Combination and Optimal Sequencing of Systemic and Locoregional Therapies in Hepatocellular Carcinoma: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

Hepatocellular carcinoma, historically, has had a poor prognosis with very few systemic options. Furthermore, most patients at diagnosis are not surgical candidates. Therefore, locoregional therapy (LRT) has been widely used, with strong data supporting its use. Over the last 15 years, there has been progress in the available systemic agents. This has led to the updated Barcelona Clinic Liver Cancer (BCLC) algorithm's inclusion of these new systemic agents, with advocacy of earlier usage in those who progress on LRT or have tumor characteristics that make them less likely to benefit from LRT. However, neither the adjunct of LRT nor the specific sequencing of combination therapies is addressed directly. This Research Consensus Panel sought to highlight research priorities pertaining to the combination and optimal sequencing of LRT and systemic therapy, assessing the greatest needs across BCLC stages.

Canadian Association of Radiologists Gastrointestinal Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Gastrointestinal Expert Panel consists of radiologists, a gastroenterologist, a general surgeon, a family physician, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 20 clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 58 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 85 recommendation statements specific to the adult population across the 20 scenarios. This guideline presents the methods of development and the referral recommendations for dysphagia/dyspepsia, acute nonlocalized abdominal pain, chronic abdominal pain, inflammatory bowel disease, acute gastrointestinal bleeding, chronic gastrointestinal bleeding/anemia, abnormal liver biopsy, pancreatitis, anorectal diseases, diarrhea, fecal incontinence, and foreign body ingestion.

Intraoperative frozen section analysis of margin status as a quality indicator in gastric cancer surgery.

INTRODUCTION: Positive pathologic margins following gastric cancer (GC) resection carries a poor prognosis. We evaluated intraoperative frozen section (IFS) analysis of resection margins (RMs) as a quality indicator in GC surgery. METHODS: Patients referred to a provincial cancer agency with surgically resected non-metastatic GC between 2004 and 2012 were included. Associations between IFS analysis, other baseline characteristics, RMs, and overall survival (OS) were assessed using logistic regression, Kaplan-Meier analyses, and Cox proportional hazards modeling. RESULTS: Among 377 patients, median age was 67 years, 68% were male, and 16% had +RMs. Thirty-four percent of patients underwent IFS analysis, which protected against +RMs (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.16-0.73, p = 0.006) and improved OS (hazards ratio [HR]: 0.72, 95% CI: 0.54-0.98, p = 0.037). OS following re-resection of IFS positive patients was similar to IFS negative patients (69 vs. 54 months, p = 0.317). Stage III disease (OR: 12.8, 95% CI: 3.00-55.0, p = 0.001) and gastroesophageal junction tumors (OR: 2.25, 95% CI: 1.05-4.78, p = 0.036) predicted +RMs. Stage III disease led to worse OS (HR: 2.89, 95% CI: 1.92-4.34, p < 0.001) while intestinal histology improved OS (HR: 0.67, 95% CI: 0.50-0.90, p = 0.007). CONCLUSIONS: IFS analysis reduce +RMs and improve OS and should be incorporated in curative intent GC surgery for patients with locally advanced GC.

Viral Disease Goes Viral: Characterizing How Cancer Patients Use Internet Resources for COVID-19 Information.

This study aims to evaluate the usage of Internet resources for COVID-19 information among cancer patients. Specifically, to understand where patients are seeking information, what topics are most frequently searched, and how physicians and web developers can improve clinical conversations and digital resources, respectively, to support cancer patients' needs. From May to June 2021, cancer patients who were attending follow-up at a tertiary cancer center completed a survey consisting of 28 closed and open-ended questions. Quantitative results were evaluated using descriptive statistics and qualitative responses were evaluated using a grounded-theory approach. Fifty-seven surveys were distributed, and fifty-two surveys were received (91% response rate). The majority of respondents (96%) were Internet users. Seventy percent used the Internet as a source of information about COVID-19 and cancer personally, with another 15% reporting that friends and family accessed online information on their behalf. The vast majority used Google as their choice of search engine, with COVID-19 rates and vaccine information being the most frequently searched topics. Three quarters (74%) considered Internet information easy to understand, and 90% stated that the Internet increased their understanding of COVID-19 and cancer. Only 15% of patients had been recommended online resource(s) by a physician, yet 100% of those patients found the physician-recommended sites useful. Most cancer patients use the Internet to search for COVID-19 information. Healthcare professionals (HCPs) should help guide patients towards credible online sources and address knowledge gaps to improve physician-patient communication and support educational needs.

