bluuebunny/crossref_metadata_2025_split huggingface dataset:
The number of lymph nodes examined as a poor prognosis factor in stage II and stage III colon cancer patients undergoing curative surgery.
Authors: JEON JEONGSEOK , Shen Lingjie , Kim Yitak , Kim Hyunwook , van Gestel Anna J. , Han Yoon Dae , Han Dai Hoon , You Seng Chan , Ahn Joong , Shin Sangjoon , Geleijnse Gijs , Kim Han Sang 
Published: June 2023

3612 Background: The number of lymph nodes (LN) examined is a key factor in determining the stage of colorectal cancer. Over the past 20 years, the examination of fewer than 12 LN has been regarded as a poor prognosis. However, surgical procedures and pathologic examination improvements have increased the number of LN examined. This raised the question of reassessing the best cutoff point for staging colon cancer patients undergoing curative surgery. Methods: We reviewed a total of 3,126 eligible patients with stage II-III colon cancer collected from the Yonsei Cancer Center Registry (YCC) database between 2005 and 2015. As a validation cohort, we used clinicodemographic data from 9,604 patients with stage II-III colon cancer identified by the Netherlands Cancer Registry (NCR) between 2006 and 2015. The hazard ratio (HR) obtained from Cox-proportional regression was used to investigate the effect of LNs' yield on 6-year overall survival (OS). The optimal LN yield was evaluated by analyzing every cutoff from 3 to 165. We used the Kaplan-Meier method to compare the effect of higher vs. lower optimal LN yield on a 6-year OS. Univariate and multivariate Cox regressions were conducted. Results: The proportion of patients with fewer than 12 LN examined dramatically decreased between 2005 and 2015 (17.4% in 2005 vs. 0.6% in 2015, P< 0.001). Based on the 12 LN examined as the conventional cutoff number, there was no significant association between 6-year OS and LN yield in all stages II-III patients (HR = 1.21, P= 0.116; n = 3,126), stage II (HR = 1.39, P= 0.068; n = 1,570), and stage III (HR = 1.18, P= 0.297; n = 1,557) colon cancer. Interestingly, a higher cutoff of 20 LN examined was associated with a significant increase in 6-year OS in all patients (HR = 1.51, P< 0.001 in patients with LN examined less than 20). Multivariate Cox-proportional hazard regression showed a significant decrease in 6-year OS in stage II (HR = 1.39, P= 0.026) and stage III (HR = 1.54, P< 0.001) with less than 20 LN yield. Consistent with the result in the YCC database, less than 20 of LN yield was associated with poorer 6-year OS in stage II-III patients (HR = 1.25, P< 0.001; n = 9,604), stage II (HR = 1.43, P< 0.001; n = 4,689), and stage III (HR = 1.13, P= 0.007; n = 4,915) in the NCR, respectively. Conclusions: Less than 20 LN examined is associated with a poorer prognosis in patients with surgically treated colon cancer, compared to the current cutoff value of 12. Further validation of re-evaluating criteria on the inadequacy of LN retrieval in high-risk stage II colon cancer is warranted.
A prospective evaluation of pelvic radiation vs. no radiation among patients with young-onset rectal cancer: Impact on patient-reported outcomes.
Authors: Corrigan Kelsey L , Holliday Emma , Guraieb-Trueba Montserrat , Peacock Oliver , Skibber John Michael , Bednarski Brian K. , Messick Craig , Tillman Matthew Murray , Johnson Benny , Smith Grace L. , Nguyen Sa Thi , Kundu Suprateek , Reinhardt Alec , Chang George J. , Das Prajnan , You Y. Nancy 
Published: June 2023

3618 Background: The rise in young-onset rectal cancer (YORC) calls for better understanding of the long-term impact of radiation therapy(RT) on gastrointestinal(GI) toxicity and pelvic organ function. We aimed to prospectively capture the longitudinal trajectories of patient-reported outcomes(PROs) in YORC patients who received RT vs. no RT and to identify factors associated with unfavorable PROs. Methods: We prospectively enrolled 120 YORC patients undergoing curative-intent treatment. The validated EORTC QLQ-CR29 was self-administered at time intervals grouped as: 0-11 months, 12-23 months, and 24+ months post-resection. Responses were stratified by receipt of neoadjuvant RT (yes vs. no). The longitudinal change in PROs was described by a linear mixed effects model. Multivariate linear regression was used to determine the impact of treatment factors on long-term PROs. Results: The median age at diagnosis was 44. The majority (N = 92, 77%) presented with cT3,4/N+ disease. Preoperative therapy included: no RT (N = 38, 32%; 8 [7%] who received chemotherapy alone, and 30 [25%] who received no neoadjuvant therapy), vs. RT (N = 82, 68%; where 59 [72%] also received concurrent capecitabine). More patients in the RT group had advanced T stage (3 or 4; 94% vs. 56%, P< 0.001), distal tumor (median 7 vs. 12.5 cm from the anal verge, P< 0.01), and underwent abdominal perineal resection (19 vs. 0%, P< 0.001). After a median follow-up of 70 months, all were alive: 103 (86%) were disease-free, 9 (8%) had recurrence with successful salvage, and 8 (7%) had disease progression. In the RT group, sore skin improved at 12-23 and 24+ months (Estimate [ B]: -16.5, P= 0.03 and B: -14.4, P= 0.03), dyspareunia improved at 12-23 months ( B: -31.8, P< 0.01), and blood/mucus in stool improved at 24+ months ( B: -8.01, P< 0.01) vs. 0-11 months. At 24+ months, RT receipt was associated with worse stool frequency ( B: 26.4, P< 0.01), urinary frequency ( B: 18.4, P= 0.04), and flatulence ( B: 23.0, P= 0.02). Conclusions: YORC often require multimodality therapy including RT. Sore skin, dyspareunia, and blood/mucus in stool improved, but flatulence and frequency can persist beyond 2 years post RT. Proactive counseling and supportive measures are needed to inform treatment choices and mitigate long-term impact. [Table: see text]
Comparison of synchronous neoplasms at colonoscopic diagnosis of early-onset versus average-onset colorectal cancer.
Authors: Emiloju Oluwadunni Eunice , Saberzadeh Ardestani Bahar , Sinicrope Frank A. 
Published: June 2023

3623 Background: Colorectal cancer (CRC) incidence has steadily increased in adults younger than 50 years (EO-CRC) since the 1990s, with a predominance in the left colon and rectum. Precursor lesions of CRCs are adenomas, including advanced adenomas, and sessile serrated polyps. Given that neoplastic development is age-related, we hypothesized that patients with early-onset CRC (EO-CRC) may have fewer adenomas compared to patients with average-onset CRC (AO-CRC) at diagnosis. Methods: We performed a retrospective review of electronic health records at Mayo Clinic or Mayo Health System [2012 to 2021] and randomly selected 150 patients with EO-CRC who met eligibility criteria and matched them with 150 AO-CRC patients based on gender and colonoscopy indication. Known hereditary syndromes or inflammatory bowel disease were excluded. At colonoscopy where CRC was diagnosed, we recorded findings of adenomas, advanced adenomas (> 1 cm, villous histology, or high-grade dysplasia), and sessile serrated polyps (SSP). Results: Median age at diagnosis was 43 years for EO-CRC and 67 years for AO-CRC. No significant differences in BMI, family history of CRC, MMR, BRAFV 600E KRAS status or SSPs were found between groups (all p > 0.05). Among patients with colon cancer, no difference was found for adenoma number yet patients with EO-colon cancer (EO-CC) had larger polyps [median of 10 mm vs 5 mm, p = 0.001] (Table) compared with AO-colon cancer (AO-CC). At least 1 adenoma was found in 56% and 47% of patients with EO-CC and AO-CC, respectively. Moreover, advanced adenomas were significantly more common in the EO-CC group compared with the AO-CC group (42% and 14%, p < 0.001) [ Table]. Among patients with rectal cancer, non-advanced adenomas were less frequent and although advanced adenoma were similar in frequency, they were more commonly located in the rectum in EO-rectal compared to AO-rectal cancers (Table). Conclusions: Patients with EO-colon cancer had a significantly higher likelihood of a synchronous advanced adenoma in the colon compared to those with AO-CRC. Together, these data suggest accelerated carcinogenesis throughout the colorectum in early onset patients, with increased risk for development of synchronous and metachronous CRC. [Table: see text]
Outcomes by occurrence of immune-mediated adverse events (imAEs) with tremelimumab (T) plus durvalumab (D) in the phase 3 HIMALAYA study in unresectable hepatocellular carcinoma (uHCC).
Authors: Lau George , Cheng Ann-Lii , Sangro Bruno , Kudo Masatoshi , Kelley Robin Kate , Tak Won Young , Gasbarrini Antonio , Reig Maria , Lim Ho Yeong , Tougeron David , De Toni Enrico N. , Tam Vincent C. , Mody Kabir , Gong Jun , McCoy Carrie L. , Gupta Charu , Makowsky Mallory , Negro Alejandra , Abou-Alfa Ghassan K. 
Published: June 2023

4004 Background: Immune checkpoint inhibitor (ICI) studies have shown an association between the occurrence of imAEs and outcomes. In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved overall survival (OS) vs sorafenib (S), and D monotherapy was noninferior to S. STRIDE and D had manageable safety (Abou-Alfa et al. NEJM Evid 2022). STRIDE is approved for uHCC in the United States and Japan and recommended for approval by the European Medicines Agency; D is approved in Japan. This exploratory analysis assessed the association between imAEs and outcomes in HIMALAYA. Methods: Safety was assessed in participants (pts) who received ≥1 dose of STRIDE (T 300 mg [one dose] plus D 1500 mg once every 4 weeks [Q4W]) or D (1500 mg Q4W). imAEs were AEs of special interest associated with drug exposure and consistent with an immune-mediated mechanism of action with no found alternate etiology. Median OS (mOS) and OS rates were estimated using the Kaplan–Meier method. OS hazard ratios (HRs) and 95% CIs were calculated using Cox modeling, with imAEs as a time-varying covariate and stratified by etiology (HBV/HCV/others), ECOG (0/1), and macro-vascular invasion (yes/no) for pts with vs without imAEs of any grade. Pts with >1 imAE were counted once. Results: In total, 388 pts (STRIDE) and 388 pts (D) were included in the analysis. Any grade imAEs, Grade 3 or 4 imAEs, and imAEs leading to discontinuation occurred in 139 (35.8%), 49 (12.6%), and 22 (5.7%) pts, respectively for STRIDE and 64 (16.5%), 25 (6.4%), and 10 (2.6%) pts, respectively for D. imAEs requiring high-dose steroids (≥40 mg prednisone or equivalent daily) occurred in 78 (20.1%) pts for STRIDE and 37 (9.5%) pts for D. An improvement in OS was seen with STRIDE in pts with imAEs vs pts without (HR, 0.73; 95% CI, 0.56–0.95). OS rates at 6, 12, and 24 months (mo) were higher for STRIDE in pts with imAEs vs pts without. The association between imAEs and OS was less clear for D and may be limited by small pt number. In a landmark analysis of pts with vs without imAEs within 6 mo of STRIDE (n=307) or D (n=287), OS HRs (95% CIs) were 0.65 (0.47–0.90) and 1.39 (0.95–2.04), respectively. Conclusions: In HIMALAYA, imAEs with STRIDE or D were manageable and generally low grade. In this exploratory analysis, the occurrence of imAEs was associated with improved OS for STRIDE, generally consistent with findings for other ICIs. Clinical trial information: NCT03298451 . [Table: see text]
A phase 2 randomized, open-label, multicentre study of sintilimab and anlotinib in combination with gemcitabine plus cisplatin (GemCis) as first-line therapy in patients (pts) with advanced biliary tract cancer (BTC): SAGC.
Authors: Jingjing Li , Xu Qi , Xu Xiaoqing , Cong Luo , Ying Jieer 
Published: June 2023

4015 Background: BTC has a higher incidence in China rather than worldwide, with extremely poor prognosis, and the efficacy of standard first-line therapy is rather limited. TOPAZ-1 study suggested the immune check-point inhibitor plus chemotherapy as first line in advanced BTC significantly improved OS and PFS with manageable safety, but the median OS was just 12.8 months. SAGC is the first randomized controlled phase 2 trial to evaluate immune check-point inhibitor plus antiangiogenic targeted drug plus chemotherapy in advanced BTC as first-line treatment. Methods: Overall 80 advanced BTC were randomized 1:1 to receive sintilimab (200mg every 3 weeks [Q3W]) and anlotinib (10mg po qd, Days 1-14 Q3W) in combination with GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by sintilimab (200mg every 3 weeks [Q3W]) and anlotinib (10mg po qd, Days 1-14 Q3W) (SAGC group) or GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles until disease progression or unacceptable toxicity (GC group). The primary objective was to assess the progression-free survival (PFS). Secondary endpoints included, objective response rate (ORR), overall survival (OS) and safety. Next generation sequencing (NGS) was performed on pre-treatment available tumor tissue in 58 patients to screen dominant patients of the therapy. Results: At the time of the final data cutoff (Sep. 22,2022), median follow-up was 13.4 mo, and 65/80 pts (81.3%) had discontinued tx. The confirmed median PFS was 8.6 months for SAGC group vs. 6.2 months for GC group (HR 0·37, p < 0.01) and ORR was 52.8% for SAGC group vs. 29.4% for GC group. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 77.5% of pts receiving sintilimab plus anlotinib plus GemCis and 40% of pts receiving GemCis. The results from NGS suggested that patients with TMB-H and ARID1A-WT may benefit more from combination therapy. Conclusions: In pts with advanced BTC, sintilimab plus anlotinib plus GemCis significantly improved PFS and ORR vs GemCis with manageable safety, indicating sintilimab plus anlotinib plus GemCis may be a new first-line standard of care regimen. Clinical trial information: NCT04300959 .
