bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: An analysis of Intergroup 0114
Authors: Meyers M. O. , Hollis D. R. , Mayer R. J. , Benson A. B. , Goldberg R. M. , Cummings B. , Gunderson L. L. , Martenson J. A. , Macdonald J. S. , O’Connell M. , Tepper J. E. 
Published: March 2020

4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, >0.25–0.50, >0.50–0.75 and >0.75. Results: 1,648 patients were evaluable. There were 251 T1/2, 1,251 T3 and 146 T4 tumors. 513 patients were N0, 743 N1 and 392 N2. Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p<0.0001). LN ratio remained significant when overall survival was analyzed by number of LN examined and grouped into <10, <15 and >15 nodes evaluated (p<0.0001 for all). LN ratio also predicted overall survival in N1 (p=0.04) and N2 (p=0.0002) disease. When comparing LN ratio (χ2=79.5, p<0.0001) to number of LN examined (χ2=4.7, p=0.03), number of positive LN (χ2=38, p<0.0001), number of negative LN (χ2=32, p<0.0001) and AJCC nodal stage (χ2=55.5, p<0.0001), LN ratio appears to be the strongest predictor of overall survival. Conclusion: LN ratio predicts overall survival in patients with resected rectal cancer. Importantly, this is true in patients who have had a small number of LN evaluated, in addition to those with a large number of LN examined. LN ratio also appears to be a stronger predictor of overall survival than other described LN prognostic factors. LN ratio may be a useful variable to stratify outcome in patients with node-positive rectal cancer. No significant financial relationships to disclose.
Assessing 12 or more lymph nodes increases the proportion of stage III disease in colorectal cancer (CRC): Evidence from the Surveillance, Epidemiology and End Results (SEER) cancer registry
Authors: Cai Q. , Sullivan P. A. , Yeh Y. , Russell M. 
Published: March 2020

4016 Background: NCCN guidelines (2001) recommend assessment of ≥12 lymph nodes (LN) to improve accuracy of CRC staging. The impact of aggressive LN sampling on CRC staging has not been explored rigorously to date. This study examines variations in CRC staging by number of LN assessed. Methods: 299,242 patients from SEER aged ≥18 years diagnosed with CRC during 1990–2003 were included. Multivariate logistic regression was used to assess the association between sampling ≥12 LN (vs. <12) and staging, adjusting for age, sex, race, region, tumor size and grade, and year of SEER entry. Results: Patients who had ≥12 LN sampled were 1.3 times more likely to be diagnosed with stage III than stage II CRC [95% CI 1.28–1.34, p< .01]. The odds of being staged as III versus II increased over time [OR=1.01, 95% CI 1.01–1.02, p< .01]. However, the introduction of the NCCN guidelines was not associated with nodal sampling. Conclusion: The proportion of CRC patients who received appropriate sampling with most recent data available is unacceptably low. The significant increase in stage III patients who had ≥12 LN sampled may increase the proportion of patients considered for aggressive treatments. Because accuracy of staging is improved with nodal sampling, clinicians will be better positioned to treat patients if LN sampling recommendations are followed. [Table: see text] [Table: see text]
Outcomes in white (W) patients (pts) and those of African (A) descent receiving adjuvant therapy for colon cancer (CC)
Authors: Yothers G. , Blackstock W. , Wolmark N. , Goldberg R. M. , O’Connell M. J. , Benedetti J. , Dignam J. , Sargent D. J. 
Published: March 2020

