Worse Survival In Stage Research Articles

Missed Follow-up is associated with worse survival in stage I lung cancer: results from a large multi-site academic hospital system

The purpose of this study is to examine the effect of early incomplete follow-up on overall survival among stage I lung cancer patients. Patients with clinical stage I lung cancer at our institution between 2007 and 2016 were identified (N = 1111). Exclusions included < 18 years of age (N = 2), missing stage or demographics (N = 56), incomplete appointment data or had only one scheduled appointment (N = 351), or did not survive for at least 1 year after diagnosis (N = 120). Missed appointments were defined as unattended follow-up appointments within the first year of diagnosis without an attended appointment in the subsequent 60 days. The primary outcome was the hazard ratio (HR) for death associated per 10% increase in missed oncology follow-up appointments. Univariable and descriptive statistics were performed, and a multivariable landmark Cox regression model was created to examine the effect of missed oncology follow-up on survival. A total of 582 patients were analyzed with median follow-up of 3.2 years and median age of 69 years. On multivariable analysis controlling for age, sex, race, insurance status, and definitive treatment type the HR for death was 1.44 (95% CI 1.05–1.97) for every 10% increase in missed appointments. Incomplete oncologic follow-up may negatively impact overall survival among survivors of early-stage lung cancer.

Impact of tumor size on overall survival and cancer-specific survival of early-onset colon and rectal cancer: a retrospective cohort study

PurposeThis study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer.MethodsEarly-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan–Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer.ResultsSeventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan–Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm.ConclusionPatients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.

Defining Optimal Management of Non-metastatic Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is an aggressive, deadly malignancy. Resection remains the primary treatment; however, there is conflicting evidence regarding the optimal approach to and extent of surgery and the role of adjuvant therapy. We evaluated the impact of surgical technique and adjuvant therapies on survival in non-metastatic ACC. We performed a retrospective cohort study of subjects who underwent surgery for non-metastatic ACC between 2010 and 2019 utilizing the National Cancer Database. The primary outcome was overall survival. Cox proportional hazards models were developed to identify associations between clinical and treatment characteristics and survival. Overall, 1175 subjects were included. Their mean age was 54 ± 15years, and 62% of patients were female. 67% of procedures were performed via the open approach, 22% involved multi-organ resection, and 26% included lymphadenectomy. Median survival was 77.1months. Age (hazard ratio [HR] 1.019; p < 0.001), advanced stage (stage III HR 2.421; p < 0.001), laparoscopic approach (HR 1.329; p = 0.010), and positive margins (HR 1.587; p < 0.001) were negatively associated with survival, while extent of resection (HR 1.189; p = 0.140) and lymphadenectomy (HR 1.039; p = 0.759) had no association. Stratified by stage, laparoscopic resection was only associated with worse survival in stage III disease (HR 1.548; p = 0.007). Chemoradiation was only associated with improved survival in patients with positive resection margins (HR 0.475; p = 0.004). Tumor biology and surgical margins are the primary determinants of survival in non-metastatic ACC. Surgical extent and lymphadenectomy are not associated with overall survival. In advanced disease, the open approach is associated with improved survival.

Adjuvant chemotherapy is not associated with improved overall survival with stage I endometrioid ovarian cancer patients in a SEER cohort

The objectives of this study was to investigate the prognostic significance of adjuvant chemotherapy in early-stage endometrioid ovarian cancer (EnOC) patients, especially those with grade II stage IA and IB and grade I stage IC, that are not explicitly recommended in the current National Comprehensive Cancer Network (NCCN) guidelines. This was a retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database, comprising 875 cases diagnosed with stage I EnOC from 2010 to 2018, of whom 441 (50%) and 434 (50%) received and did not receive chemotherapy, respectively. The Kaplan-Meier method was used for survival analysis, and the Cox multivariate regression analysis was performed to identify independent prognostic factors. Stratified survival analysis for adjuvant chemotherapy based on the recommendations of the NCCN Guidelines in stage I EnOC patients with different substages and grades showed that in this cohort adjuvant chemotherapy did not improve the survival of any of the stage I stratified substages group (p = 0.076, HR: 0.600, 95% CI: 0.342–1.054). Age ≥60 (p = 0.000, HR: 3.609, 95% CI: 2.156–6.039) and elevated CA125 (p = 0.028, HR: 2.480, 95% CI: 1.103–5.577) were independent risk factors associated with worse survival in stage I EnOC patients. In conclusion, chemotherapy would be unnecessary for stage I EnOC patients to improve the overall survival no matter substage and grade in our cohort.

Smoking Behavior and Prognosis After Colorectal Cancer Diagnosis: A Pooled Analysis of 11 Studies.

BackgroundSmoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited.MethodsWe pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival.ResultsAmong 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5 years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no association was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse overall, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] =1.94, 95% confidence interval [CI] =1.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all survival outcomes were observed for former smokers who had quit for less than 10 years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10 years.ConclusionsThis large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival.

Mutational status of main driver genes influences the prognosis of stage I-III lung adenocarcinoma patients underwent radical surgery.

BackgroundThe therapeutic strategies and prognosis of local advanced and metastatic lung cancer have been extensively investigated. However, the prognosis of early-stage lung cancer patients undergoing radical surgery has not been fully studied due to the difficulties in follow-up and assessment.MethodsWe recruited 447 stage I–III lung adenocarcinoma (LUAD) patients who underwent radical surgery and investigated the influence of main driver gene mutations and clinicopathological factors on patient overall survival (OS). Cancer tissue samples were collected retrospectively and mutational status and tumor mutational burden (TMB) were determined by whole-exome sequencing (WES).ResultsDistinct stage-dependent mutational frequency was revealed in main driver genes including EGFR, TP53, KRAS, STK11, ATM and NF1. Patients with TP53 mutations exhibited a trend of better survival than those with wild type TP53 (P=0.066), and STK11 mutations exhibited worse survival in stage III patients (P=0.031). EGFR mutations eliminated the across-stage difference in survival, which was still present in other wild type and mutant driver genes. Furthermore, patients with wild type TP53 appeared to have significantly worse survival than patients with other wild type driver genes in stage I (P<0.001). TMB cannot stratify the survival of LUAD patients in stage I–III. Age, gender, smoking status, smoking years, prior cancer history and cancer location had no stratification effect on patient survival, while T grading (P<0.001) and N grading (P<0.001) had significant stratification on survival.ConclusionsTP53, EGFR and STK11 mutational status influenced the prognosis of stage I–III LUAD. T and N grading also stratified the patient survival. T grading was an independent risk factor.

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn\u2019s disease-associated small bowel carcinoma

Most Crohn’s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.

Five Decades of Enucleations for Uveal Melanoma in One Center: More Tumors with High Risk Factors, No Improvement in Survival over Time

Background: In order to improve medical care for uveal melanoma (UM) patients, we need to monitor disease and survival to guide our research efforts. We analyzed the data of UM patients who underwent an enucleation at the Leiden University Medical Center over the last five decades and investigated trends in patient and tumor characteristics and survival. Methods: Data were collected from charts and pathology reports from all patients who underwent an enucleation for UM between 1973 and 2019 (n = 1,212), of which 1,066 were primary enucleations; data were analyzed according to five time periods: 1973–1979 (n = 209), 1980–1989 (n = 148), 1990–1999 (n = 174), 2000–2009 (n = 280), and 2010–2019 (n = 401). Results: Over time, mean patient age at the time of enucleation for UM increased from 54.9 to 64.7 years (p < 0.001), more tumors showed histopathological involvement of the ciliary body (p < 0.001), and were classified in a high TNM/AJCC class (p < 0.001). Overall, the 5- and 10-year UM-related survival rates were 0.68 and 0.59, respectively. Over time, survival showed no change in patients with tumors in AJCC stages I or III, with recently a slightly worse survival in stage II UM (p = 0.02). Conclusion: Between 1973 and 2019, we found similar rates of UM-related survival following enucleation, although we noticed a strong increase in more unfavorable patient and tumor characteristics over time, such as an older age and larger tumor size. The lack of improvement indicates that more research should take place to develop adjuvant treatments to prevent metastases and efficient treatments once metastases develop.

High cytoplasmic YAP1 expression predicts a poor prognosis in patients with colorectal cancer.

PurposeYes associated protein 1 (YAP1), which is a standout amongst the most essential effectors of the Hippo pathway, assumes a vital part in a few kinds of cancer. However, whether YAP1 is an oncogene in CRC (colorectal cancer) remains controversial, and the association between the subcellular localization of YAP1 and clinical implications in CRC remains unknown.Patients and methodsIn this study, we investigated the subcellular localization of YAP1 in CRC cells by immunohistochemistry and then associate these findings with clinical information in a large CRC cohort with 919 CRC patients.ResultsThe results show that CRC tissues has a significant higher expression of cytoplasmic YAP1 compared to adjacent normal tissues (all P < 0.001). Cytoplasmic YAP1 expression was significantly associated with the number of lymph nodes removed and differentiation grade (all P < 0.001). Furthermore, after correcting confounding variables, for example, TNM stage and differentiation grade, the multivariate Cox analysis confirmed cytoplasmic YAP1-high subgroup had a significant shorter DFS (HR = 3.255; 95% CI [2.290–4.627]; P < 0.001) and DSS (HR = 4.049; 95% CI [2.400–6.830]; P < 0.001) than cytoplasmic YAP1-low subgroup. High cytoplasmic YAP1 expression is associated with a worse survival in stage III CRC patients who received chemotherapy.ConclusionCytoplasmic YAP1 could be could be utilized as a prognosis factor in CRC patients, and may be an indicator of whether certain patients population could benefit from postoperative chemotherapy.

The implications of missed or misinterpreted cases of pancreatic ductal adenocarcinoma on imaging: a multi-centered population-based study.

To assess the proportion of missed/misinterpreted imaging examinations of pancreatic ductal adenocarcinoma (PDAC), and their association with the diagnostic interval and survival. Two hundred fifty-seven patients (mean age, 71.8years) diagnosed with PDAC in 2014-2015 were identified from the Nova Scotia Cancer Registry. Demographics, stage, tumor location, and dates of initial presentation, diagnosis, and, if applicable, surgery and death were recorded. US, CT, and MRI examinations during the diagnostic interval were independently graded by two radiologists using the RADPEER system; discordance was resolved in consensus. Mean diagnostic interval and survival were compared amongst RADPEER groups (one-way ANOVA). Kaplan-Meier analysis was performed for age (< 65, 65-79, ≥ 80), sex, tumor location (proximal/distal), stage (I-IV), surgery (yes/no), chemotherapy (yes/no), and RADPEER score (1-3). Association between these covariates and survival was assessed (multivariate Cox proportion hazards model). RADPEER 1-3 scores were assigned to 191, 27, and 39 patients, respectively. Mean diagnostic intervals were 53, 86, and 192days, respectively (p = 0.018). There were only 3/257 (1.2%) survivors. Mean survival was not different between groups (p = 0.43). Kaplan-Meier analysis showed worse survival in RADPEER 1-2 (p = 0.007), older age (p < 0.001), distal PDAC (p = 0.016), stage (p < 0.0001), and no surgery (p < 0.001); survival was not different with sex (p = 0.083). Cox analysis showed better survival in RADPEER 3 (p = 0.005), women (p = 0.002), surgical patients (p < 0.001), and chemotherapy (p < 0.001), and worse survival in stage IV (p = 0.006). Imaging-related delays occurred in one-fourth of patients and were associated with longer diagnostic intervals but not worse survival, potentially due to overall poor survival in the cohort. • One-fourth of patients (66/257, 25.7%) with pancreatic ductal adenocarcinoma (PDAC) underwent imaging examinations that demonstrated manifestations of the disease, but findings were either missed or misinterpreted; RADPEER 2 and 3 scores were assigned to 10.5% and 15.2% of patients, respectively. • Patients with imaging examinations assigned RADPEER 3 scores were associated with significantly longer diagnostic intervals (192 ± 323days) than RADPEER 1 (53 ± 86days) and RADPEER 2 (86 ± 120days) (p < 0.001). • Imaging-related diagnostic delays were not associated with worse survival; however, this may have been confounded by the overall poor survival in our cohort (only 3/257 (1.2%) survivors).

