Clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 867-867
Author(s):  
Shusuke Yagi ◽  
Eiji Shinozaki ◽  
Keisho Chin ◽  
Mitsukuni Suenaga ◽  
Daisuke Takahari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Dose Intensity ◽  
Clinical Impact ◽  
Stage Ii ◽  
Stage Iii ◽  
Diverting Ileostomy ◽  
Grade 3

867 Background: CAPOX as adjuvant chemotherapy is a standard care option for stage III and high risk stage II colorectal cancer(CRC). And then chemotherapy induced diarrhea (CID) is known as one of the dose-limiting toxicities for CAPOX. Although diverting ileostomy is useful for preventing serious complications of high risk anastomosis, it is well recognized that high ileostomy output is hard to manage. Furthermore, the effect of diverting ileostomy on CID of adjuvant chemotherapy is unclear. In this study, we addressed the clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for CRC. Methods: Patients who diagnosed with stage III colon cancer and stage II or III rectal cancer after curative surgery and received CAPOX as adjuvant chemotherapy during 2011- 2014 were reviewed retrospectively. We investigated the relationship between diverting ileostomy and dose intensity, toxicities and disease-free survival (DFS). Results: 112 patients (median age 60 years, 52% male, 69% colon cancer, 63% stage III, median follow-up 47 months) were enrolled in this study. Of 112 patients, 100 patients were received chemotherapy without ileostomy (non-ileostomy group: NIG) and 12 patients were received chemotherapy with ileostomy (ileostomy group: IG). 112 Patients received 870 chemotherapy cycles. All treatment related grade 3/4 adverse events were documented in 39% of patients in NIG and 33% of patients in IG (P = 0.77). Grade 3/4 of CID occurred in 8% of patients in NIG and 8% of patients in IG (P = 1). Grade 3/4 of neutropenia were recognized in 21% of patients in NIG and 17% of patients in IG (P = 1). Average relative dose intensity (RDI) in NIG were 75.7% and 85.8% for capecitabine and oxaliplatin, respectively. Average RDI of capecitabine and oxaliplatin in IG were 76.1% and 82.7%, respectively. Significant difference of RDI of capecitabine and oxaliplatin were not shown in comparison between NIG and IG (P = 0.93, P = 0.63). The 3-year DFS rate was 85.0% in NIG and 75.0% in IG. The HR for DFS for NIG compared to IG was 1.709 (95% CI, 0.49 to 5.95; P = 0.40). Conclusions: The presence of diverting ileostomy does not affect RDI of CAPOX as adjuvant chemotherapy.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: A multicenter retrospective analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 248-248
Author(s):  
Suganija Lakkunarajah ◽  
Daniel Adam Breadner ◽  
Hanbo Zhang ◽  
Jennifer L. Spratlin ◽  
Karen E. Mulder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Survival Data ◽  
Dose Intensity ◽  
Developed Countries ◽  
Stage Ii ◽  
Stage Iii ◽  
N2 Disease

248 Background: Colorectal cancer remains the second leading cause of cancer death in developed countries. The benefit of using fluorouracil-based chemotherapy with oxaliplatin, such as FOLFOX (fluorouracil (5-FU), leucovorin, oxaliplatin) and CAPOX (capecitabine and oxaliplatin) is well established. The optimal dose intensity (DI) under which overall survival (OS) is inferior is not established. Methods: Patients (pts) treated with adjuvant chemotherapy between 2006 and 2011 for resected stage III colon cancer (CC) from four academic cancer centres in Canada were retrospectively analysed. Patients that received CAPOX and FOLFOX were examined for the relationship between DI and OS. Results: A total of 625 pts with resected high risk stage II or stage III CC that received adjuvant chemotherapy were analysed. The median age was 63. Pts with T4 and N2 disease comprised 35.4% and 29.9% of pts, respectively. Median follow-up was 3.2 years. There was available survival data for 319 pts. The median oxaliplatin DI was 70%. The frequency of pts reaching an oxaliplatin DI of > 80% was 43%, while 76.6% of pts had a dose intensity of > 80% for their FU component. An oxaliplatin DI of > 80% was associated with a significant improvement in survival, HR = 0.42 (95%CI 0.21 – 0.81, p < 0.01). Achieving a DI of > 80% for capecitabine or 5-FU did not improve OS. Other factors associated with inferior OS included T4 (HR = 3.5, p = 0.03) and N2 (HR = 5.27, p = 0.0005) subgroups. The improvement in OS was not significant when restricting the analysis to pts with non-T4 and non-N2 disease (n = 144), HR = 0.16 (0.02 – 1.26; p = 0.08). Conclusions: Oxaliplatin DI of > 80% is associated with improved OS in patients receiving chemotherapy for high risk stage II and stage III CC.

