the standard-of-care therapy of preoperative chemoradiation followed by definitive resection (ie, chemoradiation and then surgery [CRT+S]). The purpose of this study was to evaluate the impact of therapies on overall survival (OS) for patients with stage II/III rectal cancers and determine predictors of therapy within the National Cancer Data Base (NCDB). METHODS: In the NCDB, patients who were 80 years old or older and had clinical stage II/III rectal adenocarcinoma from 2004 to 2013 were queried. Kaplan-Meier analysis, log-rank testing, logistic regression, Cox proportional hazards regression, interaction effect testing, and propensity score-matched analysis were conducted. RESULTS: The criteria were met by 2723 patients: 14.9% received no treatment, 29.7% had surgery alone, 5.0% underwent short-course radiation and then surgery (RT+S), 45.3% underwent CRT+S, and 5.1% underwent surgery and then chemoradiation (S+CRT). African American race and residence in a less educated county were associated with not receiving treatment. Male sex, older age, worsening comorbidities, and receiving no treatment or undergoing surgery alone were associated with worse OS. There was no statistical difference in OS between RT+S, S+CRT, and CRT+S. Interaction testing found that CRT+S improved OS independently of age, comorbidity status, sex, race, and tumor stage. In the propensity score-matched analysis, CRT+S was associated with improved OS in comparison with surgery alone. CONCLUSIONS: A significant portion of octogenarians and nonagenarians with stage II/III rectal adenocarcinomas do not receive treatment. African American race and living in a less educated community are associated with not receiving therapy. This series suggests that CRT+S is a reasonable strategy for elderly patients who can tolerate therapy. Cancer 2017;123:4325-36. © 2017 American Cancer Society.

Benefit of adjuvant radiotherapy after breast-conserving therapy among elderly women with T1-T2N0 estrogen receptor-negative breast cancer.

BACKGROUND: The purpose of the current study was to evaluate the impact of radiotherapy (RT) among women aged ≥ 70 years with T1-2N0 estrogen receptor (ER)-negative breast cancer using Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. METHODS: The study included 3432 women, 2850 of whom received and 582 of whom did not receive RT after breast-conserving surgery. Outcomes were estimated by the cumulative incidence method and compared with the Gray test. The Fine and Gray subdistribution hazard regression models were used to assess the impact of RT and other variables. RESULTS: Women who received RT were more commonly aged <75 years (42% vs 16%), had T1 tumors (78% vs 65%), ductal carcinoma histology (91% vs 88%), a Charlson-Deyo Comorbidity Index of 0 (41% vs 25%), and had received chemotherapy (29% vs 12%). The 5-year cumulative incidence of mastectomy and breast cancer-specific death for patients who received versus those did not receive adjuvant RT was 4.9% and 8.3% versus 10.8% and 24.1%, respectively (P<.001). On multivariable analysis, the omission of RT was found to be an independent predictor of an increased risk of mastectomy (hazard ratio, 2.33; 95% confidence interval, 1.56-3.49). Among women aged ≥ 80 years or with T1N0 tumors, the mastectomy incidence with or without receipt of RT was 3.4% vs. 6.9%, and 5.3% vs 7.7%, respectively. CONCLUSIONS: The use of adjuvant RT after breast-conserving surgery in older women with T1-2N0 estrogen receptor-negative breast cancer is associated with a reduced incidence of future mastectomy and breast cancer death. The magnitude of benefit may be small for women aged ≥80 years or those with T1 tumors. Cancer 2016;122:3059-3068. © 2016 American Cancer Society.

Transthoracic versus transhiatal resection for esophageal adenocarcinoma of the lower esophagus: A value-based comparison.

BACKGROUND AND OBJECTIVE: Our objective was to compare clinical outcomes, costs, and resource use based on operative approach, transthoracic (TT) or transhiatal (TH), for resection of esophageal cancer. METHODS: This cohort analysis utilized the Surveillance, Epidemiology, and End Results--Medicare linked data from 2002 to 2009. Only adenocarcinomas of the lower esophagus were examined to minimize confounding. Medicare data was used to determine episode of care costs and resource use. Propensity score matching was used to control for identified confounders. Kaplan-Meier method and Cox-proportional hazard modeling were used to compare long-term survival. RESULTS: 537 TT and 405 TH resections were identified. TT and TH esophagectomy had similar complication rates (46.7% vs. 50.8%), operative mortality (7.9% vs 7.1%), and 90 days readmission rates (30.5% vs. 32.5%). However, TH was associated with shorter length of stay (11.5 vs. 13.0 days, P = 0.006) and nearly $1,000 lower cost of initial hospitalization (P = 0.03). No difference in 5-year survival was identified (33.5% vs. 36%, P = 0.75). CONCLUSIONS: TH esophagectomy was associated with lower costs and shorter length of stay in an elderly Medicare population, with similar clinical outcomes to TT. The TH approach to esophagectomy for distal esophageal adenocarcinoma may, therefore, provide greater value (quality/cost).