Non–small cell lung cancer in never- and ever-smokers: Is it the same disease?

ObjectivesTo investigate differences in presentation, pathology, and outcomes after resection of non–small cell lung cancer (NSCLC) in never-smokers versus ever-smokers. MethodsFrom January 2006 to July 2016, 172 never-smokers and 1376 ever-smokers with NSCLC underwent pulmonary resection. The 2 cohorts were matched on patient characteristics, histopathological cancer cell type, and pathological stage group using a weighted balancing score, and overall survival and cancer recurrence were compared by pathological stage. Random forests for survival was used to identify granular cancer characteristics with different survival and cancer recurrence importance between groups. ResultsIn never-smokers, the prevalence of NSCLC was more frequent in women than in men (63% [n = 109] vs 45% [n = 63]). Compared with ever-smokers, never-smokers had less upper-lobe disease (53% [n = 91] vs 62% [n = 855]) and more adenocarcinoma (88% [n = 151] vs 62% [n = 845]). Postoperative complications were similar. Never-smokers had a lower prevalence of non–lung cancer deaths than ever-smokers (13% vs 23% at 5 years; P = .006). Among matched pairs, never-smokers had better overall survival at 5 years in pathological stage I (96% vs 78%), but worse survival in stage II (54% vs 78%). Tumor size, N category, and histopathological cell type were more important drivers of mortality and cancer recurrence in never-smokers than in ever-smokers. ConclusionsNSCLC in never-smokers affects women more than men and presents with different anatomic and histopathological distributions. Matched never-smokers have better or equivalent outcomes than ever-smokers in pathological stage I cancer, but are less likely to survive and to be cured of cancer as tumor burden increases. These findings suggest that there might be unique tumor or host behaviors differentially impacting survival of never- and ever-smoking patients with NSCLC.

Does race impact survival for patients with anal squamous cell carcinoma?

Racial disparities are known to impact cancer outcomes. The aim of this study was to assess current racial disparities in outcomes of anal squamous cell carcinoma (SCC). The National Cancer Database was used to identify patients with anal SCC. The primary outcome was 5-year overall survival. There were 32 255 (88.1%) White patients and 4342 (11.9%) Black patients identified with anal SCC. Compared to White patients, Black patients were more likely to be younger, have lower median income, and be insured with Medicaid (all P < .001). The 5-year overall survival of Black and White patients for stage I disease was 71.2% and 80.6% (P < .001), for stage II disease, was 64.6% and 69.3% (P = .001), for stage III disease was 50.9% and 58.1% (P < .001), and for stage IV disease was 22.1% and 21.9% (P = .20). In a cox regression analysis, Black race was associated with significantly worse survival in stage I (HR: 1.37, 95% CI: 1.07-1.76, P = .01), stage II (HR: 1.30, 95% CI: 1.14-1.48, P < .001), and stage III disease (HR: 1.31, 95% CI: 1.16-1.47, P < .001) but not for stage IV disease (HR: 1.09, 95% CI: 0.89-1.35, P = .41). Black race is correlated with worse survival in patients diagnosed with anal SCC. This disparity in survival is likely multifactorial and requires further study.

Impact of time to treatment initiation (TTI) on survival of patients with newly diagnosed non-small cell lung cancer (NSCLC).

9058 Background: Lung Cancer is the leading cause of cancer related deaths in the USA. NSCLC comprises about 85% of lung cancer cases. Although timeliness of care in patients with NSCLC is considered an important aspect of quality care, there are conflicting data about its impact on clinical outcomes. The primary objective of this study is to determine if there is an association between TTI and survival in patients with NSCLC. Methods: In this retrospective study, we reviewed data from our multi-site Mayo Clinic Cancer Center registry and identified patients with newly diagnosed NSCLC from 2000 to 2016. TTI was calculated from time of diagnosis to time of first treatment (surgery, radiation therapy or systemic therapy). Analyses were performed by SAS software 9.4. Log-Rank test was used to compare survival. Cox regression multivariate model was used to evaluate the prognostic value of variables to survival. Results: 10010 patients (53% males and 47%) were reviewed. Median age at diagnosis was 70. Median TTI was 12 days for stage I, and 20 days for stage II, III and IV. We compared outcomes of patients with TTI &gt; 20 days to TTI ≤20 days. Outcomes were stratified based on age, gender, grade, and stage. Median Overall Survival (OS) was significantly better for patients with TTI ≤20 days compared to TTI &gt; 20 days (39.1 vs 28.6 months P-value &lt; 0.0001). Further stratification, based on stage, showed significantly better OS for stage I and II patients with TTI ≤20 days compared to TTI &gt; 20 days (103.4 vs. 63.9 months P-value &lt; 0.0001 and 72.3 vs. 46.8 months P-value 0.0014 respectively). OS for stage III patients with TTI ≤20 days was not significantly different from patients with TTI &gt; 20 days (30.6 vs. 28.5 months P-value 0.118). Interestingly, stage IV patients had worse OS if TTI ≤20 days compared to TTI &gt; 20 days (8.3 vs. 12.8 months P-value &lt; 0.0001). Conclusions: Our study showed an association between TTI and survival of patients with NSCLC. Shorter TTI was associated with better survival in stage I and II patients and worse survival in stage IV patients. Our study further highlights the controversy surrounding the topic of impact of timeliness of care on survival in patients with cancer, specifically NSCLC across different stages.

Sparing Cardiac Substructures With Optimized Volumetric Modulated Arc Therapy and Intensity Modulated Proton Therapy in Thoracic Radiation for Locally Advanced Non-small Cell Lung Cancer

PurposeIncreasing radiation dose to the heart is associated with worse survival in stage III non-small cell lung cancer. We sought to evaluate the ability of optimized volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) to spare cardiac substructures. We also wanted to determine how a cardiac optimization treatment planning algorithm influences dose distribution to other thoracic organs at risk (OARs). Methods and MaterialsCardiac substructures were retrospectively contoured for all patients with stage III non-small cell lung cancer who were treated at our institution with VMAT to 60 Gy in 2-Gy fractions. The structures included valves, atrioventricular node, coronary arteries, chambers, and great vessels. New cardiac-optimized VMAT plans were created to spare these structures while preserving planning target volume coverage and maintaining standard dose constraints to OARs. Dosimetry variables for the new cardiac-optimized VMAT plans were compared via paired t test with the original VMAT plans. IMPT plans were also created, and the cardiac-optimized VMAT plans were then similarly compared with the IMPT plans. ResultsTwenty-six patients who were treated from July 2013 to September 2017 were included. Compared with the original VMAT plans, statistically significant improvements were demonstrated for all cardiac structures for the new cardiac-optimized VMAT plans while maintaining or improving appropriate lung, esophagus, and spinal cord constraints and planning target volume coverage goals. Compared with cardiac-optimized VMAT, IMPT demonstrated additional statistically significant improvements for some cardiac dosimetry metrics while maintaining or improving other thoracic OAR constraints. ConclusionsVMAT is now widely available, and high-quality VMAT plans that incorporate cardiac substructures into the optimization process can provide overall improvements in dose to OARs and, in particular, substantial sparing of critical cardiac structures. IMPT provides some incremental dosimetric improvements beyond cardiac-optimized VMAT, the clinical significance of which remains uncertain.

The Impact of Muscle and Adipose Tissue on Long-term Survival in Patients With Stage I to III Colorectal Cancer.

