Utilization of Immunotherapy in Patients with Cancer Treated in Routine Care Settings: A Population-Based Study Using Health Administrative Data.

INTRODUCTION: The introduction of immunotherapy (IO) in the treatment of patients with cancer has significantly improved clinical outcomes. Population level information on actual IO utilization is limited. METHODS: We conducted a retrospective cohort study using provincial health administrative data from Ontario, Canada to: (1) assess the extent of IO use from 2011 (pre-IO funding) to 2019; and (2) identify factors associated with IO use in patients with advanced cancers for which IO is reimbursed including melanoma, bladder, lung, head and neck, and kidney tumors. The datasets were linked using a unique encoded identifier. A Fine and Gray regression model with death as a competing risk was used to identify factors associated with IO use. RESULTS: Among 59 510 patients assessed, 8771 (14.7%) received IO between 2011 and 2019. Use of IO increased annually from 2011 (3.3%) to 2019 (39.2%) and was highest in melanoma (52%) and lowest in head and neck cancer (6.6%). In adjusted analysis, factors associated with lower IO use included older age (hazard ratio (HR) 0.91 (95% CI, 0.89-0.93)), female sex (HR 0.85 (95% CI, 0.81-0.89)), lower-income quintile, hospital admission (HR 0.78 (95% CI, 0.75-0.82)), high Charlson score and de novo stage 4 cancer. IO use was heterogeneous across cancer centers and regions. CONCLUSION: IO utilization for advanced cancers rose substantially since initial approval albeit use is associated with patient characteristics and system-level factors even in a universal healthcare setting. To optimize IO utilization in routine practice, survival estimates and potential inequity in access should be further investigated and addressed.

Cancer incidence and stage at diagnosis among people with recent-onset psychotic disorders: A retrospective cohort study using health administrative data from Ontario, Canada.

OBJECTIVE: Prior evidence on the relative risk of cancer among people with psychotic disorders is equivocal. The objective of this study was to compare incidence and stage at diagnosis of cancer for people with psychotic disorders relative to the general population. METHOD: We constructed a retrospective cohort of people with a first diagnosis of non-affective psychotic disorder and a comparison group from the general population using linked health administrative databases in Ontario, Canada. The cohort was followed for incident diagnoses of cancer over a 25-year period. We used Poisson and logistic regression models to compare cancer incidence and stage at diagnosis between people with psychotic disorders and the comparison group, adjusting for confounding factors. RESULTS: People with psychotic disorders had an 8.6% higher incidence (IRR = 1.09, 95%CI = 1.05,1.12) of cancer overall relative to the comparison group, with effect modification by sex and substantial variation across cancer sites. People with psychotic disorders also had 23% greater odds (OR = 1.23, 95%CI = 1.13,1.34) of being diagnosed with more advanced stage cancer relative to the comparison group. CONCLUSIONS: We found evidence of elevated cancer incidence in people with non-affective psychotic disorders relative to the general population. The higher odds of more advanced stage cancer diagnoses in people with psychotic disorders represents an opportunity to improve patient participation in recommended cancer screening, as well as timely access to services for cancer diagnosis and treatment. Future research should examine confounding effects of lifestyle factors and antipsychotic medications on the risk of developing cancer among people with psychotic disorders.

Factors associated with endocrine therapy adherence among post-menopausal women treated for early-stage breast cancer in Ontario, Canada.

PURPOSE: Adherence to adjuvant endocrine therapy among post-menopausal breast cancer patients is an important survivorship care issue. We explored factors associated with endocrine therapy adherence and survival in a large real-world population-based study. METHODS: We used health administrative databases to follow women (aged ≥ 66 years) who were diagnosed with breast cancer and started on adjuvant endocrine therapy from 2005 to 2010. Adherence was measured by medical possession ratio (MPR) and characterized as low (< 39% MPR), intermediate (40-79% MPR), or high (≥ 80% MPR) over a 5-year period. We investigated factors associated with adherence using a multinomial logistic regression model. Factors associated with all-cause mortality (5 years after starting endocrine therapy) were investigated using a multivariable Cox proportional hazards model. RESULTS: We identified 5692 eligible patients starting adjuvant endocrine therapy who had low, intermediate, and high adherence rates of 13% (n = 749), 13% (n = 733), and 74% (n = 4210), respectively. Lower rates of adherence were associated with increased age [low vs. high adherence: odds ratio (OR) 1.03, 95% CI 1.02-1.05 (per year); intermediate vs. high adherence: OR 1.02, 95% CI 1.01-1.04 (per year)]. High adherence was associated with previous use of adjuvant chemotherapy (low versus high adherence OR 0.42, 95% CI 0.30-0.59) and short-term follow-up with a medical oncologist within 4 months of starting endocrine therapy (low versus high adherence OR 0.83, 95% CI 0.69-0.99). Unadjusted analysis showed increased survival among patients with high endocrine therapy adherence. However, an independent association was no longer clearly detected after controlling for confounders. CONCLUSION: Interventions to improve adjuvant endocrine therapy adherence are warranted. Non-adherence may be a more significant issue among elderly patients. Short-term follow-up visit by a patient's medical oncologist after starting endocrine therapy may help to improve compliance.

Cost-effectiveness analysis of multigene expression profiling assays to guide adjuvant therapy decisions in women with invasive early-stage breast cancer.

Gene expression profiling (GEP) testing using 12-gene recurrence score (RS) assay (EndoPredict®), 58-gene RS assay (Prosigna®), and 21-gene RS assay (Oncotype DX®) is available to aid in chemotherapy decision-making when traditional clinicopathological predictors are insufficient to accurately determine recurrence risk in women with axillary lymph node-negative, hormone receptor-positive, and human epidermal growth factor-receptor 2-negative early-stage breast cancer. We examined the cost-effectiveness of incorporating these assays into standard practice. A decision model was built to project lifetime clinical and economic consequences of different adjuvant treatment-guiding strategies. The model was parameterized using follow-up data from a secondary analysis of the Anastrozole or Tamoxifen Alone or Combined randomized trial, cost data (2017 Canadian dollars) from the London Regional Cancer Program (Canada) and secondary Canadian sources. The 12-gene, 58-gene, and 21-gene RS assays were associated with cost-effectiveness ratios of $36,274, $48,525, and $74,911/quality-adjusted life year (QALY) gained and resulted in total gains of 379, 284.3, and 189.5 QALYs/year and total budgets of $12.9, $14.2, and $16.6 million/year, respectively. The total expected-value of perfect information about GEP assays' utility was $10.4 million/year. GEP testing using any of these assays is likely clinically and economically attractive. The 12-gene and 58-gene RS assays may improve the cost-effectiveness of GEP testing and offer higher value for money, although prospective evidence is still needed. Comparative field evaluations of GEP assays in real-world practice are associated with a large societal benefit and warranted to determine the optimal and most cost-effective assay for routine use.

Bone-Targeted Therapy in Early Breast Cancer.

Aromatase inhibitors (AIs) play an important role in the adjuvant treatment of hormone receptor-positive breast cancer, but they are associated with bone loss and increased fracture risk. Although several guidelines for the management of osteoporosis and osteopenia exist, their algorithms do not account for the use of AIs. In this article, we describe the role of bone-targeted therapies, specifically for managing early breast cancer, by reviewing their bone-specific and cancer-specific benefits.

Filgrastim use in patients receiving chemotherapy for early-stage breast cancer-a survey of physicians and patients.

PURPOSE: Despite its widespread use as primary febrile neutropenia (FN) prophylaxis during chemotherapy for early-stage breast cancer, the optimal duration of daily filgrastim is unknown. Using the minimum effective duration may improve patient comfort and acceptability while reducing costs. Yet, suboptimal dosing may also negatively impact patient care. A survey was performed to obtain information regarding current practices for granulocyte colony-stimulating factor (G-CSF) use. METHODS: Canadian oncologists involved in the treatment of breast cancer patients, as well as patients who had received neo/adjuvant chemotherapy for breast cancer, were surveyed. Standardized surveys were designed to collect information on perceived reasons for G-CSF use and current practices. RESULTS: The surveys were completed by 38/50 (76%) physicians and 95/97 (98%) patients. For physicians, there was variability in the choice of chemotherapy regimens that required G-CSF support, the dose of filgrastim prescribed and the number of days prescribed. The majority of physicians reported using 5 (31.6%), 7 (47.4%), or 10 (13.2%) days of therapy. Nearly half of the patients (46.3%) recalled having experienced at least one of the chemotherapy-related complications including chemotherapy delays, dose reductions, and FN. While on filgrastim, 66.3% of patients reported myalgia and bone pain. Both physicians and patients expressed interest in participating in clinical trials designed to optimize the duration of filgrastim administration. CONCLUSIONS: Significant variability in practice exists with respect to filgrastim administration. Definitive studies are therefore required to standardize and improve care, as this has the potential to impact treatment outcomes, patient quality of life, and cost savings.

The role of bisphosphonates in early- and advanced-stage breast cancer: have we finally optimized care?

Bisphosphonates have played an important role in the treatment of breast cancer, mainly in patients with bone metastasis, by reducing the risk of fracture, spinal cord compression, and hypercalcemia. Both oral and intravenous products are available and have strong supporting clinical evidence. Zoledronic acid, the most frequently used intravenous agent, has traditionally been given on a monthly dosing schedule. A novel every-12-weeks maintenance dosing schedule shows clinical equivalence and promises to improve safety, affordability, and quality of care. The Early Breast Cancer Trialists' Collaborative Group has recently helped clarify the controversial benefit of bisphosphonates in the adjuvant setting. Based on their meta-analysis, we now have strong evidence supporting the use of adjuvant bisphosphonates to help prevent the development of bone metastasis in postmenopausal breast cancer patients, which leads to a significant improvement in breast cancer-specific survival. We eagerly await the full publication of this practice-changing study, which continues the incremental advance of the treatment of patients with breast cancer.

Genomic testing in cancer: patient knowledge, attitudes, and expectations.

BACKGROUND: Genomic testing in cancer (GTC) characterizes genes that play an important role in the development and growth of a patient's cancer. This form of DNA testing is currently being studied for its ability to guide cancer therapy. The objective of the current study was to describe patients' knowledge, attitudes, and expectations toward GTC. METHODS: A 42-item self-administered GTC questionnaire was developed by a multidisciplinary group and patient pretesting. The questionnaire was distributed to patients with advanced cancer who were referred to the Princess Margaret Cancer Center for a phase 1 clinical trial or GTC testing. RESULTS: Results were reported from 98 patients with advanced cancer, representing 66% of the patients surveyed. Seventy-six percent of patients were interested in learning more about GTC, and 64% reported that GTC would significantly improve their cancer care. The median score on a 12-item questionnaire to assess knowledge of cancer genomics was 8 of 12 items correct (67%; interquartile range, 7-9 of 12 items correct [58%-75%]). Scores were associated significantly with patients' education level (P < .0001). Sixty-six percent of patients would consent to a needle biopsy, and 39% would consent to an invasive surgical biopsy if required for GTC. Only 48% of patients reported having sufficient knowledge to make an informed decision to pursue GTC whereas 34% of patients indicated a need for formal genetic counseling. CONCLUSIONS: Patients with advanced cancer are motivated to participate in GTC. Patients require further education to understand the difference between somatic and germline mutations in the context of GTC. Educational programs are needed to support patients interested in pursuing GTC.

Immunotherapy and Radiation Therapy Sequencing in Breast Cancer: A Systematic Review.

PURPOSE: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect." The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation. METHODS AND MATERIALS: We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy. RESULTS: Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT. CONCLUSIONS: In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.

Treatment and Mortality Following Cancer Diagnosis Among People With Non-affective Psychotic Disorders in Ontario, Canada: A Retrospective Cohort Study.

BACKGROUND AND HYPOTHESIS: People with psychotic disorders have a higher risk of mortality following cancer diagnosis, compared to people without psychosis. The extent to which this disparity is influenced by differences in cancer-related treatment is currently unknown. We hypothesized that, following a cancer diagnosis, people with psychotic disorders were less likely to receive treatment and were at higher risk of death than those without psychosis. STUDY DESIGN: We constructed a retrospective cohort of cases of non-affective psychotic disorder (NAPD) and a general population comparison group, using Ontario Health (OH) administrative data. We identified cases of all cancers diagnosed between 1995 and 2019 and obtained information on cancer-related treatment and mortality. Cox proportional hazards models were used to compare the probability of having a consultation with an oncologist and receiving cancer-related treatment, adjusting for tumor site and stage. We also compared the rate of all-cause and cancer-related mortality between the two groups, adjusting for tumor site. STUDY RESULTS: Our analytic sample included 24 944 people diagnosed with any cancer. People with NAPD were less likely to receive treatment than people without psychosis (HR = 0.87, 95% CI = 0.82, 0.91). In addition, people with NAPD had a greater risk of death from any cause (HR = 1.68, 95% CI = 1.60, 1.76), compared to people without NAPD. CONCLUSIONS: The lower likelihood of receiving cancer treatment reflects disparities in accessing cancer care for people with psychotic disorders, which may partially explain the higher mortality risk following cancer diagnosis. Future research should explore mediating factors in this relationship to identify targets for reducing health disparities.

The safety of seasonal influenza vaccination among adults prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. METHODS: Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1-42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. RESULTS: We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75-1.45). Subgroup and sensitivity analyses yielded similar results. CONCLUSION: Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.

Antibody-Drug Conjugates in Breast Cancer: Ascent to Destiny and Beyond-A 2023 Review.

Antibody-drug conjugates (ADCs) are revolutionizing cancer treatment, adding another important new class of systemic therapy. ADCs are a specially designed class of therapeutics that target cells expressing specific cancer antigens using directed antibody-drug delivery and release a cytotoxic chemotherapeutic payload. Over the past two decades, improvements in ADC design, development, and research, particularly in breast cancer, have led to several recent landmark publications. These advances have significantly changed various treatment paradigms and revamped traditional classifications of breast cancer with the introduction of a potential new subtype: "HER2-low". This review will focus on several ADCs developed for breast cancer treatment, including trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG) and other newer emerging agents. It will provide an overview of the role of ADCs in breast cancer and discuss the opportunities and challenges they present. Additionally, our review will discuss future research directions to improve the selection of targets, combination therapies, and aim to improve drug safety. Important first-line metastatic and adjuvant clinical trials are underway, which may expand the role of ADC therapy in breast cancer. We foresee ADCs driving a new era of breast cancer treatment, adding to the steady incremental survival advantage observed in recent years.

Early mortality in patients with cancer treated with immune checkpoint inhibitors in routine practice.

BACKGROUND: We sought to estimate the proportion of patients with cancer treated with immune checkpoint inhibitors (ICI) who die soon after starting ICI in the real world and examine factors associated with early mortality (EM). METHODS: We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada. EM was defined as death from any cause within 60 days of ICI initiation. Patients with melanoma, lung, bladder, head and neck, or kidney cancer treated with ICI between 2012 and 2020 were included. RESULTS: A total of 7126 patients treated with ICI were evaluated. Fifteen percent (1075 of 7126) died within 60 days of initiating ICI. The highest mortality was observed in patients with bladder and head and neck tumors (approximately 21% each). In multivariable analysis, previous hospital admission or emergency department visit, prior chemotherapy or radiation therapy, stage 4 disease at diagnosis, lower hemoglobin, higher white blood cell count, and higher symptom burden were associated with higher risk of EM. Conversely, patients with lung and kidney cancer (compared with melanoma), lower neutrophil to lymphocytes ratio, and with higher body mass index were less likely to die within 60 days post ICI initiation. In a sensitivity analysis, 30-day and 90-day mortality were 7% (519 of 7126) and 22% (1582 of 7126), respectively, with comparable clinical factors associated with EM identified. CONCLUSIONS: EM is common among patients treated with ICI in the real-world setting and is associated with several patient and tumor characteristics. Development of a validated tool to predict EM may facilitate better patient selection for treatment with ICI in routine practice.

Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer-A Literature Review.

BACKGROUND: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15-20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach has multiple benefits that include the potential to downgrade staging and convert previously unresectable tumors to operable tumors. In addition, achieving a pathologic complete response (pCR) following preoperative systemic treatment is prognostic of enhanced survival outcomes. Thus, optimal evaluation among the suitable strategies is crucial in deciding which patients should be selected for the neoadjuvant approach. METHODS: A literature search was conducted in the Embase, Medline, and Cochrane electronic libraries. CONCLUSION: The evaluation of tumor and LN staging and, hence, stratifying BC recurrence risk are decisive factors in guiding clinicians to optimize treatment decisions between the neoadjuvant versus adjuvant approaches. For each individual case, it is important to consider the most likely postsurgical outcome, since, if the patient does not obtain pCR following neoadjuvant treatment, they are eligible for adjuvant T-DM1 in the case of residual disease. This review of HER2-positive female BC outlines suitable neoadjuvant and adjuvant systemic treatment strategies for guiding clinical decision making around the selection of an appropriate therapy.

Impact of 18F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer.

PURPOSE: Patients with locally advanced breast cancer (LABC) typically undergo staging tests at presentation. If staging does not detect metastases, treatment consists of curative intent combined modality therapy (neoadjuvant chemotherapy, surgery, and regional radiation). Positron emission tomography-computed tomography (PET-CT) may detect more asymptomatic distant metastases, but the evidence is based on uncontrolled studies. METHODS: For inclusion, patients had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1). Consenting patients from six regional cancer centers in Ontario were randomly assigned to 18F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of the chest/abdomen and pelvis). The primary end point was upstaging to stage IV. A key secondary outcome was receiving curative intent combined modality therapy (ClinicalTrials.gov identifier: NCT02751710). RESULTS: Between December 2016 and April 2022, 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging. Forty-three (23%) PET-CT patients were upstaged to stage IV compared with 21 (11%) conventional staged patients (absolute difference, 12.3% [95% CI, 3.9 to 19.9]; P = .002). Consequently, treatment was changed in 35 (81.3%) of 43 upstaged PET-CT patients and 20 (95.2%) of the 21 upstaged conventional patients. Subsequently, 149 (81%) patients in the PET-CT group received combined modality treatment versus 165 (89.2%) patients in the conventional staging group (absolute difference, 8.2% [95% CI, 0.1 to 15.4]; P = .03). CONCLUSION: In patients with LABC, PET-CT detected more distant metastases than conventional staging, and fewer PET-CT patients received combined modality therapy. Our randomized trial demonstrates the utility of the PET-CT staging strategy.

A Multi-Centre Randomized Study Comparing Two Standard of Care Chemotherapy Regimens for Lower-Risk HER2-Positive Breast Cancer.

BACKGROUND: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. METHODS: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. SECONDARY OUTCOMES: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. RESULTS: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were -4 (-10, -1) vs. -6.5 (-15, -2) for TC-H and P-H arms, respectively. CONCLUSIONS: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens.

Clinical Utility of Multigene Profiling Assays in Early-Stage Invasive Breast Cancer: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline.

OBJECTIVE: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. METHODS: This guideline was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors.

Cancer incidence and stage at diagnosis among people with psychotic disorders: Systematic review and meta-analysis.

Research regarding the incidence of cancer among people with psychotic disorders relative to the general population is equivocal, although the evidence suggests that they have more advanced stage cancer at diagnosis. We conducted a systematic review and meta-analysis to examine the incidence and stage at diagnosis of cancer among people with, relative to those without, psychotic disorders. We searched the MEDLINE, EMBASE, PsycINFO, and CINAHL databases. Articles were included if they reported the incidence and/or stage at diagnosis of cancer in people with psychotic disorders. Random effects meta-analyses were used to determine risk of cancer and odds of advanced stage cancer at diagnosis in people with psychosis, relative to those without psychotic disorders. A total of 40 articles were included in the review, of which, 31 were included in the meta-analyses. The pooled age-adjusted risk ratio for all cancers in people with psychotic disorders was 1.08 (95% CI: 1.01-1.15), relative to those without psychotic disorders, with significant heterogeneity by cancer site. People with psychotic disorders had a higher incidence of breast, oesophageal, colorectal, testicular, uterine, and cervical cancer, and a lower incidence of skin, prostate, and thyroid cancer. People with psychotic disorders also had 22% higher (95% CI: 2-46%) odds of metastases at diagnosis, compared to those without psychotic disorders. Our systematic review found a significant difference in overall cancer incidence among people diagnosed with psychotic disorders and people with psychotic disorders were more likely to present with advanced stage cancer at diagnosis. This finding may reflect a need for improved access to and uptake of cancer screening for patients diagnosed with psychotic disorders.

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update.

PURPOSE: To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline. METHODS: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data. RESULTS: Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations. RECOMMENDATIONS: Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline.