Chest wall toxicity after stereotactic radiation in early lung cancer: a systematic review.

Background: Radiation-induced chest wall pain (cwp) and rib fracture (rf) are late adverse effects after stereotactic body radiation therapy (sbrt) for stage i non-small-cell lung cancer (nsclc); however, the literature about their incidence and risk factors shows variability. We performed a systematic review to determine the pooled incidence of cwp and rf in the relevant population. Methods: A literature search using the prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines considered English publications in medline and embase from January 1996 to August 2017. Abstracts were screened, followed by full-text review and data extraction. Results: The database searches identified 547 records. Twenty-eight publications comprising 3892 patients met the inclusion criteria. Median reported ages and follow-up durations fell into the ranges 67-82 years and 12-84 months. Prescriptions fell into the range of 40-70 Gy in 3-10 fractions. Despite study heterogeneity, the pooled incidences of cwp and rf were estimated to be 8.94% and 5.27% respectively. Nineteen studies reported cwp grade: 58 of 308 patients (18.8%) experienced grades 3-4 cwp (no grade 5 events reported). Thirteen studies reported rf grade: grades 3-4 rf were observed in 9 of 113 patients (7.96%). A high chest wall V30 was an important predictor of cwp and rf. Conclusions: In patients with stage i nsclc, rates of cwp and rf after sbrt are low; however, tumour location, accurate toxicity reporting, and dose-fractionation schemes might alter those rates. Prospective correlation with dosimetry and quality of life assessment will further improve the understanding of cwp and rf after sbrt.

Organizational guidance for the care of patients with head-and-neck cancer in Ontario.

Background: At the request of the Head and Neck Cancers Advisory Committee of Ontario Health (Cancer Care Ontario), a working group and expert panel of clinicians with expertise in the management of head-and-neck cancer developed the present guideline. The purpose of the guideline is to provide advice about the organization and delivery of health care services for adult patients with head-and-neck cancer. Methods: This document updates the recommendations published in the Ontario Health (Cancer Care Ontario) 2009 organizational guideline The Management of Head and Neck Cancer in Ontario. The guideline development methods included an updated literature search, internal review by content and methodology experts, and external review by relevant health care providers and potential users. Results: To ensure that all patients have access to the highest standard of care available in Ontario, the guideline establishes the minimum requirements to maintain a head-and-neck disease site program. Recommendations are made about the membership of core and extended provider teams, minimum skill sets and experience of practitioners, cancer centre-specific and practitioner-specific volumes, multidisciplinary care requirements, and unique infrastructure demands. Conclusions: The recommendations contained in this document offer guidance for clinicians and institutions providing care for patients with head-and-neck cancer in Ontario, and for policymakers and other stakeholders involved in the delivery of health care services for head-and-neck cancer.

Bone Health and Bone-targeted Therapies for Prostate Cancer: a Programme in Evidence-based Care - Cancer Care Ontario Clinical Practice Guideline.

AIMS: To make recommendations with respect to bone health and bone-targeted therapies in men with prostate cancer. MATERIALS AND METHODS: A systematic review was carried out by searching MEDLINE, EMBASE and the Cochrane Library from inception to January 2016. Systematic reviews and randomised-controlled trials were considered for inclusion if they involved therapies directed at improving bone health or outcomes such as skeletal-related events, pain and quality of life in patients with prostate cancer either with or without metastases to bone. Therapies included medications, supplements or lifestyle modifications alone or in combination and were compared with placebo, no treatment or other agents. Disease-targeted agents such as androgen receptor-targeted and chemotherapeutic agents were excluded. Recommendations were reviewed by internal and external review groups. RESULTS: In men with prostate cancer receiving androgen deprivation therapy, baseline bone mineral density testing is encouraged. Denosumab should be considered for reducing the risk of fracture in men on androgen deprivation therapy with an increased fracture risk. Bisphosphonates were effective in improving bone mineral density, but the effect on fracture was inconclusive. No medication is recommended to prevent the development of first bone metastasis. Denosumab and zoledronic acid are recommended for preventing or delaying skeletal-related events in men with metastatic castration-resistant prostate cancer. Radium-223 is recommended for reducing symptomatic skeletal events and prolonging survival in men with symptomatic metastatic castration-resistant prostate cancer. CONCLUSIONS: The recommendations represent a current standard of care that is feasible to implement, with outcomes valued by clinicians and patients.

Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: A systematic review.

PURPOSE: To define the optimal model of care for patients receiving outpatient chemotherapy who experience a fever. Fever is a common symptom in patients receiving chemotherapy, but the approach to evaluation of fever is not standardized. METHODS: We conducted a search for existing guidelines and a systematic review of the primary literature from database inception to November 2015. Full-text reports and conference abstracts were considered for inclusion. The search focused on the following topics: the relationship between temperature and poor outcome; predictors for the development of febrile neutropenia (FN); the timing, location, and personnel involved in fever assessment; and the provision of information to patients receiving chemotherapy. RESULTS: Eight guidelines and 38 studies were included. None of the guidelines were directly relevant to the target population because they dealt primarily with the management of FN after diagnosis. The primary studies tended to include fever as one of many symptoms assessed in the setting of chemotherapy. Temperature level was a weak predictor of poor outcomes. We did not find validated prediction models for identifying patients at risk of FN among patients receiving chemotherapy. Several studies presented approaches to symptom management that included fever among the symptoms, but results were not mature enough to merit widespread adoption. CONCLUSION: Despite the frequency and risks of fever in the setting of chemotherapy, there is limited evidence to define who needs urgent assessment, where the assessment should be performed, and how quickly. Future research in this area is greatly needed to inform new models of care.

Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline.

BACKGROUND: This guideline was prepared by the Fever Assessment Guideline Development Group, a group organized by the Program in Evidence-Based Care at the request of the Cancer Care Ontario Systemic Treatment Program. The mandate was to develop a standardized approach (in terms of definitions, information, and education) for the assessment of fever in cancer patients receiving chemotherapy. METHODS: The guideline development methods included a search for existing guidelines, literature searches in medline and embase for systematic reviews and primary studies, internal review by content and methodology experts, and external review by targeted experts and intended users. RESULTS: The search identified eight guidelines that had partial relevance to the topic of the present guideline and thirty-eight primary studies. The studies were mostly noncomparative prospective or retrospective studies. Few studies directly addressed the topic of fever except as one among many symptoms or adverse effects associated with chemotherapy. The recommendations concerning fever definition are supported mainly by other existing guidelines. No evidence was found that directly pertained to the assessment of fever before a diagnosis of febrile neutropenia was made. However, some studies evaluated approaches to symptom management that included fever among the symptoms. Few studies directly addressed information needs and resources for managing fever in cancer patients. CONCLUSIONS: Fever in patients with cancer who are receiving systemic therapy is a common and potentially serious symptom that requires prompt assessment, but currently, evidence to inform best practices concerning when, where, and by whom that assessment is done is very limited.

Systemic therapy in men with metastatic castration-resistant prostate cancer: a systematic review.

AIMS: Since 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC. MATERIALS AND METHODS: Searches were carried out in MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. Eligible articles included RCTs comparing systemic therapy or combination (excluding primary or secondary androgen deprivation therapy, bone protective agents or radionuclides) with placebo or other agents in men with mCRPC. RESULTS: Twenty-five RCTs met the selection criteria. In chemotherapy-naive patients, targeted therapy with tasquinimod conferred a benefit in progression-free survival. Immunotherapy with sipuleucel-T extended overall survival and was well tolerated, but had no effect on the time to disease progression. Hypercastration with abiraterone extended progression-free survival, whereas overall survival was improved but not statistically proven. In the chemotherapy setting, updated and new trials of docetaxel alone confirmed the survival benefit seen in previous studies. A survival benefit with the addition of estramustine to docetaxel shown in a previous study did not lead to an improvement in pain palliation or quality of life. Trials of combining targeted therapies with docetaxel generally did not extend survival. The addition of bevacizumab improved progression-free survival, but not overall survival. The addition of GVAX immunotherapy or calcitriol was harmful. In the post-chemotherapy setting, progression-free and overall survival benefits were detected with cabazitaxel, abiraterone and enzalutamide. Cabazitaxel was associated with greater toxicity, whereas abiraterone and enzalutamide had less severe adverse effects. Satraplatin and sunitinib both extended progression-free survival, but did not improve overall survival. CONCLUSION: Docetaxel-based chemotherapy remains the standard of care in men with mCRPC who are candidates for palliative systemic therapy. Promising results are emerging with sipuleucel-T and abiraterone in the pre-docetaxel setting and cabazitaxel, abiraterone and enzalutamide in patients who progress on or after docetaxel. Further research to determine the optimal choice, sequence or even the combination of these agents is necessary.