An Evaluation of the Quality of COVID-19 Internet Resources for Cancer Patients.

Cancer patients may face difficulty evaluating web-based COVID-19 resources in context with their cancer diagnosis. The purpose of this study is to systematically evaluate educational resources available for cancer patients seeking online information on COVID-19 and cancer. The term "COVID-19 and Cancer" was searched in Google and metasearch engines Yippy and Dogpile. After applying inclusion and exclusion criteria, the results from the 3 lists were systematically combined for a final ranked list. This list was analyzed using a validated structured rating tool with respect to accountability, interactivity, organization, readability, and content coverage and accuracy. Three hundred ninety-eight websites were identified, and 37 websites were included for analysis. Only 43% of sites disclosed authorship, 24% cited sources, and 32% were updated within 3 months of the search date. Fifty-four percent of websites had high school readability (8.0-12.0), 43% were at university level or above, and no websites demonstrated the recommended reading level for health information for the public (< 6.0). Topics most discussed were special considerations for cancer patients during COVID-19 (84%) and COVID-19 risk factors (73%). Topics least covered were COVID-19 incidence/prevalence (5%) and prognosis (8%). There is some COVID-19 information for cancer patients available online, but quality is variable. Healthcare professionals may direct cancer patients to the most reliable COVID-19 and cancer websites shown in this study and results may be helpful when designing future online health information resources.

Defining a Core Data Set for the Economic Evaluation of Precision Oncology.

OBJECTIVES: Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology. METHODS: We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set. RESULTS: Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use. CONCLUSIONS: Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement.

Modelling hereditary diffuse gastric cancer initiation using transgenic mouse-derived gastric organoids and single-cell sequencing.

Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome caused by germline variants in CDH1, the gene encoding the cell-cell adhesion molecule E-cadherin. Loss of E-cadherin in cancer is associated with cellular dedifferentiation and poor prognosis, but the mechanisms through which CDH1 loss initiates HDGC are not known. Using single-cell RNA sequencing, we explored the transcriptional landscape of a murine organoid model of HDGC to characterize the impact of CDH1 loss in early tumourigenesis. Progenitor populations of stratified squamous and simple columnar epithelium, characteristic of the mouse stomach, showed lineage-specific transcriptional programs. Cdh1 inactivation resulted in shifts along the squamous differentiation trajectory associated with aberrant expression of genes central to gastrointestinal epithelial differentiation. Cytokeratin 7 (CK7), encoded by the differentiation-dependent gene Krt7, was a specific marker for early neoplastic lesions in CDH1 carriers. Our findings suggest that deregulation of developmental transcriptional programs may precede malignancy in HDGC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Evaluating genomic biomarkers associated with resistance or sensitivity to chemotherapy in patients with advanced breast and colorectal cancer.

INTRODUCTION: Carcinogenesis is driven by an array of complex genomic patterns; these patterns can render an individual resistant or sensitive to certain chemotherapy agents. The Personalized Oncogenomics (POG) project at BC Cancer has performed integrative genomic analysis of whole tumour genomes and transcriptomes for over 700 patients with advanced cancers, with an aim to predict therapeutic sensitivities. The aim of this study was to utilize the POG genomic data to evaluate a discrete set of biomarkers associated with chemo-sensitivity or-resistance in advanced stage breast and colorectal cancer POG patients. METHODS: This was a retrospective multi-centre analysis across all BC CANCER sites. All breast and colorectal cancer patients enrolled in the POG program between July 1, 2012 and November 30, 2016 were eligible for inclusion. Within the breast cancer population, those treated with capecitabine, paclitaxel, and everolimus were analyzed, and for the colorectal cancer patients, those treated with capecitabine, bevacizumab, irinotecan, and oxaliplatin were analyzed. The expression levels of the selected biomarkers of interest (EPHB4, FIGF, CD133, DICER1, DPYD, TYMP, TYMS, TAP1, TOP1, CKDN1A, ERCC1, GSTP1, BRCA1, PTEN, ABCB1, TLE3, and TXNDC17) were reported as mRNA percentiles. RESULTS: For the breast cancer population, there were 32 patients in the capecitabine cohort, 15 in the everolimus cohort, and 12 in the paclitaxel cohort. For the colorectal cancer population, there were 29 patients in the bevacizumab cohort, 12 in the oxaliplatin cohort, 29 in the irinotecan cohort, and 6 in the capecitabine cohort. Of the biomarkers evaluated, the strongest associations were found between Bevacizumab-based therapy and DICER1 (P = 0.0445); and between capecitabine therapy and TYMP (P = 0.0553). CONCLUSIONS: Among breast cancer patients, higher TYMP expression was associated with sensitivity to capecitabine. Among colorectal cancer patients, higher DICER1 expression was associated with sensitivity to bevacizumab-based therapy. This study supports further assessment of the potential predictive value of mRNA expression of these genomic biomarkers.

Medical Oncologists' Perspectives on How the Results of the IDEA Collaboration Impact the Adjuvant Treatment of Stage III Colon Cancer.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists' perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer. MATERIALS AND METHODS: A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi-square tests were used to summarize information. RESULTS: Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0-8.5; p < .01 compared with pre-IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients. CONCLUSION: IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk-stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients. IMPLICATIONS FOR PRACTICE: This global survey illustrates that most gastrointestinal medical oncologists now use a risk-stratified approach for determining the duration of adjuvant chemotherapy for stage III colon cancer. Clinicians are five times more likely to choose CAPOX over FOLFOX after the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration results.

Improved structural variant interpretation for hereditary cancer susceptibility using long-read sequencing.

PURPOSE: Structural variants (SVs) may be an underestimated cause of hereditary cancer syndromes given the current limitations of short-read next-generation sequencing. Here we investigated the utility of long-read sequencing in resolving germline SVs in cancer susceptibility genes detected through short-read genome sequencing. METHODS: Known or suspected deleterious germline SVs were identified using Illumina genome sequencing across a cohort of 669 advanced cancer patients with paired tumor genome and transcriptome sequencing. Candidate SVs were subsequently assessed by Oxford Nanopore long-read sequencing. RESULTS: Nanopore sequencing confirmed eight simple pathogenic or likely pathogenic SVs, resolving three additional variants whose impact could not be fully elucidated through short-read sequencing. A recurrent sequencing artifact on chromosome 16p13 and one complex rearrangement on chromosome 5q35 were subsequently classified as likely benign, obviating the need for further clinical assessment. Variant configuration was further resolved in one case with a complex pathogenic rearrangement affecting TSC2. CONCLUSION: Our findings demonstrate that long-read sequencing can improve the validation, resolution, and classification of germline SVs. This has important implications for return of results, cascade carrier testing, cancer screening, and prophylactic interventions.

A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer.

Background Resistance to Epidermal Growth Factor inhibition (EGFRi) in patients with KRAS wild-type (wt) Colorectal Cancer (CRC) may occur as a result of PI3K/AKT/mTOR signaling. We conducted a study to establish the recommended phase II dose (RP2D) and response rate of panitumumab, an EGFRi, plus BKM120, a PI3K inhibitor, in advanced CRC. Methods Patients with chemotherapy refractory KRAS wt CRC, who were EGFRi naive were enrolled. A 3 + 3 dose escalation design was utilized. The starting dose of panitumumab was 6 mg/kg iv every 2 weeks with BKM120 at 60 mg oral daily. Results Nineteen patients were treated and 17 were evaluable for response. The starting dose was not tolerable (mucositis, fatigue). At dose level (DL) 1, three of six patients discontinued treatment due to toxicity, DL - 1 had no significant toxicity. Panitumumab 6 mg/kg iv q 2 weeks with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. One patient (5.9%) who was PTEN and PIK3CA negative by IHC had a partial response, seven had stable disease, and nine had disease progression. Conclusion Panitumumab (6 mg/kg iv q 2 weeks) with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. Toxicities including fatigue, rash and mucositis. There was little evidence of activity in this biomarker unselected cohort.

Cost-Effectiveness Analysis of Cytoreductive Surgery and HIPEC Compared With Systemic Chemotherapy in Isolated Peritoneal Carcinomatosis From Metastatic Colorectal Cancer.

