British Columbia Cancer Agency Research Articles

Detection of Melanoma Skin Lesions Using Phylogeny

Asymmetry, boundary irregularity, color variegation, and diameter are popular clinical guidelines used for early detection of melanoma. Several researchers have proposed and framed methodologies to detect the melanoma using combined and separate features with the help of statistical theory, fuzzy logic, artificial neural networks, and machine learning techniques. When we combine all the techniques to quantify the four attributes (recently derived) within a single interface to diagnose melanoma skin lesion, it will be much complex and time consuming task. Hence, this paper proposes a novel methodology to detect melanoma skin cancer through phylogeny of pigmented skin lesions and it is a pilot scale attempt using the images of skin lesions. The construction of phylogeny has the following steps namely, the construction of image matrix, construction of image blocks, phylogenetic tree, and classification. Classification is implemented through average mean rank method as well as artificial neural networks. Performance of the proposed methodology is tested with 110 different images of skin lesions (BC cancer agency) and it is shown to predict 87 % successfully (melanoma/non-melanoma). The advantage of the proposed methodology is to predict the classification of melanoma skin lesions with the help of phylogeny achieves accuracy of 87 % with less time complexity. Some additional analysis is required for the remaining 13 % of images. Finally, it is proved that both average rank method and artificial neural network classification method predict almost the same accuracy.

Benefits and risks of contralateral prophylactic mastectomy in women undergoing treatment for sporadic unilateral breast cancer: a decision analysis.

The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast cancer. A Markov model was developed to compare 18 hypothetical cohorts of 45-year-old women with newly diagnosed unilateral, sporadic breast cancer treated with or without CPM. The probability of developing distant metastases by American Joint Committee on Cancer stage and molecular subtype was derived from British Columbia Cancer Agency data. Additional model parameters were identified from the medical literature. Sensitivity analyses were performed to examine the impact of plausible variations in key model parameters on results. CPM improved LE in all cohorts (range 0.06-0.54 years). Stage had more effect on LE than subtype (stage I mean, 0.44 years, stage III mean, 0.11 years). However, after adjusting for quality-of-life, No CPM was favored in all cohorts. Univariate sensitivity analysis demonstrated that the most influential model parameter was the post-CPM health state utility. The preferred strategy shifted from No CPM to CPM when the post-CPM utility exceeded 0.83 (base case value 0.81). PSA indicated that LE gains and QALE decreases were stable in all cohorts. The primary determinant of survival after unilateral breast cancer is stage at diagnosis. Our results suggest that routine CPM would not improve quality-adjusted survival for the majority of women with unilateral sporadic breast cancer.

Reduction in cervical intraepithelial neoplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis.

We report on the rates of cervical intraepithelial neoplasia (CIN) in young women aged 15-22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency's population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15-22 years in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for young women aged 15-17 years decreased significantly from 0.91 (95% CI: 0.86-0.98 p < 0.01) to 0.36 (95% CI: 0.18-0.73 p < 0.01). During the same time period, no similar reduction was found in young women 18-22 years. After introduction of HPV vaccine program, IRR for CIN2+ in young women 15-17 was significantly reduced for CIN2+ (0.14; 95% CI: 0.04- 0.47; p < 0.01) and CIN2 (0.1; 95% CI: 0.02-0.54; p < 0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15-17 years in British Columbia after the introduction of the HPV vaccine in young women despite vaccine uptake levels below 70%.

XV. Clinical aspects of transformed lymphoma.

XV. Clinical aspects of transformed lymphoma.

IV. Masses in the mediastinum: primary mediastinal lymphoma and intermediate types.

IV. Masses in the mediastinum: primary mediastinal lymphoma and intermediate types.

Histologic classification of non-small-cell lung cancer over time: reducing the rates of not-otherwise-specified.

The importance of histologic classification in selecting the appropriate systemic therapy for non-small-cell lung cancer (nsclc) came to attention in 2007. In British Columbia, that information was communicated through international and national meetings, our centralized cancer care program, and to the medical community at large in multidisciplinary forums. We examined the effects of those education programs on the categorization of nsclc and associated systemic treatment practices. The BC Cancer Agency provides cancer care to 4.6 million residents of British Columbia. A retrospective review of all stage iiib and ivnsclc patients referred in 2007 and 2011 collected baseline characteristics, treatment, and outcomes. Histology was classified using the International Classification of Diseases for Oncology, 3rd edition, for the Canadian Cancer Registry. In 2007, 671 patients were referred, and 170 received chemotherapy; in 2011, the relevant figures were 680 and 197 respectively. Baseline characteristics in the cohorts were not statistically significantly different in 2007 and 2011. Histologic classifications in 2007 were 41% nonsquamous, 13% squamous, and 46% not otherwise specified (nos); in 2011, they were 63%, 17%, and 20% respectively. Exposure to pemetrexed in any line of therapy in 2007 was 22% for nonsquamous, 17% for squamous, and 10% for nos; in 2011, exposure was 39%, 3%, and 37% respectively. Exposure to epidermal growth factor receptor tyrosine kinase inhibitor (egfrtki) in 2007 was 36%, 22%, and 33%; in 2011, it was 64%, 60%, and 63%. Median overall survival duration, 2007 versus 2011, was 3.25 months versus 3.57 months with best supportive care, and 11.31 months versus 11.54 months with chemotherapy. The specificity of nsclc histologic categorization improved in 2011 compared with 2007, with a reduction of 26 percentage points in the rate of nos disease. The proportion of patients treated with chemotherapy over time remained the same, but the use of pemetrexed and egfrtki increased. The increased accuracy in histologic classification resulted in more appropriate utilization of systemic drugs.

Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.

Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88). In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.

Risk factors for the development of ocular graft-versus-host disease (GVHD) dry eye syndrome in patients with chronic GVHD

BackgroundTo investigate the factors associated with the development of ocular graft-versus-host disease (oGVHD) dry eye syndrome (DES) in patients with chronic GVHD (cGVHD) after receiving allogenic haematopoietic stem cell transplantation...

Abstract P2-14-02: Complications of breast reconstruction in a provincial population of breast cancer survivors

Abstract Background: Breast cancer is the most prevalent cancer in women in Canada. There are varying reports of the use of breast reconstruction in various populations and very few prospective trials or population reports of complications related to breast reconstruction in breast cancer patients. The goal of this study is to describe the use of breast reconstruction in breast cancer survivors in British Columbia, the risk of complications after breast reconstruction, and factors associated with a higher risk of complications. Methods: Electronic Records from the BC Cancer Agency were used to identify women diagnosed with invasive breast cancer between 2001-2008 in British Columbia. Administrative hospital records used with permission of the British Columbia Ministry of Health, obtained through PopulationData BC, were used to obtain details about all surgeries,hospital admissions and associated complications for the cohort. Analyses of reconstruction for those treated with breast-conserving surgery (BCS) versus mastectomy were done separately. For those who underwent mastectomy following BCS, complications after BCS before mastectomy were attributed to the BCS, and those that occurred after mastectomy were attributed to the mastectomy. These analyses included a description of the type of reconstruction procedures used in this era, and the frequency and types of complications after the reconstruction procedures. Logistic regression was used to identify risk factors for complications post reconstruction. Results: The cohort consisted of 18,642 women; 4868 had mastectomy alone, 8633 had BCS alone, 2894 had both, and 2247 had neither surgery. Of those undergoing BCS (11527), 746 had reconstructive procedures. Most of these were separate procedures; 55% were ≤50 years of age. The most common complication was "miscellaneous complication of internal prosthetic devices, implants or grafts". One hundred eight (14%) of those with reconstruction after BCS had complications within 30 days of the reconstruction procedure, 134 (18%) had complications within one year of the procedure. Of those undergoing mastectomy (7762), 7497 had their mastectomies within 1 year of diagnosis. Ninety-six had bilateral mastectomies. 1766 underwent reconstructive procedures; 74% were immediate procedures, 57% were ≤ 50 years of age. The most common complication was "miscellaneous complication of internal prosthetic devices, implants or grafts". One hundred sixty-seven (9%) of those with reconstruction after (or with) mastectomy had complications within 30 days of the reconstruction procedure, 227 (13%) had complications within one year of the procedure. Regression analysis showed that no radiotherapy (OR=0.65) and premenopausal status (OR=0.70) were significantly associated with a lower risk of complication post reconstruction. Conclusion: Complications related to reconstructive procedures for breast cancer happened in the minority of breast cancer survivors. They were more common in those with BCS, and were more likely for those who underwent adjuvant radiotherapy or were postmenopausal. Citation Format: Elaine S Wai, Ling Hong Lu, Cheryl Alexander, Mary L Lesperance, Mary L McBride, Scott Tyldesley, Chris Taylor. Complications of breast reconstruction in a provincial population of breast cancer survivors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-14-02.