The efficacy of adjuvant chemotherapy for resected high-risk stage II and stage III colorectal cancer in frail patients

2021 ◽  
Author(s):  
Kosuke Mima ◽  
Nobutomo Miyanari ◽  
Keisuke Kosumi ◽  
Takuya Tajiri ◽  
Kosuke Kanemitsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Stage Iii ◽  
Frail Patients

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
A. M. Glas ◽  
P. Roepman ◽  
R. Salazar ◽  
G. Capella ◽  
V. Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Gene Signature ◽  
Low Risk ◽  
Stage Ii ◽  
Significant Difference ◽  
Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

Evaluating the prognostic significance of lymphovascular invasion in stage II and III colon cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
Dorotea Mutabdzic ◽  
Shalana BL O'Brien ◽  
Elizabeth A. Handorf ◽  
Karthik Devarajan ◽  
Sanjay S. Reddy ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Lymphovascular Invasion ◽  
Lymph Node Involvement ◽  
Stage Ii ◽  
Stage Iii ◽  
Node Involvement

685 Background: Presence of lymphovascular invasion (LVI) is known to be a predictor of lymph node involvement in colon adenocarcinoma (CA). Lymph node involvement is associated with poorer prognosis necessitating adjuvant therapy. While some studies have suggested that LVI is a predictor of worse overall survival in early stage colon cancer, the significance of LVI on prognosis has not been tested in a comprehensive North American data set. Methods: Patients with stage II and III CA with LVI data available and those who received predefined standard of care treatment were identified from the National Cancer Data Base (NCDB) from 2011 to 2015. The relationship between LVI and overall survival was tested using Kaplan-Meier survival curves and Cox proportional hazards regression analysis after adjusting for relevant clinical and demographic variables. Hazard ratios and 95% confidence intervals are reported along with median overall survival (OS) where available. Results: The dataset included 93,070 patients with stage II and 66,701 patients with stage III CA. The proportion of patients with LVI was 13% in stage II and 47% in stage III CA. After adjusting for age, sex, gender, race, comorbidities, socioeconomic status, T, and N stage, LVI was associated with worse OS in stage II, HR 1.2 (1.15-1.25, p < 0.001), and in stage III, HR 1.25 (1.21-1.30, p < 0.001), CA. Median OS was 6.51 years with LVI versus. 6.85 years without LVI in stage II compared with 6.57 years with LVI versus not reached without LVI in stage III CA. Of the stage II patients with LVI, 20% received adjuvant chemotherapy (CT) and median OS was 6.91 years for those who did versus 6.07 years for those who did not receive CT. Conclusions: Our data suggest that LVI is an important predictor of OS in stage II and III CA. There is evidence that adjuvant chemotherapy improves OS in advanced CA but there remains uncertainty as to the benefit in stage II. Despite this uncertainty, guidelines suggest consideration of adjuvant CT in patients with high-risk stage II disease. Our data support the recommendation that LVI be considered a high-risk feature in stage II disease. Further studies are necessary to examine whether the type or duration of CT should differ for patients with CA and LVI.

