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Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey.

ABSTRACT: This retrospective study was undertaken to provide more modern data of real-life management of non-metastatic rectal cancer, to compare therapeutic strategies, and to identify prognostic factors of overall survival (OS) in a large cohort of patients. Data on efficacy and on acute/late toxicity were retrospectively collected. Patients were diagnosed a non-metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. OS was correlated with patient, tumor and treatment characteristics with univariate and multivariate analyses. Data of 593 consecutive non-metastatic rectal cancer patients were analyzed. Median follow-up was 41 months. Median OS was 9 years. Radiotherapy was delivered in pre-operative (n?=?477, 80.5%), post-operative (n?=?75, 12.6%) or exclusive (n?=?41, 6.9%) setting. In the whole set of patients, age, nutritional condition, tumor stage, tumor differentiation, and surgery independently influenced OS. For patients experiencing surgery, OS was influenced by age, tumor differentiation and nodal status. Surgical resection is the cornerstone treatment for locally-advanced rectal cancer. Poor tumor differentiation and node involvement were identified as major predictive factor of poor OS. The research in treatment intensification and in identification of radioresistance biomarkers should therefore probably be focused on this particular subset of patients.

SUBMITTER: Langrand-Escure J

PROVIDER: S-EPMC6048026 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey.

Langrand-Escure Julien J Diao Peng P Garcia Max-Adrien MA Wang Guoping G Guy Jean-Baptiste JB Espenel Sophie S Guillaume Elodie E Rehailia-Blanchard Amel A Pigné Grégoire G de Laroche Guy G Kaczmarek David D Muron Thierry T Porcheron Jack J Phelip Jean-Marc JM Vallard Alexis A Magné Nicolas N

Scientific reports 20180716 1

This retrospective study was undertaken to provide more modern data of real-life management of non-metastatic rectal cancer, to compare therapeutic strategies, and to identify prognostic factors of overall survival (OS) in a large cohort of patients. Data on efficacy and on acute/late toxicity were retrospectively collected. Patients were diagnosed a non-metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. OS was correlated with patient, tumor and treatmen ...[more]

PMID: 30013090

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Project description:Rectal Cancer (RC) is a complex disease that involves highly variable treatment responses. Currently, there is a lack of reliable markers beyond TNM to deliver a personalized treatment in a cancer setting where the goal is a curative treatment. Here, we performed an integrated characterization of the predictive and prognostic role of clinical features, mismatch-repair deficiency markers, HER2, CDX2, PD-L1 expression, and CD3-CD8+ tumor-infiltrating lymphocytes (TILs) coupled with targeted DNA sequencing of 76 non-metastatic RC patients assigned to total mesorectal excision upfront (TME; n = 15) or neoadjuvant chemo-radiotherapy treatment (nCRT; n = 61) followed by TME. Eighty-two percent of RC cases displayed mutations affecting cancer driver genes such as TP53, APC, KRAS, ATM, and PIK3CA. Good response to nCRT treatment was observed in approximately 40% of the RC cases, and poor pathological tumor regression was significantly associated with worse disease-free survival (DFS, HR = 3.45; 95%CI = 1.14-10.4; p = 0.028). High neutrophils-platelets score (NPS) (OR = 10.52; 95%CI=1.34-82.6; p = 0.025) and KRAS mutated cases (OR = 5.49; 95%CI = 1.06-28.4; p = 0.042) were identified as independent predictive factors of poor response to nCRT treatment in a multivariate analysis. Furthermore, a Cox proportional-hazard model showed that the KRAS mutational status was an independent prognostic factor associated with higher risk of local recurrence (HR = 9.68; 95%CI = 1.01-93.2; p <0.05) and shorter DFS (HR = 2.55; 95%CI = 1.05-6.21; p <0.05), while high CEA serum levels were associated with poor DFS (HR = 2.63; 95%CI = 1.01-6.85; p <0.05). Integrated clinical and molecular-based unsupervised analysis allowed us to identify two RC prognostic groups (cluster 1 and cluster 2) associated with disease-specific OS (HR = 20.64; 95%CI = 2.63-162.2; p <0.0001), metastasis-free survival (HR = 3.67; 95%CI = 1.22-11; p = 0.012), local recurrence-free survival (HR = 3.34; 95%CI = 0.96-11.6; p = 0.043) and worse DFS (HR = 2.68; 95%CI = 1.18-6.06; p = 0.012). The worst prognosis cluster 2 was enriched by stage III high-risk clinical tumors, poor responders to nCRT, with low TILs density and high frequency of KRAS and TP53 mutated cases compared with the best prognosis cluster 1 (p <0.05). Overall, this study provides a comprehensive and integrated characterization of non-metastatic RC cases as a new insight to deliver a personalized therapeutic approach.

Project description:The prognosis of early-onset sporadic colorectal cancer (CRC) patients remains controversial. The objective of this study was to assess the long-term outcome and prognostic factors of sporadic CRC in young patients.From 2006 to 2011, 8207 patients underwent curative or palliative surgery for CRCs in our institution. A total of 693 patients who were ?45 years old with sporadic CRC were enrolled as the young group. A total of 1823 patients aged between 56 and 65 years were identified as middle-aged control group for this study. Survival outcome and prognostic factors were compared between the two groups.Young patients had higher recurrence rate than older patients in stages I and II (8.8% vs 2.7%, P?<0.001). There was no significant difference of recurrence rate in stage III and IV cancers (27.5% vs 27.9%, P?=?0.325). Metachronous cancers were developed more frequently in young patients (1.4% vs 0.6%, P?=?0.038). Advanced stage CRC was diagnosed significantly more common in the young group (55.6% vs 47.9%, P?=?0.001). High microsatellite instability (MSI) tumors are less likely to have advanced stage cancers (odds ratio (OR) 0.23, 95% confidence interval (CI)?=?0.07-0.70) or cancer recurrence (OR 0.11, 95% CI?=?0.01-0.85) in young patients. Cancer-specific survival was worse in young patients than that in older patients (81.2% vs 87.8%, P?<0.001). However, there was no significant difference in cancer-specific survival for each stage between the two groups. Independent prognostic factors for survival in young patients were undifferentiated cancer (hazard ratio (HR) 2.30, 95% CI?=?1.23-4.31) and 3 months or longer duration of symptom (HR 2.57, 95% CI?=?1.34-4.94). Young women had better survival compared with young men (HR 0.55, 95% CI?=?0.33-0.90).Prognosis of sporadic CRC in young patients is poorer than older patients, because of poorer histologic differentiation and delay in diagnosis. Early detection of CRC confers survival benefit to young patients. Because of higher recurrence rate and metachronous cancer risk, post-operative surveillance is also important in young patients.

Dataset Information

Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey.

Publications

Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey.

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