Personalizing Adjuvant Therapy for Stage II/III Colorectal Cancer

2017 ◽  
pp. 232-245 ◽  
Author(s):  
Nadine Jackson McCleary ◽  
Al B. Benson ◽  
Rodrigo Dienstmann
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Stage Ii ◽  
Mesenchymal Tumors ◽  
Geriatric Population ◽  
Therapy Strategy ◽  
Colon And Rectal Cancer ◽  
Major Interest

This review focuses on three areas of interest with respect to the treatment of stage II and III colon and rectal cancer, including (1) tailoring adjuvant therapy for the geriatric population, (2) the controversy as to the optimal adjuvant therapy strategy for patients with locoregional rectal cancer and for patients with colorectal resectable metastatic disease, and (3) discussion of the microenvironment, molecular profiling, and the future of adjuvant therapy. It has become evident that age is the strongest predictive factor for receipt of adjuvant chemotherapy, duration of treatment, and risk of treatment-related toxicity. Although incorporating adjuvant chemotherapy for patients who have received neoadjuvant chemoradiation and surgery would appear to be a reasonable strategy to improve survivorship as an extrapolation from stage III colon cancer adjuvant trials, attempts at defining the optimal rectal cancer population that would benefit from adjuvant therapy remain elusive. Similarly, the role of adjuvant chemotherapy for patients after resection of metastatic colorectal cancer has not been clearly defined because of very limited data to provide guidance. An understanding of the biologic hallmarks and drivers of metastatic spread as well as the micrometastatic environment is expected to translate into therapeutic strategies tailored to select patients. The identification of actionable targets in mesenchymal tumors is of major interest.

Use of Adjuvant Chemotherapy and Radiation Therapy for Colorectal Cancer in a Population-Based Cohort

2003 ◽  
Vol 21 (7) ◽  
pp. 1293-1300 ◽  
Author(s):  
John Z. Ayanian ◽  
Alan M. Zaslavsky ◽  
Charles S. Fuchs ◽  
Edward Guadagnoli ◽  
Cynthia M. Creech ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Population Based ◽  
Stage Ii ◽  
Stage Iii Colon Cancer ◽  
Adjuvant Therapies

Purpose: Randomized trials have demonstrated that adjuvant chemotherapy improves survival for patients with stage III colon cancer and that chemotherapy combined with radiation therapy improves survival for patients with stage II or III rectal cancer. This population-based study was designed to assess use of these treatments in clinical practice. Patients and Methods: From the California Cancer Registry, we identified all patients diagnosed during 1996 to 1997 with stage III colon cancer (n = 1,422) and stage II or III rectal cancer (n = 534) in 22 northern California counties. To supplement registry data on adjuvant therapies and ascertain reasons they were not used, we surveyed physicians or reviewed office records for 1,449 patients (74%). Results: Chemotherapy rates varied widely by age from 88% (age < 55 years) to 11% (age ≥ 85 years), and radiation therapy varied similarly. Adjusting for demographic, clinical, and hospital characteristics, chemotherapy was used less often among older and unmarried patients, and radiation therapy was used less often among older patients, black patients, and those initially treated in low-volume hospitals. Adjusted rates of chemotherapy varied significantly (P < .01) among individual hospitals: 79% and 51%, respectively, at one SD above and below average (67%). Physicians’ reasons for not providing adjuvant therapy included patient refusal (30% for chemotherapy, 22% for radiation therapy), comorbid illness (22% and 14%, respectively), or lack of clinical indication (22% and 45%, respectively). Conclusion: Use of adjuvant therapy for colorectal cancer varies substantially by age, race, marital status, hospital volume, and individual hospital, indicating opportunities to improve care. With enhanced data on adjuvant therapies, population-based registries could become a valuable resource for monitoring the quality of cancer care.

Tumor Diameter Is an Easy and Useful Predictor of Recurrence in Stage II Colorectal Cancer

2015 ◽  
Vol 32 (5) ◽  
pp. 338-343 ◽  
Author(s):  
Chiyo Maeda ◽  
Eiji Hidaka ◽  
Yuichi Mori ◽  
Shumpei Mukai ◽  
Hideyuki Miyachi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Venous Invasion ◽  
Stage Ii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Stage Ii Colorectal Cancer

Background/Aims: Adjuvant chemotherapy for stage II colorectal cancer (CRC) can generally be administered to high-risk subgroups. To better identify these patients, we aimed at assessing factors that affect recurrence. Methods: In our hospital, 432 colon and 96 rectal stage II cancer patients who underwent surgical resection between 2001 and 2011 were divided into recurrence and non-recurrence groups. Age, sex, lymphatic vessel invasion, venous invasion, tumor diameter, tumor depth, histological type, preoperative carcinoembryonic antigen level, number of sampled nodes, adjuvant chemotherapy, morphology, surgical approach, anastomotic leakage, preoperative bowel obstruction, and preoperative perforation were retrospectively compared between the groups. Results: For colon cancer, multivariate analysis revealed a significant association between tumor diameter ≥40 mm and recurrence (p = 0.039). For rectal cancer, multivariate analysis revealed that tumor diameter ≥50 mm (p = 0.001) and ≤12 sampled nodes (p = 0.021) were associated with recurrence. Tumor diameter in rectal cancer was associated with worse disease-free survival (p = 0.026). Conclusion: Tumor diameter is a significant predictor of recurrence in stage II CRC. This is an important finding because tumor diameter is easy to evaluate clinically and might help to identify candidates for adjuvant chemotherapy.

scholarly journals Physicians' Beliefs About the Benefits and Risks of Adjuvant Therapies for Stage II and Stage III Colorectal Cancer

2014 ◽  
Vol 10 (5) ◽  
pp. e360-e367 ◽  
Author(s):  
Anthony C. Wong ◽  
Shannon Stock ◽  
Deborah Schrag ◽  
Katherine L. Kahn ◽  
Talya Salz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Stage Iii ◽  
Net Benefit ◽  
Stage Iii Colon Cancer ◽  
Adjuvant Therapies ◽  
Stage Ii Colorectal Cancer

Physicians agreed that the benefits of adjuvant chemotherapy for stage III colon cancer and chemotherapy, and radiation for stage III rectal cancer, outweigh the risks, but were divided over the net benefit of adjuvant therapies for stage II colorectal cancer.

Colorectal cancer survival following adjuvant chemotherapy with weekly i.v. fluorouracil 425 mg/m2 and folinic acid 50mg

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15089-e15089
Author(s):  
M. B. Jameson ◽  
M. Head ◽  
S. Deva
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Folinic Acid ◽  
Cancer Survival ◽  
Indirect Comparison ◽  
Analysis Data ◽  
Actuarial Survival ◽  
Colon And Rectal Cancer

e15089 Background: Adjuvant chemotherapy for colorectal cancer (CRC) using fluorouracil (5FU) and folinic acid (FA) has been proven effective and the QUASAR trial showed that a weekly administration schedule was as effective as, and less toxic than, the same daily doses delivered over 5 days every 4 weeks (the “Mayo regimen”). However the 5FU dose used (370 mg/m2) was lower than in some trials and a higher 5FU dose was considered desirable if tolerated. We therefore implemented a weekly regimen using 5FU 425 mg/m2 and DL-folinic acid 50mg in 2001 and retrospectively evaluated its efficacy and tolerability. Methods: Patients with non-metastatic CRC at assessment by medical oncologists in this institution between 2001 and 2004 were included in the analysis. Data was gathered on patient characteristics, duration of adjuvant chemotherapy and survival. Actuarial survival was calculated using the Kaplan-Meier method. Results: 417 patients (pts) were seen: 181 females, 236 males; median age 67 yrs (24–89); 291 with colon cancer, 126 with rectal cancer; 1 stage 1; 100 stage 2, 316 stage 3. Median follow-up was 6.2 years. 210 pts with colon cancer received adjuvant weekly 5FU/FA (32 stage 2, 178 stage 3) as did 58 pts with rectal cancer (50 of whom also received concurrent chemoradiation). 75% of pts with colon cancer received all 30 planned doses and 59% of rectal cancer pts received all 20 planned doses. 3 year survival for all pts treated with this regimen was 83.0% and for the subgroups with colon and rectal cancer it was 82.4% and 84.5% respectively. For stage 2 and 3 colon cancer pts treated with this regimen 3 year survival was 87.9% and 76.0% respectively; for stage III rectal cancer pts it was 84.1%. Conclusions: These outcomes compare favorably on indirect comparison with results from the QUASAR trial (which reported 3 year survival of 70.6%) and suggest that using a higher 5FU dose in this regimen is tolerable and may be advantageous. No significant financial relationships to disclose.

