Validation and extension of the METSSS score in a metastatic cancer patient cohort after palliative radiotherapy within the last phase of life.

Introduction and background: Choosing the right treatment for the right patient in a setting of metastatic cancer disease remains a challenge. To facilitate clinical decision-making, predictive tools have been developed to personalize treatment. Here, we aim to assess the use of the recently proposed "METSSS score" as a prognostic tool for overall survival of cancer patients after palliative radiotherapy in the last phase of life. Methods: All patients treated with palliative radiotherapy at the end-of-life at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 were included in this study. Data on demographics, diagnosis, treatment and comorbidities was extracted from the treatment planning and the electronical medical records system. To statistically assess the validity of the "METSSS score", the mortality risk score was calculated, followed by stratification of all patients to prognostic risk groups. The prediction of the 1-year overall survival estimates was subsequently calculated. Results: Over the past decade, 274 patients have received palliative radiotherapy during the end-of-life period. One third of patients was female (34%, n = 93). The most frequent primary tumor was lung cancer (n = 121, 44%), and 55% of patients (n = 152) had no comorbidities according to the Charlson-Deyo comorbidity index. The most common radiotherapy site was the brain and eye region (42%, n = 115). The median actual overall survival of all patients was 40 days from the start of radiotherapy. The "METSSS score" survival model predicted that 269 patients (98.1%) belong into the high-risk, four patients (1.5%) into the medium-risk, and one patient (0.4%) into the low-risk group. The predicted median 1-year overall survival was 10%. Discussion: The METSSS score correctly predicted the survival of our end-of-life patient cohort by assigning them into the highest risk category, and it can therefore serve as a decision-making tool when assigning patient to symptomatic radiotherapy.

Pituitary adenoma in the elderly: surgical outcomes and treatment trends in the United States.

OBJECTIVE: Decision-making in how to manage pituitary adenomas (PAs) in the elderly (age ≥ 65 years) can be challenging given the benign nature of these tumors and concerns about surgical morbidity in these patients. In this study involving a large multicenter national registry, the authors examined treatment trends and surgical outcomes in elderly compared to nonelderly patients. METHODS: The National Cancer Data Base (NCDB) was queried for adults aged ≥ 18 years with PA diagnosed by MRI (in observed cases) or pathology (in surgical cases) from 2004 to 2016. Univariate and multivariate logistic regressions were used to evaluate the prognostic impact of age and other covariates on 30- and 90-day postsurgical mortality (30M/90M), prolonged (≥ 5 days) length of inpatient hospital stay (LOS), and extent of resection. RESULTS: A total of 96,399 cases met the study inclusion criteria, 27% of which were microadenomas and 73% of which were macroadenomas. Among these cases were 25,464 elderly patients with PA. Fifty-three percent of these elderly patients were treated with surgery, 1.9% underwent upfront radiotherapy, and 44.9% were observed without treatment. Factors associated with surgical treatment compared to observation included younger age, higher income, private insurance, higher Charlson-Deyo comorbidity (CD) score, larger tumor size, and receiving treatment at an academic hospital (each p ≤ 0.01). Elderly patients undergoing surgery had increased rates of 30M (1.4% vs 0.6%), 90M (2.8% vs 0.9%), prolonged LOS (26.1% vs 23.0%), and subtotal resection (27.2% vs 24.5%; each p ≤ 0.01) compared to those in nonelderly PA patients. On multivariate analysis, age, tumor size, and CD score were independently associated with worse postsurgical mortality. High-volume facilities (HVFs) had significantly better outcomes than low-volume facilities: 30M (0.9% vs 1.8%, p < 0.001), 90M (2.0% vs 3.5%, p < 0.001), and prolonged LOS (21.8% vs 30.3%, p < 0.001). A systematic literature review composed of 22 studies demonstrated an elderly PA patient mortality rate of 0.7%, which is dramatically lower than real-world NCDB outcomes and speaks to substantial selection bias in the previously published literature. CONCLUSIONS: The study findings confirm that elderly patients with PA are at higher risk for postoperative mortality than younger patients. Surgical risk in this age group may have been previously underreported in the literature. Resection at HVFs better reflects these historical rates, which has important implications in elderly patients for whom surgery is being considered.

Active Surveillance for Early Stage Lung Cancer.

OBJECTIVES: Data describing outcomes for patients with early stage lung cancer who undergo expectant management is lacking, despite evidence of a sub-population with indolent malignancies. We used the National Cancer Data Base (NCDB) to identify factors associated with active surveillance for early stage lung cancer. Additionally, we sought to describe outcomes of three different care plans: active surveillance, no treatment, and Stereotactic Body Radiation Therapy (SBRT). METHODS: Patients diagnosed in 2010 to 2017 with early stage lung cancer who underwent active surveillance, no treatment, and SBRT were retrospectively identified in the NCDB. Multinomial logistic regression was used to assess care plan selection. Kaplan Meier analysis was used to assess overall survival (OS). RESULTS: We identified 30,107 patients that met our inclusion criteria: 838 (3%) underwent active surveillance, 6388 patients (21%) received no treatment, and 22,881 (76%) underwent SBRT. Black race (relative risk ratio (RRR): 1.66) and older age (RRR: 1.02) were significant positive predictors of active surveillance selection. Conversely, higher tumor stage (RRR: 0.26) and squamous cell carcinoma (RRR: 0.35) were significant negative predictors of active surveillance selection. Kaplan Meier analysis revealed a longer median OS associated with active surveillance compared to no treatment at 49.3 months versus 26.5 months, respectively. SBRT OS was 43.1 months. CONCLUSIONS: We identified a population of lung cancer patients who underwent expectant management with favorable outcomes. Additionally, we identified factors associated with active surveillance selection. The selection of active surveillance over no treatment was associated with significantly longer OS.

Practical demonstration of time bias with administration of adjuvant therapy in lung cancer.

PURPOSE/BACKGROUND: Immortal time bias (ITB) can hinder appropriate interpretations of studies administering adjuvant therapies. Given the increase in National Cancer Data Base (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to practically demonstrate the effects of ITB by performing a series of simulated NCDB analyses. METHODS: A simulated NCDB analysis was performed to examine how the reported benefit of PORT in stage III non-small cell lung cancer (NSCLC) may change with adjustment for ITB utilizing sequential land mark analysis (SLMA) and time dependent Cox (TDC) modeling. RESULTS: On the simulation analysis of 6440 NSCLC patients, we found that the omission of PORT without ITB adjustment was associated with an increased risk of death (HR 1.17, p < 0.0001). After performing a sequential LMA, the detrmient of omitting PORT continued to decrease until it was no longer significant at 8 months, HR 1.05 (p = 0.09). With the TDC model, although still significant, the relative benefit of PORT decreased, to a HR of 1.07 (p = 0.02). CONCLUSIONS: Immortal time bias can alter the results of survival analyses if not carefully accounted for. Adjusting for this bias is essential for accurate data interpretation and to better quantify the impact and effect size of adjuvant therapies such as PORT.

Treatment Modalities and Survival Outcomes for Sinonasal Diffuse Large B-Cell Lymphoma.

OBJECTIVES/HYPOTHESIS: This study utilizes a large population national database to comprehensively analyze prognosticators and overall survival (OS) outcomes of varying treatment modalities in a large cohort of sinonasal diffuse large B-cell lymphoma (SN-DLBCL) patients. STUDY DESIGN: Retrospective database study. METHODS: The National Cancer Database was queried for all SN-DLBCL cases diagnosed from 2004 to 2015. Kaplan-Meier log-rank test determined differences in OS based on clinical covariates. Cox proportional-hazards analysis was used to determine clinical and sociodemographic covariates predictive of mortality. RESULTS: A total of 2,073 SN-DLBCL patients were included, consisting of 48% female with a mean age of 66.0 ± 16.2 years. Overall, 82% of patients were Caucasian, 74% had early-stage disease, and 49% had primary tumors in the paranasal sinuses. Early-stage patients were more likely to receive multi-agent chemoradiotherapy compared to multi-agent chemotherapy alone (P < .001). Multivariable Cox proportional-hazards analysis revealed chemoradiotherapy to confer significantly greater OS improvements than chemotherapy alone (hazard ratio [HR]: 0.61; P < .001). However, subset analysis of late-stage patients demonstrated no significant differences in OS between these treatment modalities (P = .245). On multivariable analysis of chemotherapy patients treated post-2012, immunotherapy (HR = 0.51; P = .024) demonstrated significant OS benefits. However, subset analysis showed no significant advantage in OS with administering immunotherapy for late-stage patients (P = .326). Lastly, for all patients treated post-2012, those receiving immunotherapy had significantly improved OS compared to those not receiving immunotherapy (P < .001). CONCLUSIONS: Treatment protocol selection differs between early- and late-stage SN-DLBCL patients. Early-stage patients receiving chemotherapy may benefit from immunotherapy as part of their treatment paradigm. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2727-E2735, 2021.

Racial disparities in palliative care utilization among metastatic gynecological cancer patients living at last follow-up: An analysis of the National Cancer Data Base.

The National Comprehensive Cancer Network recommends palliative care should be integrated in to cancer care starting from cancer diagnosis. However, traditionally palliative care is prioritized for cancer patients at the end-of-life. In our main article titled "Racial and Ethnic Disparities in Palliative Care Utilization Among Gynecological Cancer Patients" we present data describing racial/ethnic disparities among metastatic gynecological cancer patients who were deceased at last follow-up. Here, we expand our population to evaluate racial disparities in palliative care utilization among (1) all metastatic gynecologic cancer patients, regardless of vital status (alive or deceased) (n = 176,899) and (2) among only patients who were alive at last follow-up (n = 66,781). We used data from the 2016 National Cancer Database (NCDB) and included patients between ages 18-90 years with metastatic (stage III-IV) gynecologic cancers including, ovarian, cervical and uterine cancer. Palliative care was defined by NCDB as non-curative treatment, and could include surgery, radiation, chemotherapy, and pain management or any combination. We used multivariable logistic regression to evaluate racial disparities in palliative care use among our two populations of interest. Overall, the mean age of gynecologic cancer patients utilizing palliative care was 66 years. Five percent of all metastatic gynecologic oncology patients utilized palliative care overall; and by cancer site palliative care use was as follows: 4% among ovarian, 9% among cervical, and 11% among uterine cancer patients. Among patients who utilized palliative care, 62% utilized surgery, radiation or chemotherapy only and 12% utilized pain management as a form of palliative care. Among ovarian cancer patients, Hispanic ovarian cancer patients were less likely to utilize palliative care compared to their NH-White counterparts (aOR: 0.79, 95% CI: 0.68-0.91). Among cervical cancer patients, we observed that Hispanic (aOR: 0.65, 95% CI: 0.56-0.75) and Asian (aOR: 0.74, 95% CI: 0.59-0.93) were less likely to utilize palliative care than NH-White cervical cancer patients. We observed no racial disparities in palliative care utilization among uterine cancer patients. When we focused on patients who were alive at last follow-up we found that only 3% of patients utilized palliative care. We also conducted multivariable analyses of racial/ethnic disparities among ovarian and cervical cancer patients who were alive at last follow-up. We were unable to conduct multivariable analyses of uterine cancer patients who were alive at last follow-up due to limited sample size of those who utilized palliative care. We observed no racial/ethnic disparities among this patient population of metastatic gynecologic patients.

Perioperative Outcomes and 5-year Survival After Open versus Thoracoscopic Sleeve Resection for Lung Cancer.

The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent sleeve lobectomy for non-small-cell lung cancer (NSCLC). Outcomes of patients with cT1-T3, N0-N2, M0 NSCLC who underwent sleeve lobectomy in the National Cancer Data Base (NCDB) from 2010-2015 were assessed using Kaplan-Meier, propensity score-matching, and Cox proportional hazards analyses. An "intent-to-treat" analysis was performed. In the NCDB, 210 sleeve lobectomy patients met inclusion criteria (VATS 44 [21%], thoracotomy 166 [79%]). Nine (20%) of the VATS cases were converted to open. Compared to an open approach, VATS was associated with no significant differences in lymph nodes examined (median 9.5 vs 9.0; p = 0.72), length of stay (median 6 days vs 6 days; p = 0.36), 30-day mortality (4.5% vs 1.8%; p = 0.28), and 90-day mortality (6.8% vs 4.8%; p = 0.70). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [85%] vs open [79%]; log-rank p = 0.91) and in a propensity score-matched analysis of 86 patients (log-rank p = 0.75). Furthermore, a VATS approach was also not associated with worse survival in multivariable analysis (HR = 0.64; 95% CI [0.23-1.78]; p = 0.39). In this national analysis, a VATS approach for sleeve lobectomy for NSCLC was not associated with worse short-term or long-term outcomes when compared to an open approach.

