Does complete pathological response increase perioperative morbidity risk in rectal cancer?

AIM: The optimal management of patients with clinical complete response after neoadjuvant treatment for rectal cancer is controversial. The aim of this study is to compare the morbidity between patients with locally advanced rectal cancer who have had a pathological complete response (pCR) or not after neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The study hypothesis was that pCR may impact the surgical complication rate. METHOD: A retrospective cohort study was conducted of a prospectively maintained database in Australia and New Zealand, the Binational Colorectal Cancer Audit, that identified patients with locally advanced rectal cancer (<15 cm from anal verge) from 1 January 2007 to 31 December 2019. Patients were included if they had locally advanced rectal cancer and had undergone NCRT and proceeded to surgical resection. RESULTS: There were 4584 patients who satisfied the inclusion criteria, 65% being male. The mean age was 63 years and 11% had a pCR (ypT0N0). TME with anastomosis was performed in 67.8% of patients, and the majority of the cohort received long-course radiotherapy (81.7%). Both major and minor complications were higher in the TME without anastomosis group (17.3% vs. 14.7% and 30.6% vs. 20.8%, respectively), and the 30-day mortality was 1.31%. In the TME with anastomosis group, pCR did not contribute to higher rates of surgical complications, but male gender (p < 0.0012), age (p < 0.0001), preoperative N stage (p = 0.0092) and American Society of Anesthesologists (ASA) score ≥3 (p < 0.0002) did. In addition, pCR had no significant effect (p = 0.44) but male gender (p = 0.0047) and interval to surgery (p = 0.015) contributed to higher rates of anastomotic leak. In the TME without anastomosis cohort, the only variable that contributed to higher rates of complications was ASA score ≥3 (p = 0.033). CONCLUSION: Patients undergoing TME dissection for rectal cancer following NCRT showed no difference in complications whether they had achieved pCR or not.

Adjuvant treatment patterns for pT3N0M0 esophageal cancer undergoing surgery.

To assess adjuvant treatment patterns on survival in patients with pT3N0M0 esophageal cancer who underwent esophagectomy without neoadjuvant chemoradiotherapy. Stage pT3N0M0 esophageal cancer patients were assessed between 2000 and 2020 from the Surveillance, Epidemiology, and End Results databases. Kaplan-Meier analysis was used to compare overall survival (OS) among various treatment patterns. We identified 445 patients: 252 (56.6%) received surgery alone, 85 (19.1%) received surgery+chemoradiotherapy, 80 (18.0%) underwent surgery+chemotherapy, and 28 (6.3%) received surgery+ radiotherapy. For squamous cell carcinoma, surgery+chemoradiotherapy ([hazard ratio] HR = 1.04, 95% confidence interval (CI): 0.65-1.66; P = 0.873), surgery+chemotherapy (HR = 0.72, 95% CI: 0.42-1.22; P = 0.221), and surgery+radiotherapy (HR = 1.33, 95% CI: 0.74-2.39; P = 0.341) had similar OS compared to surgery alone. For adenocarcinoma, surgery+chemoradiotherapy (HR = 0.51, 95% CI: 0.36-0.74; P < 0.001) and surgery+chemotherapy (HR = 0.61, 95% CI: 0.42-0.87; P = 0.006) had better OS compared to surgery alone. However, surgery+radiotherapy had a comparable OS (HR = 0.81, 95% CI: 0.44-1.49; P = 0.495).Adjuvant treatments did not improve survival in stage pT3N0M0 esophageal squamous cell carcinoma patients. In contrast, adjuvant chemoradiotherapy and chemotherapy were recommended for esophageal adenocarcinoma patients.

Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005-2015): SCAN-LEAF study.

Aim: To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Patients & methods: Adults diagnosed with incident NSCLC (2005-2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported. Results: 31,939 NSCLC patients (51.6% stage IV) were included. Increasing use of curative radiotherapy/chemoradiation for stage I, II/IIIA and IIIB NSCLC coincided with improved 2-year OS. Systemic anticancer therapy use increased for patients with stage IV non-squamous NSCLC (53.0-60.6%) but not squamous NSCLC (44.9-47.3%). 1-year OS improved in patients with stage IV non-squamous NSCLC (23-31%) but not squamous NSCLC (22-25%). Conclusion: Trends indicated improved OS as treatments evolved between 2005 and 2015, but the effect was limited to 1-year OS in stage IV disease.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP).

INTRODUCTION: In contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives. MATERIAL AND METHODS: Between January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval. RESULTS: Depending on the median time interval of 55 days (d) (95% CI 51.42-84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%). Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months). The 5-year OS rate for all patients involved was 71% (95% CI 0.55-0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48-1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42-0.80; X2(1) = 1.16, p = 0.281). Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75-0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89-1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57-0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59-0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63-0.94) and thus not significantly different from 65% (95% CI 0.45-0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589). CONCLUSIONS: The results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

Patterns and timing of recurrence in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy plus esophagectomy.

BACKGROUND: Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT. METHODS: A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT. RESULTS: The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant. CONCLUSIONS: NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).

Comparison of therapeutic effects of chemo-radiotherapy with neoadjuvant chemotherapy before radical surgery in patients with bulky cervical carcinoma (stage IB3 & IIA2).

BACKGROUND: Cervical cancer is one of the most common malignancies among women. Appropriate and timely treatment of these patients can reduce the complications and increase their survival. The objective of this study was to compare neoadjuvant chemotherapy plus radical hysterectomy (NACTRH) and chemo-radiotherapy (CRT) in patients with bulky cervical cancer (stage IB3 & IIA2). MATERIAL AND METHODS: The medical records of patients with bulky cervical cancer (stage IB3 & IIA2) that received NACTRH or CRT between 2007 and 2017 were evaluated for therapeutic effects. Demographic characteristics, complications of chemo-radiotherapy and neoadjuvant chemotherapy, were collected in a researcher-made questionnaire. Our primary outcome was comparison of overall survival (OS), and disease-free survival (DFS) between two groups receiving NACTRH and CRT modalities. RESULTS: One-hundred and twenty three patients were enrolled in the study. The median age and the proportion of patients with stage IIA2 were higher in the CRT group compared to the NACTRH group (p < 0.05). The medians (95% CI) OS were 3.64 (3.95-6.45) and 3.9 (3.53-4.27) years in the NACTRH and CRT groups, respectively (P = 0.003). There were 16 (34.8%) and 22 (43.1%) recurrences in the NACTRH and CRT group, respectively (P = 0.4). The median (95% CI) DFS was 4.5 (3.88-5.12) years in the NACTRH group and 3.6 (2.85-4.35) years in the CRT group (P = 0.004). The 3-year OS rate in NACTRH and CRT groups were 97 and 90% respectively. The 3-year DFS rate in NACTRH and CRT groups were 88 and 66% respectively. CONCLUSIONS: NACTRH is associated with a higher OS and DFS compared to CRT.

Practice patterns and survival in FIGO 2009 stage 3B endometrial cancer.

OBJECTIVE: To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. METHODS: We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p < 0.05 were considered significant. RESULTS: Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. CONCLUSION: Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Non-exenterative surgical management of recurrent endometrial carcinoma.

