Dataset Information

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomized Controlled Study (SACURA Trial).

ABSTRACT: Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patients with stage II colon cancer. POR was graded according to the ×40 objective lens rule and the intensity of poorly differentiated clusters (Grade), and its prognostic power was compared with that of the conventional tumor grade on the basis of predominant histology rule (Grade). According to Grade, 313, 526, and 152 tumors were classified as G1, G2, and G3, respectively, and the 5-year relapse-free survival (RFS) rates were 91.1%, 82.9%, and 74.7%, respectively (P<0.0001). When G3 and G3 were alternatively added to the prognostic model consisting of 8 conventional factors, only G3 was a significant factor for RFS (P=0.040, Wald test). The adverse impact of G3 on RFS was greater in the microsatellite stable/microsatellite instability-low subset than that in the full analysis set. In the microsatellite stable/microsatellite instability-low subset, the 5-year RFS rate of patients with G3 tumors in the chemotherapy group achieved greater improvement (9.1%) than the surgery-alone group. The least differentiation policy with the ×40 objective lens rule may be highlighted as the diagnostic criterion for G3 because of its validated prognostic value.

SUBMITTER: Ueno H

PROVIDER: S-EPMC7690643 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomized Controlled Study (SACURA Trial).

Ueno Hideki H Ishiguro Megumi M Nakatani Eiji E Ishikawa Toshiaki T Uetake Hiroyuki H Matsui Shigeyuki S Teramukai Satoshi S Murotani Kenta K Ajioka Yoichi Y Shimazaki Hideyuki H Maeda Atsuyuki A Takuma Kunio K Yoshida Takefumi T Kambara Takeshi T Matsuda Keiji K Takagane Akinori A Tomita Naohiro N Sugihara Kenichi K

The American journal of surgical pathology 20201201 12

Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patient ...[more]

PMID: 32868525

Similar Datasets

Project description:BackgroundAlthough American Society of Clinical Oncology and European Society for Medical Oncology guidelines have identified the negative prognostic factors that clinicians have to consider when treating their patients with stage II colon cancer (CC), the role of histological subtype is controversial.Subjects, materials, and methodsThe randomized, multicenter, phase III TOSCA trial compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. The objective of this substudy was to evaluate the influence of histological subtypes on the impact of the treatment duration of adjuvant chemotherapy in terms of relapse-free survival (RFS) and overall survival (OS) in 85 mucinous adenocarcinoma (MUC) and 389 nonmucinous adenocarcinoma (NMUC) patients with high-risk stage II, grade 3 CC.ResultsA significant interaction between treatment duration and histology was observed in both RFS (p = .027) and OS (p = .017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03-15.17; p = .045) and OS (HR, 9.56; 95% CI, 1.14-79.98; p = .037) were detected for patients treated in the 3-month arm. No statistically significant differences were found in the subgroup of patients with NMUC.ConclusionPatients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to assess the combined use of histology and other prognostic/predictive factors to define the administration of chemotherapy in patients with stage II CC and to improve their prognosis.Implications for practiceAlthough ASCO and ESMO guidelines define the prognostic factors for patients with stage II colon cancer to establish the use of adjuvant chemotherapy, the influence of histological subtypes is controversial in this population. This study underscores that patients with grade 3 mucinous adenocarcinomas may need adjuvant chemotherapy with oxaliplatin and fluoropyrimidines for a duration of 6 months rather than 3 months.

Project description:Purpose: The primary objective of the current study was to validate biomarkers to identify the 10% to 27% of patients with stage I and 35% of patients with stage IIA squamous cell carcinoma of lung (SC) who are likely to recur following surgical resection, so that these patients may be offered enrollment in clinical trials evaluating directed ACT. A secondary objective was to identify patients with stage IIB SC who are unlikely to develop recurrences and might thereby be spared the potential significant toxicity and expense of ACT. Methods: Two-stage validation used independent core laboratories, objective quality control standards, locked test parameters, and large multi-institutional specimen/data sets. First stage validation confirmed a signature’s ability to stratify patient survival. Second stage validation determined which signature(s) optimally improved risk discrimination when added to baseline clinical predictors. Participants were prospectively enrolled on institutional (Cohort I) or cooperative group (Cohort II) biospecimen/data collection protocols. All cases underwent central review of clinical, pathologic and biospecimen parameters using objective criteria to determine final inclusion (Cohort I: n=249; Cohort II: n=234). Primary selection required that a signature significantly predict 3-years survival after surgery in Cohort I. Signatures meeting this criterion were further tested in Cohort II, comparing risk prediction using baseline risk factors alone versus in combination with the signature. Results: Male sex, advanced age, and higher stage were associated with shorter survival in Cohort I and established a baseline clinical model. Of three signatures validated in Cohort I, one signature was validated in Cohort II and statistically significantly enhanced prognosis relative to the baseline model (C-index difference 0.122; p<0.05). Conclusions: These results represent the first rigorous validation of a test appropriate to direct adjuvant treatment or clinical trials for patients with lung squamous cell carcinoma.

Dataset Information

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomized Controlled Study (SACURA Trial).

Publications

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomized Controlled Study (SACURA Trial).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets