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Opioids are a critical component of pain relief strategies for the management of patients with cancer and sickle cell disease. The escalation of opioid addiction and overdose in the United States has led to increased scrutiny of opioid prescribing practices. Multiple reports have revealed that regulatory and coverage policies, intended to curb inappropriate opioid use, have created significant barriers for many patients. The Centers for Disease Control and Prevention, National Comprehensive Cancer Network, and ASCO each publish clinical practice guidelines for the management of chronic pain. A recent JAMA Oncology article highlighted perceived variability in recommendations among these guidelines. In response, leadership from guideline organizations, government representatives, and authors of the original article met to discuss challenges and solutions. The meeting featured remarks by the Commissioner of Food and Drugs, presentations on each clinical practice guideline, an overview of the pain management needs of patients with sickle cell disease, an overview of perceived differences among guidelines, and a discussion of differences and commonalities among the guidelines. The meeting revealed that although each guideline varies in the intended patient population, target audience, and methodology, there is no disagreement among recommendations when applied to the appropriate patient and clinical situation. It was determined that clarification and education are needed regarding the intent, patient population, and scope of each clinical practice guideline, rather than harmonization of guideline recommendations. Clinical practice guidelines can serve as a resource for policymakers and payers to inform policy and coverage determinations.

Opioids are a critical component of pain relief strategies for the management of patients with cancer and sickle cell disease. The escalation of opioid addiction and overdose in the United States has led to increased scrutiny of opioid prescribing practices. Multiple reports have revealed that regulatory and coverage policies, intended to curb inappropriate opioid use, have created significant barriers for many patients. The Centers for Disease Control and Prevention, National Comprehensive Cancer Network, and American Society of Clinical Oncology each publish clinical practice guidelines for the management of chronic pain. A recent JAMA Oncology article highlighted perceived variability in recommendations among these guidelines. In response, leadership from guideline organizations, government representatives, and authors of the original article met to discuss challenges and solutions. The meeting featured remarks by the Commissioner of Food and Drugs, presentations on each clinical practice guideline, an overview of the pain management needs of patients with sickle cell disease, an overview of perceived differences among guidelines, and a discussion of differences and commonalities among the guidelines. The meeting revealed that although each guideline varies in the intended patient population, target audience, and methodology, there is no disagreement among recommendations when applied to the appropriate patient and clinical situation. It was determined that clarification and education are needed regarding the intent, patient population, and scope of each clinical practice guideline, rather than harmonization of guideline recommendations. Clinical practice guidelines can serve as a resource for policymakers and payers to inform policy and coverage determinations.

The objectives of this article are to describe the ASCO Resource-Stratified Guidelines and to provide background within the context of ASCO Guidelines and efforts to address the global cancer burden.

Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .

Since the beginning of its guidelines program in 1993, ASCO has continually sought ways to produce a greater number of guidelines while maintaining its commitment to using the rigorous development methods that minimize the biases that threaten the validity of practice recommendations. ASCO is implementing a range of guideline development and implementation innovations. In this article, we describe innovations that are designed to (1) integrate consideration of multiple chronic conditions into practice guidelines; (2) keep more of its guidelines current by applying evolving signals or (more) rapid, for-cause updating approaches; (3) increase the number of high-quality guidelines available to its membership through endorsement and adaptation of other groups’ products; (4) improve coverage of its members’ guideline needs through a new topic nomination process; and (5) enhance dissemination and promote implementation of ASCO guidelines in the oncology practice community through a network of volunteer ambassadors. We close with a summary of ASCO’s plans to facilitate the integration of data from its rapid learning system, CancerLinQ, into ASCO guidelines and to develop tactics through which guideline recommendations can be embedded in clinicians’ workflow in digital form. We highlight the challenges inherent in reconciling the need to provide clinicians with more interactive, point-of-care guidance with ASCO’s abiding commitment to methodologic rigor in guideline development.

PURPOSE To provide 2019 ASCO standards on the safe handling of hazardous drugs. METHODS An Expert Panel was formed, and a systematic review of the literature on closed system transfer devices was performed to May 2017 using PubMed. The Cochrane Database of Systematic Reviews, PubMed, and Google Scholar were used to search for studies of medical surveillance and external ventilation/health effects of exposure to vapors to November 2017. Available standards were considered for endorsement. Public comments were solicited and considered in preparation of the final manuscript. RESULTS The search for primary research found no studies that addressed health outcomes as they relate to the identified interventions of interest. The ASCO Expert Panel endorses the best practices for safe handling of hazardous drugs as issued by the Occupational Safety and Health Administration, US Pharmacopeia Chapter 800, and Oncology Nursing Society with clarifications in four key areas: medical surveillance, closed system transfer devices, external ventilation of containment secondary engineering controls or containment segregated compounding areas, and alternative duties. CONCLUSION The ASCO standards address the need for clear standards concerning safe handling of hazardous oncology drugs. More research is needed in several key areas to quantify the level of risk associated with handling hazardous drugs in current workplace settings where the hierarchy of controls is consistently applied. Additional information is available at www.asco.org/safe-handling-standards .

Purpose.—Clinical use of analytical tests to assess genomic variants in circulating tumor DNA (ctDNA) is increasing. This joint review from the American Society of Clinical Oncology and the College of American Pathologists summarizes current information about clinical ctDNA assays and provides a framework for future research.Methods.—An Expert Panel conducted a literature review on the use of ctDNA assays for solid tumors, including preanalytical variables, analytical validity, interpretation and reporting, and clinical validity and utility.Results.—The literature search identified 1338 references. Of those, 390, plus 31 references supplied by the Expert Panel, were selected for full-text review. There were 77 articles selected for inclusion.Conclusions.—The evidence indicates that testing for ctDNA is optimally performed on plasma collected in cell stabilization or EDTA tubes, with EDTA tubes processed within 6 hours of collection. Some ctDNA assays have demonstrated clinical validity and utility with certain types of advanced cancer; however, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer. Evidence shows discordance between the results of ctDNA assays and genotyping tumor specimens, and supports tumor tissue genotyping to confirm undetected results from ctDNA tests. There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection. There is no evidence of clinical validity or clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial. Given the rapid pace of research, reevaluation of the literature will shortly be required, along with the development of tools and guidance for clinical practice.

