Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic review and practice guideline for North America.

BACKGROUND: Gastric cancer is a global health problem accounting for 10% of all new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and radiation therapy in gastric cancer; however, these studies have produced conflicting results. The purpose of this guidance document was to determine whether patients with resectable gastric cancer should receive neoadjuvant or adjuvant therapy in addition to surgery. Outcomes of interest were overall survival, disease-free survival, and adverse events. METHODS: A systematic review was undertaken to inform recommendations regarding neoadjuvant and adjuvant therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE databases, as well as American Society of Clinical Oncology (ASCO) annual meeting proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO) proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine trials were excluded owing to the unavailability of these agents in North America. RESULTS: Overall, 22 randomized controlled trials (RCTs), 13 meta-analyses, and two secondary analyses were included. The systematic review informed the development of a clinical practice guideline with the following recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil) chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) approach are both acceptable standards of care in North America. Choice of treatment should be made on a case-by-case basis. Adjuvant chemotherapy is a reasonable option for those patients for whom the Macdonald and MAGIC protocols are contraindicated. All patients with resectable gastric cancer should undergo a pretreatment multidisciplinary assessment to determine the best plan of care. CONCLUSIONS: Overall survival in patients with resectable gastric cancer is significantly improved with the use of either postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC protocol).

Adjuvant Chemotherapy and Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Clinical Practice Guideline.

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.

Key components of intravenous chemotherapy labeling: a systematic review and practice guideline.

OBJECTIVE: To determine the necessary components and formatting of an intravenous chemotherapy label to maximize safe delivery and minimize errors. Date sources. The MEDLINE and EMBASE databases (up to April 2009) were searched for relevant evidence. Reference lists from retained studies were then searched for additional trials. An environmental scan was also conducted to locate other published and unpublished sources of information. Study selection. Relevant articles were selected and reviewed by one methodologist. Articles were selected for inclusion if they were published English language reports of Phases II or III randomized controlled trials, other comparative studies, single-arm studies, practice guidelines, or systematic reviews with or without meta-analyses, which related to the study question. MEDLINE and EMBASE searches yielded 685 potential studies of which 17 met the inclusion criteria. The environmental scan located one guideline. Three additional relevant studies were identified during the external review process. In total, 21 documents met the inclusion criteria. Data extraction. Data were extracted by one methodologist. Quality of systematic reviews was assessed using the AMSTAR tool. All other studies were evaluated based on study characteristics applicable to the particular study design. Data synthesis. The evidence collected and the consensus of expert opinion of Cancer Care Ontario's Chemotherapy Labeling Panel form the basis of a series of recommendations for the generation of intravenous chemotherapy labels including formatting, required information, and order of information. These guidelines inform the efficient, effective, and safe administration of intravenous chemotherapy. Illustrative examples are provided.

Effective teaching strategies and methods of delivery for patient education: a systematic review and practice guideline recommendations.

The objective of this study was to determine effective teaching strategies and methods of delivery for patient education (PE). A systematic review was conducted and reviews with or without meta-analyses, which examined teaching strategies and methods of delivery for PE, were included. Teaching strategies identified are traditional lectures, discussions, simulated games, computer technology, written material, audiovisual sources, verbal recall, demonstration, and role playing. Methods of delivery focused on how to deliver the teaching strategies. Teaching strategies that increased knowledge, decreased anxiety, and increased satisfaction included computer technology, audio and videotapes, written materials, and demonstrations. Various teaching strategies used in combination were similarly successful. Moreover, structured-, culturally appropriate- and patient-specific teachings were found to be better than ad hoc teaching or generalized teaching. Findings provide guidance for establishing provincial standards for the delivery of PE. Recommendations concerning the efficacy of the teaching strategies and delivery methods are provided.

Non-surgical management of advanced hepatocellular carcinoma: A systematic review by Cancer Care Ontario.

Background: Hepatocellular carcinoma (HCC) is a global health problem, accounting for 4.7% of all new cancer cases and 8.2% of all cancer deaths worldwide in 2018. Resection and transplantation are the only modalities that offer a cure for HCC; however, most patients are diagnosed at an advanced stage, precluding these curative treatments. A number of local (ie, ablative therapies) and/or local-regional therapies (ie, chemo-embolization) are used and followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy compared with these standards is not well known. Methods: Literature searches (1/2000 to 1/2020 or 1/2005 to 1/2020, depending on the specific systematic review question) were conducted, including MEDLINE, Embase and the Cochrane Database of Systematic Reviews. Results: Over 30,000 articles were identified. In total, 49 studies were included in the systematic review. Conclusions: There is no evidence to support the addition of sorafenib to any local or regional therapy. First-line systemic therapy options for unresectable or metastatic HCC include sorafenib, lenvatinib, and atezolizumab + bevacizumab. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment.

Gastroscopy following a positive fecal occult blood test and negative colonoscopy: systematic review and guideline.

BACKGROUND: A sizeable number of individuals who participate in population-based colorectal cancer (CRC) screening programs and have a positive fecal occult blood test (FOBT) do not have an identifiable lesion found at colonoscopy to account for their positive FOBT screen. OBJECTIVE: To evaluate the evidence and provide recommendations regarding the use of routine esophagogastroduodenoscopy (EGD) to detect upper gastrointestinal (UGI) cancers in patients participating in a population-based CRC screening program who are FOBT positive and colonoscopy negative. METHODS: A systematic review was used to develop the evidentiary base and to inform the evidence-based recommendations provided. RESULTS: Nine studies identified a group of patients who were FOBT positive and colonoscopy negative. Three studies found no cases of UGI cancer. Four studies reported cases of UGI cancer; three found UGI cancer in 1% or less of the population studied, and one study found one case of UGI cancer that represented 7% of their small subgroup of FOBT-positive/colonoscopy-negative patients. Two studies did not provide outcome information that could be specifically related to the FOBT-positive/colonoscopy-negative subgroup. CONCLUSION: The current body of evidence is insufficient to recommend for or against routine EGD as a means of detecting gastric or esophageal cancers for patients who are FOBT positive/colonoscopy negative, in a population-based CRC screening program. The decision to perform EGD should be individualized and based on clinical judgement.

Provider Tools for Advance Care Planning and Goals of Care Discussions: A Systematic Review.

BACKGROUND: Advance care planning and goals of care discussions involve the exploration of what is most important to a person, including their values and beliefs in preparation for health-care decision-making. Advance care planning conversations focus on planning for future health care, ensuring that an incapable person's wishes are known and can guide the person's substitute decision maker for future decision-making. Goals of care discussions focus on preparing for current decision-making by ensuring the person's goals guide this process. AIM: To provide evidence regarding tools and/or practices available for use by health-care providers to effectively facilitate advance care planning conversations and/or goals of care discussions. DATA SOURCES: A systematic review was conducted focusing on guidelines, randomized trials, comparative studies, and noncomparative studies. Databases searched included MEDLINE, EMBASE, and the proceedings of the International Advance Care Planning Conference and the American Society of Clinical Oncology Palliative Care Symposium. CONCLUSIONS: Although several studies report positive findings, there is a lack of consistent patient outcome evidence to support any one clinical tool for use in advance care planning or goals of care discussions. Effective advance care planning conversations at both the population and the individual level require provider education and communication skill development, standardized and accessible documentation, quality improvement initiatives, and system-wide coordination to impact the population level. There is a need for research focused on goals of care discussions, to clarify the purpose and expected outcomes of these discussions, and to clearly differentiate goals of care from advance care planning.

Staging and surgical approaches in gastric cancer: A systematic review.

BACKGROUND: Gastric adenocarcinoma accounted for 6.8% of new cancer cases and 8.8% of cancer deaths worldwide in 2012. Although resection is the cornerstone for cure, several aspects of surgical intervention remain controversial or sub-optimally applied at the population level. These include staging, extent of lymph node dissection (LND), optimal requirements of LN assessment, minimum resection margins, surgical technique (laparoscopic vs. open), relationship between surgical volumes and patient outcomes, and resection of stage IV gastric cancer. METHODS: A systematic review was conducted to inform surgical care. RESULTS: The evidence included in this systematic review consists of one guideline, seven systematic reviews and 48 primary studies. CONCLUSIONS: All patients should be discussed at a multidisciplinary team meeting and a staging CT of the chest and abdomen should always be performed. Diagnostic laparoscopy should be performed in patients at risk for stage IV disease. A D2 LND is preferred for curative-intent resection in advanced non-metastatic gastric cancer. At least 16 LNs should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an RO resection margin. In the metastatic setting, surgery should only be considered for palliation of symptoms. Patients should be referred to higher volume centres, and those with adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as open resections.

American Society of Clinical Oncology Clinical Practice Guideline on uses of serum tumor markers in adult males with germ cell tumors.

PURPOSE: To provide recommendations on appropriate uses for serum markers of germ cell tumors (GCTs). METHODS: Searches of MEDLINE and EMBASE identified relevant studies published in English. Primary outcomes included marker accuracy to predict the impact of decisions on outcomes. Secondary outcomes included proportions of patients with elevated markers and statistical tests of elevations as prognostic factors. An expert panel developed consensus guidelines based on data from 82 reports. RESULTS: No studies directly compared outcomes of decisions with versus without marker assays. The search identified few prospective studies and no randomized controlled trials; most were retrospective series. Lacking data on primary outcomes, most Panel recommendations are based on secondary outcomes (relapse rates and time to relapse). RECOMMENDATIONS: The Panel recommended against using markers to screen for GCTs, to decide whether orchiectomy is indicated, or to select treatment for patients with cancer of unknown primary. To stage patients with testicular nonseminomas, the Panel recommended measuring three markers (alpha-fetoprotein [AFP], human chorionic gonadotropin [hCG], and lactate dehydrogenase [LDH]) before and after orchiectomy and before chemotherapy for those with extragonadal nonseminomas. They also recommended measuring AFP and hCG shortly before retroperitoneal lymph node dissection and at the start of each chemotherapy cycle for nonseminoma, and periodically to monitor for relapse. The Panel recommended measuring postorchiectomy hCG and LDH for patients with seminoma and preorchiectomy elevations. They recommended against using markers to guide or monitor treatment for seminoma or to detect relapse in those treated for stage I. However, they recommended measuring hCG and AFP to monitor for relapse in patients treated for advanced seminoma.

Clinical application of tissue adhesives in soft-tissue surgery of the head and neck.

PURPOSE OF REVIEW: To evaluate the clinical applications of tissue adhesives in soft-tissue surgery of the head and neck, and to highlight the practical and theoretical differences between the various synthetic and biologic products. RECENT FINDINGS: Fibrin glues have been used extensively in head and neck procedures. Fibrin glues have been successfully used to reduce wound drainage and to improve other short-term postoperative results. More recently, commercial systems have become available that allow easy and rapid isolation of autologous tissue adhesives from the patient's own blood during or immediately prior to surgery. SUMMARY: There is intuitive appeal of autologous over donor-derived products. Platelet-rich adhesives possess the added potential of improving wound healing beyond fibrin glues alone. Strong evidence for its efficacy in the clinical setting is, however, lacking. Future investigations need to evaluate the benefits of autologous products in both complex and high-risk surgical wounds, incorporating both short-term and long-term outcome metrics of wound healing and fibrosis.

HER2 testing in a population-based study of patients with metastatic breast cancer treated with trastuzumab.

CONTEXT: The development of trastuzumab has led to new therapeutic strategies for patients with breast cancer. Trastuzumab has been shown to only be effective in those patients whose cancers are HER2 positive by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). OBJECTIVE: To determine the accuracy of HER2 testing in 2 provinces in Canada. DESIGN: Patients with metastatic breast cancer diagnosed between 1999 and 2002 who were HER2 positive in the local laboratories were included in this study. All cases were retested centrally, by IHC (using 4 methods) and FISH. In addition, 205 locally reported HER2-negative metastatic breast cancer cases were retested centrally. RESULTS: Concordance between the 505 local IHC-positive cases with central IHC testing varied between 79.3% and 89.6% depending on the IHC method and scoring method used. HER2 gene amplification by FISH was present in 86.1% of local IHC-positive cases. Concordance between the 205 local IHC-negative tumors with central testing ranged between 94.8% and 100% for IHC and was 98.5% for FISH. CONCLUSIONS: This study demonstrated that locally reported HER2-negative results were highly accurate, but less accuracy was demonstrated with local HER2-positive results. These results emphasize the need for participation in a quality assurance program.

Randomizing patients by family practice: sample size estimation, intracluster correlation and data analysis.

BACKGROUND: Cluster randomized controlled trials increasingly are used to evaluate health interventions where patients are nested within larger clusters such as practices, hospitals or communities. Patients within a cluster may be similar to each other relative to patients in other clusters on key variables; therefore, sample size calculations and analyses of results require special statistical methods. OBJECTIVE: The purpose of this study was to illustrate the calculations used for sample size estimation and data analysis and to provide estimates of the intraclass correlation coefficients (ICCs) for several variables using data from the Seniors Medication Assessment Research Trial (SMART), a community-based trial of pharmacists consulting to family physicians to optimize the drug therapy of older patients. METHODS: The study was a paired cluster randomized trial, where the family physician's practice was the cluster. The sample size calculation was based on a hypothesized reduction of 15% in mean daily units of medication in the intervention group compared with the control group, using an alpha of 0.05 (one-tailed) with 80% power, and an ICC from pilot data of 0.08. ICCs were estimated from the data for several variables. The analyses comparing the two groups used a random effects model for a meta-analysis over pairs. RESULTS: The design effect due to clustering was 2.12, resulting in an inflation in sample size from 340 patients required using individual randomization, to 720 patients using randomization of practices, with 15 patients from each of 48 practices. ICCs for medication use, health care utilization and general health were <0.1; however, the ICC for mean systolic blood pressure over the trial period was 0.199. CONCLUSIONS: Compared with individual randomization, cluster randomization may substantially increase the sample size required to maintain adequate statistical power. The differences in ICCs among potential outcome variables reinforce the need for valid estimates to ensure proper study design.

Recruiting family physicians and patients for a clinical trial: lessons learned.

BACKGROUND: The randomized controlled trial (RCT) is the most definitive tool for evaluating an intervention. However, methodological deficiencies may limit the internal or external validity of the RCT. OBJECTIVE: Our aim was to describe the tactics used and the resources required randomly to select and recruit family physicians (FPs) and their patients aged 65 and older (seniors) for a community-based cluster RCT in primary care. METHODS: We randomly selected 48 FPs in 24 urban and rural sites in Southern Ontario, and 889 of their community-dwelling seniors (approximately 20 per FP) taking five or more medications daily. To accomplish this, the principal investigator (an FP) contacted the eligible FPs. The participating FPs' office staff then generated and contacted the roster of eligible seniors, with support provided by the research staff. RESULTS: Of the 163 randomly selected FPs telephoned, 94 were ineligible and 48 (69.6%) of the remaining 69 participated. The rosters were generated with the assistance of the research staff (taking 1.5-8.0 hours) in each of the 48 practices, using electronic appointment records (n = 26), electronic billing records (n = 17), electronic medical records (n = 2) or written charts or file cards (n = 3). Of the 2078 seniors approached, 799 were ineligible and 889 (69.5%) of the remaining 1279 participated. Seniors' refusal rates among practices ranged from 4.8 to 62.3%. CONCLUSIONS: Recruitment of a representative sample and generalizability of results are possible in RCTs in primary care. Involvement of an FP in physician recruitment and clinical research nurses who provided assistance to office staff were keys to success.

A randomized controlled trial of a pharmacist consultation program for family physicians and their elderly patients.

BACKGROUND: Pharmacists can improve patient outcomes in institutional and pharmacy settings, but little is known about their effectiveness as consultants to primary care physicians. We examined whether an intervention by a specially trained pharmacist could reduce the number of daily medication units taken by elderly patients, as well as costs and health care use. METHODS: We conducted a randomized controlled trial in family practices in 24 sites in Ontario. We randomly allocated 48 randomly selected family physicians (69.6% participation rate) to the intervention or the control arm, along with 889 (69.5% participation rate) of their randomly selected community-dwelling, elderly patients who were taking 5 or more medications daily. In the intervention group, pharmacists conducted face-to-face medication reviews with the patients and then gave written recommendations to the physicians to resolve any drug-related problems. Process outcomes included the number of drug-related problems identified among the senior citizens in the intervention arm and the proportion of recommendations implemented by the physicians. RESULTS: After 5 months, seniors in the intervention and control groups were taking a mean of 12.4 and 12.2 medication units per day respectively (p = 0.50). There were no statistically significant differences in health care use or costs between groups. A mean of 2.5 drug-related problems per senior was identified in the intervention arm. Physicians implemented or attempted to implement 72.3% (790/1093) of the recommendations. INTERPRETATION: The intervention did not have a significant effect on patient outcomes. However, physicians were receptive to the recommendations to resolve drug-related problems, suggesting that collaboration between physicians and pharmacists is feasible.