bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes associated with chemotherapy-induced neutropenia in the adjuvant treatment of colorectal cancer with FOLFOX.
Authors: Trincao-Batra Sara , Goodwin Rachel Anne , Marginean Horia , Maroun Jean Alfred , Vickers Michael M. , Asmis Timothy R. , Gotfrit Joanna 
Published: January 2022

81 Background: Patients undergoing adjuvant treatment with FOLFOX for colorectal cancer (CRC) are at risk of developing chemotherapy-induced neutropenia (CIN). We assessed survival outcomes in patients who develop CIN in this setting. Methods: We performed a retrospective chart review of patients with CRC treated with FOLFOX at our institution in Canada from 2013 to 2015. The survival follow-up cut-off date was August 2021. Demographic, treatment, and outcome data were collected. CIN was defined as ANC <1.5, and all episodes of neutropenia were assumed to be the result of chemotherapy. Median OS was calculated using Kaplan-Meier product limit estimates. Results: A total of 302 patients were included (baseline demographics in the table). Median follow-up was 110 months. In the overall cohort, 174 patients (58%) had at least one episode of CIN. CIN occurred in 56% of those with stage II cancer, 43% of those with low risk stage III cancer (T1-3 and N1), and 45% of those with high risk stage III cancer (T4 or N2). Median time to first CIN event was 4.3 months. Among patients with at least one episode of CIN, the first CIN event occurred during the first 3 months of treatment in 110 (63%). Among patients with at least one episode of CIN, 79 (45%) received subsequent granulocyte colony-stimulating factor (GCSF). The median OS in the overall cohort was 171 months. For patients with and without CIN the median OS had not been reached, HR 0.84 (95% CI 0.55-1.29, p=0.43). The median OS for patients with CIN treated with and without GCSF had not been reached, HR 1.02 (95% CI 0.57-1.82, p=0.94). The 5-year survival rate for patients with and without CIN was 87% vs 77%. The 10-year survival rate for patients with and without CIN was 70% vs 64%. A trend toward improved survival in those with CIN remained when results were analyzed by cancer stage. Conclusions: Patients with CIN had a trend toward improved survival compared to those who did not have CIN. There was no indication that GCSF in the setting of CIN impacted survival. The causes for the potentially protective effect of CIN in the setting of adjuvant CRC treatment require further elucidation.[Table: see text]
Anti-HER2 therapy with pyrotinib and trastuzumab in refractory HER2-positive metastatic colorectal cancer: A preliminary report from HER2-FUSCC-G study.
Authors: Li Wenhua , Chang Jinjia , Xu Midie , Zhu Xiaodong 
Published: January 2022

97 Background: Dual-targeted HER2 therapy has led to a promising antitumor effect in HER2 positive metastatic colorectal cancer. The current study was aimed to evaluate the therapeutic efficacy of pyrotinib and trastuzumab in patients with HER2 positive colorectal cancer. Methods: HER2-FUSCC-G is an ongoing, open-label, non-randomised, phase 2a study. Patients in this subset were diagnosed as HER2 positive metastatic colorectal cancer refractory to standard chemotherapies. All the enrolled patients were treated with a loading dose of trastuzumab at 8 mg/kg followed by 6mg/kg once every three weeks, and oral pyrotinib at 400 mg per day until progression. ORR was set as the primary endpoint. Estimates of PFS (progression free survival) and OS (overall survival) were obtained with the Kaplan-Meier method and compared with log-rank test. Results: Between January 2020 to June 2021, 11 patients were enrolled in this study. The ORR was 45.5% in whole population, and 55.6% in RAS wild-type patients. At a median follow-up of 17.73 months, median PFS and OS were 7.80 and 14.97 months, respectively. The KRAS wild-type group of patients had prolonged survival (PFS: 9.97 vs. 7.73 months, P = 0.19; OS: 20.67 vs. 12.43 months, P = 0.021) compared with KRAS mutant group. Nine of 11 (81.8%) patients reported≥1 grade treatment-emergent adverse events (TATEs), while 4 (36.4%) patients reported grade 3/4 TATEs. Conclusions: The combination of trastuzumab and pyrotinib showed a promising anti-tumor response and prolonged long-term survival benefit in RAS wild-type and HER2 positive mCRC with acceptable tolerance. Clinical trial information: NCT04960943.
Open-label phase 1/2 study evaluating the tolerability and antitumor activity of selinexor and pembrolizumab in colorectal cancer.
Authors: Golan Talia , Shentzer Kutiel Talia , Gottfried Maya , Zer Alona , Zick Aviad , Shai Ayelet , Ryvo Larissa , Dudnik Julia , Peled Nir , Oberkovitz Galia , Yang Fan , Sharoni Shmuel , Meng Changting , Michel Dayana , Sbar Eric , Shah Jatin J. , Kauffman Michael , Shacham Sharon , Geva Ravit 
Published: January 2022