The American Society of Clinical Oncology (ASCO) guidelines program employs a systematic review‐based methodology to produce evidence-based guidelines. This is consistent with the stance of the Institute of Medicine on guideline development, which is that high-quality evidence syntheses form the basis for recommendation development. In the absence of high-quality evidence, recommendation development becomes more complex. One option is to provide no recommendations or withdraw a guideline topic. However, it is often the areas of greatest uncertainty in which the evidentiary base is incomplete, and thus, guidelines are needed most. To provide recommendations in such circumstances, an explicit methodology is needed to ensure that a credible process is undertaken, and rigorous, reliable advice is provided. In 2010, the ASCO Board of Directors approved development of guideline recommendations using consensus methodology. A modified Delphi approach to recommendation development, based on the best available data identified in a systematic review, was piloted with an ASCO guideline. Consensus was achieved through the rating of a series of recommendations by a large group of clinicians, including academic and community-based content and methodology experts. A prespecified threshold of agreement was determined to indicate when consensus was achieved. Consensus was defined as agreement by 75% of raters. The formal consensus methodology used by ASCO enabled development of guideline recommendations on a challenging clinical issue based on limited evidence using a rigorous, transparent, and explicit method. This methodology is proposed for development of future ASCO guidelines on topics for which limited evidence is available. J Clin Oncol 30:3136-3140. © 2012 by American Society of Clinical Oncology

Our goal was to develop evidence-based recommendations for the organization and structure of cancer survivorship services, and best-care practices to optimize the health and well-being of post&ndash, primary treatment survivors. This review sought to determine the optimal organization and care delivery structure for cancer survivorship services, and the specific clinical practices and interventions that would improve or maximize the psychosocial health and overall well-being of adult cancer survivors. We conducted a systematic search of the Inventory of Cancer Guidelines at the Canadian Partnership Against Cancer, the U.S. National Guideline Clearinghouse, the Canadian Medical Association InfoBase, medline (ovid: 1999 through November 2009), embase (ovid: 1999 through November 2009), Psychinfo (ovid: 1999 through November 2009), the Cochrane Library (ovid, Issue 1, 2009), and cinahl (ebsco: 1999 through December 2009). Reference lists of related papers and recent review articles were scanned for additional citations. Articles were selected for inclusion as evidence in the systematic review if they reported on organizational system components for survivors of cancer, or on psychosocial or supportive care interventions HOWELL et al. designed for survivors of cancer. Articles were excluded from the systematic review if they focused only on pediatric cancer survivor populations or on populations that transitioned from pediatric cancer to adult services, if they addressed only pharmacologic interventions or diagnostic testing and follow-up of cancer survivors, if they were systematic reviews with inadequately described methods, if they were qualitative or descriptive studies, and if they were opinion papers, letters, or editorials. Evidence was selected and reviewed by three members of the Cancer Journey Survivorship Expert Panel (SM, TC, TKO). The resulting summary of the evidence was guided further and reviewed by the members of Cancer Journey Survivorship Expert Panel. Fourteen practice guidelines, eight systematic reviews, and sixty-thee randomized controlled trials form the evidence base for this guidance document. These publications demonstrate that survivors benefit from coordinated post-treatment care, including interventions to address specific psychosocial, supportive care, and rehabilitative concerns. Ongoing high-quality research is essential to optimize services for cancer survivors. Interventions that promote healthy lifestyle behaviours or that address psychosocial concerns and distress appear to improve physical functioning, psychosocial well-being, and quality of life for survivors.

What is the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease-free after receiving primary treatment? For women with cervical cancer who have been treated with curative intent, follow-up includes identification of complications related to treatment and intervention in the event of recurrent disease. Most women who recur with cervical cancer are not curable, however, early identification of recurrence can alter disease management or treatment-planning options, and for those with a central pelvic recurrence and no evidence of distant disease, there is a potential for cure with additional therapy. Follow-up protocols in this population are variable, using a number of tests at a variety of intervals with questionable outcomes. Outcomes of interest included recurrence, survival, and quality of life. The Gynecology Cancer Disease Site Group (dsg) conducted a systematic review of the literature and a narrative review of emerging clinical issues to inform the most appropriate follow-up strategy for patients with cervical cancer. The evidence was insufficient to specify a clinically useful recommended follow-up schedule, and therefore, the expert consensus opinion of the Gynecology Cancer dsg was used to develop recommendations on patient surveillance. The resulting recommendations were reviewed and approved by the Gynecology Cancer dsg and by the Program in Evidence-Based Care Report Approval Panel. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline. The systematic review of the literature identified seventeen retrospective studies. The Gynecology Cancer dsg used a consensus process to develop recommendations based on the available evidence from the systematic review, the narrative review, and the collective clinical experience and judgment of the dsg members. The recommendations in this practice guideline are based on the expert consensus opinion of the Gynecology Cancer dsg, informed by evidence from retrospective studies. These are some general features of an appropriate follow-up strategy: At a minimum, follow-up visits with a complete physical examination, including a pelvic&ndash, rectal exam and a patient history, should be conducted by a physician experienced in the surveillance of cancer patients. There is little evidence to suggest that vaginal vault cytology adds significantly to the clinical exam in detecting early disease recurrence. Routine use of various other radiologic or biologic follow-up investigations in asymptomatic patients is not advocated, because the role of those investigations has yet to be evaluated in a definitive manner. A reasonable follow-up schedule involves follow-up visits every 3&ndash, 4 months in the first 2 years and every 6&ndash, 12 months in years 3&ndash, 5. Patients should return to annual population-based general physical and pelvic examinations after 5 years of recurrence-free follow-up.

To determine the optimum organization for colposcopy service delivery in Ontario, Canada.A multidisciplinary expert panel was convened to develop a systematic review to inform organizational guidelines. MEDLINE, EMBASE, CINAHL, HealthSTAR, and the Cochrane Library databases were searched from 1996 to February 2006 for articles that reported guidance or outcomes relating to improved outcomes in colposcopy training, qualifications, accreditation, maintenance of competency, the delivery of colposcopy, reducing default from colposcopy clinics, and/or strategies to improve patient satisfaction or comfort. In addition, an environmental scan identified unpublished documents related to the delivery of colposcopy services.Sixteen guidance documents related to the delivery of colposcopy services were identified; 5 from the published literature and 11 from the environmental scan. These documents were used by the panel to inform the systematic review and companion guidelines.Overall, the Ontario Colposcopy Guidelines Development Group believes that the benefits associated with the implementation of colposcopy recommendations in Ontario will result in greater organization of care and improved patient outcomes. In addition, the group anticipates that these recommendations will provide useful guidance to regional planning authorities, hospital administrators, and Cancer Care Ontario, as well as colposcopists and other practitioners, in the planning of integrated regional and provincial cancer screening services.

Improving access to better, more efficient, and rapid cancer diagnosis is a necessary component of a high-quality cancer system. How diagnostic services ought to be organized, structured, and evaluated is less understood and studied. Our objective was to address this gap. As a quality initiative of Cancer Care Ontario&rsquo, s Program in Evidence-Based Care, the Diagnostic Assessment Standards Panel, with representation from clinical oncology experts, institutional and clinical administrative leaders, health service researchers, and methodologists, conducted a systematic review and a targeted environmental scan of the unpublished literature. Standards were developed based on expert consensus opinion informed by the identified evidence. Through external review, clinicians and administrators across Ontario were given the opportunity to provide feedback. The body of evidence consists of thirty-five published studies and fifteen unpublished guidance documents. The evidence and consensus opinion consistently favoured an organized, centralized system with multidisciplinary team membership as the optimal approach for the delivery of diagnostic cancer assessment services. Independent external stakeholders agreed (with higher mean values, maximum 5, indicating stronger agreement) that dap standards are needed (mean: 4.6), that standards should be formally approved (mean: 4.3), and importantly, that standards reflect an effective approach that will lead to quality improvements in the cancer system (mean: 4.5) and in patient care (mean: 4.3). Based on the best available evidence, standards for the organization of daps are offered. There is clear need to integrate formal and comprehensive evaluation strategies with the implementation of the standards to advance this field.

Background: A systematic review of the literature identifying regional collaborations in surgical practice examining practices related to quality improvement. Methods: The MEDLINE, EMBASE, and Cochrane Library databases, were searched for published reports of regional collaborations in the surgical community relating to initiatives to enhance quality improvement, quality of care, patient safety, knowledge transfer, or communities of practice. Results: Seven collaborative initiatives met the inclusion criteria and were included in the systematic review of the evidence. Motivations for initiating collaborations were often in response to external demands for performance data. Changes in the processes of clinical care and improvements in clinical outcomes were reported on the basis of the collaborative efforts. Significant improvements in clinical outcomes such as decreases in mortality rates, lower duration of postoperative intubations, and fewer surgical-site infections were reported. Quality improvement process measures were also reported to be improved across all of the collaborative initiatives. Success factors included (a) the establishment of trust among health professionals and health institutions; (b) the availability of accurate, complete, relevant data; (c) clinical leadership; (d) institutional commitment; and (e) the infrastructure and methodological support for quality management. Conclusions: A community of practice framework incorporating the success elements described in the systematic review of the literature can be used as a valuable model for collaboration amongst surgeons and healthcare organizations to improve quality of care and foster continuing professional development.

Background: Effective literature searching is particularly important for clinical practice guideline development. Sophisticated searching and filtering mechanisms are needed to help ensure that all relevant research is reviewed. Purpose: To assess the methods used for the selection of evidence for guideline development by evidence-based guideline development organizations. Methods: A semistructured questionnaire assessing the databases, search filters and evaluation methods used for literature retrieval was distributed to eight major organizations involved in evidence-based guideline development. Results: All of the organizations used search filters as part of guideline development. The medline database was the primary source accessed for literature retrieval. The OVID or SilverPlatter interfaces were used in preference to the freely accessed PubMed interface. The Cochrane Library, embase, cinahl and psycinfo databases were also frequently used by the organizations. All organizations reported the intention to improve and validate their filters for finding literature specifically relevant for guidelines. Discussion: In the first international survey of its kind, eight major guideline development organizations indicated a strong interest in identifying, improving and standardizing search filters to improve guideline development. It is to be hoped that this will result in the standardization of, and open access to, search filters, an improvement in literature searching outcomes and greater collaboration among guideline development organizations.

Background: To investigate the role of self-sampling for human papillomavirus (HPV) testing as an alternative to cervical cancer screening by clinicians (i.e., Papanicolaou [Pap] test). Methods: A systematic search of MEDLINE, EMBASE, Cochrane Library, and other sources for evidence related to the efficacy and feasibility of HPV DNA self-collection. Results: A total of 25 studies were identified. In 22 comparisons across 19 studies, the concordance between samples collected by patients and those obtained by clinicians was reasonably high in the majority of cases. Women in many countries across wide age ranges were successful in collecting samples for HPV DNA testing. In four studies, the quality of the cytology from patient samples was as good as clinician samples, with more than 95% of samples yielding HPV DNA results. The studies that examined acceptability found that women were generally very positive about collecting their own samples, although some concerns were noted. No study evaluated the effect of HPV DNA self-sampling on screening participation rates, early detection, survival, or quality of life. Conclusions: Self-sampling for HPV DNA testing is a viable screening option, but there is insufficient evidence to conclude that self-sampling for HPV DNA testing is an alternative to the Pap test. Although HPV DNA testing using self-collected samples holds promise for use in under-resourced areas or for women who are reluctant to participate in Pap testing programs, the evidence supporting it is limited. Further definitive research is needed to provide a solid evidence base to inform the use of self-sampling for HPV DNA testing for the purpose of increasing screening rates, especially in women who are never or seldom screened. Resume

Through systematic literature review and a consensus-based approach from an expert panel, standards on the organization for delivering thoracic cancer surgery in a single-payer healthcare environment were developed. Thirty-two studies and six organizational reports were identified. Results from 32 studies showed a trend toward higher volumes and improved patient outcomes, and six consensus reports provided recommendations on thoracic care standards. Thoracic surgical oncology standards in a single-payer healthcare system were developed. The benefits associated with the implementation of thoracic cancer surgery standards should result in increased regionalization of care, improved processes of care, and better patient outcomes.

To determine the front-line chemotherapeutic options for women with recurrent, metastatic, or persistent cervical cancer. The Medline, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing chemotherapy regimens for patients with recurrent, metastatic, or persistent cervical cancer. Studies were included if response rate, survival, toxicity, or quality of life data were reported. Fifteen RCTs were identified. The proportion of patients with prior chemoradiotherapy ranged from 0% to 57%. Four of the 15 RCTs detected significant improvements in overall response with combination cisplatin-based chemotherapy when compared with single-agent cisplatin. One of the 15 RCTs reported a significant median survival advantage with topotecan and cisplatin when compared with single-agent cisplatin (9.4 vs 6.5 months,P= 0.017); 57% of patients in this trial had previous chemoradiotherapy. Significant increases in grade 3 and 4 adverse events, especially severe hematologic toxicities, were detected among patients treated with that combination of chemotherapy. Thus, we conclude that cisplatin and topotecan should be discussed as a reasonable treatment option for appropriate patients who may wish to maximize the response and survival benefits associated with combination chemotherapy. Patients should understand that prior chemoradiotherapy with cisplatin may moderate the benefits observed, and that the relative benefits in response and survival outcomes come at the expense of increased toxicity. The improvement in median survival of 2.9 months represents a novel survival benefit in this difficult-to-treat patient population. Further randomized trials are needed to inform the role of single-agent or combination chemotherapy regimens, particularly in patients with prior chemoradiotherapy.

Objective. To determine the optimum follow-up of women who are clinically disease-free following potentially curative treatment for endometrial cancer. Methods. A systematic search of MEDLINE, EMBASE and the Cochrane Library databases (1980 to October 2005) was conducted. Data were pooled across trials to determine overall estimates of recurrence patterns. Results. Sixteen non-comparative retrospective studies were identified. The overall risk of recurrence was 13% for all patients and 3% or less for patients at low risk. Approximately 70% of all recurrences were symptomatic, and 68% to 100% of recurrences occurred within approximately the first 3 years of follow-up. No reliable differences in survival were detected between patients with symptomatic or asymptomatic recurrences nor were differences in patient outcomes reported by type of follow-up strategy employed. Detection of asymptomatic recurrences ranged from 5% to 33% of patients with physical examination, 0% to 4% with vaginal vault cytology, 0% to 14% with chest X-ray, 4% to 13% with abdominal ultrasound, 5% to 21% with abdominal/pelvic CT scan, and 15% in selected patients with CA 125. Conclusions. There is limited evidence to inform whether intensive follow-up schedules with multiple routine diagnostic interventions result in survival benefits any more or less than non-intensive follow-up schedules without multiple routine diagnostic interventions. Routine testing seems to be of limited benefit for patients at low risk of disease. Most recurrences tend to occur in high risk patients within 3 years, and most recurrences involve symptoms. The most appropriate follow-up strategy is likely one based upon the risk of recurrence and the natural history of the disease. Counseling on the potential symptoms of recurrence is extremely important because the majority of patients with recurrences were symptomatic. A proposed routine follow-up schedule is offered.

Objective. To evaluate the chemotherapeutic options for women with advanced or recurrent endometrial cancer. Methods. The MEDLINE, CANCERLIT and the Cochrane Library databases were searched from 1984 to March 2005 for randomized controlled trials (RCTs) comparing chemotherapy regimens in patients with advanced or recurrent endometrial cancer. Studies were included only if patients had measurable or evaluable disease, and/or response rates were reported. Results. Seventeen RCTs compared regimens involving chemotherapy and/or hormonal therapies. Three chemotherapy trials demonstrated a statistically significant difference in response rates between treatment arms, but only one of these trials showed a modest survival advantage. The addition of cisplatin to doxorubicin in two RCTs significantly improved response rates (1.7- to 2.5-fold higher) but did not impact on survival. In two other RCTs using cisplatin and doxorubicin as standard therapy, the addition of paclitaxel improved response rates (57% versus 34%) and median survival (15.3 versus 12.3 months) when combined with cisplatin and doxorubicin but not when combined with doxorubicin only. Toxicity was increased with the three-drug combination. Quality of life was assessed in one trial, which is currently only in abstract form. Medroxyprogesterone acetate (200 mg/day) was effective in one RCT, particularly in patients with well-differentiated, receptor-positive tumors. Conclusions. Combination chemotherapy with doxorubicin and cisplatin results in higher response rates than doxorubicin alone. The addition of paclitaxel to either of these regimens resulted in a small survival advantage in one trial using all three drugs. In light of the limited survival advantage associated with this regimen, the use of less toxic combinations of taxanes with carboplatin requires further study. Medroxyprogesterone acetate is useful in selected patients.

The addition of concurrent chemotherapy (CT) to standard radiotherapy (RT) for locoregional treatment has been established to improve overall survival in a variety of solid tumors. Among the many CT regimens evaluated in combination with RT in randomized controlled clinical trials and summarized in meta-analyses, platinum-containing regimens have consistently shown a survival benefit across tumor types. Cisplatin and carboplatin have been studied both as single agents and in combination with other cytotoxic drugs, concurrently with RT, but the optimal platinum-based regimen to be combined with RT continues to be explored with further investigation. In this article, the role of platinum-based CT as part of concurrent CT/RT will be discussed using 2 tumor sites in the aerodigestive tract as a paradigm: squamous-cell carcinomas of the head and neck and esophageal carcinomas. For each tumor type, we will review the state of the evidence and comment on the current state of practice and on future directions for clinical research in combined modality CT/RT.