A multicenter, open-label, randomized phase II study evaluating adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (CAPE-RT) in patients with operated gallbladder adenocarcinoma (GBC): The GECCOR-GB trial.
Authors: Ramaswamy Anant , Ostwal Vikas S. , Engineer Reena , Parulekar Manali , Mandavkar Sarika , Aier Nanda , Bhargava Prabhat Ghanshyam , Srinivas Sujay , Patkar Shraddha , KRISHNATRY RAHUL , Gudi Shivakumar , Kapoor Akhil , Pandey Durgatosh , Patel Swapnil , Shinghal Abhishek , Goel Alok , Dora Tapas Kumar , Chaudhary Debashish , Ankathi Suman Kumar , Goel Mahesh 
Published: June 2023

4017 Background: Adjuvant gemcitabine plus cisplatin (GC) and concurrent chemo-radiotherapy are commonly used treatment options for resected GBC. Methods: GB-GECCOR is a multicentre, open-label randomized non-comparative phase II study in patients of Gallbladder cancer (GBC), with R0 or R1 resection within 3 months of randomization. Patients were randomized 1:1 to GC arm (Gem 1000 mg/m2 and Cisplatin 25mg/m2 on day 1 and 8, q 3 weeks) for 6 cycles or CAPE-RT arm {Capecitabine 1000mg/m2 BD on days 1-14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825mg/m2 twice) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary end point was 1-year disease-free survival (DFS). With 80% power to detect the difference between a 59% (minimum sufficient activity of the regimen) and a 77% (sufficient activity for future larger studies with the regimen) 1-year DFS rate assuming an attrition of 10%, a total of 90 patients were required for the study. Results: Between May 2019 and February 2022, 90 patients (45 in each arm), were included. Stage II and stage III GBC were seen in 50 (56%) and 40 patients (44%) respectively, with R0 resection observed in 86 patients (96%). Patient characteristics were well balanced between the 2 arms except for R1 resections which were greater in the CAPE-RT arm (p=0.041). With a median follow-up duration of 23 months, the 1-year DFS rate was 88.9% (95% CI: 79.5-98.3) in the GC group and 77.8% (95% CI: 65.4 – 90.2) in the CAPE-RT group, respectively. The most common AEs were grade 3/4 neutropenia in 6 patients (13.3%) in the GC group and grade 2/3 HFS in 14 patients (31.1.%) in the CAPE-RT group. The distant metastases were seen in 12 patients (26.6 %) in each arm and loco-regional metastases in 3 patients (6.6 %) in the GC arm. Conclusions: In this study of operated GBC, GC and CAPE-RT successfully achieved the minimum pre-specified DFS rates. Within the confines of a non-comparative randomised study, GC had narrowed the gap in survivals of stage III vs. stage II GBCs, which was not noted in the CAPE-RT arm. This study results give credence to the use of both regimens as reasonable standards of care till evaluation in larger phase 3 studies. Clinical trial information: CTRI/2019/05/019323 . [Table: see text]
FOOTPATH: A randomized, open-label phase-2 study of liposomal irinotecan + 5-FU and folinic acid (NAPOLI) versus sequential NAPOLI and mFOLFOX6 versus gemcitabine/nab-paclitaxel in treatment-naïve metastatic pancreatic cancer (mPDAC).
Authors: Westphalen Benedikt , Gaska Tobias , Reichert Maximilian , Quante Michael , Oettle Helmut , Waldschmidt Dirk Thomas , Schlenska-Lange Anke , Angermeier Stefan , Fischer von Weikersthal Ludwig , Bohle Wolfram , Vehling-Kaiser Ursula , Stahler Arndt , Kanzler Stephan , Lamberti Christof , Pelzer Uwe , Sinn Marianne , Blau Wolfgang , Boeck Stefan Hubert , Held Swantje , Heinemann Volker 
Published: June 2023

4021 Background: The optimal first-line regimen in the treatment of mPDAC remains unknown. Recent data demonstrated superiority of 5-FU/liposomal irinotecan/oxaliplatin (NALIRIFOX) over gemcitabine/nab-paclitaxel. However, the question remains open if both irinotecan and oxaliplatin are required in first-line treatment and whether these agents can be given sequentially. Methods: Eligible patients with histologically confirmed diagnosis of mPDAC were randomized 1:1:1 to receive in Arm A standard treatment (gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2) or investigational therapy applying in Arm B the NAPOLI regimen (liposomal irinotecan 80 mg/m2 + folinic acid 400 mg/m2 + 5-FU 2400 mg/m2) or in Arm C a sequence of NAPOLI and mFOLFOX6 (oxaliplatin 85mg/m2 + folinic acid 400mg/m2 + 5-FU 2400 mg/m2). Overall, 274 patients were enrolled at 48 sites in Germany. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate, disease control rate, duration of study treatment and safety. Results: In the full analysis set (n=265), neither treatment with NAPOLI (3.1 months, HR 1.224, p= 0.2123) nor the sequence of NAPOLI and mFOLFOX6 (6.0 months, HR 0.864 p= 0.0720) lead to a statistically significant improvement of PFS over gemcitabine/nab-paclitaxel (4.3 months). Median duration of treatment was 3.5 months in Arm A, 2.0 months in Arm B and 3.7 months in Arm C, respectively. In a first analysis of overall survival, OS in Arm A was 8.7 months (95% CI, 7.1-11.9 months) versus 7.9 months in Arm B (95% CI, 6.6-12.3 months; HR 1.178, P= 0.348) and 11.0 months in Arm C (95% CI, 8.4-13.6 months; HR 0.879, P=0.154). Overall, safety was comparable with published data, with higher rates of neutropenia and peripheral neuropathy in Arm A, while diarrhea was more frequent in Arms B and C. Conclusions: The study did not show superiority of either NAPOLI or the sequence of NAPOLI/mFOLFOX6 over standard therapy with gemcitabine/nab-paclitaxel. In view of the published evidence, the present data supports the hypothesis that sequential NAPOLI/mFOLFOX6 may be equally effective with regard to OS, but less toxic, compared to mFOLFIRINOX. Clinical trial information: NCT03487016 . [Table: see text]
Survival analysis by tumor response of nivolumab treatment in previously treated advanced gastric cancer from the DELIVER trial (JACCRO GC-08).
Authors: Sunakawa Yu , Sakamoto Yasuhiro , Kawabata Ryohei , Ishiguro Atsushi , Akamaru Yusuke , Kito Yosuke , Takahashi Masazumi , Matsuyama Jin , Yabusaki Hiroshi , Makiyama Akitaka , Suzuki Takahisa , Tsuda Masahiro , Yasui Hisateru , Hihara Jun , Takeno Atsushi , Inoue Eisuke , Ichikawa Wataru , Fujii Masashi 
Published: June 2023

4039 Background: We conducted a prospective observational study, DELIVER trial (UMIN000030850), to evaluate the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC) and have reported comparable efficacy and safety data (Takahashi, et al. Gastric Cancer 2021). There are few evidence regarding the association between tumor response and survival time in later-line treatment with nivolumab alone for advanced GC. We therefore report results from post-hoc exploratory analyses of survival time by tumor response from the DELIVER trial. Methods: The DELIVER trial enrolled 501 patients (pts) with advanced gastric or GEJ adenocarcinoma treated with nivolumab alone. Primary endpoint was overall survival (OS), secondary endpoints were response rate (RR), disease control rate, progression-free survival (PFS), tumor regression rate / tumor progression rate at 1st evaluation, tumor growth rate, and safety. The exploratory analyses were performed for survival according to tumor response and depth of response (DpR) in pts with measurable lesions who were receiving nivolumab as 3rd or later-line treatment. The survival data was fixed at the timepoint of 2 years after the last enrollment. Results: 234 pts were evaluable (median age 70y [26-90], 79% male, ECOG PS0/1/2 46/43/11%, 32% pts with ascites). Median OS was 6.5 months (95%CI 5.3-8.2) and median PFS was 1.8 months (95%CI 1.6-2.0). The RR was 15.0% (95%CI 10.4-19.5) with 5 complete response (CR) and 30 partial response (PR). The median PFS and OS were not reached for pts with CR, 11.7 and 29.8 months for pts with PR, 3.8 and 11.4 months for pts with stable disease, and 1.5 and 4.2 months for pts with progressive disease, respectively. In addition, the median DpR was -14.1% and was associated with PFS and OS in the Spearman analysis (r=0.55 and r=0.44, respectively). When the DpR was divided into 5 groups according to tumor shrinkage, there was difference in PFS and OS. Conclusions: This exploratory analysis indicated the association between DpR and survival time in pts with advanced GC treated with nivolumab alone in later-line. Increasing DpR was associated with longer median PFS and OS. Clinical trial information: UMIN000030850 . [Table: see text]