110 Background: Single agent selinexor, an oral selective inhibitor of nuclear export (SINE), showed activity against heavily pretreated CRC with RAS mutations (mut) or wildtype (wt) in 2 clinical studies. In preclinical studies, selinexor showed superior potency in KRAS mut over wt with improved activity in combination with PD-1/PD-L1 blockade. A phase 1b study (NCT02419495) showed the safety and antitumor activity of combined selinexor and a PD-1/PD-L1 inhibitor. This phase 1/2 open-label study is evaluating selinexor with pembrolizumab in patients with microsatellite instability (MSI)-stable CRC. Methods: The study enrolled patients with advanced/metastatic CRC who progressed after prior chemotherapy (1-3 lines for RAS wt, 1-2 for RAS mut) and are ineligible for anti-PD-1/PD-L1 therapy. Patients received weekly oral selinexor 80 mg and pembrolizumab 200 mg IV every 3 weeks. Antitumor activity, safety and tolerability were assessed. Results: Thirty-four patients, median age 57.5 years, male 59%, RAS mut 53%, median prior lines 2, are enrolled. At data cutoff (1-SEP-21) median treatment duration was 57 days (range: 1-246) and 25 patients were evaluable for response. Best response was stable disease in 8/13 patients with RAS mut CRC (62%) and in 3/12 patients with RAS wt CRC (25%). Median overall survival (months) has not been reached for the overall population (95% CI: 6.3, NE), for RAS mut (95% CI: 7.6, NE), and for the RAS wt (95% CI: 6.1, NE). Median progression-free survival is 3.0 and 1.4 months for patients with CRC with RAS mut and wt, respectively (p=0.04; HR: 0.43 [959% CI: 0.18, 1.01]). Thirty patients (88%) discontinued therapy, mostly due to progressive disease (44%). The most common treatment-emergent adverse events (TEAEs) (total; Grade ≥3) were nausea (77%; 3%), vomiting (41%; 0%), fatigue (41%; 12%), decreased appetite (35%; 0%), diarrhea (32%; 0%). Nine patients (26%) had serious treatment-emergent adverse events. Conclusions: Combined selinexor with pembrolizumab demonstrated higher disease control rates and prolonged overall survival in patients with chemotherapy-refractory advanced/metastatic CRC with RAS mut vs RAS wt tumors. These patients would not have been eligible for anti-PD-1 mAb therapy because their tumors were not MSI-high, suggesting that the combination may be active in RAS mut CRC. Therapy was well tolerated with no unanticipated adverse events. Further investigation of this combined treatment is warranted, particularly in patients with CRC with RAS mut. Clinical trial information: NCT04256707.
Colonic endoscopic submucosal dissection using a novel robotic system.
Authors: Kim Sang Hyun , Choi Hyuk Soon , Lee Jae Min , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Lee Hong Sik , Chun Hoon Jai , Im Junghyun , Hong Daehie , Kim Byung Gon ,   Korea University College of Medicine
Published: January 2022

111 Background: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). We developed a robotic assistive traction device for colonoscopy.This is a preclinical animal study to evaluate the performance of colorectal ESD using novel robotic system. Methods: Experienced endoscopist performed ESD on ex vivo porcine colon ten times using a robot and ten times by the conventional method. The outcome measures were operating time (from starting incision to finishing dissection), completeness of resection, procedure-related adverse events, and limitations of arm manipulation in a narrow working space as assessed by counting the frequency of blind cutting.We also conducted an in vivo feasibility study on live pig. Results: Total of twenty colonic lesions were resected from ex vivo porcine colon. The submucosal dissection speed was significantly faster in robotic ESD than in conventional ESD (P = 0.002). Adverse events such as perforation were also significantly higher in the conventional group. In the in vivo feasibility study, robot was attached to the colonoscope and inserted into the proximal colon. ESD was performed successfully. Conclusions: When the robot was assisting in the ESD procedure, the dissection speed improved significantly. Our robotic device can thus provide simple, effective, and safe multidirectional traction during colonic ESD.
Frequency, molecular characteristics, and therapeutic targeting of ROS1 oncogenic fusions in colorectal cancer.
Authors: Hussung Saskia , Akhoundova Dilara , Sivakumar Smruthy , Kahraman Abdullah , Zoche Martin , Rechsteiner Markus , Angst Florian , Britschgi Christian , Töpfer Antonia , Moch Holger , Weber Achim , Sokol Ethan , Fritsch Ralph M 
Published: January 2022