Prostate cancer is the second leading cause of cancer death among American men.1,2 Recent epidemiologic trends have shown a lower proportion of men diagnosed with advanced prostate cancer and a steady decrease in prostate cancer mortality rates, with an estimated number of deaths exceeding 30,000 deaths in 20113 and 28,000 in 2012.4 Whether prostate cancer screening with prostate-specific antigen (PSA) testing is a potential explanation for these trends is uncertain. What is known, on the basis of two large and moderate quality randomized trials, is that men tested for PSA had significantly more prostate cancer detected when compared with men who did not receive PSA testing.5,6 To date, this has resulted in a significant reduction in prostate cancer–specific mortality in one of the randomized trials,6 but no difference in overall mortality detected in either of the trials.5,6 There are well-known limitations associated with the randomized trials7–9; however, they currently represent the best evidence on the topic. Recommendations from major organizations in the United States vary widely on the topic of PSA testing for prostate cancer screening.10–15 The rationale for PSA testing is the detection of prostate cancer at a stage that is potentially curable. There is evidence of an approximate 20% reduction in prostate-specific mortality over time, but the extent to which PSA screening may play a role is unclear.6 It is difficult to predict for individual men whether treatment of prostate cancer identified through screening will lead to this benefit. For many men, it will not. Approximately three out of four elevated PSA test results turn out to be false positive for prostate cancer. In one trial, approximately 167 men out of 1,000 underwent a biopsy after an elevated PSA; of those, approximately 127 did not have prostate cancer.6 The adverse effects associated with prostate biopsies are generally manageable; however, they are on the rise, especially infection-related hospitalizations, and death is a very small but real possibility.16,17 For those who do have prostate cancer, a large proportion will ultimately be diagnosed and treated for low-risk disease that may not have presented itself clinically during their lifetimes. Thus, with benefit for some (lower prostate cancer–specific mortality) and harm for others (overdiagnosis, overtreatment, and adverse events), it is important for physicians and their patients to consider whether to have PSA levels tested and to determine the likely course of action if the PSA level is suspicious for prostate cancer. Options include doing nothing, checking PSA again at a certain time point, or undergoing a prostate biopsy. Men's clinician-informed choices should depend largely on their values and preferences and how they weigh the available information. Recommendations ASCO's PSA Testing Expert Panel based their recommendations on a systematic review of recent (March 2012) evidence on the benefits and harms of PSA-based screening. Journal of Clinical Oncology (JCO) published the Provisional Clinical Opinion (PCO) in July 2012.18 The Bottom Line Box includes the recommendations from the PCO with permission from JCO. A decision aid and PowerPoint slide set are available as Data Supplements to this article and through the ASCO Web site at www.asco.org/pco/psa. Authors The PSA Testing for Prostate Cancer Screening PCO was developed and written by Ethan Basch, Thomas K. Oliver, Andrew J. Vickers, Ian Thompson, Philip W. Kantoff, Howard L. Parnes, Andrew Loblaw, Bruce J. Roth, Jim Williams, and Robert K. Nam THE BOTTOM LINE PSA SCREENING FOR PROSTATE CANCER: ASCO PROVISIONAL CLINICAL OPINION Clinical Question For asymptomatic men in the general population, do the benefits of PSA screening for prostate cancer outweigh the potential harms? Population of Interest Asymptomatic men from the general population considering PSA-based screening for prostate cancer. Target Audience Primary health care providers and asymptomatic men from the general population are the primary audience; however, it also applies to oncologists and other health care providers who treat patients for whom this PCO may apply. Interventions and Comparisons As part of prostate cancer screening for asymptomatic men in the general population: PSA testing compared with no PSA testing. Recommendations Based on the identified evidence and the expert opinion of the panel: In men with a life expectancy ≤ 10 years,* it is recommended that general screening for prostate cancer with total PSA be discouraged, because harms appear to outweigh potential benefits. Type and strength of recommendation: evidence-based, strong Strength of evidence: Moderate, based on five randomized controlled trials (RCTs) with intermediate to high risk of bias, moderate follow-up, and limited data on subgroup populations In men with a life expectancy >10 years*, it is recommended that physicians discuss with their patients whether PSA testing for prostate cancer screening is appropriate for them. PSA testing may save lives but is associated with harms, including complications, from unnecessary biopsy, surgery, or radiation treatment. Type and strength of recommendation: evidence-based, strong Strength of evidence: for benefit, moderate; for harm, strong; based on five five RCTs (and several cohort studies) with intermediate to high risk of bias, moderate follow-up, indirect data, inconsistent results, and limited data on subgroup populations It is recommended that information written in lay language be available to clinicians and their patients to facilitate the discussion of the benefits and harms associated with PSA testing prior to the routine ordering of a PSA test. Type and strength of recommendation: Informal consensus, strong Strength of evidence: Indeterminate. Evidence was not systematically reviewed to inform this recommendation; however, randomized trials are available on the topic * Calculation of life expectancy is based on a variety of individual factors and circumstances. A number of life expectancy calculators (eg, http://www.socialsecurity.gov/OACT/population/longevity.html) are available in the public domain; however, ASCO does not endorse any one calculator over another.

Purpose To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). Methods The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. Results When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 (223Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. Recommendations Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or 223Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to evaluate optimal sequences or combinations of therapies. Palliative care should be offered to all patients.

This study aims to provide recommendations on the optimal strategies and interventions for the prevention, screening, assessment, and management of cancer-related sleep disturbance (insomnia and insomnia syndrome) in adult cancer populations.A systematic search of the published health literature was conducted to identify randomized controlled trials, clinical practice guidelines, systematic reviews, and other guidance documents. The Sleep Disturbance Expert Panel [comprised of nurses, psychologists, primary care physicians, oncologists, physicians specialized in sleep disturbances, researchers, and guideline methodologists] reviewed, discussed, and approved the final version of the guideline. Health care professionals across Canada were asked to provide feedback through an external review process.Three clinical practice guidelines and 12 randomized controlled trials were identified as the evidence base. Overall, despite the paucity of evidence, the evidence and expert consensus suggest that it is important to screen and assess adult cancer patients for sleep disturbances using standardized screening tools on a routine basis. While prevention of sleep disturbance is the desired objective, cognitive behavioral therapies are effective in improving sleep outcomes. As part of the external review with 16 health care providers, 81 % indicated that they agreed with the recommendations as written.Sleep difficulty is a prevalent problem in cancer populations that needs greater recognition by health professionals. Prevention, screening, assessment, and treatment strategies supported by the best available evidence are critical. Recommendations and care path algorithms for practice are offered.

In Canada, approximately 4,400 women are diagnosed with endometrial cancer each year and approximately 800 die from the disease [1]. The majority of patients present with early-stage disease and this is reflected in an overall 5-year survival rate of approximately 85 % [1]. Five-year survival rates range from approximately 96 % for patients with local disease, 66 % for those with regional disease, and 25 % for those with more advanced disease [2]. Factors predictive of recurrence and survival include lymph node status, histological type, histological grade, stage of disease, depth of myometrial invasion, lymphovascular space involvement, and cervical involvement [3].

Cervical cancer is the second most common cancer worldwide, resulting in approximately 275,000 deaths yearly [1]. In Canada, approximately 1,350 Canadian women are diagnosed annually, and approximately 400 women per year die from their disease [2]. According to the SEER database, approximately 50 % of patients are diagnosed with local disease (stage IA or IB) that is confined to the cervix, while 35 % are diagnosed with locoregional disease that has extended beyond the cervix but not to the pelvic wall or the lower third of the vagina (stage IIA or IIB). The remaining patients represent those with more advanced disease (stage III or IV) that has spread to the lower third of the vagina, the pelvic wall, or beyond (11 %). For a small proportion of patients (5 %), staging information was not available [3]. The 5-year survival rates were approximately 92 % for patients with local disease, 58 % with locoregional disease, and 17 % with distant disease [3].

Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer. Clinical Context Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection. Recent Data Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic. Results In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern. Provisional Clinical Opinion On the basis of identified evidence and the expert opinion of the panel ( Table 1 provides a description of how recommendations and evidence are rated): In men with a life expectancy ≤ 10 years,* it is recommended that general screening for prostate cancer with total PSA be discouraged, because harms seem to outweigh potential benefits. Type and strength of recommendation. Evidence based: strong. Strength of evidence. Moderate: based on five randomized clinical trials (RCTs) with intermediate to high risk of bias, moderate follow-up, and limited data on subgroup populations. In men with a life expectancy > 10 years,* it is recommended that physicians discuss with their patients whether PSA testing for prostate cancer screening is appropriate for them. PSA testing may save lives but is associated with harms, including complications, from unnecessary biopsy, surgery, or radiation treatment. Type and strength of recommendation. Evidence based: strong. Strength of evidence. For benefit, moderate; for harm, strong: based on five RCTs (and several cohort studies) with intermediate to high risk of bias, moderate follow-up, indirect data, inconsistent results, and limited data on subgroup populations. It is recommended that information written in lay language be available to clinicians and their patients to facilitate the discussion of the benefits and harms associated with PSA testing before the routine ordering of a PSA test. Type and strength of recommendation. Informal consensus: strong. Strength of evidence. Indeterminate: evidence was not systematically reviewed to inform this recommendation; however, randomized trials are available on the topic. *Calculation of life expectancy is based on a variety of individual factors and circumstances. A number of life expectancy calculators (eg, http://www.socialsecurity.gov/OACT/population/longevity.html) are available in the public domain; however, ASCO does not endorse any one calculator over another. NOTE. ASCO PCOs reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical practice and cannot be assumed to apply to the use of these interventions in the context of clinical trials. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO PCOs or for any errors or omissions.

Context Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. Objective To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. Data Sources MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). Study Selection Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. Data Extraction Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. Results Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53 454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 247 vs 309 events per 100 000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. Conclusion Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

The impact of cancer and cancer treatment on the long-term health and quality of life of survivors is substantial, leading to questions about the most appropriate configuration of services and models of care for follow-up of post-primary treatment survivors. A systematic review and quality appraisal of the health literature for structure of services and models of follow-up care for post-treatment survivors was identified through a search of guideline sources and empirical databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Library, CINAHL, and EBSCO from 1999 through December 2009. Ten practice guidelines and nine randomized controlled trials comprised the evidence base for models of care for adult cancer survivors. Although the evidence base was rated as low quality, nurse-led and primary care physician models of follow-up care were equivalent for detecting recurrence. Consensus also suggests that cancer survivors may benefit from coordinated transition planning that includes the provision of survivorship care plans as part of standard care. Realignment of models of care is identified as a health system priority to meet the supportive care and surveillance needs of a burgeoning survivor population. Further research is needed to evaluate the efficacy of models of care in a broader population of cancer survivors with differing needs and risks. While the evidence is limited, there is research that may be used to guide the configuration of health care services and planning.

The Inventory of Cancer Guidelines (ICG) was designed to mitigate challenges associated with inconsistencies in the quality of cancer guidelines, keeping guidelines current and the duplication of effort in guideline development. The ICG is a searchable database of quality-appraised guidelines in cancer control that also includes designations of guidelines in progress, those in need of an update and those currently being updated. From a clinical perspective, the majority of the completed guidelines target breast, lung, colorectal and prostate cancers, and focus on the treatment stage of the cancer continuum. There is considerable variability in guideline quality both within and across guideline developers, as measured by the Appraisal of Guidelines for Research and Evaluation II. Quality domains of applicability and editorial independence are the guideline quality domains that score the poorest. While the ability to inform on the status of cancer control guidelines is important, the real potential of the ICG is in its ability to leverage positive change in the guideline enterprise. Pilot projects are underway to use data from the ICG to tailor audit and feedback interventions for guideline developers and to pursue collaborative updating and guideline adaptation initiatives, using the ICG as the platform from which these partnerships can evolve.

Objective To determine the optimal recommended program for the follow-up of patients who are disease free after completed primary therapy for cervical cancer. Methods Systematic search of MEDLINE, EMBASE and the Cochrane Library databases (1980–November 2007). Results Seventeen retrospective trials were identified. Most studies reported similar intervals for follow-up and ranged from a low of 9 visits to a high of 28 visits over 5 years. Follow-up visits typically occurred once every 3–4 months for the first 2 years, every 6 months for the next 3 years and then annually until year 10. All 17 trials reported that a physical exam was performed at each visit. Vaginal vault cytology was analyzed in 13 trials. Other routine surveillance tests included chest x-ray, ultrasound, CT scans, MRI, intravenous pyelography and tumour markers. Median time to recurrence ranged from 7–36 months after primary treatment. Rates of recurrence ranged from 8–26% with 14–57% of patients recurring in the pelvis, and 15–61% of patients recurring at distant or multiple sites. Of the 8–26% of patients who experienced disease recurrence, the vast majority, 89–99%, had recurred by year 5. Upon recurrence, median survival was 7–17 months. Asymptomatic recurrent disease was detected using physical exam in 29–71%, chest x-ray in 20–47%, CT in 0–34% and vaginal vault cytology in 0–17% of patients, respectively. Conclusion There is modest low quality evidence to inform the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease free after receiving primary treatment. Follow-up visits should include a complete physical examination whereas, frequent vaginal vault cytology does not add significantly to the detection of early disease recurrence. Patients should return to annual population-based screening after 5 years of recurrence-free follow-up.

What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer. Reports were sought that included at least one of the following outcomes: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest. The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (dsg). Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These differences in baseline characteristics between the randomized groups were considered to be clinically important. In addition, the results of that trial were not consistent with those of other trials, and the trial was a source of statistical heterogeneity when data were pooled across trials. In two of the nine randomized trials, statistically significant recurrence-free benefits were detected with adjuvant hormonal therapy as compared with no further therapy. In one trial, the difference between the rates of recurrence was 16%, however, the methodologic concerns related to that that trial limited its relevance. In the other trial, the difference between the rates of recurrence was 5%. In that trial, patients were at a high risk of recurrence. None of the remaining seven randomized trials reported any significant difference in recurrence rates between treatment groups. The meta-analysis identified in the literature detected no statistically significant recurrence-free or overall survival benefit associated with adjuvant hormonal therapy as compared with no adjuvant therapy [odds ratio (or): 1.05, 95% confidence interval (ci): 0.88 to 1.24). Those results are consistent with the results of the meta-analysis in the present report, which included an additional two trials (or: 1.10, 95% ci: 0.91 to 1.34).

What is the optimal chemotherapy treatment for women with recurrent ovarian cancer who have previously received platinum-based chemotherapy? Currently, standard primary therapy for advanced disease involves a combination of maximal cytoreductive surgery and chemotherapy with carboplatin plus paclitaxel or with carboplatin alone. Despite initial high response rates, a large proportion of patients relapse, resulting in a therapeutic challenge. Because these patients are not curable, the goal of therapy becomes improvement in both quality and length of life. The search has therefore been to find active agents for women with recurrent disease following platinum-based chemotherapy. Outcomes of interest included any combination of tumour response rate, progression-free survival, overall survival, adverse events, and quality of life. The medline, embase, and Cochrane Library databases were systematically searched for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. The systematic review and recommendations were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (dsg). The practice guideline was externally reviewed by a sample of practitioners from Ontario, Canada. Thirteen randomized trials compared various chemotherapy regimens for patients with recurrent ovarian cancer. In five of the thirteen trials in which 100% of patients were considered sensitive to platinum-containing chemotherapy, further platinum-based combination chemotherapy significantly improved response rates (two trials), progression-free survival (four trials), and overall survival (three trials) when compared with single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these randomized trials compared the same chemotherapy regimens: carboplatin alone versus the combination of carboplatin and paclitaxel. Both trials were consistent in reporting improved survival outcomes with the combination of carboplatin and paclitaxel. In one trial, the combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. Median survival with carboplatin alone ranged from 17 months to 24 months in four trials. In eight of the thirteen trials in which 35%&ndash, 100% of patients had platinum-refractory or -resistant disease, one trial reported a statistically significant 2-month improvement in overall survival with liposomal doxorubicin as compared with topotecan (15 months vs. 13 months, p = 0.038, hazard ratio: 1.23, 95% confidence interval: 1.01 to 1.50). In that trial, because of the limited clinical benefit and the unusual finding that a survival difference emerged only after a year of treatment with no corresponding improvement in the rate of response or of progression-free survival, the authors concluded that further confirmation by results from randomized trials were needed to establish the superiority of one agent over another in their trial. In one trial, topotecan was superior to treosulphan in patient progression-free survival by a span of approximately 2 months (5.4 months vs. 3.0 months, p < 0.001). Toxicity was reported in all of the randomized trials, and although data on adverse events varied by treatment regimen, the observed adverse events correlated with known toxicity profiles. As expected, combination chemotherapy was associated with higher rates of adverse events.

Objective To develop clinical practice guidelines for cervical screening and the primary management of abnormal cytology in Ontario, using an established methodological process. Data Sources Primary data sources were relevant articles listed in the Medline (1998 to July 2004), Embase (1998 to July 2004), and Cochrane Library (2004, Issue 2) databases. Study Selection Studies addressing quality or the optimization of cervical screening were considered eligible in the systematic review of the evidence. Specifically, clinical practice guidelines, technology assessments, systematic reviews, and randomized controlled trials were of primary interest. Given the variability of the data, other information sources were considered eligible if there was a demonstrated gap in the published literature. Data Extraction Data were identified and extracted by a methodologist and reviewed by four authors. Results were reviewed and discussed by members of an expert working group consisting of a diverse group of health professionals with expertise in cervical cancer. Data audits were conducted by independent reviewers. Data Synthesis Recommendations with evidence ratings were developed through a review of the evidence with expert consensus and were approved by more than 80% of 40 external practitioners who reviewed the document and responded to a standardized survey. Conclusion The development of comprehensive recommendations on cervical screening in Ontario was feasible using a rigorous methodological process. Recommendations for practice are provided.

Because women with advanced ovarian cancer have poor outcomes, it is imperative to continue exploring for novel therapies. The opportunity for intraperitoneal treatment, especially in the subgroup of patients with minimal residual disease, in which the intraperitoneal approach may have a biologic rationale for benefit over and above the standard intravenous route, needs to be explored to the fullest extent. The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2006 for randomized trials that compared first-line intraperitoneal-containing chemotherapy with first-line intravenous chemotherapy in the treatment of women with stage III epithelial ovarian cancer. Seven randomized, controlled trials were identified, including 3 large Phase III trials and 4 smaller randomized trials. The 3 large Phase III trials detected statistically significant overall survival benefits with intraperitoneal cisplatin-containing chemotherapy compared with intravenous chemotherapy alone. The improvements in survival were 8 months, 11 months, and 16 months, respectively. Pooled analysis from 6 of the 7 randomized trials confirmed the survival effect with intraperitoneal chemotherapy compared with intravenous chemotherapy alone (relative risk, 0.88; 95% confidence interval, 0.81-0.95). Severe adverse events and catheter-related complications with intraperitoneal chemotherapy were significantly more common and often were dose-limiting. The results from this review indicated that cisplatin-containing intraperitoneal chemotherapy should be offered to patients on the basis of significant improvements in overall survival. The appropriate clinical and institutional multidisciplinary facilities are needed for the safe delivery of this treatment in optimally debulked patients. Further research is needed concerning specific aspects of the treatment, such as optimal agent, dose, and scheduling.

Methods In an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR-group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection. Results ARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-γ enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001). Conclusions An increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime-boost regimens and/or additional target antigens. Trial Registration ClinicalTrials.gov NCT01366534

Background. This systematic review evaluates the use of postoperative chemoradiotherapy for patients with advanced (stage III or IV) squamous cell carcinoma of the head and neck at a high risk of recurrence. Methods. The literature was systematically searched for eligible randomized controlled trials (RCTs). Results. Of 4 RCTs identified, 3 reported improvements in locoregional control, 3 reported improved disease-free or progression-free survival, and 3 reported improved overall survival with chemoradiotherapy compared with radiotherapy alone. Pooling trials confirmed the benefit for chemoradiotherapy in locoregional recurrence (relative risk [RR] = 0.59; 95% confidence interval [CI] = 0.47–0.75; p < .00001) and overall survival (RR = 0.80; 95% CI = 0.71–0.90; p = .0002). More frequent and severe acute mucosal toxicity was reported with combined treatment. Conclusions. Postoperative adjuvant chemoradiotherapy is superior to radiotherapy alone. Because chemoradiotherapy is associated with significantly increased toxicity, further investigations to identify patients most likely to benefit or toxicity reduction strategies are warranted. © 2006 Wiley Periodicals, Inc. Head Neck 2007

Objectives. To evaluate the role of intraperitoneal (IP) chemotherapy as part of primary treatment in patients with advanced ovarian cancer and to develop standards of care within the context of current clinical practice. Methods. A multidisciplinary expert panel, convened to develop standards on the use of IP chemotherapy, searched the MEDLINE, EMBASE, and Cochrane Library databases up to December 2006 for randomized trials or published standards on the efficacy and/or delivery of IP chemotherapy. Results. Eight randomized trials comparing IP chemotherapy versus intravenous (IV) chemotherapy were identified. Three trials reported statistically significant improvements in median survival of 8.0, 11.0, and 15.9 months with cisplatin-based IP chemotherapy. In one trial, the 15.9-month improvement in median overall survival (RR=0.75, 95% CI=0.58–0.97) represented a 25% reduction in the risk of death with IP chemotherapy. Severe adverse events and catheter-related complications were often dose limiting with IP chemotherapy. Using a consensus-based approach with a nationally representative panel, multidisciplinary care standards were developed to review medical and surgical criteria, the practice setting, volume requirements, and the institutional criteria required to safely deliver IP chemotherapy. Conclusion. The survival benefits with cisplatin-based IP chemotherapy may represent a significant improvement in the outlook for select patients with advanced ovarian cancer. The delivery of IP chemotherapy is more challenging than the IV route; however, severe adverse events and catheter-related complications may be offset through research defining the optimum treatment regimen, and the standardization of care. System-wide standards for the delivery of IP chemotherapy in Canada for patients with optimally debulked stage III ovarian cancer are offered.

The article by Abenhaim and colleagues in this issue presents an interesting case–control study that attempts to determine the risk of ovarian cancer associated with health care use by comparing the medical history of women with and without ovarian cancer.[1][1] In this large study, 668 women with

* Abbreviations: ABP = : American Board of Pediatrics • ITE = : in-training examination • US = : United States • med/peds = : medicine/pediatrics • AMG = : American medical school graduate • LCME = : Liaison Committee for Medical Education • AOA = : American Osteopathic Association • RCPSC = : Royal College of Physicians and Surgeons of Canada • IMG = : international medical school graduate • ABIM = : American Board of Internal Medicine For a number of years, the American Board of Pediatrics (ABP) has gathered work force data using questionnaires administered in association with its various examinations. These data provide important information regarding trainees and practitioners in pediatrics; such information is particularly useful during this era of health care change and debate. The data presented in this report are based on questionnaire results from three sets of examinations: the in-training examination (ITE) administered to residents during their training, the certifying examination for general pediatrics, and the pediatric subspecialty certifying examinations. The ITE is offered to all accredited programs in the United States (US) and Canada. It is a half-day examination administered during the same week in early July at all program sites. Only residents in pediatric levels 1 through 3 (PL-1 through PL-3) years of training in categorical pediatric programs may take the examination. Residents in internal medicine/pediatrics (med/peds) 4-year dual training programs, as well as three other smaller, 5-year dual training programs (with the American Board of Psychiatry and Neurology, the American Board of Emergency Medicine, and the American Board of Physical and Rehabilitative Medicine), are permitted to take the ITE during each year of training. Demographic and work force data are obtained by appending several relevant questions to the examination registration form. Candidates who apply to take the General Pediatrics Certifying Examination for the first time are asked to complete a short questionnaire about their career intentions. Similarly, candidates who apply for the first time to take 1 of 12 subspecialty certifying examinations in pediatrics are asked to complete a separate set of demographic and work force questions. ### In-training Examination There are currently 213 accredited categorical pediatric training programs in the US and 16 accredited programs in Canada. In 1995, all but one of these 229 programs participated in the ITE. Because …

Background While the number of internal medicine–pediatrics (med/peds) residency training programs has increased considerably in the past decade, questions continue to be raised about career paths of the graduates of these programs. It is uncertain whether med/peds graduates follow a generalist career path and whether they continue to practice both specialties. Objective To determine the career outcomes of graduates of med/peds residency programs. Design A survey questionnaire of graduates of med/peds residency programs. Methods The computer databases of the American Board of Pediatrics and the American Board of Internal Medicine were used to identify 1482 individuals who had completed training in combined med/peds residency programs between 1986 and 1995 and who had applied to either board for certification. The survey questionnaire was mailed to all graduates identified. Main Outcome Measures Time spent in professional activity (patient care, teaching, administration, and research), site of principal clinical activity, ages of the patient population, types of hospital privileges, practice organization, subspecialty activity, night and weekend coverage arrangements, community size of practice, involvement in teaching, and membership in professional organizations. Results Of the total group of 1482 graduates, 87.3% are certified by the American Board of Internal Medicine, 91.3% by the American Board of Pediatrics, and 81.6% by both boards. The survey was completed by 1005 graduates (67.8%). The principal activity of almost 70% of the graduates was direct patient care. Most graduates cared for patients of all ages. More than half of all respondents noted that their principal clinical site is a community office practice. Eighty-five percent managed patients who require hospitalization. Approximately 50% of respondents had a medical school appointment. Conclusions This study, the largest survey to date of med/peds graduates, provides strong evidence that most med/peds graduates are practicing generalists who care for adults and children. In addition, the fact that 80% of graduates achieve dual board certification suggests that these physicians are well qualified to care for the spectrum of health care needs of children and adults. Because the changing US health care system mandates a strong primary care base, these physicians will play a small but important role in providing high-quality generalist care.