Temporal trends in receipt of adjuvant chemotherapy for veterans with colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19171-e19171
Author(s):  
Richard Lewis Martin ◽  
Gretchen C. Edwards ◽  
Lauren R. Samuels ◽  
Cathy Eng ◽  
Christianne L. Roumie
Keyword(s):  
Colorectal Cancer ◽  
Quality Improvement ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Temporal Trends ◽  
Stage Ii ◽  
Stage Iii ◽  
Health Administration ◽  
Co Morbidity ◽  
Over Time

e19171 Background: For patients with National Comprehensive Cancer Network (NCCN) high risk stage II or stage III colorectal cancer (CRC), adjuvant chemotherapy improves disease free (DFS) and overall survival (OS). Rates of use vary significantly across health care settings. Several demographic and healthcare factors are associated with decreased receipt of chemotherapy; however, few studies have assessed utilization patterns over time. We evaluated receipt of chemotherapy from 2000-2015 among patients treated at a Southeast Regional Veterans Health Administration (VHA) facility to determine local targets for quality improvement initiatives. Methods: We reviewed 1,107 electronic medical records of patients undergoing colorectal surgery from January 1, 2000 to December 31, 2015 at VHA Tennessee Valley Healthcare System. We included patients with NCCN eligible pathologic high risk stage II (T4/perf, R1, < 12LN, LVI) or stage III CRC and excluded for age ≥80, age ≥75 hospitalized in the prior year with a major co-morbidity, and death or hospice within 30 days of surgery. The primary predictor was year of surgery, partitioned 2000-2005 (N = 60), 2006-2010 (N = 64), 2011-2015 (N = 56) to reflect changes in NCCN guidelines. The primary outcome was receipt of any chemotherapy. Results: Of 1,107 colorectal surgeries, we excluded 623 for non-cancers, 212 for stage I or low-risk stage II cancer, 47 for metastatic disease, and 45 for age, co-morbidity, death, and hospice, yielding a final cohort of 121 colon and 59 rectal cancers. Most patients were male (96%), white (79%), with median age 64 years [Interquartile Range 60, 70]. Overall, 117 of 180 (65%) received chemotherapy with a median time to treatment of 50.5 days [40,64]. Adjusting for known correlates, receipt of chemotherapy decreased over time; 2000-2005 (72%), 2006-2010 (69%), 2011-2015 (53%) p = 0.02. Regardless of CRC stage, more patients declined chemotherapy in 2011-2015 (27%) compared to 2000-2005 (6%) and 2006-2010 (8%) p < 0.01. Conclusions: We identified decreased utilization of adjuvant chemotherapy in a non-elderly veteran cohort, which appeared to be due to patients declining chemotherapy regardless of cancer stage. Understanding patient and provider decisions around adjuvant chemotherapy and evaluating trends outside the VHA may offer important insights to implementing quality improvement measures.

scholarly journals Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

2016 ◽  
Vol 23 (6) ◽  
pp. 418 ◽  
Author(s):  
B.M. Meyers ◽  
R. Cosby ◽  
F. Quereshy ◽  
D. Jonker
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Practice Guideline ◽  
Stage Ii ◽  
Stage Iii ◽  
Cochrane Library ◽  
Stage Iii Colon Cancer ◽  
Resected Stage ◽  
Stage Ii Colon Cancer

Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken.Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline.Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer.Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.

Impact of adjuvant chemotherapy on recurrence risk in stage II colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 533-533
Author(s):  
Taiwo Adesoye ◽  
Chung-Yuan Hu ◽  
Amanda Cuddy ◽  
Amanda B. Francescatti ◽  
Jessica R. Schumacher ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Recurrence Rate ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer ◽  
The Impact

533 Background: Although clinical guidelines recommend consideration of adjuvant chemotherapy in high-risk stage II colon cancer, the impact on recurrence risk and cancer related survival is unclear. Furthermore, among Medicare patients, adjuvant chemotherapy was not associated with improved survival. We examine the effect of adjuvant chemotherapy on recurrence risk and overall survival in a diverse cohort. Methods: 6,095 patients who underwent surgery for stage II-III colon cancer (2006-2007) were randomly selected from facilities reporting to the National Cancer Data Base for additional abstraction of tumor information, 5 year recurrence and survival. Death or second cancer within 6 months were excluded. Patients were classified as high or low risk using standard pathologic factors. Multivariate Cox regression with propensity score weighting was performed to compare recurrence risk and overall survival. Results: Of 3,423 patients with stage II colon cancer, 26.9% (n = 883) received chemotherapy compared to 76.2% (n = 1,839) of stage III patients. Among stage II patients, 47.8% (n = 1,636) had at least one high risk feature and 30.8% (n = 481) of these received chemotherapy. Five year recurrence rate in stage II patients was 13% (n = 392), greater in high risk compared to non-high risk patients (13.3% vs 9.3% p < 0.0001) and 24.4% (n = 874) in stage III patients. Chemotherapy did not improve recurrence risk in stage II patients regardless of risk status (High risk: hazard ratio [HR] 1.37; 95% CI 0.96 - 1.97; Non-high risk: HR 1.39; 95% CI 0.91 - 2.11). Chemotherapy was associated with a significant improvement in recurrence risk in stage III patients (HR 0.79; 95% CI 0.63 - 0.96). However, chemotherapy was associated with improved overall survival in both high (HR 0.69; 95% CI 0.51 - 0.92) and non-high risk stage II patients (HR 0.76; 95% CI 0.55 - 1.04), and also in stage III patients (HR 0.47; 95% CI 0.41 - 0.54). Conclusions: Adjuvant chemotherapy was not associated with a lower recurrence rate among stage II colon cancer patients. The observed survival benefit associated with chemotherapy is likely attributable to non-oncologic factors such as patient selection. Decision-making regarding chemotherapy use in this cohort should be carefully approached.

Occurrence of irreversible sinusoidal obstruction syndrome during adjuvant chemotherapy for colorectal cancer using oxaliplatin: A multi-center study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 546-546
Author(s):  
Takeshi Yamada ◽  
Keiji Koda ◽  
Hiroshi Yoshida ◽  
Kohji Tanakaya ◽  
Keiichiro Ishibashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Dose Intensity ◽  
Stage Iii ◽  
Sinusoidal Obstruction Syndrome ◽  
Curative Surgery ◽  
Hepatic Sinusoidal Obstruction Syndrome ◽  
Grade 3 ◽  
Multi Center Study ◽  
Center Study

546 Background: Oxaliplatin reduces the recurrence rate after curative surgery for stage III colorectal cancer. However, it can cause hepatic sinusoidal obstruction syndrome (SOS), an adverse effect that creates morbidity after liver resection for recurrence. SOS has conventionally been diagnosed by liver biopsy, which is invasive. We have reported that a 10% increase in splenic volume (SV) indicates SOS (J Surg Oncol 2017). In this multi-center study, we measured SV to evaluate SOS caused by adjuvant chemotherapy. Methods: This multi-center study included the participants of the FACOS study, which included patients with Stage III colon cancer. Participants received 12 cycles of mFOLFOX6 or eight cycles of XELOX as adjuvant chemotherapy. We used multi-detector raw CT to measure SV three times; before surgery, on completion of adjuvant chemotherapy, and 1-year after completing adjuvant chemotherapy. CT images were taken in 5-mm slices. SV was calculated by using a volume calculator SYNAPSE VINCENT v3.0(Fujifilm, Japan). Results: The FACOS study included 130 patients, 16.9% of whom discontinued treatment. The mean relative dose intensity (RDI) of oxaliplatin was 80.3%. Grade 3 neutropenia, thrombocytopenia, and neuropathy were observed in 28.5%, 6.2%, and 4.6% of patients, respectively. The 3 year DFS was 82.2%. We analyzed data of 75 patients (57.7%) for whom the three CT studies were available. SV on completing chemotherapy (median 181 cm3) and SV 1-year after completing chemotherapy (141 cm3) were significantly higher than that before surgery (128 cm3) (P < 0.001). SV increased by more than 10% after chemotherapy in 72% and was still increased 1 year after chemotherapy in 51% of patients. Conclusions: In our previous single center study, SV had increased in 84% on completing chemotherapy and was still increased in 47% 1 year after completing chemotherapy. Adjuvant chemotherapy without oxaliplatin induced SV increases in only 20% of patients on completing chemotherapy. Thus, these results are reproducible and show the potential of oxaliplatin to induce SOS. Oxaliplatin frequently induces SOS and this SOS persists for over 1 year in half of affected patients. Clinical trial information: UMIN000005427.

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