160 Background: c-Ros oncogene 1, receptor tyrosine kinase ( ROS1) rearrangements have been reported in colorectal cancer (CRC), but little is known about the molecular and clinical features of ROS1-driven CRC and the response to ROS1-targeted treatment in CRC patients. Methods: We report disease course and treatment response of an index patient with chemotherapy-refractory right-sided metastatic CRC, harboring an activating ROS1 fusion ( GOPC-ROS1). Moreover, we examined 40,589 patients with CRC who underwent comprehensive genomic profiling as part of routine clinical care at Foundation Medicine (Cambridge, MA); all classes of alterations in at least 324 genes were assessed, including ROS1. Results: The index patient experienced a rapid and sustained partial response to molecularly targeted treatment with crizotinib. After 15 months on crizotinib, disseminated tumor progression occurred, with KRAS Q61H emerging in tumor tissue (53.7% variant allele frequency (VAF)) and liquid biopsy (13.5% VAF). Within the clinical cohort, ROS1 genomic rearrangements ( ROS1 RE (+)) were identified in 34 out of 40,589 (0.08%) CRC samples. GOPC-ROS1 was the most commonly identified ROS1 fusion (11/34 samples), followed by TTC28-ROS1 (3/34 samples). All ROS1-alterations were found in microsatellite-stable (MSS) CRCs, and ROS1 genomic alterations were significantly enriched in KRAS wild type tumors ( KRAS mutations in 23.5% of ROS1 RE(+) vs. 49.8% of ROS1 RE(-), p=0.003). Conclusions: ROS1 rearrangements represent rare but clinically actionable molecular driver alterations in MSS CRCs. The detection of ROS1 fusion oncogenes in CRC can pose diagnostic challenges since intrachromosomal ROS1 fusions including GOPC-ROS1 and non-canonical ROS1 fusions such as TTC28-ROS1 can remain negative on fluorescence in situ hybridization and immunohistochemistry assays, respectively. NGS-based comprehensive molecular profiling may be a useful tool to screen for rare fusion oncogenes.
Mismatch repair proteins (MMR) expression as predictive factor in locally advanced rectal cancer.
Authors: Pretta Andrea , Donisi Clelia , Persano Mara , Pinna Giovanna , Cimbro Erika , Parrino Alissa , Aimola Valentina , Spanu Dario , Cerrone Giulia , Deidda Simona , Deidda Maria Assunta , Lai Eleonora , Pusceddu Valeria , Puzzoni Marco , Ziranu Pina , Barbara Raffaele , Restivo Angelo , Zorcolo Luigi , Faa Gavino , Scartozzi Mario 
Published: January 2022

182 Background: Only few data on microsatellite instability in rectal cancer are available in literature, and dMMR role in pre-operative chemoradiotherapy response is under debate. The aim of our study was to evaluate the frequency and therapeutic implications of dMMR status in patients (pts) with locally advanced rectal cancer belonging to our Center. Methods: Data were retrospectively collected from 231 patients belonging to the Medical Oncology Unit of the University Hospital of Cagliari from 2011 to 2021. All patients were affected by locally advanced rectal adenocarcinoma (cT3-4 +/- N1-2). All patients included in the study underwent neoadjuvant chemoradiotherapy treatment with capecitabine and RT long course (total dose of Gy 50.4) and subsequently underwent total mesorectal excision (TME) followed by adjuvant chemotherapy. Mismatch repair (MMR) expression was evaluated through immunohistochemistry on surgical samples. Results: Of the 231 patients, 213 were suitable for final analyzes. Patients median age was 68 years (range 34-89). 145/201 were male and 68 were female. 66 (31%) had stage II disease and 147 (69%) had stage III disease. Considering MMR, 205/213 (96%) patients had proficient mismatch repair (pMMR), while 8/213 (4%) had dMMR. In dMMR patients defective proteins were: MSH2 in 4 patients, MLH1 and PMS2 combined in 2 patients and MSH6 in 2 patient. dMMR patients showed, unlike pMMR patients, poor or no response to chemoradiotherapy. Responses were assessed through TRG evaluation (Ryan and Dworak scoring systems) on the primary tumour. 5 patients presented a TRG-3 and 3 patients showed a TRG-4, according to Ryan score. All of them had a grade 1 regression, according to Dworak. Conclusions: The results of our study, albeit with limitations related to the retrospective nature and the limited number of dMMR cases, might indicate a correlation between microsatellite instability and little or no response to preoperative chemo-radiotherapy. It would be useful to analyze the data prospectively and further evaluate MMR as a predictor of response to combined chemo-radiotherapy.[Table: see text]
High immunoscore as a predictor of outcome in patients who underwent chemoimmuno-therapy in locally advanced rectal cancer: A post-hoc analysis of the correlation between immunoscore and pCR in the Averectal study.
Authors: Shamseddine Ali , Khalifeh Ibrahim Moustafa , Elias Charbel , Turfa Rim , Kattan Joseph Gergi , Mukherji Deborah , Temraz Sally Naji , Alqasem Kholoud , Amarin Rula , Alawabdeh Tala , Deeba Samer , Mohamad Issa , Daoud Faiez , Al Masri Mahmoud , Dabous Ali , Hushki Ahmad , Jaber Omar , Charafeddine Maya , Farhat Lama , Tawil Ayman 
Published: January 2022

184 Background: The immunoscore (IS), a prognostic score, was first validated in early colon cancer reflecting the immune response against the tumor. It showed potential in its ability to downstage patients with pathologic complete response (pCR) who would potentially benefit from organ-sparing therapies in locally advanced rectal cancer (LARC). We first presented our initial outcome with 37.8% pCR in patients with LARC treated with short course radiation therapy (SCRT) followed by 6 cycles of mFOLFOX plus Avelumab followed by total mesorectal excision (TME) in the ESMO 23rd World Congress on Gastrointestinal Cancer 2021 Conference (presentation # SO-30). Here we are reporting the post-hoc analysis of the correlation between pCR and pre-treatment biopsy IS to further establish the IS as a prognostic score in patients with LARC. Methods: In this Phase II study, 44 patients were accrued from three centers, of whom 40 completed radiotherapy followed by chemoimmunotherapy then TME. 39 patients with available tissue samples, containing tumor cells and its margins, were collected at baseline. CD3 and CD8 cells were counted, and the IS is then derived from the mean density percentiles of CD3 and CD8 positive T cells infiltrating the tumor and in the invasive margin of the tumor. Cutoff for a high IS was established at 62%. We then compared the tumor regression grade (TRG) with the means of IS, using the student t-test. Results: 15 patients with pCR had a mean IS of 68 +/- 22 SD as opposed to a mean IS of 52 +/- 22 SD in 24 patients without pCR (p = 0.036). Conclusions: High IS correlates with TRG as pCR and successfully predicted clinical outcome in LARC patients who underwent chemoimmuno-therapy. It is a promising potential prognostic tool in stratifying patients who would benefit from specific modalities to augment pCR and subsequent organ preservation strategy. Clinical trial information: NCT03503630.
Real-world immunotherapy biomarker testing patterns and results for patients with advanced gastroesophageal cancers in the United States.
Authors: Mehta Rutika , Liepa Astra M. , Zheng Shen , Chatterjee Anindya 
Published: January 2022