4017 Background: Published reports suggest that CC pts of A descent have inferior survival compared to W pts. Whether these differences are explained by clinical factors at diagnosis, socioeconomic factors impacting access to care, or intrinsic differences in the biology of the tumors or the response to therapy is unclear. Pts in clinical trials have data collected for important baseline clinical factors and should receive comparable oncologic care regardless of socioeconomic factors. Methods: We analyzed data from 13,435 individual pts on 11 phase III adjuvant CC trials accrued from 1977 to 2002. Analysis was restricted to stage II and III pts, with race reported as black or white. Endpoints were overall survival (OS - time to death), recurrence-free survival (RFS - time to recurrence or death), and recurrence-free interval (RFI - time to recurrence censoring for death). Cox models stratified by study controlled for gender, stage, age, and treatment type (rx) to determine the effect of race. Kaplan-Meier estimates (KM) were adjusted (adj) by the Xie-Liu method for study, gender, stage, age, and rx. Results: A pts (n=1134, 8.4%) were younger than W (median 58 vs 61, p<0.001) and more likely female (55 vs 45%, p<0.001). A pts had poorer OS than W pts ( table ). OS results were consistent in subsets defined by gender, stage, and age. RFS results were attenuated compared to OS, but still favored improved RFS in W pts ( table ). RFI results were further attenuated and not significantly different by race ( table ). Conclusions: Even with identical rx for CC in controlled clinical trials, A pts have poorer OS and RFS than W pts. The OS deficit was consistent across subgroups, and neither deficit was explained by differences in gender, stage, age, or rx. RFI was similar for both races, suggesting that the OS and RFS differences may be largely due to deaths unrelated to CC. [Table: see text] [Table: see text]
Tissue biomarkers (BIOM) in colon cancer (COC): The translational study on the randomized phase III trial comparing infused irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) to 5-FU/FA in stage II-III COC patients (pts)
Authors: Roth A. D. , Tejpar S. , Yan P. , Fiocca R. , Dietrich D. , Bodoky G. , Labianca R. , Cunningham D. , Van Cutsem E. , Bosman F. 
Published: March 2020

4022 Background and Aims: PETACC 3 is a large adjuvant trial with 3,005 COC pts. The value of BIOM in COC in adjuvant setting is still a matter of debate because of lack of large data sets. We took advantage of PETACC 3 to assess P53, SMAD4, thymidylate synthetase (TS), telomerase (HTERT) expressions, UGT1A1 genotype, KRAS and BRAF mutations, microsatellite instability (MSI), 18q and 8p LOH with regard to their prognostic and predictive value and their individual interactions on a very large homogeneous cohort of COC pts. In addition we investigated the association between UGT1A1 genotype and occurrence of diarrhoea and Gd 4 neutropenia. Methods: 1,564 formalin fixed paraffin embedded (FFPE) tissue blocks of PETACC 3 pts were prospectively collected and 5–20μ sections cut. DNA from normal (Nor) and tumoral (Tu) tissue was extracted after section microdissection. P53, SMAD4, TS and HTERT were assessed by immunohistochemistry (IHC); MSI was typed with 10 markers, KRAS exon 2 and BRAF exon 15 mutations by allele specific real time PCR on Tu DNA; 18q and 8p LOH by typing multiple SNPs by pyrosequencing on Nor/Tu DNA; UGT1A1 genotypes by PCR and fragment sizing on Nor DNA. Prognostic/predictive value of each BIOM is analysed by Cox regression for disease free survival and by logistic regression for specific toxicity. Associations between any 2 categorized BIOM and between each BIOM and each known prognostic variable are tested by chi-square tests. Results: DNA of 1405 pts was extracted and successfully analyzed in 97.1% for KRAS, 98.6% for BRAF, 94% for 18q LOH, 93.6% for MSI, 86% for UGT1A1, 8p LOH is still ongoing. Of 1530 pts slides IHC analysis was successful in 94.5% for P53, 94.2% for SMAD4, 82.9% for TS, 53.9% for HTERT. The clinical database was made available in Nov 06 and statistical analysis started on Dec 11th 2006. Conclusion: This is the largest multicenter centrally coordinated tissue BIOM study performed in COC to date. The high success rate of analysis shows that large prospective BIOM studies can be performed on routine FFPE material. Final results on the prognostic/predictive value of each molecular BIOM will be available at the meeting. No significant financial relationships to disclose.
A prospective study of oxaliplatin and capecitabine (CapOx) in metastatic colorectal cancer (MCRC) with baseline stratification according to resectability status
Authors: Watkins D. J. , Jackson C. , Chua Y. , Chong G. , Norman A. R. , Brown G. , Mudan S. , Karanjia N. , Cunningham D. 
Published: March 2020

