∼30% of patients (pts) with NSCLC present with resectable disease. In the ADAURA trial (NCT02511106), there was a significant disease-free survival (DFS) benefit with osimertinib vs placebo (PBO) in pts with completely resected stg IB–IIIA EGFRm NSCLC (hazard ratio [HR] 0.20 [adjusted 99.12% CI 0.14, 0.30], p<0.001; 11% and 46% maturity for osimertinib and PBO, respectively); overall survival (OS) data were immature (29 pts died: osimertinib n=9/339, PBO n=20/343). Payers require estimates on survival benefits of novel oncology treatments to inform reimbursement decisions.

Introduction: We have previously defined ‘next generation specimens’ as longitudinal biopsy samples collected at different time points during the disease trajectory, in a specific treatment context, either for discovery research or to guide clinical decisions (Basik, M. et al. Nat Rev Clin Oncol. 2013). The objective of the present study was to track tumor evolution at the copy number (CN) level and capture emerging resistance mechanisms in metastatic colorectal cancer (mCRC) using a standardized collection of high-quality metastasis samples, at baseline and at the time of clinical resistance, in the context of a phase IV multicenter clinical trial (NCT00984048). Methods: One hundred and forty fresh frozen liver metastasis (LM) specimens collected at baseline (pre, n = 97) and at the time of clinical resistance (post, n = 43) from 119 mCRC patients undergoing standard first-line therapy were profiled using whole exome sequencing and characterized for CN variation using Nexus Copy Number software. RNA sequencing data available for the same sample set allowed filtering the CN aberration (CNA) candidates for mRNA correlation in each analysis performed. Objective response was attributed based on the RECIST v1.0 criteria. Genomic Identification of Significant Target in Cancer (GISTIC) test was used to identify focal CNA. CNA frequency reported as being significantly different between 2 groups met a minimum p-value of 0.005 on a two-tailed Fisher’s exact test. The log-rank test was used to identify CNA associated with progression-free survival (PFS). The threshold used for significance was permutated p-value < .005. Results: The CN variation landscape of 97 pre LM samples confirmed the most common chromosome (chr) arm amplifications being on chr 7p, 7q, 8q, 13q, and 20q and the most frequent deletions on chr 1p, 1q, 4p, 4q, 8p, 17p, 18p, 18q, and 22q. Twenty-nine focal aberrations were also identified by GISTIC. Comparative analyses identified 22 focal CNA with significantly different frequencies between pre- and post- samples. The comparison between partial responder (PR, n = 47) and intrinsically resistant (IRES, n = 5) lesions revealed 34 CNA with different frequencies at baseline. Acquired resistant (ARES) and IRES post-samples (n = 8) showed significant enrichment in 36 CNA compared to pre-sample (n = 97), and these CNA were not captured when PR (n = 10) post-samples are compared to pre-samples. One hundred thirty-seven CNA regions were found to be significantly associated with PFS. Interrogation of primary tumors and LM data available in public databases validated the predictive potential of 18 regions and also revealed the metastasis specificity of 15 of them. Candidate genes in these regions with concordant genomic/transcriptomic aberrations were identified. Conclusion: Our effort to collect and profile next-generation biospecimens provided global genomic and transcriptomic data of the largest LM cohort to date. By analyzing the association between molecular aberrations and patient outcomes, we identified novel biomarker candidates predictive of drug response in LM samples, supporting the utility of collecting metastatic samples in clinical settings.

Introduction: Metastatic colorectal cancers (mCRC) are highly heterogeneous, representing a challenge in treatment management. Studies have largely investigated the genomic landscape of primary tumors at diagnosis. As metastasis is responsible for 90% of cancer patient deaths, this highlights the need to characterize the genomic landscape of metastasis over time of treatment to decipher their evolution and role in therapeutic resistance. Methods: Metastatic liver tissue samples were collected at baseline (pre-biopsies) and at relapse (post-biopsies) in responder and non-responder mCRC patients undergoing the same treatment. Paired pre/post biopsies were collected from 14 patients (4 of them had multiple post-biopsies) to assess intra-patient, inter-tumour and intra-tumour heterogeneity following treatment exposure. Biopsies were profiled using RNA and whole exome sequencing (WES) as well as high-density Single-Nucleotide Polymorphism (SNP) array. Results: Profiling of 45 samples with both high-density SNP array and WES revealed 97.4% similarity between both technologies in the identification of genes targeted by copy number (CN) changes. The metastatic and primary tumor had similar somatic copy number aberration (SCNA) profiles. Using chemo-naïve biopsies, we identified 120 CN gains and 47 CN losses that were significantly associated with patient progression free survival. Integrative analysis with transcriptomic data from the same samples revealed that only 10% of the CN gains and 17% of the CN loss regions showed concordance between SCNA and expression levels. Similarly, at the gene level, higher concordance between SCNAs and expression change was observed in CN deletions compared to CN amplifications (11% vs 4.2%), suggesting other regulatory mechanisms involved. Interestingly, some of the genes showing high correlation between SCNA and gene expression were previously known for their involvement in cancer such as MYC and CD44. For each paired sample pre/post or post/post from the same patient, we computed a heterogeneity score (HS) based on SCNA calling using as two parameters, identical type of event called and 70% reciprocal overlap. We found high temporal intra-tumor heterogeneity in our cohort with a mean value of HS = 0.84 (range: 0.47-0.98). As expected, we observed more heterogeneity when comparing intra-patient inter-tumors heterogeneity (mean = 0.89, range: 0.77-0.95). Interestingly, the intrinsically resistant lesion had a lower score, and pre/post samples from the same or different lesion having the same response to treatment were less heterogeneous. This implies that acquisition of resistance correlates with an increase in genomic changes. Conclusion: Overall, we showed that liver metastasis and primary tumors from mCRC patients have similar SCNA profiles. From a technical perspective, we concluded that the use of WES data to identify genes located in SCNAs (gain and loss) is comparable to high-density SNP array. From a clinical point of view, we showed that approximately 10% of the genes affected by SCNA showed concordant changes in expression and therefore the use of CN results may not be suitable for making therapeutic decision. Furthermore, the high intra-tumor heterogeneity observed following treatment exposure highlights the importance of post-treatment biopsies to identify and understand mechanisms of mCRC resistance.

[This corrects the article DOI: 10.3747/co.22.2603.].

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23-25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage II colon cancer.

Monoclonal antibodies against the epidermal growth factor receptor (anti-egfr) when used in the treatment of metastatic colorectal cancer are associated with improved survival. Patients whose tumours harbor a KRAS mutation in codon 12 or 13 have been shown not to benefit from anti-egfr antibodies. The importance of KRAS mutation status in the management of patients with metastatic colorectal cancer has led to the elaboration of Canadian consensus recommendations on KRAS testing, with the aim of standardizing practice across Canada and reconciling testing access with the clinical demand for testing. The present guidelines were developed at a Canadian consensus meeting held in Montreal in April 2010. The best available evidence and expertise were used to develop recommendations for various aspects of KRAS testing, including indications and timing for testing, sample requirements, recommendations for reporting requirements, and acceptable turnaround times.

In January 2010, a panel of Canadian oncologists with particular expertise in colorectal cancer (crc) gathered to develop a consensus guideline on the use of therapies against the epidermal growth factor receptor (egfr) in the management of metastatic crc (mcrc). This paper uses a case-based approach to summarize the consensus recommendations developed during that meeting.These are the consensus recommendations:Testing for the KRAS status of the tumour should be performed as soon as an egfr inhibitor is being considered as an option for treatment.Anti-egfr therapies are not recommended for the treatment of patients with tumours showing mutated KRAS status.For a patient with wild-type KRAS and an Eastern Cooperative Oncology Group status of 0-2, whose mcrc has previously been treated with a fluoropyrimidine, irinotecan, and oxaliplatin, switching to an egfr inhibitor is a recommended strategy.Cetuximab, cetuximab plus irinotecan, and panitumumab are all options for third-line therapy in patients with wild-type KRAS, provided that tolerability is acceptable.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, October 22-24, 2009. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management colorectal cancer, such as the management of hepatic and pulmonary metastases, the role of monoclonal antibodies to the epidermal growth factor receptor, and the benefits and safety of chemotherapy in elderly patients. The management of gastrointestinal neuroendocrine tumours and gastric cancer are also discussed.

In January 2010, a panel of Canadian oncologists with particular expertise in colorectal cancer ( crc ) gathered to develop a consensus guideline on the use of therapies against the epidermal growth factor receptor ( egfr ) in the management of metastatic crc (m crc ). This paper uses a case-based approach to summarize the consensus recommendations devel- oped during that meeting. These are the consensus recommendations:

Chemotherapy-induced diarrhea (cid) is a common side effect of cancer treatment and can cause significant morbidity and mortality. Diarrhea is frequently severe enough to require a dose reduction of, a delay in, or a discontinuation of chemotherapy. Diarrhea-associated mortality has been reported to be as high as 3.5% in clinical trials of irinotecan and bolus 5-fluorouracil in colorectal cancer. The frequency of cid and its impact on patient management are frequently under-recognized in clinical practice. A Canadian working group, consisting of medical oncologists and an oncology pharmacist, was formed in 2001 to review the optimal approach to managing cid and to identify and implement new areas of research. The recommendations that follow are the result of the group’s work. Acute medical management of cid includes loperamide or diphenoxylate as first-line agents. Subcutaneous octreotide is recommended for intractable grade 2 diarrhea and may be considered for grade 1 cid that does not resolve with high-dose loperamide. Hospitalization is recommended for patients with grades 3 and 4 cid; in-hospital care includes rehydration, antibiotic therapy, and octreotide. A chemotherapy dose reduction is generally advised for patients who have experienced grade 3 or 4 diarrhea in a previous chemotherapy cycle. If a dose reduction is not desired, prophylaxis with intramuscular long-acting release octreotide may be considered. The foregoing recommendations are based on expert opinion and require validation in prospective clinical trials.