Evidence-based guideline recommendations on the use of positron emission tomography imaging in head and neck cancer.

AIMS: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-D-glucose positron emission tomography (PET) for diagnosis, staging and assessing treatment response, restaging or recurrence of head and neck cancer. MATERIALS AND METHODS: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to July 2011 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Head and Neck Disease Site Group and a special meeting of clinical experts. RESULTS: The results of the Facey et al. review for head and neck cancer included five other systematic reviews and 31 primary studies. The 2005 to 2011 update search included four additional systematic reviews and 53 primary studies. Recommendations were developed based on this evidence and accepted by consensus. CONCLUSIONS: PET is recommended in the M and bilateral nodal staging of all patients with head and neck squamous cell carcinoma where conventional imaging is equivocal, or where treatment may be significantly modified. PET is recommended in all patients after conventional imaging and in addition to, or prior to, diagnostic panendoscopy where the primary site is unknown. PET is recommended for the staging and assessment of recurrence of patients with nasopharyngeal carcinoma if conventional imaging is equivocal. PET is recommended for restaging patients who are being considered for major salvage treatment, including neck dissection.

Evidence-based guideline recommendations on the use of positron emission tomography imaging in oesophageal cancer.

AIMS: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for diagnosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of oesophageal cancer. MATERIALS AND METHODS: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts. RESULTS: The results from the Facey et al. review for oesophageal cancer included four other systematic reviews and six primary studies. The 2005 to 2010 updated search included two additional systematic reviews and 29 primary studies. Recommendations were developed based on this evidence and accepted by consensus. CONCLUSIONS: PET is recommended to improve the accuracy of M staging for the staging work-up of patients with oesophageal cancer who are potential candidates for curative therapy. Due to insufficient evidence, no recommendation was made for or against the use of PET for the assessment of treatment response and the evaluation of suspected recurrence.

Evidence-based guideline recommendations on the use of positron emission tomography imaging in colorectal cancer.

AIMS: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-d-glucose positron emission tomography (PET) for diagnosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of colorectal cancer. MATERIALS AND METHODS: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts. RESULTS: The results from the Facey et al. review for colorectal cancer included three other systematic reviews and 24 primary studies. The 2005 to 2010 updated search included 10 additional systematic reviews and 28 primary studies. Recommendations were developed based on this evidence and accepted by consensus. CONCLUSIONS: The routine use of PET is not recommended for the diagnosis or staging of clinical stage I-III colorectal cancers. PET is recommended for determining management and prognosis if conventional imaging is equivocal for the presence of metastatic disease. PET is also not recommended for routine surveillance in patients with colorectal cancer treated with curative surgery at high risk for recurrence. It is recommended to determine the site of recurrence in the setting of rising CEA when conventional work-up fails to unequivocally identify metastatic disease. Finally, PET is recommended in the preoperative assessment of colorectal cancer liver metastasis before surgical resection.

Delivery of brachytherapy for cervical cancer: organisational and technical advice to facilitate high-quality care.

AIMS: Brachytherapy is a standard therapy for cervical cancer; it allows for the delivery of a high dose of radiation to the tumour while sparing the surrounding healthy tissues. With this document, the Brachytherapy Cervical Cancer Expert Working Group (BCCEWG) aimed to provide advice on organisational and technical aspects of the delivery of brachytherapy services in Ontario, Canada. MATERIALS AND METHODS: We sought technical documents, practice guidelines and standards through an environmental scan of internet resources, an iterative search of the literature on MEDLINE and EMBASE, and a search of reference lists of included documents. RESULTS: We identified 20 guidance documents authored by 10 organisations; 11 documents were identified through the environmental scan, five through the literature search and four from reference lists. The recommendations included in this document were developed by the BCCEWG through the selection and review of the evidence and informal consensus. CONCLUSIONS: These organisational recommendations aim to set the stage for high-quality delivery of brachytherapy for cervical cancer services in the province of Ontario, Canada. They address the characteristics of the practice setting, including facilities, equipment, delivery suite, imaging technologies, treatment planning and dosimetry; the practice team, including team members, roles, training, team caseload/volumes and qualifications; and the quality assurance domain, including documentation, audit, safety and quality control.

