Sonal Gandhi

Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer? Meta-analysis of randomized trials.

Despite the advantages from using aromatase inhibitors (AIs) compared with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3 and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of Canada‐Common Toxicity Criteria [version 2.0] was demonstrated.

Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: A Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline

Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .

Non-invasive evaluation of breast cancer response to chemotherapy using quantitative ultrasonic backscatter parameters

Tumor response to neoadjuvant chemotherapy in patients (n=30) with locally advanced breast cancer (LABC) was examined using quantitative ultrasound. Three ultrasound backscatter parameters, the integrated backscatter coefficient (IBC), average scatterer diameter (ASD), and average acoustic concentration (AAC), were estimated from tumors prior to treatment and at four times during neoadjuvant chemotherapy treatment (weeks 0, 1, 4, 8, and prior to surgery) and compared to ultimate clinical and pathological tumor responses. Results demonstrated that among all parameters, AAC was the best indicator of tumor response early after starting treatment. The AAC parameter increased substantially in treatment-responding patients as early as one week after treatment initiation, further increased at week 4, and attained a maximum at week 8. In contrast, the backscatter parameters from non-responders did not show any changes after treatment initiation. The two patient populations exhibited a statistically significant difference in changes of AAC (p<0.001) and ASD (p=0.023) over all treatment times examined. The best prediction of treatment response was achieved with the combination of AAC and ASD at week 4 (82% sensitivity, 100% specificity, and 86% accuracy) of 12-18 weeks of treatment. The survival of patients with responsive ultrasound parameters was higher than patients with non-responsive ultrasound parameters (35 ± 11 versus 27 ± 11 months, respectively, p=0.043). This study demonstrates that ultrasound parameters derived from the ultrasound backscattered power spectrum can potentially serve as non-invasive early measures of clinical tumor response to chemotherapy treatments.

Evaluating an Oncology Systemic Therapy Computerized Physician Order Entry System Using International Guidelines

Chemotherapy is prone to medication error resulting from complexities in ordering and administration. Computerized physician order entry (CPOE) has been established as an important tool to minimize such errors and hence improve patient safety. As a leading Canadian advisory body in oncology, Cancer Care Ontario (CCO) has been a champion in developing and implementing its own cancer systemic therapy CPOE, the Oncology Patient Information System (OPIS). This article reviews and consolidates principles for oncology CPOE systems as found in the literature and in guidelines created by three international oncology organizations (American Society of Clinical Oncology, Clinical Oncological Society of Australia, and CCO). It then evaluates OPIS by these standards and provides a working example of what a cancer CPOE system should look like. This document can therefore be used as a framework to help develop and evaluate cancer CPOE platforms in different national settings. As end users, oncologists are considered key stakeholders in developing such systems and thus should be well informed about CPOE principles to help make decisions on the appropriate implementation of these platforms in their local practice settings. In addition, oncologists are also important champions for the successful uptake of oncology CPOE platforms and would benefit from a better understanding of whether proposed or existing local CPOE systems meet established standards.

Oral Anticancer Medication Adherence, Toxicity Reporting, and Counseling: A Study Comparing Health Care Providers and Patients

PURPOSE Oral anticancer medications (OACMs) have created new treatment opportunities, but also challenges for patients and practitioners. We aimed to compare health care provider (HCP) and patient perceptions on OACM adherence, toxicity reporting, and patient educational needs. METHODS An online survey for HCPs and paper survey for patients were analyzed using descriptive statistics. Bivariate analysis using the χ(2) test was used for some questions. RESULTS There were 169 HCP and 143 patient responses; 91% of patients reported taking their OACMs as prescribed more than 75% of the time, but only 40% of HCPs believed their patients were as adherent; 97% of HCPs believed patients reported their adverse effects some or most of the time; 61% of patients reported toxicities sometimes, often, or very often, but 30% never or rarely reported; 66% of HCPs believed patients did not report toxicity because of fear of treatment interruption, compared with 2% of patients. HCPs (53%) and patients (62%) both believed adverse effect tolerance was a common reason not to report. Most HCPs (70%) believed patients reported adverse effects first to a nurse. Patients seemed to report equally to nurses (42%) and oncologists (38%). Both HCPs and patients favored paper-based educational materials and call-back programs. CONCLUSION This study highlights disparities in patient and HCP perceptions of OACM adherence principles and toxicity reporting. Opportunities for improved patient education are identified, particularly around reporting significant toxicities. Different HCPs may benefit from complimentary counseling tools to encompass the entire spectrum of patient needs and provider practice.

