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Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care’s update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development. Recommendations New or revised recommendations include the following. Regarding first-line treatment for patients with non–squamous cell carcinoma or squamous cell carcinoma (without positive markers, eg, EGFR/ALK /ROS1), if the patient has high programmed death ligand 1 (PD-L1) expression, pembrolizumab should be used alone; if the patient has low PD-L1 expression, clinicians should offer standard chemotherapy. All other clinical scenarios follow 2015 recommendations. Regarding second-line treatment in patients who received first-line chemotherapy, without prior immune checkpoint therapy, if NSCLC tumor is positive for PD-L1 expression, clinicians should use single-agent nivolumab, pembrolizumab, or atezolizumab; if tumor has negative or unknown PD-L1 expression, clinicians should use nivolumab or atezolizumab. All immune checkpoint therapy is recommended alone plus in the absence of contraindications. For patients who received a prior first-line immune checkpoint inhibitor, clinicians should offer standard chemotherapy. For patients who cannot receive immune checkpoint inhibitor after chemotherapy, docetaxel is recommended; in patients with nonsquamous NSCLC, pemetrexed is recommended. In patients with a sensitizing EGFR mutation, disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy, and T790M mutation, osimertinib is recommended; if NSCLC lacks the T790M mutation, then chemotherapy is recommended. Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.

Purpose To provide evidence-based recommendations to oncology clinicians, patients, family and friend caregivers, and palliative care specialists to update the 2012 American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) on the integration of palliative care into standard oncology care for all patients diagnosed with cancer. Methods ASCO convened an Expert Panel of members of the ASCO Ad Hoc Palliative Care Expert Panel to develop an update. The 2012 PCO was based on a review of a randomized controlled trial (RCT) by the National Cancer Institute Physicians Data Query and additional trials. The panel conducted an updated systematic review seeking randomized clinical trials, systematic reviews, and meta-analyses, as well as secondary analyses of RCTs in the 2012 PCO, published from March 2010 to January 2016. Results The guideline update reflects changes in evidence since the previous guideline. Nine RCTs, one quasiexperimental trial, and five secondary analyses from RCTs in the 2012 PCO on providing palliative care services to patients with cancer and/or their caregivers, including family caregivers, were found to inform the update. Recommendations Inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment. Referral of patients to interdisciplinary palliative care teams is optimal, and services may complement existing programs. Providers may refer family and friend caregivers of patients with early or advanced cancer to palliative care services.

Purpose To update the 2006 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSFs). Methods The American Society of Clinical Oncology convened an Update Committee and conducted a systematic review of randomized clinical trials, meta-analyses, and systematic reviews from October 2005 through September 2014. Guideline recommendations were based on the review of the evidence by the Update Committee. Results Changes to previous recommendations include the addition of tbo-filgrastim and filgrastim-sndz, moderation of the recommendation regarding routine use of CSFs in older patients with diffuse aggressive lymphoma, and addition of recommendations against routine dose-dense chemotherapy in lymphoma and in favor of high–dose-intensity chemotherapy in urothelial cancer. The Update Committee did not address recommendations regarding use of CSFs in acute myeloid leukemia or myelodysplastic syndromes in adults. Recommendations Prophylactic use of CSFs to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of febrile neutropenia in patients who are at high risk on the basis of age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. Dose-dense regimens that require CSFs should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death as a result of injury to other organs, include the prompt administration of CSFs.

Purpose Previous studies report that early palliative care is associated with clinical benefits, but there is limited evidence on economic impact. This article addresses the research question: Does timing of palliative care have an impact on its effect on cost? Patients and Methods Using a prospective, observational design, clinical and cost data were collected for adult patients with an advanced cancer diagnosis admitted to five US hospitals from 2007 to 2011. The sample for economic evaluation was 969 patients; 256 were seen by a palliative care consultation team, and 713 received usual care only. Subsamples were created according to time to consult after admission. Propensity score weights were calculated, matching the treatment and comparison arms specific to each subsample on observed confounders. Generalized linear models with a γ distribution and a log link were applied to estimate the mean treatment effect on cost within subsamples. Results Earlier consultation is associated with a larger effect on total direct cost. Intervention within 6 days is estimated to reduce costs by −$1,312 (95% CI, −$2,568 to −$56; P = .04) compared with no intervention and intervention within 2 days by −$2,280 (95% CI, −$3,438 to −$1,122; P < .001); these reductions are equivalent to a 14% and a 24% reduction, respectively, in cost of hospital stay. Conclusion Earlier palliative care consultation during hospital admission is associated with lower cost of hospital stay for patients admitted with an advanced cancer diagnosis. These findings are consistent with a growing body of research on quality and survival suggesting that early palliative care should be more widely implemented.

Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the integration of palliative care services into standard oncology practice at the time a person is diagnosed with metastatic or advanced cancer. Clinical Context Palliative care is frequently misconstrued as synonymous with end-of-life care. Palliative care is focused on the relief of suffering, in all of its dimensions, throughout the course of a patient's illness. Although the use of hospice and other palliative care services at the end of life has increased, many patients are enrolled in hospice less than 3 weeks before their death, which limits the benefit they may gain from these services. By potentially improving quality of life (QOL), cost of care, and even survival in patients with metastatic cancer, palliative care has increasing relevance for the care of patients with cancer. Until recently, data from randomized controlled trials (RCTs) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving standard oncology care have not been available. Recent Data Seven published RCTs form the basis of this PCO. Provisional Clinical Opinion Based on strong evidence from a phase III RCT, patients with metastatic non–small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care—when combined with standard cancer care or as the main focus of care—leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panel's expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research. NOTE. ASCO's provisional clinical opinions (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 trials and cannot be assumed to apply to the use of these interventions in the context of clinical practice. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions.

Advances in early detection, prevention, and treatment have resulted in consistently falling cancer death rates in the United States. In parallel with these advances have come significant increases in the cost of cancer care. It is well established that the cost of health care (including cancer care) in the United States is growing more rapidly than the overall economy. In part, this is a result of the prices and rapid uptake of new agents and other technologies, including advances in imaging and therapeutic radiology. Conventional understanding suggests that high prices may reflect the costs and risks associated with the development, production, and marketing of new drugs and technologies, many of which are valued highly by physicians, patients, and payers. The increasing cost of cancer care impacts many stakeholders who play a role in a complex health care system. Our patients are the most vulnerable because they often experience uneven insurance coverage, leading to financial strain or even ruin. Other key groups include pharmaceutical manufacturers that pass along research, development, and marketing costs to the consumer; providers of cancer care who dispense increasingly expensive drugs and technologies; and the insurance industry, which ultimately passes costs to consumers. Increasingly, the economic burden of health care in general, and high-quality cancer care in particular, will be less and less affordable for an increasing number of Americans unless steps are taken to curb current trends. The American Society of Clinical Oncology (ASCO) is committed to improving cancer prevention, diagnosis, and treatment and eliminating disparities in cancer care through support of evidence-based and cost-effective practices. To address this goal, ASCO established a Cost of Care Task Force, which has developed this Guidance Statement on the Cost of Cancer Care. This Guidance Statement provides a concise overview of the economic issues facing stakeholders in the cancer community. It also recommends that the following steps be taken to address immediate needs: recognition that patient-physician discussions regarding the cost of care are an important component of high-quality care; the design of educational and support tools for oncology providers to promote effective communication about costs with patients; and the development of resources to help educate patients about the high cost of cancer care to help guide their decision making regarding treatment options. Looking to the future, this Guidance Statement also recommends that ASCO develop policy positions to address the underlying factors contributing to the increased cost of cancer care. Doing so will require a clear understanding of the factors that drive these costs, as well as potential modifications to the current cancer care system to ensure that all Americans have access to high-quality, cost-effective care.

DOI: 10.1200/JCO.2007.15.6208 Mr S takes you aside after his wife enters the chemotherapy room. “Doctor, how much longer is this going to continue? We already sold our house, but the20%copayonour$14,000-a-monthchemotherapy bills (paclitaxel, carboplatin, trastuzamab, and pamidronate) are adding up quickly. I’m glad she’s doing OK, but do you think she’ll last another 3 months? A year? I don’t mean to sound morbid, but I need to plan.” Mrs O is a 72-year-old rural widow on a fixed income and is enrolled in Medicare without supplemental insurance. She has stopped taking her aromatase inhibitor because she reached her “donut hole” of $2,400 for all of her chronic medicines. She searched for the least expensive medication, but 30 tablets of letrozole costs $266, anastrazole costs $279, and exemestane costs $266. Should she go back to generic tamoxifen at $22 per month? (All prices are from www.drugstore.com.). Ms S is a 43-year-old single mother whose metastatic breast cancer is shrinking on sixth-line chemotherapy with fluorouracil, leucovorin, and mitomycin injections 5 days in a row, monthly. She asks if you can do something else instead, because she cannot afford the daily $35 copayment. Your practice is obligated to collect this under insurance law. The breaking of bad news is universal to medicine, and particularly commonplace in oncology. There are several accepted ways to break bad news, including the use of a common format of structured listening to what the patient knows and wants to know, giving information in understandable amounts, reacting to the news, and checking for understanding. One of the most common protocols is the SPIKES protocol: establishing an appropriate setting; checking the patient’s perception; determining the amount of information known, wanted, and to be transferred; knowing the medical facts beforehand; exploring the emotions raised during the interview; and establishing a strategy for support. Alongside clinical bad news, oncologists are increasingly confronted with giving economic bad news. The larger societal issues are well known: medical costs are inflating at a double-digit rate, which is unsustainable. Cancer drug costs to Medicare alone were $5.3 billion in 2004 and are likely much higher today. The cost of individual regimens for metastatic colon cancer has risen from a few hundred dollars to more than $30,000 per year; the added costs of bisphosphonates (up to $1,700 per dose), pegylated filgrastim ($2,700 per dose), diagnostic computed tomography scan ($2,500 per set) or positron emission tomography scan ($3,200 per scan) easily raise the cost of treatment to more than $100,000 per year per patient. Countering this bad news, there are equally important examples of medical good news about successes of new drugs, such as 2 additional months of survival with preserved quality of life using erlotinib (Tarceva [OSI Pharmaceuticals, Melville, NY], $3400 month) compared with placebo for advanced lung cancer. There is growing evidence that patients are feeling the pinch, too. Copayments for some drugs have risen to as much as 20%. For a regimen such as carboplatin, paclitaxel, and bevacizumab for advanced non–small-cell lung cancer, the copay itself could be as much as 20% of $17,000 per month. In one study, the median out-of-pocket expense for 156 women receiving breast cancer therapy was $1,455 per month, and all of these women had some form of health insurance. On a fixed income this is not manageable, and given that this study was published in 2004, the costs are, no doubt, higher today. Additionally, out-of-pocket costs tend to mirror medical expenditures, and we know of several patients in our own practice for whom these issues have become paramount. Patients have sold their homes, tapped other resources such as college funds, switched from aromatase inhibitors (about $270 per month) to tamoxifen (available for as little as $10 per month via the Internet) for breast cancer, asked if the practice can forgo the $35 to $50 copayment for each daily visit, or, too commonly, just stopped coming for treatment. In our own practice, during one short discussion, we quickly named more than a dozen patients whose finances had changed their care options. Some of these issues came to the billing manager, and some large denials from insurance companies came to individual physicians, but we are concerned that most cost issues never came to the attention of the physicians. JOURNAL OF CLINICAL ONCOLOGY T H E A R T O F O N C O L O G Y: When the Tumor Is Not the Target VOLUME 26 NUMBER 25 SEPTEMBER 1 2008

To update the 2004 American Society of Clinical Oncology (ASCO) guideline on initial hormonal management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer (PCa).The writing committee based its recommendations on an updated systematic literature review. Recommendations were approved by the Expert Panel, the ASCO Health Services Committee, and the ASCO Board of Directors.Seven randomized controlled trials (four new), one systematic review, one meta-analysis (new), one Markov model, and one delta-method 95% CI procedure for active controlled trials (new) informed the guideline update.Bilateral orchiectomy or luteinizing hormone-releasing hormone agonists are recommended initial androgen-deprivation treatments (ADTs). Nonsteroidal antiandrogen monotherapy merits discussion as an alternative; steroidal antiandrogen monotherapy should not be offered. Combined androgen blockade should be considered. In metastatic or progressive PCa, immediate versus symptom-onset institution of ADT results in a moderate decrease (17%) in relative risk (RR) for PCa-specific mortality, a moderate increase (15%) in RR for non-PCa-specific mortality, and no overall survival advantage. Therefore, the Panel cannot make a strong recommendation for early ADT initiation. Prostate-specific antigen (PSA) kinetics and other metrics allow identification of populations at high risk for PCa-specific and overall mortality. Further studies must be completed to assess whether patients with adverse prognostic factors gain a survival advantage from immediate ADT. For patients electing to wait until symptoms for ADT, regular monitoring visits are indicated. For patients with recurrence, clinical trials should be considered if available. Currently, data are insufficient to support use of intermittent androgen blockade outside clinical trials

Purpose To update the 1999 American Society of Clinical Oncology (ASCO) guideline on breast cancer follow-up and management in the adjuvant setting. Methods An ASCO Expert Panel reviewed pertinent information from the literature through March 2006. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. Results The evidence supports regular history, physical examination, and mammography as the cornerstone of appropriate breast cancer follow-up. All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination. Examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling. The use of CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose–positron emission tomography scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination. Conclusion Careful history taking, physical examination, and regular mammography are recommended for appropriate detection of breast cancer recurrence.

