Ottawa Hospital Cancer Centre Research Articles

Perspectives on shorter durations of anti-HER2 therapy in early-stage HER2-positive breast cancer: a patient survey.

Despite previous studies proposing shorter durations of anti-HER2 therapy for selected patients with HER2-positive early breast cancer (EBC), 12-months remains standard of care. A survey was performed to assess patient perspectives and willingness to participate in studies evaluating shorter durations of anti-HER2 therapy. Patients with HER2-positive EBC completing or having previously completed anti-HER2 therapy, were recruited by healthcare professionals at The Ottawa Hospital Cancer Centre to participate in an anonymous online survey. The primary objective was to learn about patients' perspectives on shorter durations (less than 12-months) of anti-HER2 therapy. Secondary objectives were to explore patients' interest in clinical trials of shorter durations of anti-HER2 therapy and the degree of increased breast cancer risk they would accept with a shorter treatment duration. Responses were received from 94 eligible patients. Most patients received Trastuzumab alone (78%, 73/94), while 13% (12/94) received trastuzumab and pertuzumab. Side effects were experienced by 52% (46/89), the most common being; fatigue (61%, 28/46), myalgia (37%, 17/46), and diarrhea (24%, 11/46). Most patients (88%, 78/89) did not find treatment bothersome. Regarding perspectives on shorter durations of anti-HER2 therapy, most (79%, 74/94) respondents stated they would agree to less treatment if it were possible to receive fewer treatments with the same cancer benefits. 56% of patients were interested in clinical trials, however, about half stated they would not be accepting of any increase in breast cancer recurrence risk. Trials to investigate who can safely and effectively be treated with shorter durations of anti-HER2 therapy are needed. This study provides important insights to patients' perspectives on shorter durations of anti-HER2 treatment, and their concerns regarding potential increased cancer risk with less treatment.

Real-world evaluation of clinical outcomes and long-term survivors in patients with BRAF-V600E metastatic colorectal cancer.

166 Background: BRAF-V600E mutant metastatic colorectal cancer (BRAF-V600E mCRC) is associated with poor prognosis but confers response to combination BRAF/EGFR blockade. The goal of this study is to evaluate the clinicopathologic features and natural history of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR inhibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mCRC who did not receive combination BRAF/EGFR therapy. Patients diagnosed with colorectal cancer prior to March 31, 2021, were included. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included duration of therapy, as a surrogate of progression free survival, and overall survival (OS). Long-term survivor was defined as OS greater than 2 years. Results: 74 patients were included. Median age was 70 years (IQR=61-78), and 39 (53%) patients were female. There were 17 (23%) patients alive at the end of the follow-up period. 31 (42%) patients had poorly differentiated grade and 26 (35%) were mismatch repair deficient (dMMR). Locations of metastases included liver (40, 54%), peritoneum (30, 41%), lung (18, 24%), bone (5, 7%) and brain (5, 7%). Overall, 64 (86%) patients received first line systemic therapy, 19 (26%) second line, and 5 (7%) third line (see Table). Median duration of therapy in the first line was 4.3 months (IQR=2.0-9.6), second line was 2.9 months (IQR=1.4-4.1), and third line 1.0 months (IQR=1.0-1.9). Overall survival in the entire cohort was 13.2 months (IQR=4.6-25.4). Importantly, 21 (28%) patients were long-term survivors, of which 8 (11%) were dMMR. Conclusions: Patients with BRAF-V600E mCRC generally have poor clinical outcomes with traditional systemic therapies. In this study, we identified approximately 25% of patients who are long-term survivors (OS >2 years). This reflects the real-world heterogeneity of clinical outcomes for patients with BRAF-V600E mCRC who did not receive BRAF/EGFR targeted therapy.[Table: see text]

Cancer Center Staff Satisfaction: Descriptive Results of a Canadian Study.

Caring for cancer patients is generally considered very rewarding work, but it can also be stressful and demanding. Therefore, it is important for oncology healthcare professionals to feel satisfied with their work environment in order to provide the best care possible. An ethics-approved 61-item staff satisfaction survey was developed in-house to gain insights regarding workplace satisfaction among all staff at The Ottawa Hospital Cancer Center. Descriptive statistics were used to analyze the responses. A total of 478 individuals completed the online survey, with 75.1% women, 23.2% men, and 1.7% preferring not to say. This represented the vast majority (>75%) of cancer center staff. The approximate breakdown according to healthcare professional type was as follows: 21% nurses, 20% radiation therapists, 18% physicians, 13% clerical staff, and 28% other types of staff. Almost all (97.4%) generally enjoyed their work, with 60% stating "very much" and 37.4% stating "a little bit", and 93.3% found working with cancer patients rewarding. The overall satisfaction level at work was high, with 30.1% reporting "very satisfied" and 54.2% "somewhat satisfied". However, in terms of their work being stressful, 18.6% stated it was "very much" and 62.1% "a little bit". Also, in terms of their workload, 61.3% stated it was "very busy" and 10% stated it was "excessively busy". The most enjoyable aspects of work were listed as interactions with colleagues, interactions with patients, and learning new things. The least enjoyable aspects of work were excessive workload, a perceived unsupportive work environment, and technology problems. Levels of satisfaction and stress at work varied according to role at the cancer center. Most cancer center staff seem to enjoy their work and find it rewarding. However, the work environment can be challenging and stressful. Areas for improvement include managing workloads, ensuring staff feel supported, and improving the user-friendliness of technology.

Real world sequence of peptide receptor radionucleotide therapy (PRRT) and chemotherapy in patients with metastatic pancreatic neuroendocrine tumors (pNETs).

e16237 Background: Peptide Receptor Radionuclide Therapy (PRRT) is an effective therapy for advanced pNETs but carries long-term risks of myeloid neoplasia. Early data from United States centres may suggest a higher risk of myelodysplasia and leukemia in patients treated with temozolomide prior to PRRT. The objective of this study is to characterize the sequence of PRRT and chemotherapy at two Canadian pNET treatment centres, distinguished by the availability of PRRT. Methods: This is a multicentre retrospective cohort study involving The Ottawa Hospital Cancer Centre (TOHCC; PRRT non-treatment centre (PRRT-NTC)) and London Regional Cancer Centre (LRCC; PRRT treatment centre (PRRT-TC). Patients with histologically confirmed pNETs between January 2010 – June 2021 over the age 18 (n=226), with metastatic disease (n=177) were included. Demographic, clinical and cancer treatments were collected. Descriptive statistics were used to evaluate the sequence of systemic therapy. Results: 177 patients with metastatic pNET were identified. Systemic therapies included octreotide (n=59, 40%), lanreotide (n=47, 32%), targeted agents (n=40, 27%), chemotherapy (n=48, 33%) and PRRT (n=47, 32%). Of patients receiving chemotherapy, 22 (46%) received temozolomide-containing regimens. The most frequent first line therapies were somatostatin analogues (SSAs, n=76, 43%), chemotherapy (n=23, 13%) and observation (n=18, 10%), second-line were PRRT (n=24, 14%), targeted therapy (n=26, 15%) and SSA (n=13, 7%), and third-line were PRRT (n=15, 9%), chemotherapy (n=11, 6%) and targeted therapy (n=8, 5%). There were 83 (47%) patients treated at the PRRT-TC, of which 33 (40%) received PRRT prior to chemotherapy and 7 (8%) received temozolomide-containing therapy prior to PRRT. In comparison, 94 (53%) patients were treated at the PRRT-NTC, of which 1 (1%) received PRRT prior to chemotherapy and 0 (0%) received PRRT prior to temozolomide-containing therapy. Conclusions: In this large cohort of metastatic pNET patients, the sequence of chemotherapy and PRRT showed centre-to-centre variability with patients treated at a PRRT-TC being more likely to receive chemotherapy, including temozolomide, prior to PRRT. This may be explained in-part by referral/practice patterns, and PRRT availability. These findings suggest an opportunity to evaluate and optimize the sequence of systemic therapy with the increasing availability of PRRT.

INNV-31. PROTECT: PROCARBAZINE, LOMUSTINE, AND VINCRISTINE VERSUS TEMOZOLAMIDE IN HIGH-RISK, LOW-GRADE GLIOMAS: A RETROSPECTIVE COHORT STUDY

Abstract INTRODUCTION Low-grade gliomas (LGG), specifically WHO grade 2 diffuse astrocytoma and oligodendroglioma, are increasingly considered for adjuvant chemotherapy with high-risk features (age ≥ 40y or subtotal resection). This is based on prospective studies showing improvement in survival with adjuvant procarbazine, CCNU, vincristine (PCV) or temozolomide (TMZ) in this cohort. Use of PCV or TMZ is variable without published head-to-head comparison. PROTECT is a Canadian multicentre retrospective study aiming to compare overall survival (OS) in high-risk LGGs receiving PCV or TMZ. We are presenting results from The Ottawa Hospital Cancer Centre (TOHCC). METHODS Patients age ≥ 18y with LGG that received PCV or TMZ within 6 months of primary brain tumor resection at TOHCC from 2005 to 2019 were included. The primary outcome is OS. Secondary outcomes include 1)time to progression (TTP), 2)rate of completion of 6 cycles of PCV or TMZ, and 3)rate of hospitalization or death due to chemotherapy-related complications. RESULTS Of 250 cases, 20 patients (11 diffuse astrocytoma, 9 oligodendroglioma) were eligible. IDH status was mutated in 11, wild-type in 1, and unknown in 5 cases. 1p/19q co-deletion was present in 6, non-co-deleted in 1, and unknown in 13 cases. Six patients received PCV, and 14 received TMZ. Hematologic toxicity (CTCAE Grade 1-2) occurred in 3 PCV patients and 0 of 11 of assessable TMZ patients; no severe toxicity was observed. Median follow-up was 64.5 (IQR 42.5–88) months. The median OS and TTP for PCV and TMZ groups were not reached. The 5-year OS and TTP were 75% vs. 100 % (p=0.08) and 83.3% vs 81.3% (p=0.7) respectively. CONCLUSIONS There are insufficient cases and follow-up time to determine OS and TTP amongst patients treated with PCV or TMZ. Hematologic toxicity appears to be more common with PCV. Patient screening and data collection is ongoing at 8 other cancer centres.

Delivery of cancer care via an outpatient telephone support line: A cross-sectional study of oncology nursing perspectives on quality and challenges.

427 Background: Patient support lines (PSLs) help in triaging clinical problems, addressing patient queries and assist in navigating a complex multi-disciplinary oncology team. While providing support and training to nursing staff who operate these lines is key, there is limited data on their experience and feedback to guide this. Our objective was to identify areas of quality improvement for The Ottawa Hospital Cancer Centre (TOHCC) patient support lines. Methods: We conducted a cross-sectional study of oncology nurses’ (ONs’) perspectives on the provision of care via PSLs at a tertiary referral cancer center via an anonymous, descriptive survey. Measures collected included nursing/patient characteristics, nature of questions addressed by the PSL, patient/nursing satisfaction with the service, common challenges faced, and initiatives to improve the patient and nursing experience. Results: Seventy-one percent (30/42) of eligible nurses responded to the survey. The most common disease site, stage, issue, and symptom addressed were breast cancer, metastatic disease, treatment-related toxicity, and pain, respectively. Despite majority of nurses reporting personal and patient satisfaction with the care provided by the PSL, there was variance in the perceived appropriate use of PSL by physicians and patients. As such, fifty-nine percent (17/29) of nurses recommended redefining the responsibilities of the PSL to achieve its maximal potential, with 75% (6/8) ONs identifying high call volumes due to inappropriate questions as a barrier to care. Sixty percent (18/30) of nurses reported that having TOHCC-specific management plans for common issues would improve their experience, and the quality of care provided on PSL. Lastly, 80% (24/30) of nurses denied experiencing a reduction in PSL call volumes with increased patient access to their electronic medical record. Conclusions: Our study identified several important areas for improvement warranting further investigation, despite high reported rates of satisfaction with care provided on PSL. A need for TOHCC standardized management algorithms for common issues addressed on the PSL as well as increased physician and patient education to redefine goals of the PSL to address problems with high volume, and inappropriate calls was identified.

The impact of virtual oncology care on chemotherapy continuity and clinical outcomes in patients treated for colorectal cancer: A pre-post analysis of the COVID-19 pandemic.

e13649 Background: The coronavirus (COVID-19) pandemic has resulted in an abrupt transition to virtual oncology care at most cancer centres worldwide. A pillar of the American Medical Association’s proposed framework for digitally enabled care is assessing clinical quality, safety, and outcomes. This study’s objective is to evaluate chemotherapy quality and clinical outcomes in patients receiving intravenous chemotherapy for colorectal cancer before and during the COVID-19 pandemic. Methods: This is an observational study assessing patients treated with intravenous chemotherapy for colorectal cancer consecutively at the Ottawa Hospital Cancer Centre from June 2019 to September 2021. Patients with non-metastatic rectal cancer were excluded. Patient were stratified by whether they were started on chemotherapy pre-pandemic (June 2019 – Jan 2020) versus intra-pandemic (Feb 2020 – Sept 2021). Baseline characteristics and treatment data were collected from the electronic medical records. Outcomes of interest included chemotherapy delays, dose reductions, emergency department (ED) visits and hospitalizations. We used generalized linear and binary logistic regression modelling to compare outcomes between pre- and intra-pandemic periods. Results: There were 220 patients included in this study with 108 (49%) diagnosed with metastatic disease. In total, there were 66 (30%) patients treated in the pre-pandemic and 154 (70%) in the intra-pandemic period. As expected, virtual care consultations increased during the pandemic from 1.5% to 43.5% (p < 0.001). Likewise, the proportion of follow-up visits also increased from 37% to 84% (p < 0.001). There was no difference in the incidence of treatment delays (odds ratio [OR] = 1.01, p = 0.78), dose reductions (OR = 0.99, p = 0.69), ED visits (OR = 1.23, p = 0.37), hospitalizations (OR = 0.73, p = 0.43) or the total length of time off treatment (OR = 0.85, p = 0.17) between the pre- and intra-pandemic periods by multivariable analysis. A subgroup analysis was performed based on stage, which showed no difference in outcomes independent of the presence of metastases. Conclusions: This study demonstrates no significant difference in chemotherapy interruptions, dose intensity, or clinical outcomes in patients treated for colorectal cancer during the COVID-19 pandemic. These findings serve as an important quality-care indictor and demonstrate that virtual oncology care appears safe in a cohort of high-risk colorectal cancer patients. Future work dedicated to other tumor sites would allow for broader application of these findings.

Histologic and Genotypic Characterization of Lung Cancer in the Inuit Population of the Eastern Canadian Arctic.

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer’s mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut’s Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011. Demographics were compiled from medical records and tumor samples underwent pathologic/histologic confirmation. Tumors were analyzed by next generation sequencing (NGS) with a cancer hotspot mutation panel. Of 98 patients, the median age was 66 years and 61% were male. Tobacco use was reported in 87%, and 69% had a history of lung disease (tuberculosis or other). Histological types were: non-small cell lung carcinoma (NSCLC), 81%; small cell lung carcinoma, 16%. Squamous cell carcinoma (SCC) represented 65% of NSCLC. NGS on 55 samples demonstrated mutation rates similar to public lung cancer datasets. In SCC, the STK11 F354L mutation was observed at higher frequency than previously reported. This is the first study to characterize the histologic/genomic profiles of lung cancer in this population. A high incidence of SCC, and an elevated rate of STK11 mutations distinguishes this group from the North American population.

Abstract OT1-11-02: A pragmatic, randomised, multicentre trial evaluating the dose timing (morning vs evening) of endocrine therapy and its effects on tolerability and compliance (REaCT-CHRONO Study)

Abstract Background. Endocrine therapy (ET) is the mainstay treatment for hormonal receptor positive (HR+) breast cancer. ET non-compliance and non-persistence vary from 30 to 70% and are associated with reduced disease-free and overall survival. ET side effects are an important cause of non-adherence. In clinical practice, there are anecdotal reports that time of the day at which ET is taken may affect ET side effects and compliance. However, we are not aware of any high-quality studies supporting this practice. In other fields of medicine, there is evidence to suggest that the time of the day at which medication is taken can alter its effect and/or the adherence. This is known as chronotherapy. Methods. In this pragmatic, open-label, multicenter trial, eligible and consented patients with an early stage or locally advanced HR+ breast cancer will be randomized (1:1) to receive either: an ET morning dose (Arm A: within 1 hour of the patient wake up time) or an ET evening dose (Arm B: within 1 hour of patient bed time). The primary endpoint is endocrine toxicity and tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline to 12 weeks following the beginning of ET. Secondary endpoints include: endocrine toxicity/tolerability and quality of life measured respectively by the change in total score and individual items of FACT-ES and FACT-B (a validated Functional Assessment of Cancer Therapy for patients with a Breast cancer) from baseline to 4, 8, 12 and 52 weeks following the beginning of ET, rates of non-persistence or non-compliance and cost-effectiveness. A timing preference questionnaire will be filled out at the beginning and the end of the study by patients to evaluate their preferred time. As per the Rethinking Clinical Trials (REaCT) program, the integrated consent model will be used and patients will complete questionnaires in the online patient portal. For randomization, a permuted block design developed by the Ottawa Methods Centre will be used and patients will be stratified by center, type of endocrine therapy (tamoxifen yes/no) and if prior chemotherapy was received. Using a two-sided, alpha=0.05 Fisher’s exact test, and assuming a 10% of loss to follow up, the planned sample size is 235 patients. Accrual. This study opened for enrollment at The Ottawa Hospital Cancer Centre on June 30, 2021 and will open soon at the Thunder Bay Regional Health Sciences Centre. The maximum accrual period is 2 years. Conclusion. This will be world’s first prospective randomized clinical trial to evaluate ET dose timing (morning versus evening) and its effects on tolerability and adherence. Changing the time of the day at which a medication is taken is a new, simple and easy intervention that does not generate additional costs and can improve the quality of life of breast cancer patients. Funding provided by: NOAMA (Northern Ontario Academic Medicine Association) Innovation Grant (2021) Clinical Trial Registration: NCT04864405 Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Ana-Alicia Beltran-Bless, Lesley Fallowfield, Mark Clemons. A pragmatic, randomised, multicentre trial evaluating the dose timing (morning vs evening) of endocrine therapy and its effects on tolerability and compliance (REaCT-CHRONO Study) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-11-02.

Consolidative durvalumab outcomes in stage III non-small cell lung cancer in a multi-centre study

AimTo investigate the impact of PD-L1 expression status on consolidative durvalumab efficacy and safety in stage III NSCLC patients. MethodsThis retrospective, ethics board approved, multi-centre study included all patients with histologically and/or cytologically confirmed unresectable stage III NSCLC, EGFR/ALK wild-type patients who completed concurrent chemoradiation therapy (cCRT) from January 2018 to August 2020 at the Cancer Centre of Southeastern Ontario and The Ottawa Hospital Cancer Centre. PD-L1 status was grouped as ≥50% vs. 1–49% vs. <1%. Primary study endpoint was overall survival (OS). ResultsOf the total 63 patients, 27 (43%), 16 (25%), 8 (13%), and 12 (19%) patients in the PD-L1 ≥50%, PD-L1 1–49%, PD-L1 <1%, and PD-L1 unknown groups (reported separately), respectively. With the median follow-up of 17.0 months, our multivariable Cox analysis suggested PD-L1≥50% was independently associated with improved OS compared to PD-L1<1% group (HR 0.18, 95%CI 0.04–0.86, P = 0.03). There were no significant differences in OS outcomes between PD-L1 1–49% and PD-L1 <1% group (HR 0.36, 95%CI 0.08–1.63, P = 0.18). Any grade treatment-related pneumonitis was observed in 46% of patients. Sixty-two percent, 38%, and 18% of patients required systemic corticosteroid use, hospitalization, and permanent treatment discontinuation due to pneumonitis, respectively. ConclusionsOur multi-centre, real-world study supported the use of consolidative durvalumab in inoperable stage III PD-L1 expressing NSCLC. Pneumonitis was significant, and higher than expected. Benefit appeared greater in high PD-L1 expressing patients, consistent with the subgroup analysis from the landmark PACIFIC trial. Our results need to be interpreted with cautions due to small sample size and a relatively short follow-up duration.

Recurrent vulvar squamous cell carcinoma: An analysis of clinical outcomes by treatment modality including surgery, chemotherapy, and radiation.

e18033 Background: Recurrent VSCC carries a poor prognosis, but real-world data on outcomes with standard treatment options are lacking. Specifically, progression free survival (PFS) in recurrent VSCC is ill-defined which is problematic for the design of clinical trials with novel therapies. We aim to address the paucity of outcome data in recurrent VSCC and to compare PFS and overall survival (OS) in patients (pts) undergoing surgery, chemotherapy, radiotherapy or a combination of these treatments. Methods: A retrospective chart review identified 246 pts from 2000-2018 diagnosed with VSCC treated at the Ottawa Hospital Cancer Center and 61 pts with recurrent disease. Data collected included patient demographics, tumour characteristics, recurrence pattern, and treatment modality (surgery only, surgery with chemotherapy, surgery with radiation, surgery with chemoradiation, chemoradiation only, chemotherapy only, or radiation only). Descriptive statistical analysis is reported. Results: Among all study pts, the stage distribution was stage I: 28%, II: 19%, III: 43% and IV: 10%. 61% of pts had one recurrence, 36% had two recurrences, and 3% had three recurrences. The 5-year survival rate was 78% for non-recurrent VSCC vs. 33% for recurrent cases. The median OS for all recurrent and non-recurrent cases was 3.7 years and 13.5 years, respectively. For primary treatment, 87% underwent surgical treatment, of which 60% also had radiation or chemoradiation. The most common treatments for first recurrence were: surgery (25%), radiation (20%), no treatment (16%) and chemotherapy (14%), and for second recurrence: no treatment (50%), radiation (25%), surgery (17%) and chemotherapy (8%). The median PFS after primary treatment and after first and second recurrences were 8.7, 5.3 and 1.4 months (mo), respectively, with no significant difference between treatment regimens. However, when grouped (surgery with or without chemotherapy, radiation or chemoradiation vs. non-surgical management), there was a significant PFS benefit for surgical (15.6 mo) over non-surgical management (0.7 mo) in the treatment of a second recurrence (p = 0.05). Conclusions: At our centre, surgery and radiation have been the mainstay of treatment for recurrent VSCC with particular advantage of surgery in the treatment of a second recurrence. Our study establishes a baseline for VSCC outcomes following standard treatment. Accurate PFS data is an important outcome for the design of future studies in recurrent VSCC with new drug therapies.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA). Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09-1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61-0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02-1.36, P = 0.026). Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.

Trial in Progress: Feasibility and Validation Study of the LSC17 Score in Acute Myeloid Leukemia Patients

Trial in Progress: Feasibility and Validation Study of the LSC17 Score in Acute Myeloid Leukemia Patients

32 Long Term Results of 120 Cases of Vestibular Schwannoma Treated with Cyberknifetm Robotic Stereotactic Radiosurgery at the Ottawa Hospital Cancer Centre

32 Long Term Results of 120 Cases of Vestibular Schwannoma Treated with Cyberknifetm Robotic Stereotactic Radiosurgery at the Ottawa Hospital Cancer Centre

Dosimetric and radiobiological investigation of permanent implant prostate brachytherapy based on Monte Carlo calculations

PurposePermanent implant prostate brachytherapy plays an important role in prostate cancer treatment, but dose evaluations typically follow the water-based TG-43 formalism, ignoring patient anatomy and interseed attenuation. The purpose of this study is to investigate advanced TG-186 model-based dose calculations via retrospective dosimetric and radiobiological analysis for a new patient cohort. Methods and MaterialsA cohort of 155 patients treated with permanent implant prostate brachytherapy from The Ottawa Hospital Cancer Centre is considered. Monte Carlo (MC) dose calculations are performed using tissue-based virtual patient models. Dose–volume histogram (DVH) metrics (target, organs at risk) are extracted from 3D dose distributions and compared with those from calculations under TG-43 assumptions (TG43). Equivalent uniform biologically effective dose and tumor control probability are calculated. ResultsFor the target, D90 (V100) is 136.7 ± 20.6 Gy (85.8% ± 7.8%) for TG43 and 132.8 ± 20.1 Gy (84.1% ± 8.2%) for MC; D90 is 3.0% ± 1.1% lower for MC than TG43. For organs at risk, MC D1cc = 104.4 ± 27.4 Gy (TG43: 106.3 ± 28.3 Gy) for rectum and 80.8 ± 29.7 Gy (TG43: 78.4 ± 28.4 Gy) for bladder; D1cc = 185.9 ± 30.2 Gy (TG43: 191.1 ± 32.0 Gy) for urethra. Equivalent uniform biologically effective dose and tumor control probability are generally lower when evaluated using MC doses. The largest dosimetric and radiobiological discrepancies between TG43 and MC are for patients with intraprostatic calcifications, for whom there are low doses (cold spots) in the vicinity of calcifications within the target, identified with MC but not TG43. ConclusionsDVH metrics and radiobiological indices evaluated with TG43 are systematically inaccurate by upward of several percent compared with MC patient-specific models. Mean cohort DVH metrics and their MC:TG43 variances are sensitive to patient cohort and clinical practice, underlining the importance of further retrospective MC studies toward widespread clinical adoption of advanced model-based dose calculations.

Implementing a quality improvement curriculum for medical oncology residents: A pilot study at the Ottawa Hospital Cancer Centre.

10540 Background: With increasing cancer care costs and demands in Canada, quality improvement (QI) efforts are urgently needed. Yet no formal QI education exists in the Canadian Medical Oncology setting. We created an Oncology-specific QI curriculum and sought to assess its feasibility and efficacy among Medical Oncology residents. Methods: In this prospective, pre-experimental pilot study using a pre-post curriculum design, Medical Oncology residents at The Ottawa Hospital Cancer Centre participated in a new QI curriculum. It consisted of four 2-hour sessions encompassing a combination of didactic and interactive learning. The primary measures were self-assessment of confidence in QI skills with the Self-Assessment Program (SAP) and objective assessment of QI knowledge with the revised QIKAT (QIKAT-R). The SAP and QIKAT-R were completed at baseline and post-curriculum. The primary outcome was feasibility of the educational approach. Results: Five Medical Oncology participated, while four (80%) completed the assessments at both timepoints. Self-assessment in the skills needed to execute a process improvement project improved with participation in the curriculum. Mean SAP scores improved from 19.6 pre-curriculum to 33.5 post-curriculum. SAP scores improved for each of the 10 quality improvement skills evaluated. Objective assessment using the QIKAT-R also improved post-curriculum, with a mean score of 17 pre-curriculum and 24 post-curriculum. Mean scores of each domain of “Aim, Measure, and Change” evaluated by the QIKAT-R improved. Conclusions: Self-assessed confidence and objective knowledge in QI concepts in Medical Oncology residents improved after participation in this Oncology-specific QI curriculum. Feasibility of this approach was demonstrated, and therefore a larger scale study will be implemented in the future.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

e16501 Background: Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). Methods: We have identified all the patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 - September 2017. For each patient we calculated the relative dose intensity (RDI) and assessed whether it’s associated with OS using univariate and multivariate cox-proportional hazards analysis. Results: Eighty-0ne patients were included in the analysis. Nineteen patients (23.5%) had their body surface area capped at 2 which resulted with de facto median dose reduction of 7% (IQR 6% - 9%). Ten patients had upfront dose reduction (usually due to significant co-morbidities) with a median dose reduction of 20% (IQR 19.25 – 20.75). Only 35 patients (43.2%) were able to complete the planned treatment with a RDI of at least 90%. After a median follow-up of 29.4 months, 32 patients (39.5%) died. The median OS was 43.9 months. On a univariate analysis RDI and number of cycles of docetaxel received were found to be statistically significant associated with OS. For every 10% decrease in RDI the risk of death increased by 23% (HR 1.23, 95% CI 1.09 – 1.4, P = 0.0011). For every incremental cycle (up to a total of 6) the risk of death decreased by 27% (HR 0.73, 95% CI 0.61- 0.88, P = 0.001). On multivariate analysis we included age, Gleason score, burden of disease, visceral involvement and baseline PSA. Reduced RDI remained the only significant variable associated with OS (HR 1.2, 95% CI 1.04 – 1.39, P = 0.0117). Conclusions: Reduced docetaxel DI administrated to mCSPC patients is associated with worse survival. Therefore unnecessary docetaxel dose reductions, treatments delays and early discontinuation should be avoided. Granulocyte-colony stimulating factor should be considered in order help maintain standard DI.

Prognostic Significance of Lymphovascular Space Invasion in the Absence of Lymph Node Metastases in Early-Stage Endometrial Cancer

Lymphovascular space invasion (LVSI) has been defined as a significant adverse prognostic factor in early-stage endometrial cancer, primarily because of its high association with nodal metastases. This study aimed to determine if LVSI provides any prognostic significance in pathologic node-negative surgically staged (T1N0) endometrial cancer patients. This retrospective cohort study included all patients with pathologic stage T1N0 endometrial carcinoma treated at The Ottawa Hospital Cancer Centre from 1998 to 2007. Patient demographics, pathologic findings, treatment, and outcome data were collected. Univariate and multivariate cox regression modeling was used to assess significance and adjust for demographic and histopathologic covariates. Kaplan-Meier curves were used to estimate the 5-year overall and recurrence-free survival. Our study included 400 pathologic stage T1N0 patients who received an initial total hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. The median age at diagnosis was 62 years, and the median follow-up was 66 months. Fifty-four patients (13.5%) had a positive LVSI status, and 346 (86.5%) had a negative LVSI status. The 5-year overall survival was 97.3% in patients without LVSI and 90.9% in those with LVSI (P < 0.001). The 5-year recurrence-free survival was 95.2% in patients without LVSI and 85.9% in those with LVSI (P = 0.006). Univariate analysis identified grade, stage, and LVSI as the covariates significantly associated with time to recurrence, and identified age, grade, stage, and LVSI to be significantly associated with overall survival. There were no significant covariates for recurrence-free survival by multivariate analysis, and only age and LVSI were significant for overall survival. Lymphovascular space invasion is an overall poor prognostic factor in T1N0 endometrial cancer. After adjusting for other factors, LVSI remains an independent risk factor for worse overall survival. Therefore, estimation of overall survival in patients with early-stage, node-negative endometrial cancer should take into account LVSI status.

Influence of aggressive-variant prostate cancer (AVPC) features on outcome of metastatic hormone-sensitive prostate cancer (mHSPC) treated by chemohormonal therapy (CHT).

193 Background: Outcomes of patients (pts) undergoing CHT for mHSPC are heterogeneous, with some rapidly developing castration-resistance (CRPC). While AVPC ("anaplastic") features are described in CRPC, less is known in the mHSPC setting. In this multi-institutional cohort, we explored pre-treatment factors associated with poor outcome. Methods: De-novo mHSPC pts treated with CHT from June 2014 to July 2017 at The Ottawa Hospital Cancer Centre (TOHCC) and London Regional Cancer Centre (LRCC) were retrospectively identified. AVPC features (defined below) were collected and cumulatively scored (0, 1, or 2+), along with baseline, treatment and outcome data. Statistical comparisons utilized Cox regression analysis and Kaplan-Meier method for association with CRPC and survival. Results: 92 pts (58 TOHCC, 34 LRCC) met inclusion for study; 83 (90%) had "high-volume" disease (≥4 bone lesions; or ≥1 visceral metastasis), 69/73 (95%) prostate biopsies scored Gleason 8-10, and 55 (60%) had AVPC features: &gt;5 cm nodal/pelvic mass (28), visceral metastases (21), lytic bone metastases (16), elevated LDH (12), low PSA (4), or neuroendocrine differentiation (2). Pre-docetaxel PSA fall of &lt;50, 50-75, 75-90, and ≥90% baseline occurred in 12, 13, 19, and 56% respectively. Docetaxel was initiated a median of 66 days after androgen-deprivation, with 82% completing 5 or 6 cycles. 9 pts (10%) progressed during docetaxel, and 31 pts (34%) developed CRPC &lt; 12 months. Median time to CRPC was 18.4, 14.0, and 11.0 months for 0, 1, and 2+ AVPC features (log rank p=0.009). CRPC was also associated with pre-docetaxel PSA fall &lt;75% (p&lt;0.001) and high alkaline phosphatase (p=0.016). At 18 months median follow-up, 16/55 (29%) with AVPC features have died versus 1/37 (3%) without (log rank p=0.001). In multivariable analysis, AVPC features and pre-docetaxel PSA fall were independently (p&lt;0.05) associated with survival. Conclusions: In our study, mHSPC pts with AVPC features and suboptimal (&lt;75%) pre-docetaxel PSA decline had poor prognosis. These features should be validated in larger cohorts to potentially identify mHSPC pts suitable for further study in clinical trials.

Abstract P2-03-12: Incidence and implications for hormone receptor status change pre- and post- neoadjuvant chemotherapy for locally advanced breast cancer: A retrospective single-center cohort study

Abstract Background: Hormone receptors (HR) and Human Epidermal Growth Factor Receptor 2 (HER2) status are variables that significantly influence the treatment regimens chosen for each patient (pt). The main objective of this study present was to determine the incidence of HR status change pre- and post- neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). Methods: A single-centre study was retrospectively conducted at The Ottawa Hospital Cancer Centre looking at a group of 546 pts diagnosed with LABC from 2006-2015. A number of variables were observed including HR and HER2 status, tumor size and grade, regional lymph nodes involvement, presence of DCIS, treatment regimens. 'Positive to Negative' considered pts who were HR and/or HER2 positive pre-NAC and negative post-NAC, 'No Change' represented the pts whose pathology did not change before and after NAC, and 'Negative to Positive' characterized those pts whose HR and/or HER2 pathology was initially negative and became positive post-NAC. Wilcoxon signed-rank test for paired dichotomous variables has been performed in order to estimate statistical significance of changes in status of HR and HER2. To explore possible relationship between HR and HER2 status change and other factors we used Logistic regression method. Results: Of the 386 pts who were examined for Estrogen Receptor (ER) twice, 285 had positive status before surgery, after surgery there were 12 pts (3.11%*) with a 'Positive to Negative' change, 362 pts (93.78%) with no change, and 12 pts who represented a 'Negative to Positive' change. 254 of 378 pts, who had two tests for Progesterone Receptor (PR), had positive results at first time, and 29 (7.67%*) of those represented a 'Positive to Negative' change, there were 337 (89.15%) with no change, and 12 (3.17%) with a 'Negative to Positive' change. From 387 pts who were tested for HER2 before and after surgery, 105 had initially positive status. Of those, 12 (3.10%*) represented a 'Positive to Negative' change, there were 364 (94.06%) with 'No Change' and 11 (2.84%*) with a 'Negative to Positive' change. Logistic regression analysis did not reveal any significant factors that can predict changes in receptors` status. *-Statistically significant changes (p&amp;lt;0.001). The results are comparable with previously published works, which demonstrated changes in IHC status during treatment in metastatic disease (E.Amir, 2011) and a in patients with LABC (Y.Yang, 2013; R.Gahlaut, 2016). Results of comparative meta-analysis will be presented also. Conclusions: Our study shows that a change in HR and HER2 status is common in this population, indicating that close monitoring of biopsy results should be closely compared to surgical pathology specimens to determine a change in biomarkers, and therefore, a potential change in treatment regimen. None of analyzed factors can predict change in status of ER, PR, and HER2 after neoadjuvant treatment. Even though the incidence of change in status is small, the implications for accurate and personalized treatment are important and HR and HER2 testing should be performed as a routine practice on the biopsy and at the time of definitive surgery. Citation Format: Aseyev O, Simmonds L, Gertler M, Verma S. Incidence and implications for hormone receptor status change pre- and post- neoadjuvant chemotherapy for locally advanced breast cancer: A retrospective single-center cohort study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-12.