255 Background: With the advent of immunotherapy as an option for gastric, gastroesophageal junction (GEJ), or esophageal cancer, guidelines recommend testing for mismatch repair (MMR) or microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) at time of advanced cancer diagnosis. However, little real-world information is available on testing patterns and results for MMR/MSI and PD-L1. Methods: This study used the nationwide Flatiron Health electronic health record-derived de-identified database. Starting with a subset of 1594 patients (pts) from the Advanced Gastric/ Esophageal Cancer database who had initiated first-line (1L) treatment 01Jan2017-31Aug2020 and for whom additional abstraction for details on MMR/MSI and PD-L1 testing was conducted, adult pts with ≥3 months (mos) of follow-up were selected. 1L initiation was index date. For each biomarker, pts were classified as tested vs not. Pt and disease characteristics and test results were summarized. Testing relative to line of therapy and PD-1 inhibitor use were evaluated (data will be presented later). Results: Of 1142 eligible pts, 88% were initially diagnosed with advanced disease and 92% treated in community practice. 582 (51%) were tested for MMR/MSI and 571 (50%) for PD-L1; 451 pts were tested for both. MMR/MSI testing rates were 59% for gastric, 51% for GEJ, and 46% for esophageal. PD-L1 testing rates were similar across primary tumor sites (48-54%), but lower in those with squamous histology (38% for esophageal/GEJ). For both, testing increased over time with ̃40% in 2017 and 60% in 2020. For both, median number of tests per pt was 1 (range 1-6 for MMR/MSI, 1-4 for PD-L1). For both, mean time from initial diagnosis to first test was approximately 4 mos (> 5 mos in pts in 2017 and < 2 mos for those in 2020). Majority (> 68%) of all tests used tissue from primary tumor site. 46% of all MMR/MSI tests were performed with immunohistochemistry and 43% with next-generation sequencing; 5% were dMMR/MSI-H. 71% of all PD-L1 tests were performed using the commercial 22C3 assay. Reported composite positive score (CPS) results are summarized below. Conclusions: Rates of MMR/MSI and PD-L1 biomarker testing are increasing and time relative to initial diagnosis is shortening. A high proportion of pts tested positive for PD-L1 with CPS > 1. PD-L1 CPS varies by primary tumor site, histology, and tissue collection site. In the new era of 1L immunotherapy, increased rates of testing and reduced time to testing are likely to make more meaningful impact on treatment decisions.[Table: see text]
Beyond median overall survival: Estimating multiple survival scenarios in patients with metastatic esophagogastric cancer.
Authors: Pape Marieke , Kuijper Steven , Vissers Pauline A.J. , Creemers Geert-Jan , Van Laarhoven Hanneke W.M. , Verhoeven Rob 
Published: January 2022

261 Background: Recent clinical trials of novel systemic therapies showed improved survival of patients with metastatic esophageal cancer (EC) and gastric cancer (GC). Survival improvements observed in clinical trials might be unrepresentative for the total population as the percentage of patients whom participate in clinical trials is limited and more than half of all patients receive best supportive care (BSC). The aim of our study is to assess the best-case, typical and worst-case survival scenarios in patients with metastatic esophagogastric cancer. Methods: We selected patients with metastatic EC (including junction) or GC diagnosed in 2006-2019 from the Netherlands Cancer Registry. Survival scenarios were calculated based on percentiles of the survival curve stratified by tumor location and treatment (tumor-directed therapy or BSC). Survival scenarios were calculated for the 10th (best-case), 25th (upper-typical), 75th (lower-typical) and 90th (worst-case) percentiles. Linear trend analysis was performed to test if changes in survival over the diagnosis years were significant. Results: We identified 12739 patients with EC and 6833 patients with GC. Percentage of patients receiving tumor-directed therapy increased from 34% to 47% and 30% to 45% for patients with EC and GC, respectively. The median survival remained unchanged for patients with EC (5.0 months) and improved slightly for patients with GC (3.1 to 3.7 months; P=0.006). For patients with EC survival of the best-case scenario improved (17.4 to 22.8 months; P=0.001), whereas the other scenarios remained unchanged: upper-typical 11.2 to 11.7 (P=0.11), lower-typical 2.1 to 2.0 (P=0.10) and worst-case 0.9 to 0.8 months (P=0.22). For patients with GC survival improved for the best-case (13.1 to 19.5; P=0.005) and upper-typical scenario (6.7 to 10.6 months; P=0.002), whereas the lower-typical (1.2 to 1.4 months; P=0.87) and worst-case (0.6 to 0.6 months; P=0.60) remained unchanged. For patients with EC receiving tumor-directed therapy survival in all scenarios remained unchanged while for patients receiving BSC survival decreased: best-case 11.8 to 9.8 (P=0.005), upper-typical 6.0 to 5.0 (P=0.002), lower-typical 1.4 to 1.0 (P=0.003) and worst-case 0.7 to 0.5 months (P=0.03). For patients with GC receiving tumor-directed therapy survival improved for all scenarios: best-case 19.8 to 30.4 (P=0.005), upper-typical 6.4 to 10.3 (P=0.002), lower-typical 3.6 to 5.4 (P<0.001) and worst-case 1.4 to 2.6 months (P<0.001), and for patients receiving BSC survival for all scenarios remained unchanged. Conclusions: The proportion of patients with EC and GC receiving tumor-directed therapy increased over time. Despite the fact that survival improvements were not observed across all scenarios, at least an increase in survival was observed in certain subgroups of patients.