Duration of Adjuvant Chemotherapy for Stage III Colon Cancer

Grothey, Axel; Sobrero, Alberto; Shields, Anthony F.; Yoshino, Takayuki; Paul, James; Taı̈eb, Julien; Souglakos, John; Shi, Qian; Kerr, David J.; Labianca, Roberto; Meyerhardt, Jeffrey A.; Vernerey, Déwi; Yamanaka, T.; Boukovinas, Ioannis; Meyers, Jeffrey P.; Renfro, Lindsay A.; Niedzwiecki, Donna; Watanabe, Toshiaki; Torri, Valter; Saunders, Mark; Sargent, Daniel J.; Thewis, André; Iveson, Tim

doi:10.1056/nejmoa1713709

Cited by 804 publications

(838 citation statements)

References 16 publications

Supporting

Mentioning

777

Contrasting

Unclassified

Order By: Relevance

“…Pharmaceutical companies are not typically interested in sponsoring trials for neglected cancers (eg, liver, brain) or for investigating de‐escalation of established cancer medicines that are no longer under patent . PHARE (described above) was funded by the French National Cancer Institute, whereas the International Duration of Evaluation of Adjuvant Therapy (IDEA) analysis of colon cancer was funded by various noncommercial grants …”

Section: Optimizing Cancer Medicine Researchmentioning

confidence: 99%

Enhancing global access to cancer medicines

Cortés

Peréz-García

Llombart-Cussac

et al. 2020

CA A Cancer J Clinicians

153

108

View full text Add to dashboard Cite

Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high‐quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.

show abstract

Section: Optimizing Cancer Medicine Researchmentioning

confidence: 99%

Enhancing global access to cancer medicines

Cortés

Peréz-García

Llombart-Cussac

et al. 2020

CA A Cancer J Clinicians

153

108

View full text Add to dashboard Cite

show abstract

“…1 TNM staging system is an important guide for physicians regarding treatment and prognosis. 3,4 The current staging method is suboptimal due to the variation in outcomes that exist among patient in the same stage. Adjuvant chemotherapy provides a survival benefit in patients with Stage III disease, and possibly in those with high-risk Stage II colon cancer.…”

Section: Introductionmentioning

confidence: 99%

High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Cui

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the fivegene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis, Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.

show abstract

“…Given the cumulative neurotoxicity associated with oxaliplatin exposure, the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration conducted a prospective pooled analysis and showed that 3 months of adjuvant therapy appeared to be sufficient in a lower‐risk group (defined as patients with T1, T2, or T3/N1 disease), especially when the capecitabine and oxaliplatin combination was chosen. In a higher‐risk group (patients with T4, N2, or both), 6 months of adjuvant therapy may be needed, particularly when the fluorouracil and oxaliplatin combination was the chosen regimen (Grothey et al , ). Notably, our study showed that patient survival was heterogeneous even within the high‐ or low‐risk stage II/III groups; that is, patients with high‐risk stage II and low‐ and high‐risk stage III disease could be further stratified by the cirScore into subsets with distinct outcomes, suggesting a room for tailoring treatment strategies and avoiding overtreatment or undertreatment in selected patients.…”

Section: Discussionmentioning

confidence: 99%

A circRNA signature predicts postoperative recurrence in stage II/III colon cancer

et al. 2019

View full text Add to dashboard Cite

Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA‐based signature that could improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA‐seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four‐circRNA‐based cirScore to classify patients into high‐risk and low‐risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease‐free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss‐of‐function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four‐circRNA‐based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer.

show abstract

Duration of Adjuvant Chemotherapy for Stage III Colon Cancer

Cited by 804 publications

References 16 publications

Enhancing global access to cancer medicines

Enhancing global access to cancer medicines

High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

A circRNA signature predicts postoperative recurrence in stage II/III colon cancer

Contact Info

Product

Resources

About