The burden of overtreatment: comparison of toxicity between single and combined modality radiation therapy among low risk prostate cancer patients.

INTRODUCTION: To compare radiation related toxicities among men with low risk prostate cancer treated with single or multimodal radiation therapy. MATERIALS AND METHODS: The SEER-Medicare linked database was used to assess the relationship between treatment type and toxicity among men with low risk prostate cancer treated with brachytherapy (BT), external beam radiation therapy (EBRT), or combined therapy between 2004 and 2007. Inverse probability of treatment weighting was utilized to minimize selection bias and control for confounding. Multivariate logistic regression models were used to explore the relationship between treatment and outcomes. RESULTS: Overall 1915 (43.9%), 1893 (43.4%), and 555 (12.7%) patients were treated with EBRT, BT, and combined therapy, respectively. In univariate analyses, combined modality radiation was more toxic than BT alone for GU incontinence (56.76% versus 49.08%), GU obstruction (21.26% versus 19.70%), and erectile dysfunction (22.52% versus 22.24%) (p < 0.01, all comparisons). Compared to EBRT alone, combined modality radiation was more toxic for GI bleeding (7.21% versus 6.21%), GU incontinence (56.76% versus 29.24%), GU obstruction (21.26% versus 14.15%), and erectile dysfunction (22.52% versus 15.35%) (p < 0.01, all comparisons). Among the most frequent radiation toxicity events, the probability of treatment associated toxicity was highest for patients receiving combined modality treatment and lowest for the group treated with EBRT. After multivariate adjustment, EBRT alone demonstrated protective effects against GU obstruction (OR 0.56 [CI 0.50-0.63]), GI bleeding (OR 0.57 [CI 0.48-0.67]), GU incontinence (OR 0.39 [CI 0.36-0.43]), and erectile dysfunction (OR 0.68 [CI 0.61-0.76]) when compared to combined therapy. CONCLUSIONS: The use of combined modality radiation therapy in low risk prostate cancer patients is discordant with clinical guidelines and associated with a significantly increased burden of associated toxicity when compared to EBRT monotherapy. Prudent patient selection and judicious use of combined therapy among men with low risk prostate cancer represents a targetable area to reduce the burden of overtreatment.

Natural History and Real-World Treatment Outcomes for Patients With NSCLC Having EGFR Exon 20 Insertion Mutation: An International Association for the Study of Lung Cancer-American Society of Clinical Oncology CancerLinQ Study.

Introduction: EGFR exon 20 insertion (ex20ins) mutations account for approximately 10% of EGFR mutations in lung adenocarcinoma. Patients with ex20ins mutation do not respond to standard EGFR tyrosine kinase inhibitor therapy. In this work, we analyzed the characteristics, treatment patterns, and outcomes in this subgroup of patients with NSCLC. Methods: The American Society of Clinical Oncology CancerLinQ Discovery data set was queried to identify patients with initial diagnosis of NSCLC between the years 1995 and 2018 and with EGFR ex20ins mutations. Data were extracted on patient demographics, tumor characteristics, treatments, and outcomes, and compared using chi-square and analysis of variance. Kaplan-Meier curves were generated to compare overall survival with log-rank tests. All analyses were performed using Python 3.6 (Python Software Foundation). Results: A total of 357 patients were eligible. Patient characteristics include a median age of 68 years comprising female sex of 54%, White race of 63%, and Black race of 9%. Approximately 62% of total patients had stage 4 disease, and 30% of all patients had brain metastasis. There were 54% of patients who were treated with chemotherapy and 15% with immune checkpoint inhibitors (ICIs). In patients with brain metastasis, 16% were treated with ICI, 18% with targeted therapy, and 59% with chemotherapy. The median survival of the entire group was 23.8 months. Among patients with stage 4 disease (n = 222): 51% were women, 64% were white, 37% had brain metastasis, 18% were treated with ICI, 14% had targeted therapy, and 60% were treated with chemotherapy. Stage 4 patients treated with targeted therapy had better survival compared with those who did not receive targeted therapy (20.6 versus 16.1 mo, p = 0.02). Univariate and multivariate analyses suggested favorable outcomes for patients treated with immunotherapy. Conclusions: EGFR ex20ins mutation represents a unique subset of NSCLC; it is associated with a higher propensity for brain metastases and a relatively modest overall survival. Novel treatment approaches are urgently needed to improve patient outcomes.

Impact of concomitant fibrates on immunotherapy outcomes for advanced non-small cell lung cancer.

BACKGROUND: Peroxisome proliferator-activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T-lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI. METHODS: In this cohort study of Veterans with non-small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed. RESULTS: The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75-0.99) and in a matched subset (HR 0.75, 95%CI 0.63-0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79-1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75-1.39). CONCLUSIONS: Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis-generating observation supports a potential role for fibrates as an adjunct to immunotherapy.

The Association of Improved Overall Survival with NSAIDs in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications. PATIENTS AND METHODS: In this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI. RESULTS: We identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001). CONCLUSION: This study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated.