Electronic malignant bowel obstruction symptom monitoring smartphone application for patients with gynecologic cancers.

OBJECTIVES: Implementation of an interprofessional program at Princess Margaret Cancer Centre, including nurse-led proactive calls to support patients with gynecologic cancers with malignant bowel obstruction, demonstrated improved outcomes compared with historical controls. The aim of the study was to convert the proactive calls into an electronic monitoring program to assess it's feasibility and scalability in patients with gynecologic cancers with or at risk of malignant bowel obstruction. METHODS: 'My Bowels on Track' smartphone application included weekly/biweekly electronic patient-reported outcomes (PROs), educational materials, and a secure messaging system. Based on PRO answers, an alerting system flagged patients with symptoms or uncompleted PROs. Nurses tracked and called patients on receiving clinical or compliance alerts. The primary objective was to assess adherence (≥70% PRO completion per patient considered an adherent patient) in the first 2 months on the program. A secondary objective was to assess the positive predictive value (PPV) of the alerts to trigger recommendations. RESULTS: Forty patients were enrolled between August 2021 and September 2022. Median age was 64.5 years (range 29-79 years). Primary diagnosis was ovarian (75%), endometrial (17.5%), or cervical (7.5%) cancer, and 92.5% of patients were receiving systemic therapy. Median duration on the program was 55 days (range 8-121 days). The 2-month adherence was 65% (95% CI 50% to 80%) and the overall adherence was 60% (95% CI 43% to 75%). Sixty-five symptom-related alerts (75% severe, 25% moderate) were reported in 60% (24/40) of patients. There were 59 recommendations triggered by the alerts. The PPV of the alerts to trigger actions was 72% (95% CI 58% to 82%). CONCLUSIONS: This pilot electronic malignant bowel obstruction monitoring program with real-time PRO assessment was feasible, and 65% of participants were adherent during the first 2 months on the program. The PRO response-based alerting system flagged concerning symptoms in 60% of participants, with a PPV of 72% to trigger nurse-led actions and/or management recommendations. TRIAL REGISTRATION NUMBER: NCT03260647.

Optimism Bias in the Design of Phase III Randomized Control Trials Evaluating PD-1/PD-L1 Targeting Monoclonal Antibodies.

BACKGROUND: Many randomized control trials (RCTs) evaluating programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) targeting monoclonal antibodies (mAbs) have been completed or are in progress. We examined hypothesized hazard ratios (HHRs) and observed hazard ratios (OHRs) from published RCTs evaluating these mAbs. METHODS: Publications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary reports of RCTs were retrieved. Two investigators extracted HHR, OHR for the primary endpoint among other data elements independently. The differences (∆HR) in HHR and OHR were analyzed statistically. A separate search was conducted for secondary reports after longer follow-ups, the updated OHR was extracted. RESULTS: Forty-nine RCTs enrolling 36 867 patients were included. The mean HHR and OHR were 0.672 and 0.738 respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895; 95% confidence interval (CI), 0.003-0.130). HHR was met or exceeded in 22 (45%) RCTs. OHR was ≥ 1.0 in 6 RCTs (12%). PD-L1 expression was not associated with the magnitude of effect. Of 18 RCTs with follow-up reports, the magnitude of benefit decreased in 8 RCTs with extended follow-ups. CONCLUSION: The majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of benefit. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in a variety of disease settings.

The Survival Outcomes of the Metastatic Nonclear Cell Renal Cell Carcinoma in the Immunotherapy Era: Princess Margaret Cancer Centre Experience.

Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients with metastatic clear cell renal cell carcinoma (RCC). The evidence supporting their use in metastatic nonclear cell renal cell carcinoma (nccRCC) subtypes is based on small prospective trials and retrospective analyses. Here, we report survival outcomes for patients with metastatic nccRCC treated with IO and/or TT at the Princess Margaret Cancer Centre, Toronto, ON, Canada. Demographics, disease characteristics, and survival outcomes were collected retrospectively. Overall (OS), progression-free survival (PFS), and objective response rates (ORR) were calculated. We identified 69 patients with metastatic nccRCC treated with IO and/or TT as the first-line treatment, and 36 (52.1%) patients as the second-line treatment. Median OS of the first line IO recipients (n = 12) and non-IO recipients (n = 57) was not reached (NR) and 17.2 months (95% confidence interval (95% CI): 7.3-27.0; P = 0.23), respectively. Median PFS of first-line IO recipients and non-IO recipients was NR and 4.7 months (95% CI: 3.7-5.6; P = 0.019), respectively. The ORR of IO recipients versus non-IO recipients was 50% versus 12.3% (P = 0.007). Median OS of the second-line IO recipients (n = 8) and non-IO recipients (n = 28) was NR and 6.3 months (95% CI: 3.2-9.3; P = 0.003), respectively. Median PFS of second-line IO recipients and non-IO recipients was 4.8 months (95% CI: 2.7-6.8) and 2.8 months (95% CI: 1.8-3.7; P = 0.014), respectively. ORR of IO recipients and non-IO recipients was 37.5% and 3.5%, respectively; P = 0.028. While the number of patients included in our retrospective review was small, our analysis suggested that patients with nccRCC have improved survival outcomes with IO treatment. Validation of prospective dataset is required before widespread clinical utilization.

Heterogeneity and treatment landscape of ovarian carcinoma.

Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. The interactions of cancer and stromal cells within the tumour microenvironment further affects disease evolution and response to therapy. In past decades, researchers have characterized the cellular, molecular, microenvironmental and immunological heterogeneity of ovarian carcinoma. Traditional treatment approaches have considered ovarian carcinoma as a single entity. This landscape is slowly changing with the increasing appreciation of heterogeneity and the recognition that delivering ineffective therapies can delay the development of effective personalized approaches as well as potentially change the molecular and cellular characteristics of the tumour, which might lead to additional resistance to subsequent therapy. In this Review we discuss the heterogeneity of ovarian carcinoma, outline the current treatment landscape for this malignancy and highlight potentially effective therapeutic strategies in development.

Inoperable Bowel Obstruction in Ovarian Cancer: Prevalence, Impact and Management Challenges.

Malignant bowel obstruction (MBO) is one of the most severe complications in patients with advanced ovarian cancer, with an estimated incidence up to 50%. Its presence is related to poor prognosis and a life expectancy measured in weeks for inoperable cases. Symptoms are usually difficult to manage and often require hospitalization, which carries a high burden on patients, caregivers and the healthcare system. Management is complex and requires a multidisciplinary approach to improve clinical outcomes. Patients with inoperable MBO are treated medically with analgesics, antiemetics, steroids and antisecretory agents. Parenteral nutrition and gut decompression with nasogastric tube, venting gastrostomy or stenting may be used as supportive therapy. Treatment decision-making is challenging and often based on clinical expertise and local policies, with lack of high-quality evidence to optimally standardize management. The present review summarizes current literature on inoperable bowel obstruction in ovarian cancer, focusing on epidemiology, prognostic factors, clinical outcomes, medical management, multidisciplinary interventions and quality of life.

The prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma treated with first-line platinum-based chemotherapy.

Background: In metastatic urothelial cancer (mUC), bone metastasis (BM) are associated with significant morbidity and mortality, yet their role as an independent prognostic variable remains unclear. We aimed to determine the impact of BM on overall survival (OS) in patients with mUC treated with first-line platinum-based chemotherapy (PBC). Methods: mUC patients receiving PBC at the Princess Margaret Cancer Center, Tom Baker Cancer Center, or Cross Cancer Institute from January 2005 to January 2018 were identified retrospectively using central pharmacy database records. Patient disease, treatment, and response characteristics were collected. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Variables reaching significance (p < 0.05) in univariable analysis (UVA) of survival (OS) were included in multivariable analysis (MVA) (Cox). Results: Overall, 376 patients with a median follow-up of 16.8 (range: 2.2-218.3) months were included. Median age was 67 (range: 28-91) years, 76% were male, 63% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and 41% had BM. All patients received first-line PBC. Patients with BM had inferior median PFS (4.9 months (95% CI 3.6-6.2) versus 6.5 months (95% CI 5.4-7.6), p = 0.03) and median OS (8.8 months (95% CI 7.8-9.7) versus 10.8 months (95% CI 9.1-12.5), p = 0.002). In UVA, ECOG PS 2-3 (p < 0.001), presence of BM (p = 0.002), and WBC count ⩾ 11,000 cells/mm3 (p = 0.001) were associated with inferior survival. Prior cystectomy (p < 0.001) and lack of progression (stable disease, partial or complete response) on treatment was associated with improved OS (p < 0.001). These variables maintained significance in MVA. Conclusion: In this retrospective study, mUC patients with BM had worse OS suggesting that BM may be an independent negative prognostic factor and including BM as a stratification factor in future mUC clinical trial designs may be warranted. A greater focus must be placed on novel therapeutic strategies to better manage BM to reduce both morbidity and mortality.

Clinicopathologic factors that influence prognosis and survival outcomes in men with metastatic castration-resistant prostate cancer treated with Radium-223.

BACKGROUND: In men with metastatic castration-resistant prostate cancer (mCRPC) with primarily bone metastases, radium-223 (223 Ra) improves overall survival (OS). However, the selection of 223 Ra is not guided by specific validated clinicopathologic factors, and thus outcomes are heterogeneous. PATIENTS AND METHODS: This retrospective survival analysis was performed in men with mCRPC treated with 223 Ra at our cancer center. Demographics and disease characteristics were collected. OS was calculated using the Kaplan-Meier method (log-rank). The potential prognostic factors were determined using both univariable (UVA) and multivariable analysis (MVA) (Cox-regression) methods. RESULTS: In total, 150 patients with a median age of 74 years (52-93) received 223 Ra between May 2015 and July 2018, and 58% had 6-20 bone metastases. Ninety-four (63%) patients received >4 223 Ra doses, and 56 (37%) received ≤4. The following pre-treatment factors were analyzed (median [range]): eastern cooperative oncology group performance status (ECOG PS), (1 [0-3]); Albumin (ALB), (39 g/L [24-47]); alkaline phosphatase (ALP), (110 U/L [35-1633]); and prostate-specific antigen (PSA), (49 µg/L [0.83-7238]). The median OS for all patients was 14.5 months (95% CI: 11.2-18). These factors were associated with poor survival outcomes in UVA and MVA: ALB <35 g/L, ALP >150 U/L, ECOG PS 2-3, and PSA >80 µg/L. By assigning one point for each of these factors, a prognostic model was developed, wherein three distinct risk groups were identified: good, 0-1 (n = 103); intermediate, 2 (n = 30); and poor risk, 3-4 points (n = 17). The median OS was 19.4, 10.0, and 3.1 months, respectively (p < 0.001). CONCLUSIONS: Pre-treatment ALB, ALP, ECOG, and PSA, were significantly correlated with OS and could guide treatment selection for men with mCRPC by identifying those who are most or least likely to benefit from 223 Ra. Validation in an independent dataset is required prior to widespread clinical utilization.