4024 Background: Consideration of metastasectomy is now standard practice in the management of selected patients (pts) with stage IV MCRC. As a result, modification to the current staging system has been suggested to more clearly define subgroups of stage IV pts. As yet, there are no prospective data comparing the outcomes of pts according to resectability status. This phase II study evaluates the outcomes of pts according to baseline resectability status, and examines the utility of CapOx chemotherapy as a neoadjuvant treatment strategy. Methods: Eligible pts had received no prior chemotherapy for MCRC. At study entry imaging review was undertaken and pts stratified into 3 groups according to resectability status; non-resectable (group 1), potentially resectable liver disease (group 2), resectable liver disease (group 3). All pts received identical chemotherapy; capecitabine 2,000mg/m2 d1–14 and oxaliplatin 130mg/m2 d 1 repeated every 3 weeks. Repeat imaging was undertaken every 4 cycles. For pts in groups 2 & 3, all imaging was reviewed by a specialist hepatic MDT, where feasible metastasectomy was undertaken following 4 or 8 cycles of chemotherapy. Planned enrolment was 130 pts, with study endpoints including; response rate, PFS & OS. Results: 129 pts are enrolled. Median age 62 (range 29–78). Median number of cycles delivered 8 (range 1–12). Grade III/IV toxicities; diarrhoea 14%, neutropenia 7.8%, peripheral neuropathy 2%. 60 day all cause mortality 3.1%. There have been no post operative deaths following liver resection. Median follow up is 19.3 months. Outcome data for each group is summarised below. Conclusion: CapOx chemotherapy is safe and well tolerated when used as a neoadjuvant treatment strategy. This prospective study clearly demonstrates the wide variation in outcomes according to baseline resectability status, and highlights the need for modification to the staging system to account for these patient subgroups in future studies. [Table: see text] [Table: see text]
XELOX compared to FOLFOX4: Survival and response results from XELOX-1/ NO16966, a randomized phase III trial of first-line treatment for patients with metastatic colorectal cancer (MCRC)
Authors: Cassidy J. , Clarke S. , Diaz-Rubio E. , Scheithauer W. , Figer A. , Wong R. , Koski S. , Lichinitser M. , Yang T. , Saltz L. 
Published: March 2020

4030 Background: In a phase II study in untreated MCRC patients, XELOX (capecitabine + oxaliplatin) appeared to have similar efficacy compared with previously published FOLFOX4 data [1]. We therefore started a phase III 2-arm open-label non-inferiority study comparing XELOX with FOLFOX4. In 2003 the addition of bevacizumab (Bev) to irinotecan/5-FU/LV was shown to improve progression-free survival (PFS) and overall survival [2]. We then amended our trial to a 2x2 partially blinded study to assess the addition of Bev. Methods: Original 2-arm study: XELOX (oxaliplatin 130 mg/m2 iv, capecitabine 1,000 mg/m2 bid oral d1- 14, q3w) vs. FOLFOX4 (oxaliplatin, 5-FU, leucovorin as described previously) [3]. In August 2003, amended to 2x2 partially blinded study: by adding Bev 7.5 mg/kg iv q3w or placebo (Pla) to XELOX and Bev 5 mg/kg iv q2w or Pla to FOLFOX4. Results: The original 2-arm study recruited 634 pts; after transition to 2x2, an additional 1400 patients were recruited. We previously reported non-inferiority in terms of PFS of XELOX vs. FOLFOX4 for the whole study population [4]. With 404 events, the overall survival data from the original 2-arm study are mature and show a HR for XELOX vs. FOLFOX4 of 0.93 (97.5% CI, 0.74–1.16). The response rates by investigator and independent review for the whole study population are shown in the table . Conclusions: XELOX is non-inferior to FOLFOX4. Overall survival data for the whole 2034 patient study population will be presented at the meeting. *no response assessment. 1. Cassidy J et al. J Clin Oncol 2004;22:2084–91. 2. Hurwitz H et al. N Eng J Med 2004;350:2335–42 3. De Gramont A et al. J Clin Oncol 2000;18:2938–47. 4. Cassidy J et al. Ann Oncol 2006;17(Suppl. 9):LBA3. [Table: see text] [Table: see text]
Comparable safety and response rate with bevacizumab in combination with capecitabine/oxaliplatin (CapOx/Bev) versus capecitabine/irinotecan (CapIri/Bev) in advanced CRC (mCRC): A randomized phase II study of the AIO GI tumor study group
Authors: Schmiegel W. H. , Reinacher-Schick A. , Freier W. , Dietrich G. , Arnold D. , Kanzler S. , Geissler M. , Graeven U. , Hegewisch-Becker S. , Schmoll H. 
Published: March 2020