Abstract P6-08-40: Survival of metastatic hormone receptor (HR) positive/HER2 negative; HER2+; and triple negative (TN) breast cancer based on initial presentation

Abstract Introduction: Median overall survival (OS) for patients (pts) with metastatic breast cancer (MBC) is described as 2-3 years, but few reports compare OS for de novo versus relapsed disease. The recognized clinical subtypes of breast cancer (HR positive[+] /HER2 negative; HER2+; TN) are known to have variable OS clinically, but this has not been systematically documented. We hypothesized that pts relapsing from a non MBC stage (relapsed) might have different OS than those presenting initially with metastases (de novo), and that OS would differ for the three clinical biomarker subgroups. Methods: Using the Breast Cancer Outcomes Unit database, we identified all women diagnosed with MBC, de novo or relapsed, in British Columbia between 01/2001 and 12/2009 and referred to the BC Cancer Agency. Review of medical records confirmed ER, PR and HER2 status. Survival from MBC diagnosis was calculated for relapsed vs de novo in the three biomarker subgroups. Results: After excluding pts with a synchronous or prior contralateral disease, we identified 3645 women with known ER. Median follow up was 91 months. HER2 known (n=3010) and unknown (n=635, 17%) cases had the same median OS (17 months [m]) and HR status (72% ER+). Trastuzumab (T) was standard in MBC during this era, but fewer than 10% had adjuvant T (introduced mid 2005) which explains the high number of HER2+ MBC cases. We previously reported longer OS for HER2+ disease relapsing after adjuvant therapy without T (older cohort) than after adjuvant T (SABCS 2013 Lohrisch). HER2 unknown pts were excluded from further survival analyses. Three percent of cases with known PR were ER negative/PR +. Therefore ER was used as the main determinant of HR status. For the entire cohort and all biomarker groups, OS was longer for denovo than for relapsed MBC. Overall Survival - relapsed vs de novo MBC for each biomarker subtype Relapsed MBCDe novo MBC SubgroupsN dead/totalMedian OS, mN dead/totalMedian OS, mP-valueAll cases with known ER2124/231115593/69926&amp;lt;.0001HR+/ HER2 negAll821/91224290/36434&amp;lt;.0001PR known414/47720251/31934&amp;lt;.0001PR unknown407/4352839/45330.1315TNBCAll368/3919110/126150.0001HER2+All935/100811193/209170.0061ER neg268/278758/609.50.2191ER+667/73015135/149250.0088 OS was longest for denovo HR+/HER2 negative (34m) and shortest for HER2+/ER negative (7m) and TN (9m) relapsers. The difference in OS for relapsed vs denovo HER2+ disease was significant for HR+ but not HR negative cases, likely due to small numbers in the latter subset. Conclusion: Relapsers experience shorter OS than their denovo biomarker counterparts, possibly due to the selective pressure of adjuvant therapy on disease biology. When restricted to pts who received systemic therapy for MBC, OS figures may be higher. Novel therapies may decrease the total number of relapsers, and improve OS in MBC for all, but are unlikely to narrow the OS gap between relapsed and denovo groups. Trials exploring therapies for MBC of all biomarker types should therefore stratify by stage at initial diagnosis. Citation Format: Wendie-Lou D den Brok, Caroline Speers, Gondara Lovedeep, Emily Baxter, Scott Tyldesley, Lohrisch Caroline. Survival of metastatic hormone receptor (HR) positive/HER2 negative; HER2+; and triple negative (TN) breast cancer based on initial presentation [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-40.

DIDA: Distributed Indexing Dispatched Alignment.

One essential application in bioinformatics that is affected by the high-throughput sequencing data deluge is the sequence alignment problem, where nucleotide or amino acid sequences are queried against targets to find regions of close similarity. When queries are too many and/or targets are too large, the alignment process becomes computationally challenging. This is usually addressed by preprocessing techniques, where the queries and/or targets are indexed for easy access while searching for matches. When the target is static, such as in an established reference genome, the cost of indexing is amortized by reusing the generated index. However, when the targets are non-static, such as contigs in the intermediate steps of a de novo assembly process, a new index must be computed for each run. To address such scalability problems, we present DIDA, a novel framework that distributes the indexing and alignment tasks into smaller subtasks over a cluster of compute nodes. It provides a workflow beyond the common practice of embarrassingly parallel implementations. DIDA is a cost-effective, scalable and modular framework for the sequence alignment problem in terms of memory usage and runtime. It can be employed in large-scale alignments to draft genomes and intermediate stages of de novo assembly runs. The DIDA source code, sample files and user manual are available through http://www.bcgsc.ca/platform/bioinfo/software/dida. The software is released under the British Columbia Cancer Agency License (BCCA), and is free for academic use.

Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001–2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan–Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6–12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57–4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28–2.23), CA 19.9 > 1000 versus ≤1000 (HR 1.59, 95% CI 1.19–2.14) and female gender, (HR 1.57, 95% CI 1.19–2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

Regional radiation dose susceptibility within the parotid gland: effects on salivary loss and recovery.

Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head-and-neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose-dependence of salivary output loss and recovery in a prospective study. Salivary output was collected from patients undergoing radiotherapy treatment for head-and-neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose-dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearman's rank correlation coefficients, local linear regression) and parametric (least-sum of squares, least-median of squares) techniques. Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left- and right parotid combined dose φ = min (DL, 45 Gy) + min (DR, 45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A3m = 0.0604 Gy(-1) and A1y = 0.0379 Gy(-1). Recovery was not significantly associated with dose. Hints of lateral organ sub-segment dose-response dimorphism were observed. Sub-segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post-treatment. It seems unlikely that a population's mean recovery will exceed 20%-30% of baseline output at 1 yr after radiotherapy treatment using current (whole-organ based) clinical guidelines.

Surveillance for asymptomatic recurrence in resected stage III colon cancer: does it result in a more favorable outcome?

Evidence from dated and moderate quality trials supports a modest survival benefit for intensive surveillance in resected colon cancer (CC). This study evaluates surveillance in a modern population-based cohort of stage III CC patients (pts). Records of pts who initiated oxaliplatin-based adjuvant chemotherapy (AC) for stage III CC between 2006-2011 at the British Columbia Cancer Agency (BCCA) were reviewed. Kaplan-Meier and log rank test were generated to investigate whether diagnosis of recurrence based on symptoms was associated with worse overall survival (OS). OS1 and OS2 were measured from date of recurrence or date of initial surgery, respectively. Of 635 pts who received AC for stage III CC, 175 pts (27.5%) recurred and 118 (18.6%) died at a median follow-up of 67.7 months. Recurrences were detected by surveillance in 149 pts (41% by CEA elevation and 44% by abnormal imaging), and symptoms in 26 pts (15%). Patients with surveillance-detected recurrences had a shorter median relapse-free survival (RFS) (18.5 vs. 25.3 months, HR 1.82, P<0.001), and longer median OS1 (28.5 vs. 6.5 months, HR 0.37, P<0.001). However, median OS2 was not significantly different (50.9 vs. 39.1 months, HR 0.66, P=0.091). Pts with surveillance-detected recurrence received more potentially curative metastasectomy (39% vs. 7%, P=0.002) and chemotherapy (70% vs. 50%, P=0.03). In this modern population-based cohort study, the OS impact of detecting asymptomatic recurrences in stage III CC is unclear. However, pts with asymptomatic recurrences were more likely to receive potentially curative metastasectomy and chemotherapy.

Adjuvant Chemotherapy in Resected Stage II Non-small Cell Lung Cancer: Evaluating the Impact of Dose Intensity and Time to Treatment

AimsPlatinum-based adjuvant chemotherapy is the standard of care for resected stage II non-small cell lung cancer (NSCLC). The purpose of this population-based study was to identify factors that predict for receiving adjuvant therapy and to assess the effect of delayed administration and dose reduction on survival. Materials and methodsThe British Columbia Cancer Agency provides cancer care to 4.6 million individuals across a large and varied geographical area. A retrospective review was conducted of all referred patients with resected stage II NSCLC between 2005 and 2010. Baseline characteristics, systemic therapy details and outcomes were recorded. ResultsOf 258 stage II NSCLC patients, 158 received adjuvant chemotherapy (61%). No-adjuvant versus adjuvant population: men 52%/57%, median age 67/62, Eastern Cooperative Oncology Group (ECOG) ≤ 1 55%/75%, Charlson comorbidity score (CCS) ≤ 1 61%/74%, pneumonectomy 11%/26%. In patients who received chemotherapy, treatment details were: cisplatin/carboplatin based 81%/19%, median cycles delivered 4, median time from surgery to adjuvant chemotherapy 8 weeks, 72% received ≥ 80% (cisplatin < 256 mg/m2 and carboplatin < AUC 19.2) total planned dose. On multivariate analysis younger age, better ECOG and pneumonectomy were predictive of adjuvant treatment. Overall survival of adjuvant-treated patients was inferior for those with CCS ≥ 2, age ≥ 70 and reduced dose intensity on multivariate analysis. The surgery to chemotherapy interval did not affect overall survival. ConclusionsPneumonectomy and factors associated with better functional status predicted for receiving adjuvant chemotherapy. For patients who received adjuvant chemotherapy the total platinum dose given affected survival but time from surgery did not. A higher platinum dose delivery was important in maintaining the efficacy of adjuvant chemotherapy for resected stage II NSCLC in this retrospective population-based study.

Esophageal Irradiation Induced Weight Loss: Is There a Role for a Prophylactic Gastric Feeding Tube?

Nutritional complications are a major concern in patients with esophageal cancer, due to tumour and treatment side effects. The purpose of this research is to identify whether inserting a gastric feeding tube (g-tube) prior to radical radiation therapy (RT) treatment shows better weight maintenance compared to patients with no g-tube insertion during their complete course of radical RT. Prior research has shown that maintaining a steady weight during treatment has been linked to reduced breaks in treatment, less unplanned hospital admissions, better treatment efficacy, increased quality of life and better survival rates. Despite clear evidence supporting the use of prophylactic g-tubes to minimize weight loss during treatment in head and neck cancers, there is a lack of research for the use of prophylactic g-tubes for patients with esophageal cancer. This retrospective study (2009-2013) evaluated the weight of patients with esophageal cancer at the start and end of radical-intent RT, between patients with placement of a prophylactic g-tube sand patients with no placement of g-tubes throughout their course of treatment. Other factors considered were gender, age, pathology, stage, interventional placement of g-tube, adjuvant chemotherapy and surgery. The observed difference between the sample means was 0.37 kg lost for patients with prophylactic g-tubes and 2.81 kg lost for patients with no g-tube placement (p=0.20). Patients with the insertion of interventional g-tubes had the highest mean weight loss (3.26 kg) relative to the other samples. The observed difference between sample means between prophylactic g-tube and no g-tube was not strong enough to conclude that the placement of prophylactic g-tubes significantly affected maintenance of patient weight during radical RT for esophageal cancer. This study should be followed by a prospective-based nutritional intervention study for patients with esophageal cancer at the British Columbia Cancer Agency, to aid in constructing guidelines concerning nutritional management.

AIDS incidence and AIDS-related mortality in British Columbia, Canada, between 1981 and 2013: a retrospective study

Appropriate use of highly active antiretroviral therapy (ART) can substantially decrease the risk of progression to AIDS and of premature mortality. We aimed to characterise the trends between 1981 and 2013 in AIDS-defining illnesses (ADIs) and the number AIDS-related deaths in British Columbia, Canada, where ART has been fully subsidised since 1996. We included data on HIV-positive individuals, aged 19 years or older, from four administrative databases in British Columbia: the British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, the British Columbia Vital Statistics Agency, the British Columbia Cancer Agency. We estimated the relative risk of developing an ADI over time by use of a negative binomial model, and we investigated trends in the proportion of all deaths associated with AIDS by use of generalised additive models. Data were available for 3550 people with HIV. 6205 ADIs were recorded. In 2013, 84 ADIs occurred, the lowest number since 1990. The peak of the AIDS epidemic in the region happened in 1994 with 696 ADIs reported (42 ADIs per 100 person-years). Since 1997, the number of ADIs decreased from 253 (7 per 100 person-years) to 84 cases in 2013 (1 per 100 person-years; p<0·0001 for trend in number of ADIs). We have also shown that of 22 ADIs included, only Pneumocystis jirovecii pneumonia remained prominent (albeit with much reduced overall prevalence). 2828 deaths were from AIDS-related causes, peaking in 1996 with 241 (96%) of 252 deaths in people with HIV and declining to 44 (20%) of 218 in 2013. Our results provide further evidence that integrated comprehensive free programmes that facilitate testing and deliver treatment and care can be eff ective in decreasing AIDS-related morbidity and mortality, thus suggesting that control of and eventually an end to AIDS are possible.

Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.

753 Background: Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. Methods: We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). Results: 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. 176 pts recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first line in 3 pts (13.6%), as second line in 14 (63.6%), and third line in 5 (22.7%). Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and OS were 3.3 (95% CI 1.4-5.1) and 10.0 months (95% CI 5.3-14.6), respectively. There was no difference in PFS for patients who were re-exposed to oxaliplatin in less than 36 months or later than that (3.6 versus 3.1 months, p=0.793, HR=0.88). Conclusions: In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.

Treatment and outcomes of goblet cell adenocarcinomas (GCAs) of the appendix.

551 Background: GCAs are rare mucinous neoplasms with mixed epithelial and endocrine differentiation, which behave more like mucinous adenocarcinomas than appendiceal neuroendocrine tumors. Optimal therapy is poorly described. Objectives of this study were to define prognostic factors and describe management of patients presenting with stage I-IV disease. Methods: Patients diagnosed with GCAs between 1990-2010 were identified from the British Columbia province-wide cancer registry and linked to an electronic pathology archive. Pathology was reviewed in 79 of 87 cases where archival tissue was available. Treatment and outcome data were obtained from the BC Cancer Agency, GI Cancer Outcomes Unit, and Provincial Pharmacy databases, combined with chart review. Kaplan Meier survival analysis was used to compare outcomes. There were insufficient events for robust multivariate analysis. Results: 87 cases of appendiceal GCAs were identified for an annual population incidence of 0.2/200,000. Median age was 54 (range 25-91) years, and 42 (48%) were male. There were no stage I patients. For stage II-III (n=68) and stage IV (n=19) patients, median overall survival (OS) was 42.8 and 15.4 months, respectively (p=0.009). Of stage II-III patients, 51 (76%) underwent right hemicolectomy and 9 (16%) received adjuvant chemotherapy: 5-FU (n=5), 5FU/oxaliplatin (n=4). Median recurrence-free survival (RFS) was 38.2 months (10 recurrences: 9 peritoneal, 1 hepatic). Univariate analysis demonstrated no prognostic effect of adjuvant chemotherapy, surgical approach (hemicolectomy vs. appendectomy), T4 tumors, number of nodes resected, or lymph node positivity. 5-year RFS was 90.2% in patients who presented with appendicitis, compared to 63.7% in those without appendicitis (p=0.016). Of 19 patients with stage IV disease, 10 (63%) received palliative chemotherapy including FOLFOX (n=4), FOLFIRI (n=1), FOLFIRI/bevacizumab (n=2), and capecitabine (n=2). Only high mitotic rate was associated with reduced OS. Conclusions: GCAs are rare tumors and the majority present with non-metastatic disease. Presentation with metastatic disease carries a poor prognosis and chemotherapy agents used for advanced colorectal tumors are most commonly applied.

Maintenance chemotherapy in advanced NSCLC: a population-based assessment of eligibility.

Maintenance chemotherapy has been incorporated into treatment paradigms for advanced NSCLC. Eligibility criteria include stable disease/partial response and PS 0-1 after a first line platinum doublet. In practice, maintenance can be difficult to deliver due to patient factors and preferences. We propose to examine the proportion of patients eligible for maintenance and factors associated with the delivery of subsequent lines of chemotherapy. The BC Cancer Agency provides care to a population of 4.5 million. A retrospective review was conducted of all referred Stage IIIB/IV patients in 2009 who received first line systemic therapy. Baseline characteristics, PS and response after first line and subsequent systemic therapy details were recorded. Patients were deemed potentially maintenance eligible or not based on clinical trial criteria; however maintenance therapy was not delivered to these patients as it was not yet available. 330 patients were identified; 98 were potentially maintenance eligible. The reason for maintenance ineligibility in n = 232; no upfront doublet (n = 41), PS ≥ 2 (n = 38), progressive disease (PD) (n = 53), PS ≥ 2 and PD (n = 62), PS ≥ 2 and unknown response (n = 35), PD and unknown PS (n = 3). Further chemotherapy (2nd line or beyond) was administered in maintenance eligible 68% vs ineligible 56%. Reasons for no further chemotherapy were predominantly decline in PS and brain metastasis. Median OS: 7 m for 1st line only versus 16.8m for ≥ 2 nd line (p < 0.001). In our population based study, 30% of advanced NSCLC patients were eligible to receive maintenance chemotherapy based on the clinical trial criteria. Despite a good initial PS and disease control only 68% of maintenance eligible patients received subsequent therapy. A clear survival benefit was seen with ≥ 2 nd line treatment. Maintenance therapy or initiation of early second line therapy should be considered for advanced NSCLC patients to improve survival outcomes.