Epirubicin, alone or in combination chemotherapy, for metastatic breast cancer. Provincial Breast Cancer Disease Site Group and the Provincial Systemic Treatment Disease Site Group.

GUIDELINE QUESTION: How effective is epirubicin compared with doxorubicin in the treatment of metastatic breast cancer? OBJECTIVE: To make recommendations about the use of epirubicin, particularly compared with doxorubicin, in women with metastatic breast cancer. OUTCOMES: Outcomes of interest are response rate, survival and toxicity. PERSPECTIVE (VALUES): Evidence was reviewed and summarized by a member of the Provincial Systemic Treatment Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative. Drafts of the practice guideline were reviewed and discussed by the Breast Cancer DSG of the Cancer Care Ontario Practice Guidelines Initiative. The 2 DSGs comprise medical oncologists, radiation oncologists, surgeons, epidemiologists, pathologists, nurses, pharmacists, a medical sociologist and a community representative. QUALITY OF EVIDENCE: Thirteen randomized controlled trials (11 published reports and 2 reports in abstract form) were reviewed that compared epirubicin and doxorubicin at equal doses, epirubicin at a higher dose than that of doxorubicin, and epirubicin at escalating doses. BENEFITS: No significant differences were observed in response rate or median survival in the 7 trials comparing equal doses of epirubicin and doxorubicin or in the 3 trials comparing epirubicin at a higher dose than that of doxorubicin. An increased response rate was observed with higher doses of epirubicin in the 3 trials that compared escalating doses; no difference in survival was observed. HARMS: Compared with doxorubicin, epirubicin was associated with less nausea and vomiting (risk ratio [RR] 0.76; 95% confidence interval [CI] 0.63 to 0.92; p = 0.0048), less neutropenia (RR 0.52; 95% CI 0.35 to 0.78; p = 0.0017) and less cardiotoxicity (RR 0.43; 95% CI 0.24 to 0.77; p = 0.0044), including a trend toward fewer episodes of congestive heart failure (RR 0.38; 95% CI 0.14 to 1.04; p = 0.059). PRACTICE GUIDELINE: For the treatment of metastatic breast cancer in which the goal of treatment is palliation, epirubicin (at doses equivalent to doxorubicin) has been shown to be equally efficacious and less toxic than doxorubicin. Doxorubicin, however, is an acceptable alternative. CLINICAL PRACTICE GUIDELINE DATE: Oct. 2, 1997.

Adjuvant therapy for stage III colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group.

GUIDELINE QUESTIONS: Should patients with resected stage III colon cancer receive adjuvant therapy? If so, which therapy should be recommended? OBJECTIVE: To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage III colon cancer. OUTCOMES: Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 4 members of the Gastrointestinal Disease Site Group (GI DSG) of the Ontario Cancer Treatment Practice Guidelines Initiative. Earlier drafts of the guideline were reviewed, discussed and approved by the GI DSG, which comprises medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this guideline but will participate in future guidelines development. QUALITY OF EVIDENCE: There are 3 meta-analyses, 33 published randomized controlled trials (RCTs) and 1 consensus statement. The GI DSG pooled data from 10 of the 33 RCTs that allowed for such an analysis. BENEFITS: Two of 3 RCTs reported improved survival rates with 5-fluorouracil (5-FU) plus semustine or mitomycin C (MMC) compared with no treatment (observation) after surgical resection. Three trials reported a benefit in both overall and disease-free survival with 5-FU plus levamisole compared with observation after surgery. In 2 trials, levamisole alone did not produce a survival benefit compared with observation. One trial reported improved disease-free, but not overall, survival rates with oral HCFU (1-hexylcarbamoyl-5-fluorouracil) compared with observation. In 3 trials of 5-FU plus leucovorin, disease-free and overall survival rates were improved compared with observation. Nine trials compared portal vein infusion (PVI) of 5-FU with observation after surgery. In 2 of the trials, for which data were available for stage III patients only, improved overall survival was reported. There was a trend in all studies favouring PVI. One trial reported a survival benefit for stage III and IV patients who received oral HCFU maintenance therapy for 1 year compared with no maintenance therapy. In a trial comparing MMC plus oral HCFU with MMC alone, a survival benefit was reported in the combined treatment group; however, the stages of cancer were unevenly distributed among the treatment groups. Only 1 study tested monoclonal antibody; a benefit was reported for both overall and disease-free survival. A meta-analysis of 10 trials comparing adjuvant therapy with observation in patients with stage III disease detected a significant reduction in the odds ratio (OR) for death (OR 0.69; 95% confidence interval [CI] 0.57 to 0.85), with an absolute improvement in survival of 4% to 13%. When trials were separated according to the type of treatment given, the significant ORs were for 5-FU plus either levamisole (OR 0.61; 95% CI 0.46 to 0.80) or leucovorin (OR 0.51; 95% CI 0.36 to 0.73). Three recently reported trials comparing various combinations of 5-FU plus leucovorin, with or without levamisole, showed similar improvements in disease-free and overall survival.

Adjuvant therapy for stage II colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group.

GUIDELINE QUESTION: Should patients with resected stage II colon cancer receive adjuvant therapy? OBJECTIVE: To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage II colon cancer. OUTCOMES: Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The recommendations resulting from this review have been approved by the GI DSG, which comprise medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this practice guideline but will do so in future guidelines development. QUALITY OF EVIDENCE: There are 25 published randomized controlled trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs that provided adequate data. BENEFITS: The 25 RCTs are grouped according to the type of therapy and whether the control patients received no treatment (observation) or other adjuvant therapy after resection. Because the trials usually included patients with stage II and III cancer, the complete trial results and those for a subset of patients with stage II disease were analysed. Although the overall trial results showed a survival benefit for adjuvant treatments, the benefit was not significant for stage II patients. A meta-analysis of 11 trials comparing adjuvant treatment with observation in patients with stage II cancer indicated no significant reduction in the odds ratio (OR) for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95% CI 0.35 to 1.11). HARMS: The toxic effects of 5-fluorouracil (5-FU) with either levamisole or leucovorin, or both, were mild to moderate and consisted mostly of stomatitis, diarrhea and myelosuppression; 5% of patients required hospital admission. 5-FU plus levamisole was associated with transient neurotoxic effects in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly consisted of leukopenia and diarrhea; 1% of patients experienced bowel perforation. PRACTICE GUIDELINE: Adjuvant therapy is not recommended at this time for the routine management of patients with resected stage II colon cancer. Patients with stage II disease and high-risk factors (bowel obstruction, tumour adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar to that of patients with stage III colon cancer. For individual management, these patients should be made aware of their prognosis; treatment can be considered after the uncertainty of the value of adjuvant therapy has been explained to the patient. The enrolment of patients with high-risk stage II disease in clinical trials is encouraged. Trials comparing adjuvant therapy with observation are needed and are ethically acceptable in stage II colon cancer.

The quality and impact of MEDLINE searches performed by end users.

Evidence suggests that MEDLINE is becoming an important clinical tool that can improve the care and health of patients. Efforts to improve the quality and impact of end-user searching are needed and ongoing. End users are completing many MEDLINE searches. They appreciate and value training along with feedback on their searching techniques. Practice, is however, the biggest single factor in improving the quality of searching. Key roles for the library in end-user searching include, providing the most effective MEDLINE access possible to the maximum number of users, and providing training that includes feedback and practice opportunities. System-wide advances in structured abstracts, indexing, system design, informatics research and the literature itself will make searching easier and more effective in the future. More important than the quality of search results per se is the impact that end-user searches have on patient care and patient outcomes. Growing evidence shows that both patient care and patient outcomes are improved by end-user searches.