Abstract 5728
Background
The current literature on stage IV colorectal cancer (CRC) indicates a survival advantage for left-sided CRC. Still, the biological basis remains unclear. We assessed the interaction of cancer location with microsatellite instability (MSI) and KRAS mutation to elaborate how key molecular features modify the effect of cancer location on overall survival.
Methods
The 2010-2015 United States National Cancer Database was searched for stage IV colorectal adenocarcinomas. Overall survival (OS) was assessed via Cox models, implementing 2/3-way interaction terms.
Results
A total of 73,685 patients were included, of which n = 11,720/n=25,433 had data on microsatellite and KRAS status. Left-sided CRC was an independent predictor of improved OS (vs. right: HR = 0.75, p < 0.001). Rectal cancer had highest OS (2/5-year OS: 43%/10%) compared to cancers of the rectosigmoid junction (HR = 1.07), sigmoid (HR = 1.12), descending colon (HR = 1.19), transverse colon (HR = 1.41), ascending colon (HR = 1.45) or cecum/appendix (HR = 1.45, p < 0.001 respectively). Patients with stable microsatellites (MSS) had improved OS versus MSI (HR = 0.93, p = 0.027); KRAS wildtype showed superior OS over KRAS mutation (HR = 0.88, p < 0.001). CRC location interacted with microsatellite status and KRAS mutation: the prognostic impact of MSS was more pronounced in rectal cancers versus other locations (interaction p < 0.001); the prognostic impact of KRAS wildtype was larger in rectal cancers (interaction p < 0.001). In a 3-way interaction model, the largest prognostic impact of MSS and KRAS wildtype was noted for rectal cancer (interaction term p < 0.05). The table summarizes 2/4-year OS rates.Table: 529P
Adjusted 2-year and 4-year OS rates by cancer location and mutational status
| Location / mutational status | Two year OS | Four year OS |
|---|---|---|
| rectal CRC, MSS, KRAS wildtype | 68% | 38% |
| rectal CRC, MSS, KRAS mutation | 56% | 29% |
| rectal CRC, MSI, KRAS wildtype | 66% | 39% |
| rectal CRC, MSI, KRAS mutation | 43% | 18% |
| other CRC, MSS, KRAS wildtype | 60% | 31% |
| other CRC, MSS, KRAS mutation | 52% | 24% |
| other CRC, MSI, KRAS wildtype | 47% | 25% |
| other CRC, MSI, KRAS mutation | 48% | 20% |
Conclusions
Survival for stage IV CRC shows marked variation depending on location, MSI and KRAS mutation. The prognostic effects of molecular features varies by CRC location, demonstrating largest impact in rectal cancers.
Clinical trial identification
NA
Legal entity responsible for the study
Hyun S. Kim, MD.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5720 - Evaluation of stemness and proliferation of human breast cancer stem cells (ALDH+) supplemented with heat-activated TGF-beta1 in the secretomes of stem cells from human exfoliated deciduous teeth (SHED)
Presenter: Septelia Wanandi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4844 - Estrogen-related receptor _ as a potential molecular target for endometrial cancer therapy
Presenter: TETSUYA KOKABU
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1200 - Good tolerability and limited target-specific tissue distribution of an anti-L1CAM antibody administered to cynomolgus monkey indicates favorable safety profile of L1CAM-targeting therapies
Presenter: Jacques Gaudreault
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2905 - Pharmacokinetic drug-drug interaction between mitotane and etoposide in the treatment of adrenocortical carcinoma
Presenter: Anne Jouinot
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2597 - Real-world dosing of regorafenib (REG) in metastatic colorectal cancer (mCRC): final results from the prospective, observational CORRELATE study
Presenter: Juan Manuel O'Connor
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2663 - Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in metastatic colorectal cancer (mCRC) patients according to previous treatment with regorafenib in the international phase 3b PRECONNECT study
Presenter: Julien Taieb
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1670 - Treatment pattern and outcomes of trifluridine/tipiracil therapy for metastatic colorectal cancer in the real-world data from the JFMC50 study
Presenter: Takeshi Kawakami
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1088 - Phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients (pts) over 70 with previously treated metastatic colorectal adenocarcinoma (mCRC) FFCD 1404 - REGOLD
Presenter: thomas Aparicio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2548 - Prospective Evaluation of Regorafenib Dose Escalation Strategy with Low Starting Dose in Patients with Colorectal Cancer
Presenter: Toshiki Masuishi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3244 - Regorafenib for metastatic colorectal carcinoma: a registry-based analysis
Presenter: Katerina Kopeckova
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract