A prospective comparison of costs between robotics, laparoscopy, and laparotomy in endometrial cancer among women with Class III obesity or higher.

BACKGROUND AND OBJECTIVES: To compare the immediate operating room (OR), inpatient, and overall costs between three surgical modalities among women with endometrial cancer (EC) and Class III obesity or higher. METHODS: A multicentre prospective observational study examined outcomes of women, with early stage EC, treated surgically. Resource use was collected for OR costs including OR time, equipment, and inpatient costs. Median OR, inpatient, and overall costs across surgical modalities were analyzed using an Independent-Samples Kruskal-Wallis Test among patients with BMI ≥ 40. RESULTS: Out of 520 women, 103 had a BMI ≥ 40. Among women with BMI ≥ 40: median OR costs were $4197.02 for laparotomy, $5524.63 for non-robotic assisted laparoscopy, and $7225.16 for robotic-assisted laparoscopy (p < 0.001) and median inpatient costs were $5584.28 for laparotomy, $3042.07 for non-robotic assisted laparoscopy, and $1794.51 for robotic-assisted laparoscopy (p < 0.001). There were no statistically significant differences in the median overall costs: $10 291.50 for laparotomy, $8412.63 for non-robotic assisted laparoscopy, and $9002.48 for robotic-assisted laparoscopy (p = 0.185). CONCLUSION: There was no difference in overall costs between the three surgical modalities in patient with BMI ≥ 40. Given the similar costs, any form of minimally invasive surgery should be promoted in this population.

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial.

BACKGROUND: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. METHODS: Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. RESULTS: In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. CONCLUSIONS: This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013.

Perioperative adherence to continuous positive airway pressure and its effect on postoperative nocturnal hypoxemia in obstructive sleep apnea patients: a prospective cohort study.

BACKGROUND: Although continuous positive airway pressure (CPAP) is the first line treatment for obstructive sleep apnea (OSA) patients, the perioperative adherence rate is unclear. The objective of this study was to determine the perioperative adherence rate of patients with OSA with a CPAP prescription and the effect of adherence on nocturnal oxygen saturation. METHODS: This prospective cohort study included adult surgical patients with a diagnosis of OSA with CPAP prescription undergoing elective non-cardiac surgery. Patients were divided into CPAP adherent and non-adherent groups based on duration of usage (≥ 4 h/night). Overnight oximetry was performed preoperatively and on postoperative night 1 and 2 (N1, N2). The primary outcome was adherence rate and the secondary outcome was nocturnal oxygen saturation. RESULTS: One hundred and thirty-two patients completed the study. CPAP adherence was 61% preoperatively, 58% on postoperative N1, and 59% on N2. Forty-nine percent were consistently CPAP adherent pre- and postoperatively. Using a linear fixed effects regression, oxygen desaturation index (ODI) was significantly improved by CPAP adherence (p = 0.0011). The interaction term CPAP x N1 was significant (p = 0.0015), suggesting that the effect of CPAP adherence varied on N1 vs preoperatively. There was no benefit of CPAP adherence on postoperative mean SpO2, minimum SpO2, and percentage of sleep duration with SpO2 < 90%. Use of supplemental oxygen therapy was much lower in the CPAP adherent group vs non-adherent group (9.8% vs 46.5%, p <  0.001). CONCLUSIONS: Among patients with a preoperative CPAP prescription, approximately 50% were consistently adherent. CPAP adherence was associated with improved preoperative ODI and the benefit was maintained on N1. These modest effects may be underestimated by a higher severity of OSA in the CPAP adherent group and a higher rate of oxygen supplementation in the non-adherent group. TRIAL REGISTRATION: ClinicalTrials.Gov registry ( NCT02796846 ).

Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. METHODS: This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60­7·60]; p=0·0016). At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9­23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9­25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2­29·2) versus 31·3% (21·9­40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5­35·1) in the anti-thymocyte globulin group and 41·3% (31·3­51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 70·6% (95% CI 60·6­78·6) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 53·3% (42·8­62·8) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35­0·90]; p=0·017). Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient in the anti-thymocyte globulin plus GVHD prophylaxis group died of Epstein-Barr virus hepatitis, but no deaths were attributable to anti-thymocyte globulin. INTERPRETATION: The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including decreases in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin should be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. FUNDING: Canadian Institutes of Health Research and Sanofi.

Health-Related Internet Use Among Men With Prostate Cancer in Canada: Cancer Registry Survey Study.

BACKGROUND: After a prostate cancer diagnosis, men want information about their disease and treatment options. The internet offers a convenient means to deliver health information to patients with prostate cancer. However, there are concerns about the use of the internet among this largely senior population. OBJECTIVE: This study aimed to determine the patterns and factors associated with the use of the internet as a source of health information among Canadian men with prostate cancer and the features and information required in a website. METHODS: Population surveys were conducted in four Canadian provinces (British Columbia, Alberta, Saskatchewan, and Ontario) in 2014-2015. Data analyses included descriptive, bivariable, and multivariable analyses. The Pearson Chi-square and univariable regression were used to examine associations between independent variables and health-related internet use. Correlates of health-related internet use were analyzed using multivariable logistic regression. RESULTS: A total of 1362 patients responded across the four provinces. The mean age of respondents was 69 years (SD 8.2). In addition, 82% (n=1071) were internet users and 71% (n=910) used the internet daily. Further, 65% (n=784) used the internet as a source of prostate cancer information, and 40% (n=521) were confident about using information obtained from the internet to make health decisions. Men who used the internet to obtain prostate cancer information were more likely to be active information seekers (odds ratio [OR]: 4.5, 95% CI 2.6-7.8), be confident using information from the internet to make health decisions (OR: 3.6, 95% CI 2.3-5.7), have broadband internet access (OR: 1.8, 95% CI 1.2-2.7), and have more unmet supportive care needs (OR: 1.05, 95% CI 1.0-1.1). Top features wanted in a website, reported by more than 50% of respondents, were a library of resources (n=893, 65.6%), tools to support treatment decision making (n=815, 59.8%), and tools to help navigate the prostate cancer journey (n=698, 51.2%). Top three topics of information wanted in such a website were treatment options (n=916, 67.3%), disease progression (n=904, 66.4%), and management of side effects (n=858, 63%). CONCLUSIONS: Over two-thirds of Canadian patients with prostate cancer surveyed use the internet as a source of health information about prostate cancer, but over half did not feel confident using information from the internet to make health decisions. Being an active information seeker, having confidence in using information from the internet to make health decisions, having broadband internet, and having more unmet supportive care needs were significantly associated with health-related internet use. Future work should examine electronic health literacy interventions as a means to boost men's confidence in using information from the internet and design websites that include information and features that help men navigate the prostate cancer journey and support treatment decision making and management of side effects.

Detection of Relapse by Low-dose Computed Tomography During Surveillance in Stage I Testicular Germ Cell Tumours.

BACKGROUND: Standard-dose computed tomography (SDCT) scans are associated with radiation exposure during stage I testicular cancer surveillance. OBJECTIVE: To evaluate low-dose CT (LDCT) for clinical use. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm prospective study, patients on surveillance for stage I testicular germ cell tumour underwent SDCT and LDCT scans on their first visit after enrolment. The adequacy of LDCT image quality was assessed for subsequent use. Patients were followed with LDCT only and suspected relapse was confirmed by SDCT. OUTCOME MEASURES AND STATISTICAL ANALYSIS: We assessed whether initial LDCT scans were of sufficient quality for routine clinical use. We compared mean differences in nodal size at relapse between LDCT and SDCT using a one-sample paired t test. The relapse free-rate was calculated using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Of 257 patients, one was excluded because of inadequate image quality. At median follow-up of 5.25 yr, 35 patients had relapsed, 33 with retroperitoneal lymphadenopathy. The 2- and 5-yr relapse-free rates were 89.5% and 85.3%, respectively. The mean size of retroperitoneal nodal relapse was 17.3 and 17.5mm on the short axis, 23.2 and 22.7mm on the long axis, and 26.1 and 26.7mm on craniocaudal length for LDCT and SDCT, respectively. The mean difference between LDCT and SDCT was 0.14mm (p=0.55) short axis, -0.54mm (p=0.092) long axis, and -0.51mm (p=0.086) length. A limitation was the lack of a control arm. CONCLUSIONS: LDCT image quality was adequate for clinical use, and retroperitoneal nodal relapse was detected with minimal differences seen between LD and SDCT. LDCT can be safely adopted and will decrease overall radiation exposure in stage I germ cell tumour surveillance. PATIENT SUMMARY: We studied the use of low-dose computed tomography scans for detecting testicular cancer recurrence in lymph nodes of the abdomen and pelvis and found that they were safe, effective and would potentially reduce overall X-ray exposure. This trial is registered at ClinicalTrials.gov as NCT03142802.

Management of Polycythemia Vera: A Survey of Canadian Physician Practice Patterns.

BACKGROUND: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 WHO diagnostic criteria of PV are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm Group. MATERIALS AND METHODS: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society using an online survey-distributing website. Univariate and multivariate analysis was performed. RESULTS: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all patients with PV (P = .0009). Respondents who were aware of the Canadian Myeloproliferative Neoplasm Group guidelines were more likely to phlebotomize patients to a target hematocrit of < 45% irrespective of gender (P = .042). Younger practitioners were more likely to use age over 60 years as an indication for initiating cytoreductive therapy (P = .0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. CONCLUSION: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria.

The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes.

There is a paucity of data regarding the impact of mutations on outcomes in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs). Moreover, it is unknown whether mutational status affects survival, as seen in chronic-phase MPNs. Therefore, we performed a retrospective analysis of all patients treated at our institution with AP/BP MPNs (N = 122; AP = 14; BP = 108) to comprehensively describe the mutational profile and correlate with clinical outcomes. Targeted sequencing with a 54-gene panel was performed. Forty-four patients were treated with intensive therapy, 27 with nonintensive therapy, and 51 with best supportive care (BSC). The most common mutation was JAK2V617F, occurring in 55% of subjects; CALR was found in 13% of patients and MPL in 6%. Thirty-two (26%) patients were triple negative. Other frequently mutated genes were ASXL1 (30%), TET2 (25%), SRSF2 (22%), RUNX1 (20%), and TP53 (17%). Mutations in 1, 2, 3, and ≥4 genes were seen in 15%, 13%, 25%, and 46% of patients, respectively. There was no difference in survival between patients treated with intensive vs nonintensive therapy, and the benefit of intensive therapy was limited to patients who were able to undergo transplantation. TP53 was the only individual mutation to correlate with shorter overall survival (hazard ratio, 1.89; P = .03). In the multivariate analysis, mutated TP53, ≥4 mutations, low albumin, increased peripheral blood blasts, ≥3 cytogenetic abnormalities, and BSC were associated with shorter survival. In conclusion, mutational data enhance the understanding of patients with AP/BP MPN who are likely to benefit from current therapeutic options.

Prospective cohort study comparing quality of life and sexual health outcomes between women undergoing robotic, laparoscopic and open surgery for endometrial cancer.

OBJECTIVE: To evaluate patient-reported outcomes (PROs) between women treated by laparoscopic, robotic and open approaches for endometrial cancer. METHODS: Prospective cohort study comparing PRO at baseline, short- (1 and 3 weeks) and long-term (12 and 24 weeks) follow-up postoperatively. Quality of life (QOL) measures were the Functional Assessment of Cancer Therapy (FACT-G), EuroQol Five Dimensions (EQ-5D), and Brief Pain Inventory (BPI). Sexual health measures were the Female Sexual Function Index (FSFI) and the Sexual Adjustment and Body Image Scale for Gynecologic Cancer (SABIS-G). RESULTS: 468 eligible patients (laparotomy = 92, laparoscopy = 152, robotic = 224) were recruited. There were no significant differences between the laparoscopy and robotic groups for any PRO (P > 0.05). At short-term follow-up, patients who underwent minimally invasive surgery (robotic or laparoscopy) had significantly higher FACT-G (P < 0.0001) and EQ-5D (P < 0.0001) scores, with less pain (P = 0.02) and improved pain interference (P = 0.0008), than patients undergoing laparotomy. At long-term follow-up, there were sustained improvements in the FACT-G (P = 0.035) and the health state EQ-5D visual analogue scale (P = 0.022). Surgical approach had no impact on sexual health (P > 0.05); however the mean FSFI score for the entire cohort met clinical cut-offs for sexual dysfunction. CONCLUSION: Minimally invasive approaches result in improved QOL beyond the short-term postoperative period, with benefits noted up to 12 weeks after surgery. This prolonged QOL advantage provides further evidence that MIS should be the standard surgical approach for women with early stage endometrial cancer.

CD56bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft-versus-host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results.

Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow were grouped together, a higher chronic graft-versus-host disease frequency was associated with lower proportions of CD56bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm-Associated Myelofibrosis: A Retrospective Cohort Study.

BACKGROUND: We sought to describe the distribution and impact of comorbidities on outcomes in patients with myelofibrosis, a disease characterized by aberrant bone marrow function with eventual fibrosis. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), in which a score ≥ 3 indicates severe comorbidities. PATIENTS AND METHODS: We conducted a retrospective study of 306 patients with a confirmed diagnosis of myelofibrosis. Patients were seen from 1999 to 2014 with a median follow-up of 2 years. Multivariable Cox proportional hazards models were constructed to assess the impact of comorbidities on overall survival and leukemic transformation from the date of presentation to our center. A series of descriptive analyses were performed examining the distribution of comorbidities captured by the scales. RESULTS: On multivariable survival analysis, an ACE-27 score of 3 was associated with an almost twofold increase in the risk of all-cause death (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.06-3.58; P = .03) compared with a lower score of 0 to 1. An HCT-CI score ≥ 3 was marginally significantly associated with an increased risk of all-cause death (HR 1.60; 95% CI 0.96-2.68; P = .07). ACE-27 captured a greater spectrum of cardiovascular and venous thrombotic disease. No impact of comorbidities on leukemic transformation was observed. CONCLUSIONS: Although the presence of severe comorbidities was lower when assessed by ACE-27 (13%) compared with HCT-CI (23%), and the spectrums of comorbidities captured were different, the overall impact of severe comorbidities as assessed by both scales appears to be similar and associated with a survival disadvantage.

Long term responders to palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND: Patients with advanced biliary tract cancer (BTC) are often treated with palliative chemotherapy (PC). Standard PC since 2010 is a cisplatin/gemcitabine doublet, with median overall survival (OS) of 11.7 months from the ABC-02 trial. Prior to this, our institutional standard was gemcitabine and fluoropyrimidine. The ABC-02 study used 8 cycles of PC as standard with treatment stopped even in the absence of disease progression, but some patients may benefit from continuing PC longer than 8 cycles. METHODS: Patients treated with at least 2 cycles of PC for advanced BTC in Princess Margaret Cancer Centre between 1987 and 2015 were included, and divided into 2 groups for analysis-long-term responders (LTR) who received 9 or more cycles, and controls (2-8 cycles). Data was collected on demographics, clinicopathological features, PC regimen, toxicities, and survival. The primary outcome measure was OS, with secondary analyses including progression-free survival (PFS) and toxicity rates between groups. RESULTS: A total of 382 patients were identified, 123 who met the criteria for LTR and 259 who were included as controls. The baseline demographic and clinical characteristics were similar, although more patients in the control group had gallbladder cancer or extrahepatic cholangiocarcinoma than LTR (P=0.024), and more patients in the LTR group were treated with combination chemotherapy regimens (93% vs. 82% in controls, P=0.003). The LTR patients had significantly longer PFS (median 13.3 vs. 4.1 months, P<0.001) and longer OS than controls (median 22.1 vs. 9.2 months, P<0.001). In LTR patients, 15% had a break from chemotherapy of 3 months or more and restarted the same regimen. The LTR patients reported higher rates of nausea, cutaneous and hematologic toxicity, but also more frequently went on to receive second-line chemotherapy (47% vs. 33%, P=0.007). In multivariable analysis of OS, LTR, good performance status and intrahepatic site of cancer were associated with better survival. CONCLUSIONS: From this institutional dataset, a significant proportion of patients continued chemotherapy past 8 cycles, and appeared to derive benefit from longer duration of treatment. Toxicity rates were higher in this group, but manageable as evidenced by second-line treatment rates. Discontinuation of chemotherapy for reasons other than toxicity or progression may result in loss of disease control and impact survival in this population; these data suggest the use of continued chemotherapy to disease progression in patients with advanced BTC is a favorable option.

Long-Term Responders on Olaparib Maintenance in High-Grade Serous Ovarian Cancer: Clinical and Molecular Characterization.

Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib.Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo >2 years, ST as <3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort.Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation.Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. Clin Cancer Res; 23(15); 4086-94. ©2017 AACR.

Endometrioid Carcinoma of the Ovary: Outcomes Compared to Serous Carcinoma After 10 Years of Follow-Up.

OBJECTIVES: The prognostic significance of endometrioid ovarian cancer is unclear. In this study we compared rates of overall survival (OS) and disease-free survival between patients with endometrioid and serous ovarian cancers using long-term follow-up data. METHODS: We included patients with endometrioid or serous ovarian cancers diagnosed at a single regional cancer centre between 1988 and 2006. Data on baseline and treatment characteristics were collected retrospectively. We used multivariate Cox proportional hazard models to determine the independent effect of histology on death or recurrence, adjusting for age, tumour grade, primary cytoreductive surgery, year of diagnosis, adjuvant treatment, and stage. RESULTS: Five hundred and thirty-three women with ovarian cancer were included in the study cohort; 98 (18.4%) had endometrioid histology and 435 (81.6%) serous histology. The five-year OS rate for women with endometrioid cancer was 80.6%, and for women with serous ovarian cancer, it was 35.0%. The 10-year OS rates were 68.4% and 18.4% for endometrioid and serous histology, respectively. After adjusting for confounders excluding stage, there was a significantly lower risk of death from endometrioid cancer compared to serous ovarian cancer (hazard ratio [HR] 0.41, 95% CI 0.26 to 0.66). However, the difference was no longer significant after adding tumour stage to the model (HR 0.74, 95% CI 0.45 to 1.24). We found similar results for the risk of recurrence (HR 0.41, 95% CI 0.27 to 0.62 with stage not included, compared to HR 0.77, 95% CI 0.49 to 1.21 with stage included). CONCLUSION: In this large cohort, in comparison with women with serous ovarian cancer, women with endometrioid ovarian cancer presented at a younger age, had earlier stage disease, and had disease almost always confined to the pelvis. The earlier stage of presentation of endometrioid ovarian cancer resulted in improved five-year and 10-year OS rates compared to serous ovarian cancer.

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy.

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had ≥3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies.

The uptake of active surveillance for the management of prostate cancer: A population-based analysis.

INTRODUCTION: Active surveillance (AS) is a strategy for the management of low-risk prostate cancer (PCa). However, few studies have assessed the uptake of AS at a population level and none of these were based on a Canadian population. Therefore, our objectives were to estimate the proportion of men being managed by AS in Ontario and to assess the factors associated with its uptake. METHODS: This was a retrospective, population-based study using administrative databases from the province of Ontario to identify men ≤75 years diagnosed with localized PCa between 2002 and 2010. Descriptive statistics were used to estimate the proportion of men managed by AS, whereas mixed models were used to assess the factors associated with the uptake of AS. RESULTS: 45 691 men met our inclusion criteria. Of these, 18% were managed by AS. Over time, the rates of AS increased significantly from 11% to 21% (p<0.001). Older age, residing in an urban centre, being diagnosed in the later years of the study period, having a neighborhood income in the highest quintile, and being managed by urologists were all associated with greater odds of receiving AS. CONCLUSIONS: There has been a steady increase in the uptake of AS between 2002 and 2010. However, only 18% of men diagnosed with localized PCa were managed by AS during the study period. The decisions to adopt AS were influenced by several individual and physician characteristics. The data suggest that there is significant opportunity for more widespread adoption of AS.

Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.