bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of local therapy on survival among patients with metastatic anal squamous cell carcinoma.
Authors: Alese Olatunji B. , Zhang Yining , Zakka Katerina Mary , Jiang Renjian , Atallah Rami , Diab Maria , Shaib Walid Labib , Akce Mehmet , Wu Christina , El-Rayes Bassel F. 
Published: January 2022

4 Background: About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease, and are usually treated with systemic chemotherapy. The role of local therapy to control the primary tumor is controversial in this setting. We evaluated survival impact of local therapy in metastatic anal SCCa. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. We excluded patients who did not receive palliative systemic chemotherapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: 1,160 patients were identified over 12 years. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with a significant improvement in OS on MVA (HR 0.66; 0.55-0.79; p < 0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; p < 0.001), age > 70 years (HR 1.28; 1.02-1.62; p = 0.034), lack of health insurance (HR 1.32; 1.02-1.71; p = 0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; p = 0.008). There was no benefit from abdominoperineal resection (mOS = 19.7mos; HR 1.05; 0.48-2.29; p = 0.909), but both local resection of the primary (mOS = 24.8mos, HR 0.48; 0.29-0.80; p = 0.005) and palliative radiation (mOS = 22.6 mos; HR 0.66; 0.55-0.79; p < 0.001) were associated with improved OS. Conclusions: This is the largest reported study on management of de novo stage IV SCCa. The data suggest that local control of the primary tumor through resection or radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local therapy include age over 70 years, male, lack of health insurance and cloacogenic carcinoma.
One-year duration of nivolumab plus ipilimumab in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up of the GERCOR NIPICOL phase II study.
Authors: Cohen Romain , Meurisse Aurelia , Pudlarz Thomas , Bennouna Jaafar , Tournigand Christophe , De La Fouchardiere Christelle , Tougeron David , Borg Christophe , Mazard Thibault , Chibaudel Benoist , Garcia-Larnicol Marie-Line , Svrcek Magali , Menu Yves , Vernerey Dewi , Andre Thierry 
Published: January 2022

13 Background: Optimal treatment duration with immune checkpoint inhibitors (ICI) for MSI/dMMR mCRC pts remains to be determined. Different durations are used, usually a fixed duration of 2 years or treatment until progression or toxicity. The GERCOR NIPICOL phase II study evaluated 1 year of therapy with nivolumab plus ipilimumab for MSI/dMMR mCRC pts. Here, we present the efficacy data with 16 months of additional follow-up since the primary analysis. Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidine, oxaliplatin, and irinotecan ± targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W for 4 cycles, then nivolumab 3 mg/kg Q2W until progression or a maximum of 20 cycles. Second course of nivolumab was permitted for pts who completed the predefined year of treatment and had later progressive disease (PD). Objectives were to evaluate response rates, progression-free survival (PFS) per iRECIST, and overall survival (OS). A landmark analysis was performed for PFS in pts who remained alive and progression-free at 1 year (theoretical end of treatment). Results: Of 57 pts included between Dec 2017 and Nov 2018, 36 (63%) completed the predefined 1-year duration of treatment. Reasons of premature treatment discontinuation were PD or death (n = 13), adverse event (n = 7), and the pt wish (n = 1). Overall median follow-up was 34.5 months. One, 2, and 3-year PFS rates were respectively 75.4% (95% CI 62.0-84.6), 70.0% (95% CI 56.2-80.1), and 70.0% (95% CI 56.2-80.1). One, 2, and 3-year OS rates were 84.1 (95% CI 71.7-91.4), 78.4% (95% CI 65.1-87.1), and 73.1% (95% CI 58.4-83.4), respectively. 42/57 pts were progression-free and alive at 1 year. Among them, median follow-up was 35.0 months and the 24-month PFS rate was 92.9% (95% CI 79.5-97.6%). PD was observed in three pts whose 12-month status was stable disease (SD). These three pts received a second course of nivolumab: two achieved PR and one had PD. Conclusions: Nivolumab plus ipilimumab with a fixed duration of 1 year continued to show durable activity in pts with chemoresistant MSI/dMMR mCRC after 3 years of follow-up. Reexposure to nivolumab seems to provide additional antitumor activity for pts experiencing late resistance after discontinuation of immunotherapy. Clinical trial information: NCT033501260.
The association between preoperative CEA, the systemic inflammatory response and survival in colon cancer.
Authors: Golder Allan Matthew , Park James Hugh , Mansouri David , Horgan Paul G. , McMillan Donald C. , Roxburgh Campbell SD 
Published: January 2022