Computed tomography-derived body composition parameters are emerging prognostic factors in colorectal cancer. This study aimed to determine the roles of sarcopenia, myosteatosis, and obesity as independent and overlapping parameters in stage I to III colorectal cancer. This is a retrospective cohort study from a prospectively collected database. Multivariate Cox proportional hazards models were performed to assess the associations between body composition parameters and survival. All patients were seen in a tertiary care cancer center. Adult patients with stage I to III colorectal cancer, undergoing curative resection from 2007 to 2009, were included. Computed tomography-derived quantification of skeletal muscle and adipose tissues was used to determine population-specific cutoffs for sarcopenia, myosteatosis, and total adiposity. Primary outcome measures were overall, recurrence-free, and cancer-specific survival. In the 968 patients included, there were a total of 254 disease recurrences and 350 deaths. Body mass index and CT-derived measures of adiposity did not result in worse survival outcomes. Sarcopenia was independently predictive of worse overall (HR, 1.45; 95% CI, 1.16-1.84), recurrence-free (HR, 1.32; 95% CI, 1.00-1.75), and cancer-specific survival (HR, 1.46; 95% CI, 1.09-1.94) in a multivariate model. Myosteatosis was also independently predictive of overall survival (HR, 1.53; 95% CI, 1.19-1.97). In a model considering joint effects of sarcopenia and myosteatosis, the presence of both predicted the worst overall (HR, 2.23; 95% CI, 1.62-3.06), recurrence-free (HR, 1.53; 95% CI, 1.06-2.21), and cancer-specific survival (HR, 2.40; 95% CI, 1.69-3.42) in a multivariate model. The limitations of this study are inherent in retrospective observational studies. Sarcopenia and myosteatosis are independent predictors of worse survival in stage I to III colorectal cancer, and their joint effect is highly predictive of reduced overall, recurrence-free, and cancer-specific survival. See Video Abstract at http://links.lww.com/DCR/A923.

Comparative outcomes of adenosquamous carcinoma of the pancreas: An analysis of the National Cancer Database

A paucity of data exists regarding the natural history and outcome measures of adenosquamous carcinoma of the pancreas (ASCP), a histology distinct from pancreatic adenocarcinoma (PDAC). The aim of this study is to characterize the clinicopathological features of ASCP in a large cohort of patients comparing outcome measures of surgically resected patients to PDAC. We identified patients diagnosed with ASCP or PDAC from the National Cancer Database from 2004 to 2012. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. We identified 207 073 patients: 205 328 (99%) in the PDAC group and 1745 (1%) in the ASCP group. ASCP tumors were larger, located more frequently in a body/tail location (36% vs 24%, P < 0.001), undifferentiated/anaplastic histology (41% vs 17%, P < 0.001), and early stage presentation, (39% vs 32%, P < 0.001). There was no significant difference in OS when comparing all patients with PDAC and ASCP (6.2 months and 5.7 months, P = 0.601). In surgical patients ASCP histology was associated with worse OS (14.8 months vs 20.5 months, P < 0.001) but had lower nodal involvement (55% vs 61%, P < 0.001). ASCP histology was independently associated with worse OS, after adjusting for tumor characteristics, treatment, and patient demographics. In patients with only resected ASCP histology, negative lymph node status, R0 surgical resection, and receipt of chemotherapy was independently associated with improved overall survival following surgical resection. Although patients with ASCP and PDAC tumors have similar survival when non-surgical and surgical patients are combined, ASCP is associated with worse survival in stage I/II resected patients.

Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage I lung squamous cell carcinoma, but not in stage II and III

ObjectivesTumor spread through air spaces (STAS) is a newly identified invasion pattern in lung adenocarcinoma. This study aimed to analyze and validate the clinical impact of tumor STAS in surgically resected lung squamous cell carcinoma (SQCC). Materials and methodsWe retrospectively reviewed 220 patients with lung SQCC. Tumor STAS was defined as detached tumor cells within the air spaces in the lung parenchyma beyond the edge of the main tumor. Statistical analyses were conducted to investigate the proportion of STAS and the relationship between the presence of STAS and clinicopathological factors, including clinical outcome. ResultsSTAS was identified in 42 of 220 patients (19.1%). The patients with STAS had a significantly worse 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) than those without STAS (5-year RFS: 37.4% vs. 68.4%; p = 0.0006; 5-year OS: 50.2% vs. 71.4%, p = 0.0078) in stage I, but not in stage II and III. A multivariate analysis showed that the presence of STAS was an independent predictive factor of recurrence (hazard ratio = 3.27; 95% confidence interval, 1.7–6.29; p = 0.0004) and an independent prognostic factor (hazard ratio = 3.01; 95% confidence interval, 1.54–5.89; p = 0.0013) in stage I, but not in stage II and III. ConclusionWe found that STAS was detected in 19.1% of surgical resected SQCC, and it was associated with recurrence and worse survival in stage I SQCC, but not in stage II and III SQCC. Therefore, we suggest that STAS is a useful predictor of recurrence and prognosis in stage I lung SQCC.

Squamous Cancers of the Rectum Demonstrate Poorer Survival and Increased Need for Salvage Surgery Compared With Squamous Cancers of the Anus

Squamous cell cancers of the anus are rare GI malignancies for which neoadjuvant chemoradiation is the first-line treatment for nonmetastatic disease. Squamous cancers of the rectum are far less common, and it is unclear to what degree chemoradiotherapy improves their outcomes. The purpose of this study was to compare stage-specific survival for anal and rectal squamous cancers stratified by treatment approach. This was a retrospective cohort study. The study was conducted at Commission on Cancer designated hospitals. Patients (2006-2012) identified in the National Cancer Database with pretreatment clinical stage I to III cancers who underwent chemoradiotherapy, with and without subsequent salvage surgical resection (low anterior resection or abdominoperineal resection), ≥12 weeks after chemoradiotherapy were included in the study. Overall survival and the need for salvage surgery were measured. Anal cancers (n = 11,224) typically presented with stage II (45.7%) or III (36.3%) disease, whereas rectal cancer stages (n = 1049) were more evenly distributed (p < 0.001). More patients with rectal cancer underwent low anterior or abdominoperineal resections 12 weeks or later after chemoradiotherapy versus those undergoing abdominoperineal resection for anal cancer (3.8% versus 1.2%; p < 0.001). Stage I and II rectal cancer was associated with poorer survival compared with anal cancer (stage I, p = 0.017; stage II, p < 0.001); survival was similar for stage III disease. Salvage surgery for anal cancer was associated with worse survival for stage I to III cancers; salvage surgery did not significantly affect survival for rectal cancer. This was a retrospective study without cancer-specific survival measures. Squamous rectal cancers are associated with significantly worse survival than squamous cancers of the anus for clinical stage I and II disease. Despite both cancers exhibiting squamous histology, rectal cancers may be less radiosensitive than anal cancers, as suggested by the greater incidence of salvage surgery that does not appear to significantly improve overall survival. See Video Abstract at http://links.lww.com/DCR/A422.

Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

PD-L1 Negative Status is Associated with Lower Mutation Burden, Differential Expression of Immune-Related Genes, and Worse Survival in Stage III Melanoma.

Understanding why some melanomas test negative for PD-L1 by IHC may have implications for the application of anti-PD-1 therapies in melanoma management. This study sought to determine somatic mutation and gene expression patterns associated with tumor cell PD-L1 expression, or lack thereof, in stage III metastatic melanoma to better define therapeutically relevant patient subgroups. IHC for PD-L1 was assessed in 52 American Joint Committee on Cancer stage III melanoma lymph node specimens and compared with specimen-matched comprehensive clinicopathologic, genomic, and transcriptomic data. PD-L1-negative status was associated with lower nonsynonymous mutation (NSM) burden (P = 0.017) and worse melanoma-specific survival [HR = 0.28 (0.12-0.66), P = 0.002] in stage III melanoma. Gene set enrichment analysis identified an immune-related gene expression signature in PD-L1-positive tumors. There was a marked increase in cytotoxic T-cell and macrophage-specific genes in PD-L1-positive melanomas. CD8A(high) gene expression was associated with better melanoma-specific survival [HR = 0.2 (0.05-0.87), P = 0.017] and restricted to PD-L1-positive stage III specimens. NF1 mutations were restricted to PD-L1-positive tumors (P = 0.041). Tumor negative PD-L1 status in stage III melanoma lymph node metastasis is a marker of worse patient survival and is associated with a poor immune response gene signature. Lower NSM levels were associated with PD-L1-negative status suggesting differences in somatic mutation profiles are a determinant of PD-L1-associated antitumor immunity in stage III melanoma. Clin Cancer Res; 22(15); 3915-23. ©2016 AACR.