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

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.684 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4036 ◽

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]

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Adjuvant treatment in extreme elderly patients with colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.784 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 784-784

Author(s):

Marta Llopis Cuquerella ◽

Maria del Carmen Ors Castaño ◽

María Ballester Espinosa ◽

Alejandra Magdaleno Cremades ◽

Vicente Boix Aracil ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Colon Cancer ◽

Elderly Patients ◽

Cancer Patients ◽

Adjuvant Treatment ◽

Stage Ii ◽

Stage Iii ◽

Complementary Treatment ◽

Colorectal Cancer Patients

784 Background: Surgical and adjuvant treatment in extreme elderly ( > 80 years) patients with localized colorectal cancer is an unresolved issue. Owing to the lack of available neither clinical practice nor investigational data in this field we present our experience in this scenario. Methods: We retrospectively reviewed data regarding surgical and complementary treatment for colorectal cancer patients aged more than 80 consecutively attended by General Surgery Department in Vega Baja Hospital between 2008 and 2013. Results: A total number of 115 colorectal cancer patients were registered. 95 patients diagnosed of localized disease were selected for analysis. Colon vs rectal cancer ratio was 4:1. Median age was 83.6 years (80-94). Male sex was predominant (60 patients, 63.2%). Emergency surgery was performed in 15 patients (15.8%). Complementary treatment to surgery was advised, according to international guidelines, in 53 patients (55.8%). 10 patients (18.9%) with an advise of adjuvant treatment finally received it. More patients with rectal cancer received recommended treatment (41.7% rectal vs 12.2% colon cancer). Patients with stage III disease were more frequently finally treated according to guidelines (22.2 % stage III vs 11.8% stage II). More patients with stage II rectal cancer were advised and received treatment (recommendation: 66.7% rectal vs 36.1% colon cancer; administration: 25% rectal vs 7.7% colon cancer). Treatment was also more frequently administered to stage III rectal cancer (50% rectal vs 14.3% rectal cancer) (Table). Conclusions: Our experience in localized colorectal cancer in extreme elderly patients ( > 80 years) showed that, although advised according to guidelines, most of them did not receive adjuvant treatment to surgery. Complementary treatment administration was more common in rectal cancer patients and with more advanced disease. [Table: see text]

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

Journal of Clinical Oncology ◽

10.1200/jco.2003.06.178 ◽

2003 ◽

Vol 21 (7) ◽

pp. 1293-1300 ◽

Cited By ~ 219

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.

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

Journal of Oncology Practice ◽

10.1200/jop.2013.001309 ◽

2014 ◽

Vol 10 (5) ◽

pp. e360-e367 ◽

Cited By ~ 5

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.

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Nomogram incorporated the number of adjuvant chemotherapy cycles for predicting the prognosis in stage II-III rectal cancer patients without neoadjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15163 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15163-e15163

Author(s):

Weiwei Chen ◽

Wenling Wang

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Locally Advanced ◽

Stage Ii

e15163 Background: Current recommendations for adjuvant chemotherapy in rectal cancer are based on the studies in colon cancer. However, it is now known that rectal cancer differs from colon cancer significantly regarding clinical course and biology. No RCTs in the TME era have evaluated the value of postoperative chemotherapy and are unlikely to be performed as neoadjuvant treatment has become a “gold standard” approach. However, we found that not all patients with locally advanced rectal cancer underwent neoadjuvant chemoradiotherapy before TME in real-world clinical practice in China. Whether the number of adjuvant chemotherapy cycles is significantly related to the prognosis of these patients deserves further study. Methods: A total of 246 patients with stage II-III rectal cancer from January 2013 to April 2018 were enrolled. All patients underwent surgery and had not received neoadjuvant therapy. The survival curve was drawn by the Kaplan-Meier method, and the log-rank method was used for statistical analysis. The Cox proportional hazard model was used for multivariate analysis to determine the independent prognostic factors. Then, MFP(Multiple Fractional Polynominal) and stepwiseAIC were used for variable selection. The R software was used to establish the nomogram. The bootstrap method was employed to internal verification. Concordance index(C-index) was applied to evaluate the predictive power of nomogram. Calibration curves were drawn to compare the 3-year overall survival rate predicted by nomogram and that of actual observation. Results: 87.8% of patients received adjuvant chemotherapy including oxaliplatin combined with fluorouracil or capecitabine. Univariate and multivariate analysis showed that the number of adjuvant chemotherapy cycles was independent prognostic factors. Patients who received more than 5 cycles of chemotherapy (HR = 0.09, 95%CI(0.01,0.80)) had a significantly better overall survival than patients with less than 5 cycles (HR = 0.33,95%CI(0.12,0.89)) or no chemotherapy (p < 0.05).Through MFP and the stepwiseAIC screening, a nomogram was established based on CEA, PLR, N, and the number of chemotherapy cycles, and the C-index of the model was 0.86. Conclusions: The number of adjuvant chemotherapy cycles is an independent prognostic factor in stage II-III rectal cancer patients without neoadjuvant therapy. Moreover, nomogram incorporated the number of chemotherapy cycles was accurate and visible.

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