Dataset Information

A Retrospective Review of Chemotherapy for Patients with Small Bowel Adenocarcinoma in British Columbia.

ABSTRACT: Background: Small bowel adenocarcinoma (SBA) is associated with a poor prognosis. It is an uncommon malignancy and therefore difficult to study. Randomized phase III trials are not available to guide best approaches. The Provincial Cancer Registry of the British Columbia Cancer Agency contains long-term data on patients with SBA. The authors analyzed characteristics and treatment outcomes for SBA patients diagnosed between 1990 and 2008. Material and methods: Charts of 150 patients with a histological diagnosis of SBA were retrospectively analyzed. Epidemiological and treatment data were collected. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: Baseline characteristics, such as median age at diagnosis (64.5 years), tumor stage (I-II 33%, III-IV 58%, unknown 9%), and location (duodenum 48%, jejunum 31%, ileum 21%) were consistent with published data. 55% of patients had a positive family history of cancer. DFS and OS of 29 patients treated with adjuvant chemotherapy were not significantly different to that of 47 patients without (p = 1 and p = 0.211, respectively). In the palliative setting patients treated with polychemotherapy (21 patients) had statistically better OS than patients treated with monochemotherapy (12 patients) (p = 0.0228). Conclusions: Our study suggests a survival benefit for advanced-stage SBA patients treated with poly- versus monochemotherapy. This, however, was a retrospective analysis with several potential confounders. Nevertheless, our study adds to the evidence suggesting that chemotherapy may be beneficial for patients with SBA, at least in the palliative setting.

SUBMITTER: Duerr D

PROVIDER: S-EPMC5166539 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Retrospective Review of Chemotherapy for Patients with Small Bowel Adenocarcinoma in British Columbia.

Duerr Donat D Ellard Susan S Zhai Yongliang Y Taylor Marianne M Rao Sanjay S

Journal of Cancer 20161125 15

<b>Background:</b> Small bowel adenocarcinoma (SBA) is associated with a poor prognosis. It is an uncommon malignancy and therefore difficult to study. Randomized phase III trials are not available to guide best approaches. The Provincial Cancer Registry of the British Columbia Cancer Agency contains long-term data on patients with SBA. The authors analyzed characteristics and treatment outcomes for SBA patients diagnosed between 1990 and 2008. <b>Material and methods:</b> Charts of 150 patients ...[more]

PMID: 27994666

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Project description:BackgroundMetastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Due to its rarity, high-quality data are lacking to guide treatment. This retrospective analysis was conducted to help characterize the treatment options for patients with metastatic SBA while providing clinically meaningful prognostic information.Patients and methodsIn total, 437 patients who initially presented with or developed metastatic SBA between September 1977 and September 2019 were identified from the MD Anderson Tumor Registry. Clinical data were collected from review of the medical record. Overall response rates (ORR), time to progression (TTP), and overall survival (OS) were assessed across various treatments and treatment lines.ResultsThe median OS from diagnosis of metastatic disease was 15.9 months [95% confidence interval (CI): 14.3-17.9]. Seventy-five patients (17.1%) underwent metastasectomy, which was associated with a median OS of 34.5 versus 17.1 months among patients who received chemotherapy alone (P < 0.001). Fluoropyrimidine plus platinum (n = 164) was the most common first-line chemotherapy, associated with an ORR of 59% and TTP of 8.1 months. Irinotecan with 5-FU (n = 101) was the most common second-line therapy associated with an ORR of 31% and TTP of 4.0 months. Twenty-two patients received immunotherapy; 5 of 6 patients with deficient mismatch repair (dMMR) responded, while 0 of 16 with proficient mismatch repair (pMMR) responded. Taxane-based chemotherapy was given to 34 patients with an ORR of 21% and a median TTP of 2.4 months. Among 11 patients who received anti-epidermal-growth-factor-receptor (EGFR) monotherapy, the best response was stable disease (SD) in 1 patient.ConclusionsIn well-selected patients with SBA, metastasectomy appears to be associated with improved OS. This improvement was seen across metastasectomy sites, including liver, lung and peritoneal. Anti-programmed cell death protein 1 (PD-1) based immunotherapy was active for dMMR SBA but not pMMR SBA. While taxane-based chemotherapy demonstrates therapeutic activity, the activity of anti-EGFR therapy was limited.

Project description:ImportanceSmall-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking.ObjectiveTo perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations.Design, setting, and participantsProspective analysis was performed of clinical samples from patients with SBA (n?=?317), colorectal cancer (n?=?6353), and gastric carcinoma (n?=?889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions.ResultsOf the 7559 patients included in analysis, 4138 (54.7%) were male; the median age was 56 (range, 12-101) years. The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P?<?.001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P?<?.001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P?<?.001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P?<?.001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P?<?.001). BRAF was mutated in 7.6% (484 of 6353) of colorectal cancer and 9.1% (29 of 317) of SBA samples, but V600E mutations were much less common in SBA, representing only 10.3% (3 of 29) of BRAF-mutated cases. The ERBB2/HER2 point mutations (8.2% [26 of 317]), microsatellite instability (7.6% [13 of 170]), and high tumor mutational burden (9.5% [30 of 317]) were all enriched in SBA. Significant differences were noted in the molecular profile of unspecified SBA compared with duodenal adenocarcinoma, as well as in inflammatory bowel disease-associated SBAs. Targetable alterations in several additional genes, including PIK3CA and MEK1, and receptor tyrosine kinase fusions, were also identified in all 3 series.Conclusions and relevanceThis study presents to our knowledge the first large-scale genomic comparison of SBA with colorectal cancer and gastric carcinoma. The distinct genomic differences establish SBA as a molecularly unique intestinal cancer. In addition, genomic profiling can identify potentially targetable genomic alterations in the majority of SBA cases (91%), and the higher incidence of microsatellite instability and tumor mutational burden in SBA suggests a potential role for immunotherapy.

Project description:BackgroundLate HIV diagnosis is associated with increased AIDS-related morbidity and mortality as well as an increased risk of HIV transmission. In this study, we quantified and characterized missed opportunities for earlier HIV diagnosis in British Columbia (BC), Canada.DesignRetrospective cohort.MethodsA missed opportunity was defined as a healthcare encounter due to a clinical manifestation which may be caused by HIV infection, or is frequently present among those with HIV infection, but no HIV diagnosis followed within 30 days. We developed an algorithm to identify missed opportunities within one, three, and five years prior to diagnosis. The algorithm was applied to the BC STOP HIV/AIDS population-based cohort. Eligible individuals were ≥18 years old, and diagnosed from 2001-2014. Multivariable logistic regression identified factors associated with missed opportunities.ResultsOf 2119 individuals, 7%, 12% and 14% had ≥1 missed opportunity during one, three and five years prior to HIV diagnosis, respectively. In all analyses, individuals aged ≥40 years, heterosexuals or people who ever injected drugs, and those residing in Northern health authority had increased odds of experiencing ≥1 missed opportunity. In the three and five-year analysis, individuals with a CD4 count <350 cells/mm3 were at higher odds of experiencing ≥1 missed opportunity. Prominent missed opportunities were related to recurrent pneumonia, herpes zoster/shingles among younger individuals, and anemia related to nutritional deficiencies or unspecified cause.ConclusionsBased on our newly-developed algorithm, this study demonstrated that HIV-diagnosed individuals in BC have experienced several missed opportunities for earlier diagnosis. Specific clinical indicator conditions and population sub-groups at increased risk of experiencing these missed opportunities were identified. Further work is required in order to validate the utility of this proposed algorithm by establishing the sensitivity, specificity, positive and negative predictive values corresponding to the incidence of the clinical indicator conditions among both HIV-diagnosed and HIV-negative populations.

Dataset Information

A Retrospective Review of Chemotherapy for Patients with Small Bowel Adenocarcinoma in British Columbia.

Publications

A Retrospective Review of Chemotherapy for Patients with Small Bowel Adenocarcinoma in British Columbia.

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