BACKGROUND: Cost-effectiveness evaluations of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from metastatic colorectal cancer (mCRC) in the United States are lacking. METHODS: The authors developed a Markov model to evaluate the cost-effectiveness of CRS/HIPEC compared with systemic chemotherapy for isolated PC from mCRC from a societal perspective in the United States. The systemic treatment regimens consisted of FOLFOX, FOLFIRI, bevacizumab, cetuximab, and pantitumumab. The model inputs including costs, probabilities, survival, progression, and utilities were taken from the literature. The cycle length for the model was 2 weeks, and the time horizon was 7 years. A discount rate of 3% was applied. The model was tested for internal and external validation, and robustness was established with univariate sensitivity and probabilistic sensitivity analyses (PSA). The primary outcomes were total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $100,000 per QALY was assumed. RESULTS: The ICER for treatment with CRS/HIPEC compared with systemic chemotherapy was $91,034 per QALY gained ($74,098 per LY gained). The univariate sensitivity analysis showed that the total costs for treatment with CRS/HIPEC had the largest effect on the calculated ICER. The CRS/HIPEC treatment was a cost-effective strategy during the majority of simulations in the PSA. The average ICER for 100,000 simulations in the PSA was $70,807 per QALY gained. The likelihood of CRS/HIPEC being a cost-effective strategy at the WTP threshold was 87%. CONCLUSIONS: The CRS/HIPEC procedure is a cost-effective treatment for isolated PC from mCRC in the United States.

Prophylactic versus reactive treatment of acneiform skin rashes from epidermal growth factor receptor inhibitors in metastatic colorectal cancer.

PURPOSE: There are concerns regarding potential negative effects of prophylactic treatment of epidermal growth factor receptor (EGFR)-inhibitor-related rashes on metastatic colorectal cancer (mCRC) outcomes. We aimed to characterize treatment patterns of EGFR-inhibitor-induced rashes and evaluate prophylactic versus reactive approaches to rash management in relation to overall survival (OS). METHODS: Patients diagnosed with KRAS wild-type mCRC from July 2010 to June 2012 in British Columbia and prescribed cetuximab or panitumumab were reviewed to describe patterns of use of oral antibiotics and steroid creams. Using Cox regression, the relationship between prophylactic versus reactive rash management and OS was characterized. RESULTS: A total 119 patients were analyzed: median age was 63 years, 61 % were male, 34 % received cetuximab, 66 % received panitumumab, and median number of EGFR inhibitor treatment was nine cycles. Rash occurred in >90 % of patients, and reactive was favored over prophylactic treatment (66 vs. 34 %). Older patients and those with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 were more likely to receive prophylactic creams (44 vs. 20 % for age <60, p = 0.01) and oral antibiotics (62 vs. 12 % for ECOG ≥2, p = 0.01), respectively. Median OS was 7.0 months. The number of treatment cycles and OS were similar in both prophylactic and reactive groups (both p > 0.05). In Cox regression, ECOG >2 correlated with worse survival (hazard ratio (HR) 22.01, 95 % confidence interval (CI) 5.25-92.30, p < 0.01). However, survival outcomes were similar between patients prescribed antibiotics prophylactically versus reactively (HR = 1.10, 95 % CI 0.43-2.80, p = 0.85), and steroid creams prophylactically versus reactively (HR = 2.00, 95 % CI 0.58-6.92, p = 0.27). CONCLUSION: Prophylactic treatment of EGFR-inhibitor-related rashes is associated with similar outcomes compared to reactive rash treatment in mCRC.

Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer.

BACKGROUND: Adjuvant chemotherapy (AC) is frequently considered in patients with stage II colon cancer who are considered to be at high risk. However, to the authors' knowledge, the survival benefits associated with AC in these patients remain largely unproven. In the current study, the authors sought to examine the use of AC in patients with AJCC stage II colon cancer and to compare the impact of AC on outcomes in patients with high-risk versus low-risk disease in a population-based setting. METHODS: Patients with stage II colon cancer who were evaluated at 1 of 5 regional cancer centers in British Columbia from 1999 to 2008 were analyzed. Kaplan-Meier and Cox regression methods were used to correlate high-risk versus low-risk status and receipt of AC with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 1697 patients were identified: 1286 (76%) with high-risk and 411 (24%) with low-risk disease, among whom 373 (29%) and 51 (12%),respectively, received AC. Individuals with high-risk disease treated with AC were younger (median age, 62 years vs 72 years; P<.001) and had better Eastern Cooperative Oncology Group performance status (0/1: 47% vs 33%; P = .001). For high-risk patients, AC was associated with improved OS (hazard ratio [HR], 0.65; 95% confidence interval [95% CI], 0.50-0.83 [P = .001]). However, no significant benefits with regard to RFS or DSS were observed. Subgroup analyses revealed that AC in patients with T4 disease was associated with significantly improved RFS (HR, 0.63; 95% CI, 0.42-0.95 [P = .03]), DSS (HR, 0.59; 95% CI, 0.37-0.93 [P = .02]), and OS (HR, 0.50; 95% CI, 0.33-0.77 [P = .002]). For patients with low-risk disease, AC was associated with inferior RFS (HR, 2.18; 95% CI, 1.00-4.79 [P = .05]) and DSS (HR, 3.01; 95% CI, 1.10-8.23 [P = .03]). CONCLUSIONS: In this population-based analysis, AC was associated with an OS advantage in high-risk patients, most likely due to patient selection. RFS, DSS, and OS benefits were mainly observed in patients with T4 disease, suggesting a limited role for AC in patients deemed to be high risk by non-T4 features.