Improved survival in women versus men with merkel cell carcinoma.

BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies. OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC). METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality. RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

A National Analysis of Minimally Invasive Vs Open Segmentectomy for Stage IA Non-Small-Cell Lung Cancer.

The objective of this study was to compare long-term outcomes of open vs minimally invasive (MIS) segmentectomy for early stage non-small-cell lung cancer (NSCLC), which has not been previouslyevaluated using national studies. Outcomes of open vs MIS segmentectomy for clinical T1, N0, M0 NSCLC in the National Cancer Data Base (2010-2015) were evaluated using propensity score matching. Of the 39,351 patients who underwent surgery for stage IA NSCLC from 2010 to 2015, 770 underwent segmentectomy by thoracotomy and 1056 by MIS approach (876 thoracoscopic [VATS], 180 robotic). The MIS to open conversion rate was 6.7% (n = 71). After propensity score matching, all baseline characteristics were well-balanced between the open (n = 683) and MIS (n = 683) groups. When compared to the open group, the MIS group had shorter median length of stay (4 vs 5 days, P< 0.001) and lower 30-day mortality (0.6% vs 1.9%, P = 0.037). There were no significant differences between MIS and open groups with regard to 30-day readmission (5.0% vs 3.7%, P = 0.43), or upstaging from cN0 to pN1/N2/N3 (3.1% vs 3.6%, P = 0.89). The MIS approach was associated with similar long-term overall survival as the open approach (5-year survival: 62.3% vs 63.5%, P = 0.89; multivariable-adjusted hazard ratio: 0.99, 95% Confidence Intervial (CI): 0.82-1.21, P = 0.96). In this national analysis of open vs MIS segmentectomy for clinical stage IA NSCLC, MIS was associated with shorter length of stay and lower perioperative mortality, and similar nodal upstaging and 5-year survival when compared to segmentectomy via thoracotomy. MIS segmentectomy does not appear to compromise oncologic outcomes for clinical stage IA NSCLC.

Racial and ethnic disparities in palliative care utilization among gynecological cancer patients.

BACKGROUND: Palliative care (PC) is recommended for gynecological cancer patients to improve survival and quality-of-life. Our objective was to evaluate racial/ethnic disparities in PC utilization among patients with metastatic gynecologic cancer. METHODS: We used data from the 2016 National Cancer Database (NCDB) and included patients between ages 18-90 years with metastatic (stage III-IV) gynecologic cancers including, ovarian, cervical and uterine cancer who were deceased at last contact or follow-up (n = 124,729). PC was defined by NCDB as non-curative treatment, and could include surgery, radiation, chemotherapy, and pain management or any combination. We used multivariable logistic regression to evaluate racial disparities in PC use. RESULTS: The study population was primarily NH-White (74%), ovarian cancer patients (74%), insured by Medicare (47%) or privately insured (36%), and had a Charlson-Deyo score of zero (77%). Over one-third of patients were treated at a comprehensive community cancer program. Overall, 7% of metastatic gynecologic deceased cancer patients based on last follow-up utilized palliative care: more specifically, 5% of ovarian, 11% of cervical, and 12% of uterine metastatic cancer patients. Palliative care utilization increased over time starting at 4% in 2004 to as high as 13% in 2015, although palliative care use decreased to 7% in 2016. Among metastatic ovarian cancer patients, NH-Black (aOR:0.87, 95% CI:0.78-0.97) and Hispanic patients (aOR:0.77, 95% CI:0.66-0.91) were less likely to utilize PC when compared to NH-White patients. Similarly, Hispanic cervical cancer patients were less likely (aOR:0.75, 95% CI:0.63-0.88) to utilize PC when compared to NH-White patients. CONCLUSIONS: PC is highly underutilized among metastatic gynecological cancer patients. Racial disparities exist in palliative care utilization among patients with metastatic gynecological cancer.

Factors associated with worse outcomes for colorectal neuroendocrine tumors in radical versus local resections.

BACKGROUND: Colorectal neuroendocrine tumors (NETs) are the most common NETs of the gastrointestinal tract. Due to the rarity, colorectal NETs are understudied and are not clearly understood. Our study sought to identify the factors associated with worse outcomes for colorectal NETs following resection. METHODS: We identified patients diagnosed with colorectal NETs [2004-2014] who underwent resection from the National Cancer Data Base. Non-NETs were excluded. Overall survival (OS) was evaluated using the Kaplan Meier method. Cox proportional hazards and logistic regression models were used to assess factors associated with radical versus local resection, OS and LOS. RESULTS: A total of 7,967 colon and 11,929 rectal NETs were analyzed. The majority of colon (93.4%) and rectal (89.1%) NETs underwent radical and local resection respectively. The 5-year OS was 69% and 92% for colon and rectal NETs respectively. Older age (OR 1.45, CI 1.37-1.53) and clinical stage 4 (OR 9.91, CI 4.56-21.52) were associated with higher odds for colonic radical resection. Lowest median income quartile (OR 1.41, CI 1.21-1.64) and African Americans (OR 1.26, CI 1.07-1.49) experienced higher mortality for colon and rectal NETs respectively. CONCLUSIONS: Racial minority and low-income patients experience worse outcomes for colorectal NETs following resection.

Adjuvant Chemotherapy and Tumor Sidedness in Stage II Colon Cancer: Analysis of the National Cancer Data Base.

Background: Current guidelines recommend discussion of adjuvant chemotherapy (AC) for stage II colon cancer (CC) with high-risk features despite lacking conclusive randomized trial data. We examined AC administration in this population and its effect on overall survival (OS) for available patient, tumor, and treatment characteristics Methods: Using National Cancer Data Base, a cohort of 42,971 stage II CC patients diagnosed from 2004 to 2009, who underwent surgery with curative intent, was identified. Chi-square test and multivariate logistic regression were used to analyze baseline characteristics and to calculate odds of chemotherapy administration, respectively. Survival analysis was conducted using Kaplan Meier survival analysis with log-rank test and Cox proportional hazards regression modeling. Results: AC was administered to 26% patients. The use decreased with advancing age and elderly patients received more single-agent than multi-agent chemotherapy (3 vs. 2.4%, p < 0.0001). Major predictors of AC use included pT4 status, evaluation of <12 lymph nodes, high grade tumors, positive resection margins, age <65 years, left sided tumors, and low comorbidity score. AC was associated with improved OS regardless of high-risk features (pT4, undifferentiated histology, <12 lymph node evaluation, or positive resection margins), tumor location, age, gender, comorbidity index, chemotherapy regimen or type of colectomy (adjusted HR: single-agent 0.55, multi-agent 0.6; p < 0.0001). In subgroup analysis, AC use compensated for the survival differences otherwise seen between left and right sided tumors in the non-chemotherapy population. Conclusion: AC in stage II CC was associated with improved OS regardless of age, chemotherapy type or high-risk features. It improved 5-years OS irrespective of tumor location and seemed to compensate for the survival difference seen between right and left sided tumors noted in the non-chemotherapy group.

Treatment Selection and Survival Outcomes in Locally Advanced Proximal Gastric Cancer: A National Cancer Data Base Analysis.

Background: We aimed to assess long-term survival between locally advanced proximal gastric cancer (LAPGC) patients who underwent proximal gastrectomy (PG) and those who underwent total gastrectomy (TG) to evaluate the optimal extent of resection and adjuvant therapy. Materials and Methods: Patients diagnosed with locally advanced proximal gastric adenocarcinoma were selected from the National Cancer Data Base (2004-2015) in America. Survival analysis was performed via Kaplan-Meier and Cox proportional hazards models. Results: A total of 4,381 eligible patients were identified, 1,243 underwent PG and 3,138 underwent TG. Patients in TG group had a poor prognosis (hazard ratio [HR] = 1.13, 95% confidence interval [CI]: 1.03-1.25) compared with those in PG group. Moreover, postoperative chemoradiation therapy was associated with improved overall survival compared to surgery alone (HR = 0.71, 95% CI: 0.53-0.97) in LAPGC patients who had PG, while preoperative chemotherapy (HR = 0.74, 95% CI: 0.59-0.92) was associated with improved survival among patients who had TG. Conclusions: Our study suggested that LAPGC patients underwent PG experienced better long-term outcomes than those underwent TG. It also suggested that multimodality treatment of LAPGC, including preoperative chemotherapy followed by TG or postoperative chemotherapy followed by PG, should be considered to achieve better long-term outcomes.

Liver-first approach to stage IV colon cancer with synchronous isolated liver metastases.

BACKGROUND: The only possibility for cure in patients with colon adenocarcinoma (CAC) with isolated liver metastases (ILM) is resection of both primary and metastatic tumors. Little is known about the implication of the sequence in which a colectomy and hepatectomy are performed on outcomes. This study analyzes whether resection sequence impacts clinical outcomes. METHODS: The National Cancer Database was queried for CAC cases with hepatic metastases from 2010-2015 with exclusion of extrahepatic metastases. We compared patients treated with a liver-first approach (LFA) to those treated with a colectomy-first or simultaneous approach using Kaplan Meier and multivariable Cox proportional hazards analysis. RESULTS: In 21,788 CAC patients identified, the LFA was uncommon (2%), but was associated with higher rates of completion resection of remaining tumor (41% vs. 22%, P<0.001). Patients selected for LFA were younger, less comorbid, and more commonly received upfront chemotherapy (P<0.05). The LFA was associated with increased median survival [34 months, 95% CI (30.5-39.6 months) vs. 24 months, 95% CI (23.7-24.6 months), logrank P<0.001] and decreased risk of death [HR 0.783; 95% CI (0.67-0.89), P=0.001]. CONCLUSIONS: The LFA to CAC with synchronous ILM is uncommon but is associated with greater likelihood of receiving chemotherapy prior to surgery and increased survival in selected candidates.

Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer-a distinct view on lymph node yield.

PURPOSE: While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined. METHODS: The National Cancer Data Base 2006-2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA-IIB). Patients were dichotomized into the following two groups, those with 1-14 resected lymph nodes and those with ≥ 15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival. RESULTS: A total of 21,912 patients were included; median age was 66 years (IQR 59-73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10-22), 10,163 (46.4%) had 1-14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88-0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57-0.62, p < 0.001; adjusted HR 0.86, CI 0.83-0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy. DISCUSSION: While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.

National treatment trends in human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV-negative OPC and can be successfully treated with surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB). METHODS: The NCDB was reviewed for primary HPV-mediated OPC in 2010-2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT). RESULTS: There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple-modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R2  = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R2  = 0.89). Hospitals in the top treatment volume quartile (quartile 1 [Q1]; n = 29) had a lower rate of positive margins (16.3%) than bottom-quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use. CONCLUSIONS: The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient-, geographic-, and hospital-specific factors. Lower hospital volume remains independently associated with increased triple-modality therapy after adjustments for positive margins, ENE, and pathologic staging.

National Practice Patterns and Overall Survival After Adjuvant Radiotherapy Following Radical Cystectomy for Urothelial Bladder Cancer in the USA, 2004-2013.

BACKGROUND: Adjuvant radiation therapy (ART) after radical cystectomy (RC) for urothelial bladder cancer (UBC) may play a role in the management of muscle-invasive BC, particularly in patients with locally advanced disease and adverse pathologic features (pT3/4 or positive surgical margins [PSMs]). Evidence regarding the effect of ART on overall survival (OS) is lacking. OBJECTIVE: To evaluate national practice patterns for the use of ART and assess its impact on OS for patients with adverse pathologic features (APF) after RC. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base, we analyzed all UBC cases with APF after RC from 2004 to 2013. Patients were divided into ART and no-ART groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with oncological outcomes were analyzed using multivariable Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: Use of ART decreased during the study period from 3.1% in 2004 to 1.7% in 2013 (p=0.03). ART was administered in 1.4%, 4.0% and 5.2% of patients with pT3 UBC, pT4 UBC, and PSMs (any pT stage), respectively. The rate of ART was significantly higher among younger ages, female sex, low-volume hospitals, nonacademic community care centers, higher stages, PSMs, perioperative chemotherapy, and lymph node-positive disease. Predictors of ART receipt were PSMs (odds ratio [OR] 3.4; p<0.0001), pT4 (OR 2.6; p=0.02), community based centers (OR 2.1; p<0.0001), and female sex (OR 1.8; p<0.0001). Risk factors for worse OS included age, higher tumor stage and comorbidities, PSMs, positive nodes, and suboptimal lymph node dissection (<10 nodes removed; all p<0.001). ART was not independently associated with better OS in the full cohort (p=0.54). However, subgroup analyses suggested an OS benefit for patients with PSMs (hazard ratio 0.73; p=0.047). Limitations include the retrospective design and limited details regarding cancer-specific survival. CONCLUSIONS: Use of ART for APF following RC is not common in the USA and the rate of ART has been decreasing over time. ART may have an OS benefit after RC for patients with PSMs. PATIENT SUMMARY: In this report we looked at the outcomes for patients with locally advanced bladder cancer receiving adjuvant radiation therapy following cystectomy in a large US population. We found that adding radiation therapy after removing the bladder cancer may have some survival benefits for patients with positive surgical margins.

Survival advantage of chemoradiotherapy in anaplastic thyroid carcinoma: Propensity score matched analysis with multiple subgroups.

BACKGROUND: We compared overall survival (OS) between radiation therapy (RT) and chemoradiotherapy (CRT) in patients with anaplastic thyroid carcinoma (ATC) using a large database. METHODS: The National Cancer Data Base was queried for ATC patients diagnosed between 2004 and 2013 who received RT or CRT. Groups were balanced by propensity score matching (PSM) on nine relevant variables. OS was also examined in five paired subgroups given known patient heterogeneity. RESULTS: Of 858 total patients, 575 received CRT and 283 received RT. CRT was associated with decreased risk of death (hazard ratio [HR] 0.66, P < .001), 1-year OS 25.5% vs 14.3%. A survival advantage to CRT was seen using PSM cohorts (HR 0.75, P = .006). Those receiving definitive surgery saw the greatest benefit to CRT over RT (HR 0.65, P = .009), 1-year OS 39.6% vs 20.4%. CONCLUSIONS: CRT is associated with decreased risk of death in ATC; the magnitude of CRT vs RT benefit varied by subgroup.

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.

Adjuvant radiotherapy and chemotherapy in early-stage diffuse large B cell lymphoma of head and neck with extranodal involvement.

Objectives: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma with a variety of presentations and treatment modalities. With the introduction of immunotherapy as an addition to chemotherapy (CT), there is ongoing debate about the role of radiotherapy (RT) in treatment and a need to clarify differences by specific anatomic locations.Methods: We identified a cohort of 1929 individuals with limited stage (stage I and II) head and neck DLBCL with extranodal involvement from the National Cancer Data Base. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity score-matched analysis.Results: Multi-agent CT plus RT was associated with longer OS (HR, 0.763; 95% CI, 0.614 to 0.948; p = 0.015) when compared with multi-agent CT alone on multivariate analysis. After propensity score matching to account for confounding variables, multi-agent CT plus RT was associated with longer OS than those who received multi-agent CT alone (HR = 0.769; 95% CI, 0.609-0.971; p = 0.027). The survival benefit persisted in patients over the age of 60 years and those who received RT within 180 days of CT. However, there was no significant difference in OS between the two groups in subgroup analysis of patients who received immunotherapy.Conclusion: The addition of RT to CT resulted in longer OS in patients with limited stage head and neck DLBCL with extranodal involvement.