4034 Background: Bevacizumab (Bev) combined with 5-FU/FA and both, irinotecan or oxaliplatin are standard regimens for mCRC. Recently, a phase III trial has demonstrated that infusional 5-FU can be substituted by capecitabine (cape) when combined with oxaliplatin and Bev whereas conflicting data are available for feasibility and efficacy of cape/irinotecan combinations. This randomized phase II trial was to compare safety and efficacy of Bev with either CapOx or CapIri in untreated mCRC. Methods: Eligibility criteria: untreated mCRC pts, ECOG PS <= 2, measurable lesion(s), adequate hematologic and organ function. Primary endpoint was % of pts progression-free after 6 months. Treatment plan: Bev 7.5 mg/kg day (d)1 with either oxaliplatin (130 mg/m2 d1)/cape (1,000 mg/m2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200 mg/m2 d1)/cape (800 mg/m2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were 20% lower for both, cape and irinotecan, compared to previous trials reporting an unacceptable toxicity profile (Köhne, ASCO 2005). Treatment was continued until progression or unacceptable toxicity. Results: So far, toxicity data are available on 228 (118/110 pts arm A/B) of total 240 pts. Baseline characteristics (arm A/B): median age 64/65 yrs, male 67%/68%. A total of 684/719 cycles (median 6/6 cycles) have been administered. Most common CTC grade 3/4 toxicities (% of pts): Diarrhea 17.0/15.5, hand-foot-syndrome 5.9/2.7, peripheral neuropathy 15.3/0.0. Specific AE′s such as thrombosis, 3° hypertension and GI perforation occurred in 3.4/4.5%, 3.4/0.9% and 0.9/0.9% of pts, respectively. Among 185 evaluable pts (96/89), tumor control rates (CR+PR+SD) in arm A/B were 81.4%/82.8%, overall response rates (CR+PR) were 49.0%/52.7%. Conclusions: Both regimens, CapOx/Bev and CapIri/Bev, are well tolerated without differences in toxicity (except neuropathy). Interestingly, despite the protocol defined dose reduction of CapIri there is seemingly no difference in efficacy as measured by tumor control and response rate. Meanwhile, the trial has finished accrual and data including PFS rate will be presented at the meeting. [Table: see text]
Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)
Authors: Hamaguchi T. , Shirao K. , Moriya Y. , Yoshida S. , Kodaira S. , Ohashi Y. 
Published: March 2020

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.
Adherence to surveillance guidelines following curative resection for stage II and III colorectal cancer
Authors: Cheung W. Y. , Pond G. R. , Rother M. , Krzyzanowska M. , Brierley J. , Swallow C. , Kaizer L. , Myers J. , Phillips S. , Siu L. L. 
Published: March 2020

4051 Background: The risk of disease recurrence in stage II and III colorectal cancer (CRC) patients (pts) following curative resection underscores the need for post-operative surveillance. However, there is continual controversy as to whether an intensive or conservative strategy is more appropriate. Our aims were to determine adherence in the ‘real world‘ to ASCO guidelines on CRC surveillance and to evaluate differences in practice patterns and outcomes between an academic instituation, Princess Margaret Hospital (PMH), and a community cancer center, Credit Valley Hospital (CVH). Methods: Stage II and III CRC pts diagnosed between 1999 and 2001 were identified from hospital cancer registries. Surveillance practices and outcomes in the first 5 years of follow-up were retrospectively reviewed. Results: A total of 244 and 97 pts were identified at PMH and CVH, respectively: 80 stage II and 119 stage III colon cancers (CC), and 66 stage II and 76 stage III rectal cancers (RC). Median age at diagnosis was 61.8 years. Surveillance patterns over a 5-year period, adherence to ASCO guidelines and comparisons between hospitals were tabulated (see table ). There were a total of 70 CRC recurrences: 53/244 (22%) at PMH and 17/97 (18%) at CVH. Among them, 53 (76%) were detected by surveillance (44 PMH, 9 CVH) and 17 (24%) by symptoms (9 PMH, 8 CVH). For recurrences detected by surveillance, 20/53 (38%) were resectable, whereas only 3/17 (18%) of those detected by symptoms were resectable. Of the 20 resectable recurrences detected by surveillance, 40% were CC and 60% were RC; CT scan was the method of detection in 55% of cases, and sites of recurrence included liver (7), lung (6), local (5), and nodes (2). Conclusions: CRC surveillance revealed significant departures from ASCO guidelines with a large academic institution employing a more intensive surveillance strategy with imaging than a community cancer center. Surveillance was associated with a higher proportion of resectable tumor recurrences than detection by symptoms. [Table: see text] No significant financial relationships to disclose.
Impact of timing of initiation of adjuvant chemotherapy on survival after resection of colorectal cancer
Authors: Ahmad I. , Anan G. , Alvi R. , Haider K. , Sami A. , Yadav S. , Arnold F. , McLeann L. , Popkin S. , Ahmed S. 
Published: March 2020

4054 Background: Based on the results of intergroup trials, adjuvant chemotherapy has become the standard of care for patients with Duke stage C colon and Duke stages B and C rectal cancer. Although initiation of adjuvant chemotherapy soon after recovery from surgery is desirable, only few studies have examined whether a delay in starting adjuvant chemotherapy affect clinical outcomes. Our objective in this study is to determine the impact of timing of adjuvant chemotherapy on survival after resection of Duke stage C colon and Duke stages B and C rectal cancer. Methods: Study involves use of the information available from patients chart review in the province of Saskatchewan, Canada. Patients 18 years of age and older (median age 66 years), diagnosed with Duke Stage C colon and Duke stages B and C rectal cancer between 1993 and 2000 were included. Median followup was 54.8 months. All patients with rectal cancer received radiation treatment as per institution policy. Cox proportional hazards models were used to analyze the impact of timing of adjuvant chemotherapy on survival. Results: Among 701 patients eligible for study, 453 (64.6%) patients received adjuvant chemotherapy within 56 days of surgery (group I) and 248 patients (35.3 %) received adjuvant chemotherapy after 56 days of surgery (group II). Median time interval between surgery and the initiation of adjuvant chemotherapy in group I, and II were 41 days and 70 days respectively. Five year DFS for group I was 39% as compared to 37% for group II (HR 0.94, CI 0.76–1.16, p = 0.58). Median OS for group I was 97.5 months as compared to 68.9 months (HR 1.08, CI 0.85–1.37, p= 0.54). Age, histology and number of lymph nodes analyzed, were identified as independent prognostic factors in multivariate analysis. Conclusions: In this study, patients with Duke stage C colon and Duke stages B and C rectal cancer who received adjuvant chemotherapy within 56 days of resection has similar outcomes as compared to patients who received adjuvant chemotherapy after 56 days of resection. [Table: see text]