Phase 2 study of MK-2206, an allosteric inhibitor of AKT, as second-line therapy for advanced gastric and gastroesophageal junction cancer: A SWOG cooperative group trial (S1005).

BACKGROUND: The AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers. METHODS: Patients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK-2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation. RESULTS: Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4-86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression-free survival was 1.8 months (95% confidence interval, 1.7-1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7-9.4 months) CONCLUSIONS: MK-2206 as second-line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population.

Retrospective review using targeted deep sequencing reveals mutational differences between gastroesophageal junction and gastric carcinomas.

BACKGROUND: Adenocarcinomas of both the gastroesophageal junction and stomach are molecularly complex, but differ with respect to epidemiology, etiology and survival. There are few data directly comparing the frequencies of single nucleotide mutations in cancer-related genes between the two sites. Sequencing of targeted gene panels may be useful in uncovering multiple genomic aberrations using a single test. METHODS: DNA from 92 gastroesophageal junction and 75 gastric adenocarcinoma resection specimens was extracted from formalin-fixed paraffin-embedded tissue. Targeted deep sequencing of 46 cancer-related genes was performed through emulsion PCR followed by semiconductor-based sequencing. Gastroesophageal junction and gastric carcinomas were contrasted with respect to mutational profiles, immunohistochemistry and in situ hybridization, as well as corresponding clinicopathologic data. RESULTS: Gastroesophageal junction carcinomas were associated with younger age, more frequent intestinal-type histology, more frequent p53 overexpression, and worse disease-free survival on multivariable analysis. Among all cases, 145 mutations were detected in 31 genes. TP53 mutations were the most common abnormality detected, and were more common in gastroesophageal junction carcinomas (42% vs. 27%, p = 0.036). Mutations in the Wnt pathway components APC and CTNNB1 were more common among gastric carcinomas (16% vs. 3%, p = 0.006), and gastric carcinomas were more likely to have ≥3 driver mutations detected (11% vs. 2%, p = 0.044). Twenty percent of cases had potentially actionable mutations identified. R132H and R132C missense mutations in the IDH1 gene were observed, and are the first reported mutations of their kind in gastric carcinoma. CONCLUSIONS: Panel sequencing of routine pathology material can yield mutational information on several driver genes, including some for which targeted therapies are available. Differing rates of mutations and clinicopathologic differences support a distinction between adenocarcinomas that arise in the gastroesophageal junction and those that arise in the stomach proper.

A review of conventional and drug-eluting chemoembolization in the treatment of colorectal liver metastases: principles and proof.

The management of colorectal liver metastasis has undergone a significant change since the development of novel ablation and embolization. Drug-eluting microsphere platforms, designed to deliver targeted concentrations of systemic therapy directly into the tumor via its arterial vasculature, have garnered interest and gained in popularity in recent years. Based on in vitro and in vivo data, multiple factors contribute to locoregional exposure including carrier base, smaller particle size (larger surface area), chemotherapeutic and chemotherapeutic intensity. Based on the current published clinical data, therapy appears well tolerated but the questions remain as to the ideal technique, patient population and overall efficacy. The purpose of this article is to provide a perspective on the scientific basis, and clinical review of the current data supporting the use of this platform in the setting of metastatic colorectal carcinoma.

Colonoscopy after CT-diagnosed acute diverticulitis: Is it really necessary?

BACKGROUND: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis. METHODS: We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed. RESULTS: A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%. CONCLUSION: Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.

CONTEXTE: La tomodensitométrie (TDM) est couramment utilisée pour le diagnostic de la diverticulite aiguë, mais des caractéristiques sont communes à la diverticulite et au cancer colorectal (CCR) aux épreuves d'imagerie. On recommande donc en général la coloscopie après un épisode de diverticulite aiguë pour écarter un diagnostic de cancer sous-jacent. À l'heure actuelle, les appareils de TDM multidétecteurs à 64 barrettes peuvent fournir des images de haute résolution et permettent même de distinguer le cancer d'une inflammation diverticulaire. Nous avons voulu déterminer la prévalence du CCR chez les patients ayant présenté une diverticulite aiguë diagnostiquée par TDM. MÉTHODES: Nous avons procédé à une étude rétrospective sur des patients porteurs d'une diverticulite aiguë diagnostiquée à l'aide de TDM entre décembre 2005 et décembre 2010 à l'Hôpital St. Paul's de Vancouver, en Colombie-Britannique. Les non-résidents ont été exclus. Nous avons examiné les rapports de TDM incluant le terme « diverticulite ¼, les rapports d'examens du côlon au cours de l'année suivant le diagnostic et les rapports d'anatomopathologie. Nous avons interrogé le registre provincial sur le cancer pour nous assurer qu'aucun cas de CCR ne nous avait échappé. RÉSULTATS: En tout, 293 patients ont reçu un diagnostic de diverticulite à l'aide de la TDM; 8 étaient des non-résidents et ont été exclus. Parmi les 285 patients inclus dans l'analyse, l'âge moyen était de 59,4 ± 15,1 ans et 167 (58,6 %) étaient des hommes. Parmi les 114 patients qui ont subi un examen de suivi, le cancer a été diagnostiqué chez 4 (3,5 %). La prévalence globale du cancer chez les patients porteurs d'un diagnostic de diverticulite posé par TDM était de 1,4 %. CONCLUSION: L'évaluation endoscopique de routine après un épisode de diverticulite diagnostiquée à l'aide d'une TDM de haute résolution ne semble pas nécessaire. Une approche sélective chez les patients qui présentent une évolution clinique lente ou ceux qui présentent une lésion ou obstruction tumorale à la TDM pourrait être utile.

Diagnostic value of next-generation sequencing in an unusual sphenoid tumor.

Extraordinary advancements in sequencing technology have made what was once a decade-long multi-institutional endeavor into a methodology with the potential for practical use in a clinical setting. We therefore set out to examine the clinical value of next-generation sequencing by enrolling patients with incurable or ambiguous tumors into the Personalized OncoGenomics initiative at the British Columbia Cancer Agency whereby whole genome and transcriptome analyses of tumor/normal tissue pairs are completed with the ultimate goal of directing therapeutics. First, we established that the sequencing, analysis, and communication with oncologists could be completed in less than 5 weeks. Second, we found that cancer diagnostics is an area that can greatly benefit from the comprehensiveness of a whole genome analysis. Here, we present a scenario in which a metastasized sphenoid mass, which was initially thought of as an undifferentiated squamous cell carcinoma, was rediagnosed as an SMARCB1-negative rhabdoid tumor based on the newly acquired finding of homozygous SMARCB1 deletion. The new diagnosis led to a change in chemotherapy and a complete nodal response in the patient. This study also provides additional insight into the mutational landscape of an adult SMARCB1-negative tumor that has not been explored at a whole genome and transcriptome level.

Association between palliative resection of the primary tumor and overall survival in a population-based cohort of metastatic colorectal cancer patients.

BACKGROUND: The impact of palliative resection of the primary tumor on outcomes in patients with metastatic colorectal cancer (mCRC) remains unclear. The primary objective of this study was to evaluate the association between palliative resection and overall survival (OS) in a population-based cohort of mCRC. METHODS: Patients diagnosed with mCRC between 2006 and 2008 and treated at the BC Cancer Agency were reviewed. Survival analysis was conducted using Kaplan-Meier methods. Cox proportional hazards regression models were fitted to evaluate the relationship between palliative resection and OS while controlling for potential confounders, such as age, gender, Eastern Cooperative Oncology Group status, carcinoembryonic antigen level, primary tumor location, metastatic site and number, and receipt of systemic therapy. To adjust for the heterogeneity and selection bias between the group that underwent palliative resection and the group that did not, a propensity score-matched analysis was also performed. RESULTS: A total of 517 patients were included. Among these cases, 378 (73 %) patients underwent palliative resection of their primary tumor, and 139 (27 %) patients did not. A total of 327 patients (63 %) were treated with palliative chemotherapy. Palliative resection was associated with a longer median OS (17.9 vs. 7.9 months) and more favorable unadjusted and adjusted hazard ratios (HRs) for death (HR 0.46, 95 % CI 0.37-0.56, p < 0.0001 and HR 0.56, 95 % CI 0.40-0.78, p = 0.0007, respectively) when compared with no resection. In a propensity score-matched analysis, prognosis was also more favorable in the resected group (p = 0.0017). CONCLUSIONS: In this cohort of mCRC patients, palliative resection of the primary tumor was associated with improved OS.