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.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review.

The purpose of the present review was to describe evidence-based indications for hyperthermic intraperitoneal chemotherapy (HIPEC), with cytoreductive surgery (CRS), in patients with a diagnosis of mesothelioma, appendiceal (including appendiceal mucinous neoplasm), colorectal, gastric, ovarian or primary peritoneal carcinoma. Relevant studies were identified from a systematic MEDLINE and EMBASE search of studies published from 1985 to 2019. Studies were included if they were RCTs. If no RCTs were identified, prospective and retrospecctive comparative studies (where confounders are controlled for studies with greater than 30 patients) were included. Overall survival, progression-free survival, recurrence-free survival, adverse events and quality of life data were extracted. For patients with newly diagnosed, primary stage III epithelial ovarian, fallopian tube or primary peritoneal carcinoma, HIPEC with CRS should be considered for those with at least stable disease following neoadjuvant chemotherapy at the time of interval CRS if complete or optimal cytoreduction is achieved. There is insufficient evidence to recommend the addition of HIPEC when primary CRS is performed for patients with newly diagnosed, primary advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma or in those with recurrent ovarian cancer outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of peritoneal colorectal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of gastric peritoneal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS in patients with malignant peritoneal mesothelioma or in those with disseminated mucinous neoplasm in the appendix as a standard of care; however, these patients should be referred to HIPEC specialty centres for assessment for treatment as part of an ongoing research protocol.

Patient Indications for Mohs Micrographic Surgery: A Systematic Review.

The purpose of the present review was to describe evidence-based indications for Mohs micrographic surgery (MMS) in patients with a diagnosis of skin cancer. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 1970 to 2017. Randomized controlled trials (RCTs), prospective and retrospective comparative studies with greater than 30 patients, and single-arm retrospective studies with multivariate analyses were included. A total of 2 RCTs, 3 prospective studies, and 16 retrospective studies (14 comparative and 2 single-arm) were included. Data on recurrence rate, cure rate, complications, cosmesis, and quality of life were extracted. Surgery (with postoperative or intraoperative marginal assessment) or radiation for those who are ineligible for surgery should remain the standard of care for patients with skin cancer given the lack of high-quality, comparative evidence. MMS is recommended for those with histologically confirmed recurrent basal cell carcinoma (BCC) of the face and is appropriate for primary BCCs of the face that are >1 cm, have aggressive histology, or are located on the H zone of the face. The available evidence is difficult to generalize to all patients with skin cancer because the evidence did not adequately cover non-BCC skin cancers; however, those skin cancers can be considered on a case-by-case basis for MMS. MMS should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in MMS.

Postoperative Adjuvant Systemic Therapy in Completely Resected Non-Small-Cell Lung Cancer: A Systematic Review.

The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016. All phase III randomized controlled trials (RCTs) and relevant systematic reviews were included. Data on overall survival (OS), disease-free survival, adverse events, and quality of life were extracted from each of the studies. Two relevant systematic reviews, 13 RCTs, and a series of pooled analyses by Lung Adjuvant Cisplatin Evaluation-Biomarker were included in the present review. Adjuvant chemotherapy statistically significantly improved OS for resected stage II-IIIA NSCLC and is recommended. For patients with stage IB NSCLC, no significant improvement was seen in OS; however, the results from subgroup analyses indicate that it would be reasonable to consider adjuvant chemotherapy for patients with larger tumors (≥ 4 cm). The present data do not support the use of adjuvant novel therapies (ie, epidermal growth factor receptor tyrosine kinase inhibitor, bevacizumab, and immunotherapy) either as an addition to, or instead of, cytotoxic chemotherapy. No predictive biomarkers are available to select patients more likely to benefit from adjuvant chemotherapy. Cytotoxic chemotherapy remains the standard of care as adjuvant therapy for patients with resected stage II-IIIA NSCLC. Additional clinical trials are needed to evaluate targeted agents in molecularly defined subgroups before these agents can be recommended in the adjuvant setting.