Predicting Breast Cancer Response to Neoadjuvant Chemotherapy Using Pretreatment Diffuse Optical Spectroscopic-Texture Analysis

Background:Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pretreatment DOS functional maps for predicting LABC response to NAC.Methods:Locally advanced breast cancer patients (n=37) underwent DOS breast imaging before starting NAC. Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction. Ground truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller–Payne pathological response criteria. The capability of DOS textural features computed on volumetric tumour data before the start of treatment (i.e., ‘pretreatment’) to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naive Bayes, and k-nearest neighbour classifiers.Results:Data indicated that textural characteristics of pretreatment DOS parametric maps can differentiate between treatment response outcomes. The HbO2 homogeneity resulted in the highest accuracy among univariate parameters in predicting response to chemotherapy: sensitivity (%Sn) and specificity (%Sp) were 86.5% and 89.0%, respectively, and accuracy was 87.8%. The highest predictors using multivariate (binary) combination features were the Hb-contrast+HbO2-homogeneity, which resulted in a %Sn/%Sp=78.0/81.0% and an accuracy of 79.5%.Conclusions:This study demonstrated that the pretreatment DOS texture features can predict breast cancer response to NAC and potentially guide treatments.

A systematic review and quality appraisal of international guidelines for early breast cancer systemic therapy: Are recommendations sensitive to different global resources?

The breast cancer incidence in low and middle income countries (LMCs) is increasing globally, and patient outcomes are generally worse in these nations compared to high income countries (HICs). This is partly due to resource constraints associated with implementing recommended breast cancer therapies. Clinical practice guideline (CPG) adherence can improve breast cancer outcomes, however, many CPGs are created in HICs, and include costly recommendations that may not be feasible in LMCs. In addition, the quality of CPGs can be variable. The aim of this study was to perform a systematic review of CPGs on early breast cancer systemic therapy with potential international impact, to evaluate their content, quality, and resource sensitivity. A MEDLINE and gray literature search was completed for English language CPGs published between 2005 and 2010, and then updated to July 2014. Extracted guidelines were evaluated using the AGREE 2 instrument. Guidelines were specifically analyzed for resource sensitivity. Most of the extracted CPGs had similar recommendations with regards to systemic therapy. However, only one, the Breast Health Global Initiative, made recommendations with consideration of different global resources. Overall, the CPGs were of variable quality, and most scored poorly in the quality domain evaluating implementation barriers such as resources. Published CPGs for early breast cancer are created in HICs, have similar recommendations, and are generally resource-insensitive. Given the visibility and influence of these CPGs on LMCs, efforts to create higher quality, resource-sensitive guidelines with less redundancy are needed.

A Canadian national expert consensus on neoadjuvant therapy for breast cancer: linking practice to evidence and beyond

BACKGROUND Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (nat) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (rcts) in this area. METHODS A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing nat for breast cancer. All rcts published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the rcts were analyzed to determine if the methods used matched the expert consensus for specific areas of nat management. A scoring system determined the strength of the agreement between the literature and the expert consensus. RESULTS Consensus was achieved for all areas of the pathway of care for patients undergoing nat for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published rcts varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. CONCLUSIONS A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving nat for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of nat management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving nat.

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients.

Perceived Barriers to Goals of Care Discussions With Patients With Advanced Cancer and Their Families in the Ambulatory Setting: A Multicenter Survey of Oncologists

Background: Earlier goals of care (GOC) discussions in patients with advanced cancer are associated with less aggressive end-of-life care including decreased use of medical technologies. Unfortunately, conversations often occur late in the disease trajectory when patients are acutely unwell. Here, we evaluate practitioner perspectives of patient, family, physician, and external barriers to early GOC discussions in the ambulatory oncology setting. Methods: A previously published survey to assess barriers to GOC discussions among clinicians on inpatient medical wards was modified for the ambulatory oncology setting and distributed to oncologists from 12 centers in Ontario, Canada. Physicians were asked to rank the importance of various barriers to having GOC discussions (1 = extremely unimportant to 7 = extremely important). Results: Questionnaires were completed by 30 (24%) of 127 physicians. Respondents perceived patient- and family-related factors as the most important barriers to GOC discussions. Of these, patient difficulty accepting prognosis or desire for aggressive treatment were perceived as most important. Patients’ inflated expectation of treatment benefit was also considered an important barrier to discontinuing active cancer-directed therapy. While physician barriers were ranked lower than patient-related factors, clinicians’ self-identified difficulty estimating prognosis and uncertainty regarding treatment benefits were also considered important. Patient’s refusal for referral was the most highly rated barrier to early palliative care referral. Most respondents were nonetheless very or extremely willing to initiate (90%) or lead (87%) GOC discussions. Conclusion: Oncologists ranked patient- and family-related factors as the most important barriers to GOC discussions, while clinicians’ self-identified difficulty estimating prognosis and uncertainty regarding treatment benefits were also considered important. Further work is required to assess patient preferences and perceptions and develop targeted interventions.