Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

Boisen, Mogens K.; Johansen, Julia S.; Dehlendorff, Christian; Larsen, Jim S.; Østerlind, Kell; Hansen, Jørgen; Nielsen, Svend Erik; Pfeiffer, Per; Tarpgaard, Line Schmidt; Holländer, Niels Henrik; Keldsen, Nina; Hansen, Torben Frøstrup; Jensen, Brita B.; Jensen, Benny Vittrup

doi:10.1093/annonc/mdt253

Cited by 79 publications

(74 citation statements)

References 20 publications

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“…22 The current study, which was based on resected CCLM, confirmed that the pathologic response to preoperative chemotherapy, which had previously been demonstrated to be associated with survival, 12 also differed according to embryonic origin.…”

Section: Discussionsupporting

confidence: 82%

Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases

et al. 2018

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Background To determine the prognostic value of embryonic origin in patients undergoing resection after chemotherapy for colon cancer liver metastases (CCLM). Methods We identified 725 patients with primary colon cancer and known RAS mutation status who underwent hepatic resection after preoperative chemotherapy for CCLM (1990-2015). Survival after resection of CCLM from midgut origin (n=238) and hindgut origin (n=487) was analyzed. Predictors of pathologic response and survival were determined. Prognostic value of embryonic origin was validated with a separate cohort of 252 patients with primary colon cancer who underwent resection of CCLM without preoperative chemotherapy. Results Recurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with midgut origin tumors (RFS rate at 3 years: 15% vs. 27%, P<0.001; OS rate at 3 years: 46% vs. 68%, P<0.001). Independent factors associated with minor pathologic response were midgut embryonic origin (odds ratio [OR] 1.55, P=0.010), absence of bevacizumab (OR 1.42, P=0.034), and mutant RAS (OR 1.41, P=0.043). Independent factors associated with worse OS were midgut embryonic origin (hazard ratio [HR] 2.04, P<0.001), carcinoembryonic antigen value ≥5 ng/mL at hepatic resection (HR 1.46, P=0.0021), synchronous CCLM (HR 1.45, P=0.012), and mutant RAS (HR 1.43, P=0.0040). In the validation cohort, patients with CCLM of midgut origin had a worse 3-year OS rate (55% vs. 78%, P=0.003). Conclusion Compared to CCLM from hindgut origin, CCLM from midgut origin are associated with worse pathologic response to chemotherapy and worse survival after resection. This effect appears to be independent of RAS mutation status.

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Section: Discussionsupporting

confidence: 82%

Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases

et al. 2018

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“…Proximal colonic location outside of the context of MSI-High CRC is associated with greater mortality, especially among stage IV CRC patients (16, 31–33). Recent evidence has also documented a poorer response to treatment in patients with proximal CRC (20). …”

Section: Discussionmentioning

confidence: 99%

“…One of the reasons for the poorer survival in AAs compared to EAs may be due to the higher prevalence of proximal neoplasia in AAs (10–15), which is often associated with worse survival (16–19), especially in the context of metastatic disease. A recent investigation has found that treatment with biologic agents appears to be less effective in patients with proximal CRC compared to distal or rectal cancer (20). …”

Section: Introductionmentioning

confidence: 99%

Racial Differences in Stage IV Colorectal Cancer Survival in Younger and Older Patients

Wallace

DeToma

Lewin

et al. 2017

Clinical Colorectal Cancer

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Introduction African Americans (AA) compared to European Americans (EA) have poorer stage specific survival from colorectal cancer (CRC). Recent reports have indicated that the racial difference in survival has worsened over time, especially among younger patients. To better characterize this association, we used population-based SEER registry data to evaluate the impact of race on stage IV CRC survival in patients < 50 and ≥ 50. Patients and Methods The population was comprised of 16,782 patients diagnosed with stage IV colon and rectal adenocarcinoma between 01 January 2004 and 31 December 2011. Cox proportional hazards regression was used to evaluate the association between race and other prognostic factors and the risk of death in each age group. Results Younger AAs compared to EAs had a higher prevalence of proximal CRC at diagnosis, a factor associated with significantly higher risk of death in both races. Among patients < 50 years of age, AAs had a higher risk of death compared to EAs (HR 1.35, 95% CI 1.20 to 1.51)), which was attenuated in patients ≥ 50 years of age (HR 1.10, 95% CI 1.04 to 1.16); p for interaction 0.01. Conclusion The results revealed poor overall survival in AA compared to EA, especially in those < 50 years of age. The higher prevalence of proximal CRC at diagnosis among younger aged AA (vs. EA) may contribute to the racial difference in survival. Future studies will be needed to understand how colonic location impacts the efficacy of treatment regimens.

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“…Antiangiogenic therapy could improve patient survival from advanced colon cancer, in which the benefit differs by tumor location. Boisen et al [18] analyzed the data of metastatic CRC patients who received CapeOX +/bevacizumab as standard first-line therapy. Patients treated with CapeOX + bevacizumab with primary tumors located in the sigmoid colon and rectum had a significantly better outcome than patients with primary tumors located anywhere between the cecum to the descending colon, with results showing PFS (9.3 vs 7.2 mo, HR = 0.68) and OS (23.5 vs 13.0 mo, HR = 0.47).…”

Section: Anti-angiogenic Therapymentioning

confidence: 99%

Different treatment strategies and molecular features between right-sided and left-sided colon cancers

Shen¹

2015

WJG

181

183

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The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.

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Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

Abstract: NCT00212615.

Cited by 79 publications

References 20 publications

Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases

Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases

Racial Differences in Stage IV Colorectal Cancer Survival in Younger and Older Patients

Different treatment strategies and molecular features between right-sided and left-sided colon cancers

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