OBJECTIVE: To examine the role of non-exenterative secondary cytoreductive surgery (SCS) compared with non-surgical treatments and identify predictors of improved survival for patients with recurrent endometrial cancer (EC). METHODS: All patients undergoing primary surgical management for EC 1/1/2009-12/31/2017 who subsequently developed recurrence were retrospectively identified. Survival was determined from date of diagnosis of first recurrence to last follow-up and estimated using Kaplan-Meier method. Differences in survival were analyzed using Log-rank and Wald tests, based on Cox Proportional Hazards model. RESULTS: Among 376 patients with recurrent EC, median time to recurrence was 14.3 months (range, 0.2-102.2), post-recurrence median survival 29 months, median follow-up 29.2 months (range, 0-116). Sixty-one patients (16.2%) received SCS, 257 (68.4%) medical management (MM) (chemotherapy and/or radiation therapy), 32 (8.5%) hormonal therapy, 26 (6.9%) no further therapy. Patients selected for SCS were younger, had more endometrioid histology, more stage I disease at initial diagnosis, no residual disease after primary surgery, longer interval to first recurrence or progression, and the longest OS (57.6 months) (95% CI, 33.3-not reached). On multivariate analysis SCS was an independent predictor of improved survival. Among the 61 SCS patients, age < 70 at time of initial diagnosis, and endometrioid histology, were associated with improved post-relapse survival univariately (p = 0.008, 0.03, respectively). CONCLUSIONS: While MM was the most common treatment for first recurrence of EC, patients selected for surgery demonstrated the greatest survival benefit even after controlling for tumor size, site, histology, stage, time to recurrence. Careful patient selection and favorable tumor factors likely play a major role in improved outcomes. Surgical management should be considered whenever feasible in medically eligible patients, with additional consideration given to our suggested criteria.

Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer.

OBJECTIVE: Main controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades. METHODS: All consenting endometrial cancer patients receiving primary treatment at Haukeland University Hospital from 2001 to 2019 were included (n = 1308). Clinicopathological variables were evaluated for year-to-year changes. Clinical outcome before and after discontinuing adjuvant radiotherapy and individualizing extent of lymphadenectomy was analyzed. RESULTS: The rate of lymphadenectomy was reduced from 78% in 2001-2012 to 53% in 2013-2019. The rate of patients with verified lymph node metastases was maintained (9% vs 8%, p = 0.58) and FIGO stage I patients who did not undergo lymphadenectomy had stable 3-year recurrence-free survival (88% vs 90%, p = 0.67). Adjuvant chemotherapy for completely resected FIGO stage III patients increased from 27% to 97% from 2001 to 2009 to 2010-2019, while adjuvant radiotherapy declined from 57% to 0% (p < 0.001). These patients had improved 5-year overall- and recurrence-free survival; 0.49 [95% CI: 0.37-0.65] in 2001-2009 compared to 0.61 [0.45-0.83] in 2010-2019, p = 0.04 and 0.51 [0.39-0.68] to 0.71 [0.60-0.85], p = 0.03, respectively. For stage I, II and IV, survival rates were unchanged. CONCLUSIONS: Our study demonstrates that preoperative stratification by imaging and histological assessments permits a reduction in lymphadenectomy to around 50%, and is achievable without an increase in recurrences at 3 years. In addition, our findings support that adjuvant chemotherapy alone performs equally to adjuvant radiotherapy with regard to survival, and is likely superior in advanced stage patients.

Effects of Adjuvant Therapy Compliance and Anastomotic Leakage on the Oncologic Outcomes of Patients With Rectal Cancer After Curative Resection.

BACKGROUND: Anastomotic leakage might be directly or indirectly related to the prognosis of patients with rectal cancer. OBJECTIVE: This study aimed to investigate whether anastomotic leakage affects the oncologic outcomes in patients with rectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a teaching hospital between January 2009 and December 2013. PATIENTS: Patients who underwent curative resection for primary rectal cancer were included. MAIN OUTCOME AND MEASURE: Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival. RESULTS: The overall incidence of anastomotic leakage was 2.7% (107/3865). Local recurrence was more frequent in patients with anastomotic leakage than in those without (14.0% vs 6.7%; p = 0.007). By multivariate analysis, anastomotic leakage was associated with increased local recurrence rate (p = 0.014) and poorer overall survival (p = 0.011). In subgroup analysis, compared with other pathologic risk factors, anastomotic leakage was associated with higher occurrence of local and distant recurrence in patients with stage II rectal cancer (p = 0.031 and <0.001). In patients with stage III rectal cancers, adjuvant therapy was more likely to be delayed or canceled in those experiencing anastomotic leakage (63 vs 39 d, p < 0.001; 37.3% vs 66.7%, p < 0.001). In addition, this patient group had the worst survival outcome when compared with those without anastomotic leakage and those with timely adjuvant therapy (5-year disease-free survival rate, p = 0.013; 5-year overall survival rate, p = 0.001). LIMITATIONS: This study is limited by its retrospective nature. CONCLUSIONS: There was a robust association between anastomotic leakage and local recurrence, while also potentially affect long-term survival of the patient group. Delayed or cancelled adjuvant therapy administration because of anastomotic leakage may partly account for the poorer survival in those patients with advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B459. EFECTOS DE OBSERVANCIA DE TERAPIA ADYUVANTE Y FUGA ANASTOMTICA, EN RESULTADOS ONCOLGICOS DE PACIENTES CON CNCER RECTAL, DESPUS DE UNA RESECCIN CURATIVA: ANTECEDENTES:La fuga anastomótica podría estar relacionada directa o indirectamente, con el pronóstico de los pacientes con cáncer de recto.OBJETIVO:El estudio tuvo como objetivo investigar si la fuga anastomótica afecta los resultados oncológicos, en pacientes con cáncer de recto.DISEÑO:Fue un análisis retrospectivo de datos recolectados prospectivamente.AJUSTE:El estudio se realizó en un hospital universitario entre enero de 2009 y diciembre de 2013.PACIENTES:Pacientes sometidos a resección curativa por cáncer rectal primario.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizaron análisis de Kaplan-Meier para evaluar la supervivencia libre de enfermedad y supervivencia general.RESULTADOS:La incidencia global de fuga anastomótica fue del 2,7% (107/3865). La recurrencia local fue más frecuente en pacientes con fuga anastomótica, que en aquellos sin ella (14,0% frente a 6,7%, p = 0,007). Por análisis multivariado, la fuga anastomótica se asoció con una mayor tasa de recurrencia local (p = 0,014) y una peor supervivencia general (p = 0,011). En el análisis de subgrupos, en comparación con otros factores de riesgo patológicos, la fuga anastomótica se asoció con una mayor incidencia de recidiva local y a distancia en pacientes con cáncer rectal en estadio II (p = 0,031 y <0,001, respectivamente). En pacientes con cáncer rectal estadio III, la terapia adyuvante tuvo más probabilidades de retrasarse o cancelarse en aquellos que sufrían fuga anastomótica (63 vs 39 días, p <0,001; 37,3% vs 66,7%, p <0,001). Y este grupo de pacientes tuvo el peor resultado de supervivencia en comparación con aquellos sin fuga anastomótica y aquellos con terapia adyuvante oportuna (tasa de supervivencia libre de enfermedad a 5 años, p = 0,013; tasa de supervivencia global a 5 años, p = 0,001).LIMITACIONES:El estudio está limitado por su naturaleza retrospectiva.CONCLUSIONES:Hubo una sólida asociación entre la fuga anastomótica y la recurrencia local, mientras que también afecta potencialmente la supervivencia a largo plazo, del grupo de pacientes. La administración de terapia adyuvante retrasada o cancelada debido a una fuga anastomótica, puede explicar en parte, la menor supervivencia en aquellos pacientes con cáncer rectal avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B459.

Association Between Preoperative Patient-Reported Symptoms and Postoperative Outcomes in Rectal Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: Rectal cancer patients undergoing preoperative radiotherapy experience a significant symptom burden. However, it is unknown whether symptoms during radiotherapy may portend adverse postoperative outcomes and healthcare utilization. METHODS: A retrospective cohort study was performed of rectal cancer patients undergoing neoadjuvant radiotherapy and proctectomy in Ontario from 2007 to 2014. The primary outcome was a complicated postoperative course-a dichotomous variable created as a composite of postoperative mortality, major morbidity, or hospital readmission. Patient-reported Edmonton Symptom Assessment System (ESAS) scores, collected routinely at outpatient provincial cancer center visits, were linked to administrative healthcare databases. The receiver-operating characteristic analysis was used to compare ESAS scoring approaches and to stratify patients into low versus high symptom score groups. Multivariable regression models were constructed to evaluate associations between preoperative symptom scores and postoperative outcomes. RESULTS: 1455 rectal cancer patients underwent sequential radiotherapy and proctectomy during the study period and recorded symptom assessments. Patients with high preoperative symptom scores were significantly more likely to experience a complicated postoperative course (OR 1.55, 95% CI 1.23-1.95). High preoperative ESAS scores were also associated with the secondary outcomes of emergency department visits (OR 1.34, 95% CI 1.08-1.66) and longer length of stay (IRR 1.23, 95% CI 1.04-1.45). CONCLUSIONS: Rectal cancer patients reporting elevated symptom scores during neoadjuvant radiotherapy have increased odds of experiencing a complicated postoperative course. Preoperative patient-reported outcome screening may be a useful tool to identify at-risk patients and to efficiently direct perioperative supportive care.

Evaluating the Impact of ESPAC-1 on Shifting the Paradigm of Pancreatic Cancer Treatment.

BACKGROUND: In 2004, the European Study Group for Pancreatic Cancer (ESPAC)-1 long-term data concluded that adjuvant chemotherapy provided a survival benefit for patients with pancreatic ductal adenocarcinoma (PDAC), whereas adjuvant chemoradiation was associated with worse overall survival. In this study, we investigated how long it took for US practice patterns to change following this trial. METHODS: The National Cancer Database was used to identify patients with stage I-III PDAC who underwent R0 or R1 resection followed by adjuvant chemotherapy or chemoradiation between 1998 and 2015. A multivariate analysis was performed to determine predictors of receiving adjuvant chemoradiation in the post-ESPAC-1 era. RESULTS: Between 1998 and 2015, adjuvant chemotherapy use increased from 2.9% to 51.6%, whereas adjuvant chemoradiation decreased from 49.5% to 22.9%. In 2010, adjuvant chemotherapy utilization surpassed that of chemoradiation. For patients diagnosed in the post-ESPAC-1 era, adjuvant chemotherapy (n = 7733) and chemoradiation (n = 6969) groups were compared. Patients who underwent adjuvant chemoradiation were younger, had private insurance, underwent surgery at nonacademic centers, and had more pathologically advanced cancers (all P < 0.01). After 2010, R1 resection was the strongest independent predictor of adjuvant chemoradiation use by multivariate analysis (OR 2.05, CI 1.8-2.3, P < 0.01). CONCLUSIONS: Adjuvant chemotherapy use exceeded that of adjuvant chemoradiation 6 y after the final publication of ESPAC-1 in 2004, highlighting the challenges of disseminating and adopting clinical data. After 2010, R1 disease was the most significant predictor of receiving adjuvant chemoradiation. Prospective studies are underway to definitively address the role of adjuvant chemoradiation in PDAC.

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.

Perioperative change in neutrophil count predicts worse survival in esophageal squamous cell carcinoma.

Aims: This study aimed to investigate the relationship between perioperative change in neutrophil count and survival of patients with esophageal squamous cell carcinoma. Method: Neutrophil change (Nc) (where Nc = post-surgery neutrophil count - pre-surgery neutrophil count) was counted according to data within 1 week before surgery and 2 weeks after surgery. Patients were divided into two groups, Nc ≥2.60 and Nc <2.60, according to the median of Nc. Results: Multivariate analysis revealed that Nc ≥2.60 was an independent prognostic marker for overall survival. Subgroup analysis suggested that the overall survival of male patients, patients aged ≤60 years, patients without vessel invasion and patients without nerve infiltration was dramatically worse for those with Nc <2.60. Conclusion: Perioperative change in neutrophil count predicts worse survival in esophageal squamous cell carcinoma after surgery.

Nomograms to predict lung metastasis probability and lung metastasis subgroup survival in malignant bone tumors.

The aim of this study was to construct and validate nomograms for predicting lung metastasis and lung metastasis subgroup overall survival in malignant primary osseous neoplasms. Least absolute shrinkage and selection operator, logistic and Cox analyses were used to identify risk factors for lung metastasis in malignant primary osseous neoplasms and prognostic factors for overall survival in the lung metastasis subgroup. Further, nomograms were established and validated. A total of 3184 patients were collected. Variables including age, histology type, American Joint Committee on Cancer T and N stage, other site metastasis, tumor extension and surgery were extracted for the nomograms. The authors found that nomograms could provide an effective approach for clinicians to identify patients with a high risk of lung metastasis in malignant primary osseous neoplasms and perform a personalized overall survival evaluation for the lung metastasis subgroup.

Adjuvant treatment and outcomes for patients with stage IIIA grade 1 endometrioid endometrial cancer.

OBJECTIVE: The role and type of adjuvant therapy for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA grade 1 endometrioid endometrial adenocarcinoma are controversial. This retrospective cohort study aimed to determine associations between adjuvant therapy use and survival among patients with stage IIIA grade 1 endometrial cancer. METHODS: Patients who underwent primary surgery for stage IIIA (FIGO 2009 staging) grade 1 endometrial cancer between January 2004 and December 2016 were identified in the National Cancer Database. Demographics and receipt of adjuvant therapy were compared. Overall survival was analyzed using Kaplan-Meier curves, log-rank test, and multivariable Cox proportional hazard models. RESULTS: Of 1120 patients, 248 (22.1%) received no adjuvant treatment, 286 (25.5%) received chemotherapy alone, 201 (18.0%) radiation alone, and 385 (34.4%) chemotherapy and radiation. Five-year overall survival rate was 83.0% (95% CI 80.1% to 85.6%). Older age, increasing comorbidity count, and lymphovascular space invasion status were significant negative predictors of survival. Over time, there was an increasing rate of chemotherapy (45.4% in 2004-2009 vs 69.2% in 2010-2016; p<0.001). In the multivariable analysis, chemotherapy was associated with significantly improved overall survival compared with no adjuvant therapy (HR 0.49 (95% CI 0.31 to 0.79); p=0.003). There was no survival association when comparing radiation alone with no treatment, and none when adding radiation to chemotherapy compared with chemotherapy alone. Those with lymphovascular space invasion (n=124/507) had improved overall survival with chemotherapy and radiation (5-year overall survival 91.2% vs 76.7% for chemotherapy alone and 27.3% for radiation alone, log-rank p<0.001), but there was no survival difference after adjusting for age and comorbidity (HR 0.25 (95% CI 0.05 to 1.41); p=0.12). CONCLUSIONS: The use of adjuvant chemotherapy for the treatment of stage IIIA grade 1 endometrial cancer increased over time and was associated with improved overall survival compared with radiation alone or chemoradiation. Patients with lymphovascular space invasion may benefit from combination therapy.

Favorable prognosis in pediatric brainstem low-grade glioma: Report from the German SIOP-LGG 2004 cohort.

Reports on pediatric low-grade glioma (LGG) of the caudal brainstem are retrospective with heterogeneous cohorts, variable treatments and inconsistent outcome data. We analyzed their natural history and asked whether brainstem location proved unfavorable for survival within the framework of the comprehensive SIOP-LGG 2004 management strategy. Within the prospectively registered, population-based German SIOP-LGG 2004 cohort 116 patients (age 0.2-16.5 years, 10% Neurofibromatosis NF1) were diagnosed with LGG of the pons (27%) and medulla oblongata (73%). After biopsy (23%), variable resection (63%) or radiologic diagnosis only (14%), 59 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemo- (n = 39) or radiotherapy (n = 18). After further progression (28/57), salvage treatments included multiple treatment lines for 12/28 patients. Five-years event-free survival dropped to 0.40, while 5-years overall survival was 0.95 (median observation time 6.8 years). Higher extent of resection yielded lower progression rate (p = 0.001), but at a cost of 21/100 patients suffering from new postsurgical complications including respiratory insufficiency. Central review confirmed pilocytic astrocytoma (56%), diffuse astrocytoma (8%) or glioneuronal histology (16%) (others 4%, no histology 17%). Malignant evolution was documented in five patients associated with Histone3 mutation in 2/5. Our treatment algorithm conveyed high overall survival for pediatric brainstem LGG. Extensive neurosurgical resection did increase additional postoperative neurologic deficits but not overall survival in this often-chronic disease. More than half of all patients can be safely followed by observation, while multimodal adjuvant treatment can control progressive tumors. Molecular assessment should confirm low-grade diagnosis and may detect patterns prognostic for malignant evolution.

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.

A contemporary analysis of racial disparities in recommended and received treatment for head and neck cancer.

BACKGROUND: Racial disparities in squamous cell carcinoma of the head and neck (HNSCC) negatively affect non-Hispanic black (NHB) patients. This study was aimed at understanding how treatment is prescribed and received across all HNSCC subsites. METHODS: With the National Cancer Database, patients from 2004 to 2014 with surgically resectable HNSCCs, including tumors of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (LX), were studied. The treatment received was either upfront surgery or nonsurgical treatment. Treatment patterns were compared according to race and subsite, and how these differences changed over time was evaluated. RESULTS: NHB patients were less likely than non-Hispanic white (NHW) patients to receive surgery across all subsites (relative risk [RR] for OC, 0.87; RR for OP, 0.75; RR for HP, 0.73; RR for LX, 0.87; all P values <.05). They were also more likely to refuse a recommended surgery (RR for OC, 1.50; RR for OP, 1.23; RR for HP, 1.23; RR for LX, 1.34), and this difference was significant except for HP. NHB patients were more likely to not be offered surgery across all subsites (RR for OC, 1.38; RR for OP, 1.07; RR for HP, 1.05; RR for LX, 1.03; all P values <.05). Rates of surgery increased and rates of not being offered surgery declined for both NHB and NHW patients from 2004 to 2014, but the absolute disparities persisted in 2014. CONCLUSIONS: Across all HNSCC subsites, NHB patients were less likely than NHW patients to be recommended for and receive surgery and were more likely to refuse surgery. These differences have closed over time but persist. Enhanced shared decision making may improve these disparities.

A nomogram model to predict death rate among non-small cell lung cancer (NSCLC) patients with surgery in surveillance, epidemiology, and end results (SEER) database.

BACKGROUND: This study aimed to establish a novel nomogram prognostic model to predict death probability for non-small cell lung cancer (NSCLC) patients who received surgery.. METHODS: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict mortality of NSCLC patients who received surgery. RESULTS: A total of 44,880 NSCLC patients who received surgery from 2004 to 2014 were included in this study. Gender, ethnicity, tumor anatomic sites, histologic subtype, tumor differentiation, clinical stage, tumor size, tumor extent, lymph node stage, examined lymph node, positive lymph node, type of surgery showed significant associations with lung cancer related death rate (P < 0.001). Patients who received chemotherapy and radiotherapy had significant higher lung cancer related death rate but were associated with significant lower non-cancer related mortality (P<0.001). A nomogram model was established based on multivariate models of training data set. In the validation cohort, the unadjusted C-index was 0.73 (95% CI, 0.72-0.74), 0.71 (95% CI, 0.66-0.75) and 0.69 (95% CI, 0.68-0.70) for lung cancer related death, other cancer related death and non-cancer related death. CONCLUSIONS: A prognostic nomogram model was constructed to give information about the risk of death for NSCLC patients who received surgery.