The 12-gene colon cancer assay validation and utility: Summary of clinical evidence.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 523-523
Author(s):  
Emily Burke ◽  
Haluk Tezcan ◽  
Margarita Lopatin ◽  
Kim Michelle Clark-Langone ◽  
Mark Lee ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Biology ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Validation ◽  
Cancer Specific Survival ◽  
Colon And Rectal Cancer ◽  
Gene Assay

523 Background: The 12-gene colon cancer assay is the first commercially available molecular assay to predict the risk of recurrence in stage II/III colon and rectal cancer. Rigorous evidence for clinical validity and utility of an assay is imperative since the result is used for treatment decision-making. This summary outlines the studies that meet an established definition of clinical validation and additional studies that support the utility of the assay. Methods: Prospectively designed studies using archival tissue with pre-specified methods, clinical outcomes, and analysis plan were considered clinical validation studies (Simon et al. JNCI 2009). Additional studies that demonstrated the utility of the assay in a clinical setting were considered supportive. Results: The assay has been clinically validated in four independent studies with 3315 patients (2390 stage II/628 stage III colon and 130 stage II/167 stage III rectal). All four studies demonstrated a significant association (p<0.05) between the result and outcome (e.g. recurrence risk and cancer specific survival). The score was examined in the context of other variables, including T and N stage, MMR status, number of nodes examined, lymphovascular invasion, and tumor grade; across all studies, the result consistently contributed to risk stratification beyond these variables. Three clinical utility studies with 502 patients showed that 29-45% of initial treatment recommendations in stage IIA colon cancer were changed, with a net reduction in use of adjuvant chemotherapy. Conclusions: Clinical validation of the 12-gene assay followed a now-standard approach of using archived tissue from multiple large, prospectively-designed studies with documented long-term outcomes; the 12-gene colon assay meets level IB evidence criteria. Subsequent studies showed the assay has impact on clinical practice. The underlying tumor biology assessed by the score is relevant in both colon (stage II and III) and rectal cancer, providing information beyond conventional features, and can help guide treatment decisions regarding adjuvant chemotherapy.

scholarly journals Patterns of colorectal cancer care in the United States: 1990-2010.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 684-684
Author(s):  
Caitlin C. Murphy ◽  
Linda C Harlan ◽  
Jennifer Leigh Lund ◽  
Charles Lynch ◽  
Ann M. Geiger
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
The United States ◽  
Stage Ii ◽  
Stage Iii ◽  
Adjuvant Therapies

684 Background: Colorectal cancer (CRC) incidence and mortality have declined in the U.S. over the past two decades. Much of the decline can be attributed to screening and advances in treatment. Few studies have evaluated the extent to which recommended therapies have been adopted in community settings and temporal changes in patterns of care. Methods: Patients diagnosed with stages II and III CRC were randomly sampled from the population-based Surveillance, Epidemiology, and End Results (SEER) program in 1990-91, 1995, 2000, 2005, and 2010 (n=7,056). Treatment data were obtained through medical record review and physician verification. We described the receipt of adjuvant chemotherapy among colon cancer patients and preoperative or postoperative radiation therapy among rectal cancer patients. Log-binomial regression was used to examine factors associated with receipt of therapy. Results: Receipt of adjuvant chemotherapy increased among stages II and III colon cancer patients from 1990 (stage II: 22%, stage III: 55%) to 2005 (stage II: 32%, stage III: 72%) and decreased in 2010 (stage II: 29%, stage III: 65%). Chemotherapy regimens changed over time; there was an increase in the use of capecitabine (3% in 2000 to 24% in 2010) and oxaliplatin (6% in 2000 to 79% in 2010). Stage III colon cancer patients who were older (75-79 years: RR 0.82, 95% CI 0.72, 0.94; ≥80 years: RR 0.36, 95% CI 0.27, 0.49) or had a comorbidity score ≥ 2 (RR 0.54, 95% CI 0.34, 0.86) were less likely to receive adjuvant chemotherapy. Receipt of radiation therapy among stages II and III rectal cancer patients increased across all study years from 46% to 66%, with a shift toward preoperative therapy in 2005. From 2005 to 2010, receipt of neoadjuvant chemoradiation followed by surgery and postoperative chemotherapy nearly doubled (11% in 2005 to 21% in 2010). Increasing age (75-79 years: RR 0.60, 95% CI 0.48, 0.75; ≥80 years: RR 0.34, 95% CI 0.25, 0.45) was associated with lower chemoradiation use in rectal cancer. Conclusions: Our findings demonstrate increased adoption of adjuvant therapies for both colon and rectal cancer patients and differences in therapy receipt by age, comorbidity, and diagnosis year. Improved receipt of adjuvant therapies in the community may further reduce CRC mortality.

Adjuvant Systemic Therapies in Patients with Colorectal Cancer: An Audit on Clinical Practice in Italy

2005 ◽  
Vol 91 (6) ◽  
pp. 472-476 ◽  
Author(s):  
◽  
Fausto Roila ◽  
Benedetta Ruggeri ◽  
Enzo Ballatori ◽  
Lucio Patoia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Clinical Practice ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Daily Clinical Practice ◽  
Stage Ii ◽  
International Consensus ◽  
Systemic Therapies

Aims and Background Rarely are conclusions from clinical trials summarized in international consensus conferences and promptly transferred to patient care. The adjuvant therapy for colorectal cancer used in daily clinical practice in Italy is described and compared with the recommendations of the 1990 NIH Consensus Conference. Patients and Methods We audited prescriptions of adjuvant systemic therapies for Italian colorectal cancer patients in 82 centers during a fixed one-week period. Results Among 434 patients receiving adjuvant chemotherapy there were 139 (42.5%) colon cancer patients with N- and 169 (51.7%) with N+ regional nodal involvement. Treatment at academic centers, a young age, T4 and a low total number of lymph nodes removed at surgery were the factors potentially justifying the decision for adjuvant chemotherapy in stage II colon cancer patients. The most common chemotherapy used was a bolus of 5-fluorouracil/folinic acid for 6 months (75.8%). Adjuvant radiotherapy was not administered to 37 (38.5%) of 96 patients with stage II and III rectal cancer. Conclusions The study shows that a substantial proportion of patients on adjuvant treatment at a certain time point in a large enough sample of Italian centers are stage II (potential over-treatment) and that an under-treatment of stage II and III rectal cancer patients (lack of radiotherapy) occurs too often in daily clinical practice in this country.

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

scholarly journals German oncology certification system for colorectal cancer – relative survival rates of a single certified centre vs. national and international registry data

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maximilian Richter ◽  
Lena Sonnow ◽  
Amir Mehdizadeh-Shrifi ◽  
Axel Richter ◽  
Rainer Koch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
International Comparison ◽  
Cancer Registry ◽  
Survival Data ◽  
Survival Rates ◽  
Relative Survival ◽  
Registry Data ◽  
Cancer Registry Data ◽  
Colon And Rectal Cancer

Abstract Objectives To evaluate how the certification of specialised Oncology Centres in Germany affects the relative survival of patients with colorectal cancer (CRC) by means of national and international comparison. Methods Between 2007 and 2013, 675 patients with colorectal cancer, treated at the Hildesheim Hospital, an academic teaching hospital of the Hannover Medical School (MHH), were included. A follow-up of the entire patient group was performed until 2014. To obtain international data, a SEER-database search was done. The relative survival of 148,957 patients was compared to our data after 12, 36 and 60 months. For national survival data, we compared our rates with 41,988 patients of the Munich Cancer Registry (MCR). Results Relative survival at our institution tends to be higher in advanced tumour stages compared to national and international cancer registry data. Nationally we found only little variation in survival rates for low stages CRC (UICC I and II), colon, and rectal cancer. There were notable variations regarding relative survival rates for advanced CRC tumour stages (UICC IV). These variations were even more distinct for rectal cancer after 12, 36 and 60 months (Hildesheim Hospital: 89.9, 40.3, 30.1%; Munich Cancer Registry (MCR): 65.4, 28.7, 16.6%). The international comparison of CRC showed significantly higher relative survival rates for patients with advanced tumour stages after 12 months at our institution (77 vs. 54.9% for UICC IV; raw p<0.001). Conclusions Our findings suggest that patients with advanced tumour stages of CRC and especially rectal cancer benefit most from a multidisciplinary and guidelines-oriented treatment at Certified Oncology Centres. For a better evaluation of cancer treatment and improved national and international comparison, the creation of a centralised national cancer registry is necessary.

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