27 Background: Prior to curative surgery for colon cancer, carcinoembryonic antigen (CEA) has been reported to be a poor prognostic factor recommended for routine measurement, however the majority of studies evaluating this have not adjusted for the preoperative systemic inflammatory response (SIR) –widely shown to be associated with worse outcomes. The present study aims to analyse the association between preoperative CEA and long-term outcomes when adjusted for other factors including Systemic Inflammatory Grade (SIG). Methods: The effect on overall/cancer specific survival (OS/CSS) of preoperative CEA (<5/5+) was examined in a regional cohort of patients undergoing surgery for colon cancer after adjustment for other clinicopathological factors including the SIR as measured by Systemic Inflammatory Grade (SIG). Results: 624 patients were identified undergoing curative surgery for colon cancer with a preoperative CEA available. For 3-year OS stratified by TNM Stage, CEA offered further prognostic value in patients with TNM Stage I (98% vs 75%, p=0.002), but not Stage II (p=0.444) or Stage III (p=0.351) disease. For 3-year OS stratified by SIG, CEA did not add further significant prognostic value for any SIG (all p>0.05). On multivariate analysis, age (HR 1.65, p=0.020), sex (HR 0.53, p=0.001), mode of presentation (HR 1.93, p=0.008), TNM Stage (HR 1.83, p<0.001) and SIG (HR 1.30, p<0.001) remained significant for OS, but not CEA (p=0.620). Conclusions: The present results show that there is limited prognostic value of preoperative CEA. The SIR as measured by SIG should be routinely measured prior to curative colonic surgery. A mandatory reporting dataset is required in colorectal cancer and should include SIG. [Table: see text]
A twice-daily or a three-times-daily tegafur-uracil and leucovorin calcium regimen as adjuvant therapy in patients with resected colorectal cancer: A phase III study.
Authors: Iwamoto Kazuya , Hata Taishi , Miyake Masakazu , Ohue Masayuki , Shingai Tatsushi , Tei Mitsuyoshi , Takemoto Hiroyoshi , Ikenaga Masakazu , Fujie Yujiro , Miyoshi Norikatsu , Takahashi Hidekazu , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Murata Kohei , Ohno Yuko , Doki Yuichiro , Eguchi Hidetoshi 
Published: January 2022

38 Background: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The schedule of 28-day oral administration followed by a 7-day rest period was repeated. Five 35-day cycles were repeated. The primary endpoint was 3-year disease-free survival. The secondary endpoints included 5-year overall survival and toxicity. Results: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The 5-year overall survival rates of group A and B were 89.7% and 91.0% (95% confidence interval, 83.3-92.8-84.8-93.8), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusions: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase. Clinical trial information: UMIN000005594.
Real-world data analysis of antiangiogenic targeted treatments in second-line following anti-EGFR antibodies and FOLFOX in first-line for patients with metastatic colorectal cancer.
Authors: Kagawa Yoshinori , Satake Hironaga , Shinozaki Eiji , Tanizawa Yoshinori , Cai Zhihong , Jin Long , Makiyama Akitaka 
Published: January 2022

43 Background: Three antiangiogenic (AA) drugs, bevacizumab (BEV), ramucirumab (RAM) and aflibercept (AFL) are recommended as the second-line (2L) treatment for metastatic colorectal cancer (mCRC) in the CRC treatment guidelines of multiple countries and regions including the US, EU and Japan. However, little evidence of 2L RAM and AFL after anti-EGFR antibodies (EGFRab) in first- line (1L) has been reported. This study assessed treatment sequence for mCRC patients who received 2L irinotecan-based chemotherapy with AA drug after FOLFOX + EGFRab in 1L, treatment duration from the start of 2L to the end of last treatment line (treatment duration from 2L) and factors associated with the treatment duration from 2L. Methods: This is a real-world observational study using a hospital-based claims database of 393 hospitals in Japan. The mCRC patients who started 1L treatment with FOLFOX + EGFRab between May 2016 and Sep 2019 (identification period) and further treated with irinotecan-based chemotherapy + AA drug were enrolled. The key outcomes were the treatment sequence, treatment duration from 2L by AA drug, and factors associated with the treatment duration from 2L. Survival curves were estimated using the Kaplan–Meier method. Associated factors were investigated using Cox regression analysis. Results: Among 2,453 patients with 1L FOLFOX + EGFRab during the identification period, 506 patients who received the intended 2L therapies were enrolled in this study (mean age 63.5 years, male 66.6%). Number (%) of patients who used BEV, RAM and AFL in 2L was 345 (68.2), 120 (23.7) and 41 (8.1), respectively. Patient characteristics involving tumor location, metastatic site and prior anti-tumor therapy before starting 2L were similar among BEV, RAM and AFL. The treatment duration from 2L (median month and its 95%CI) was 11.1 (10.2-12.5) in the overall population and was similar among the patients who received BEV (10.8 [9.9-13.1]), RAM (11.2 [10.0-14.2]) and AFL (12.8 [6.9-NA]) in 2L. The treatment duration from 2L (median month and its 95%CI) for the patients who took or didn’t take proteinuria tests during 2L was 12.5 (11.1-15.2) and 8.5 (6.5-11.2), respectively. Factors positively associated with treatment duration from 2L were left-sided CRC (HR [95%CI] = 0.71 [0.53-0.96]) and ≥6 months of 1L duration (0.72 [0.56-0.93]); having renal disease (1.92 [1.28-2.88]) or received NSAIDs (1.63 [1.25-2.13]) within 60 days before starting 2L were associated negatively. Conclusions: The real-world data revealed that treatment duration were similar among BEV, RAM and AFL in 2L after EGFRab. Tumor location and 1L duration were associated with the treatment duration from 2L positively, while negative association was observed with renal disease and received NSAIDs. Treatment management was important for treatment continuation.
General and mental health status following colorectal cancer treatment and its association with mortality among a racially diverse population-based cohort.
Authors: Yoon Paul , Navarro Stephanie , Ochoa Carol , Garrett Elleyse , Arizpe Angel , Farias Albert 
Published: January 2022

45 Background: Patient-reported outcomes (PROs) are recognized as strong predictors of cancer prognosis, outcomes, and care. However, racial/ethnic minorities with colorectal cancer (CRC) tend to report poorer general health status (GHS) and mental health status (MHS) compared to non-Hispanic whites. The objectives of this study were to determine: (1) if there are racial/ethnic differences in GHS and MHS within 36 months of CRC diagnosis and (2) if poorer GHS and MHS in recently diagnosed CRC patients are associated with mortality. Methods: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-Consumer Assessment of Healthcare Providers and Systems (CAHPS) dataset to analyze Medicare beneficiaries aged ≥65 years who were diagnosed with CRC between 1998 and 2011, received surgical resection for their tumor, and completed a CAHPS survey within 6-36 months post-diagnosis. CAHPS surveys captured patient-reported GHS and MHS on a five-point Likert scale ranging from “poor” to “excellent.” We used stepwise multivariable logistic regression to examine associations between patient race/ethnicity and fair or poor health status, adjusting for clinical and sociodemographic factors. Additionally, a multivariable Cox proportional hazards regression was used to determine the risks of mortality associated with fair or poor GHS and MHS. Results: Of 1,867 patients with CRC, 79.5% were non-Hispanic white (NHW), 6.4% were non-Hispanic black (NHB), 7.5% were Hispanic, and 6.6% were non-Hispanic Asian (NHA). In Model 1 of our stepwise logistic regression, NHB patients had higher unadjusted odds for fair or poor GHS (OR 1.56, 95% CI 1.06-2.28) compared to NHW patients while Hispanic patients had higher unadjusted odds for both fair or poor GHS (1.48, 1.04-2.11) and MHS (1.92, 1.23-3.01). In Model 2, this relationship persisted after adjusting for clinical factors, with NHB patients being more likely to report fair or poor GHS (1.62, 1.10-2.40) and Hispanic patients being more likely to report fair or poor GHS (1.49, 1.04-2.13) and MHS (1.92, 1.22-3.00). In Model 3, after adjusting for both clinical and sociodemographic factors, the association between race/ethnicity and fair or poor GHS ( p = 0.53) and MHS ( p = 0.23) no longer remained. Reporting fair or poor GHS and MHS was associated with a greater risk of mortality among all CRC patients (HR 1.52, 95% CI 1.31-1.76 and 1.62, 1.34-1.99, respectively). Conclusions: Our study illustrates that racial/ethnic differences in PROs are largely driven by sociodemographic factors as opposed to clinical factors. As fair or poor GHS and MHS shortly after diagnosis reflect a higher risk of mortality in CRC patients, efforts to understand unmet biopsychosocial concerns may help further elucidate racial differences in CRC survival that may be otherwise overlooked in standard clinical practice.
Metastasectomy in colorectal cancer patients with concurrent lung and liver metastasis: Trends in utilization and impact on survival.
Authors: Khatib Jude , Goksu Suleyman Yasin , Reddy Sarah , Chowattukunnel Nivan , Sanford Nina Niu , Sanjeevaiah Aravind , Beg Muhammad Shaalan , Kazmi Syed Mohammad Ali 
Published: January 2022

53 Background: Colorectal cancer (CRC) frequently presents with concurrent metastasis to the lung and liver. Metastasectomy may offer extended disease control in a select group of patients but its utilization is unknown. We aimed to investigate the trends in utilization of metastasectomy in CRC patients with concurrent lung and liver metastasis and explore its impact on survival. Methods: We queried the National Cancer Database and identified stage 4 CRC patients with concurrent lung and liver metastasis between 2010 – 2016 and categorized them into those that underwent metastasectomy vs. those that did not. Categorical variables were compared using the chi-square test, and statistically significant factors were included in multivariable logistic regression analysis. In addition, 1:2 propensity score matching was performed, and a multivariable Cox regression model was used to define survival predictors among matched cohorts. The Kaplan-Meier method was used to estimate the median survival. Results: Out of total 77,719 stage 4 CRC patients, 10,106 (13.0%) patients had concurrent lung and liver metastasis. Six percent (n = 630) of these patients underwent metastasectomy of both sites. Patients that underwent metastasectomy were more likely to be younger (< 50 years; p = 0.009), female ( p < 0.001), and White ( p = 0.01). These patients were also more likely to have right-sided CRC ( p = 0.001) and had resection of the primary site (p < 0.001). Additionally, they were more likely to have private health insurance ( p < 0.001) and receive treatment at an academic center ( p = 0.03). On adjusted multivariable analysis, female gender, care at an academic center, primary tumor resection and receiving chemotherapy were associated with the metastasectomy group. We did not find a statistically significant difference between comorbidity score, KRAS status and microsatellite status between the 2 groups. In the matched analysis, overall survival (OS) was significantly improved for patients who underwent metastasectomy (23.2 months) vs. those who did not (11.6 months, p < 0.001). On multivariable analysis, this difference remained, and metastasectomy was an independent predictor of better OS (HR 0.74 [0.65-0.85], p < 0.001). Conclusions: The utilization of metastasectomy in concurrent lung and liver metastasis is low. It is more frequently used in younger, female and White patients, as well as in patients treated at an academic center. Metastasectomy is independently associated with improved overall survival in patients eligible for such an approach.
Real-world experience of pembrolizumab in microsatellite instability-high CRC: A Scottish multicenter analysis.
Authors: Ghaus Aisha , Pheely Ashley , Murdock Victoria , Shareef Hala , Samuel Leslie M. , Clive Sally , Tough Fay , Rodgers Lisa Jane 
Published: January 2022

54 Background: KEYNOTE-177 established pembrolizumab as a new standard of care in untreated microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Patients within clinical trials are not always representative of the general population. This underpins the importance of real-world data to offer insights into the outcomes achieved with anti-cancer therapies in routine practice. We report the initial efficacy and safety outcomes of patients treated with pembrolizumab for MSI-H CRC in Scotland. Methods: A retrospective analysis of all patients with advanced MSI-H CRC treated with pembrolizumab in the Scottish National Health Service was undertaken. Patient demographic and clinico-pathological data were collated via a standardised collection tool. Statistical analysis was performed using SPSS version 28. Results: 39 patients were identified (37 metastatic, 2 with locally advanced unresectable disease). All but 2 patients were treated in the first line setting. The median age was 68 years (range 48-82). 23 (59%) were age ≥65 years. 12 (30.7%) of patients were of Eastern Cooperative Oncology Group performance status (PS) 0, 23 (58.9%) of PS 1 and 4 (10.2%) of PS 2. 21 (53.8%) had BRAF V600E mutations. The median duration of pembrolizumab therapy was 24 weeks (range 2-104). After a median follow-up of 36 weeks (range 3-193), 5 deaths had occurred. The median progression free survival had not been reached. The overall response rate was 51% (20/39 patients), with 1 complete response observed. Radiological disease progression occurred in 7 patients (18%), 6 (86%) of which were BRAF V600E mutant. Treatment failure (radiologically confirmed disease progression or clinical suspicion of progression without radiological confirmation) occurred in 15 patients (38%). 3 out of 4 patients with PS 2 achieved a partial response. There were no grade ≥3 immune related adverse events. There was 1 treatment suspension due to grade 2 immune toxicity but no permanent discontinuations. Conclusions: Our real-world Scottish population was of poorer performance status than those recruited to KEYNOTE-177 (31% PS 0 vs. 49% in KEYNOTE-177). They were also older (59% age ≥65 years vs. 48% in the trial). Patients of PS 2 were excluded from the study, however 3 of our 4 PS 2 patients demonstrated a partial response to treatment, suggesting that PS 2 should not be an absolute contraindication to treatment. Our observed overall response rate was greater than that observed in KEYNOTE-177 (43.8%). Pembrolizumab was safe and well tolerated in this setting. These preliminary findings support the results of KEYNOTE-177. Long term survival data in our population is awaited. Further follow-up and patient numbers will allow for determination of possible clinico-pathological predictors (BRAF and KRAS status, Glasgow Prognostic Score, metastatic burden) of response to immunotherapy in this population.