Purpose To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). Update Methodology The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. Recommendations The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.

PURPOSE: We describe the impact of clinical practice guidelines (CPGs) on improvement in oncology treatment processes or outcomes. METHODS: We performed a comprehensive search of the literature from 1966 to the present and a directed review of the literature. RESULTS: Improvements have been demonstrated in compliance with evidence-based guidelines or evidence-based medicine, and in short-term length of stay, complication rates, and financial outcomes. The data suggest that patient satisfaction can be maintained despite a shorter length of stay. There has been one example of province-wide improvement in disease-free and overall survival of breast cancer patients coincident with the adoption of CPGs. The components of successful guidelines can be summarized as follows: (1) development is based on evidence, with the guideline formulated by key physicians in the group; (2) the guidelines are disseminated to all affected health care professionals for critique; (3) implementation includes direct feedback on performance to physicians or general feedback on system performance; and (4) there is accountability for performance according to the guidelines. This accountability can consist of voluntary peer pressure to conform to evidence-based medicine, and it does not require a financial reward or penalty. CONCLUSION: Some attempts to improve practice have been moderately successful in achievement of reduced health care costs, reduced hospital length of stay, and possibly improved outcomes. Other methods that are still in use have been demonstrated to have little effect. Programs that have not succeeded have relied on voluntary change in practice behavior without incentives to change or have had no accountability component. Further research is needed to assess how guidelines are enacted in organizations other than those demonstrably committed to improvement, ways to improve compliance of health care providers who are not committed to change, and methods to improve accountability.

PURPOSE: To estimate the cost-effectiveness of tamoxifen in the prevention of breast cancer. PATIENTS AND METHODS: Clinical trial results of National Surgical Adjuvant Breast Program P−1 compared tamoxifen versus placebo in the prevention of breast cancer, and direct medical care costs were estimated from the Agency for Health Care Policy and Research and local sources. The base estimate of effectiveness included all women on the trial. RESULTS: For every 100 women treated for 5 years, 1.665 expected cancers would not be detected. If breast cancer death is fully prevented by this strategy, then the cost-effectiveness of tamoxifen compared with no intervention is $8,479 per additional year of life gained. If lifetime prevention of the risk of death from breast cancer exceeded 17%, then the cost-effectiveness ratio would be less than $50,000 per year of life gained (a common benchmark). CONCLUSIONS: Tamoxifen for breast cancer prevention should be cost-effective under nearly all circumstances. Its use will require additional resources because it is not cost saving, but it fits within accepted guidelines.

OBJECTIVE: To determine the most effective, evidence-based, postoperative surveillance strategy for the detection of recurrent colon and rectal cancer. Tests are to be recommended only if they have an impact on the outcomes listed below. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOMES: Outcomes of interest included overall and disease-free survival, quality of life, toxicity reduction, and cost-effectiveness. The American Society of Clinical Oncology (ASCO) Colorectal Cancer Surveillance Expert Panel was guided by the principle of cost minimization, ie, when two strategies were believed to be equally effective, the least expensive test was recommended. EVIDENCE: A complete MEDLINE search was performed of the past 20 years of the medical literature. Keywords included colorectal cancer, follow-up, and carcinoembryonic antigen, as well as the names of the specific tests. The search was broadened by articlesfrom the tumor marker ASCO panel literature search, as well as from bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COSTS: The possible consequences of false-positive and false-negative tests were considered in evaluating a preference for one of two tests that provide similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The expert panel's recommended postoperative monitoring schema is discussed in this article. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board of Directors examined this document. SPONSOR: American Society of Clinical Oncology.

OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness. EVIDENCE: A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans. VALIDATION: The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors. SPONSOR: American Society of Clinical Oncology.

PURPOSE Interferon alfa-2b (IFN) in a randomized clinical trial (E1684) prolonged relapse-free and total survival in high-risk resected melanoma. However, the costs and toxicities of IFN are barriers to its widespread use. This study was undertaken to analyze the projected costs and long-term benefits of IFN by combining prospectively collected data on IFN actual dosage, time of recurrence, and survival with secondary data on long-term melanoma recurrence risks to project the cost-effectiveness of adjuvant IFN compared with observation. PATIENTS AND METHODS Two hypothetical cohorts of 50-year-old melanoma patients whose mean IFN dosage and clinical results were directly taken from E1684 were included in the study. Melanoma recurrence risks beyond 5 years were derived from international databases. Melanoma recurrence care costs and quality-of-life adjustments, when considered, were based on expert consensus. End points were incremental costs, life-years gained, and cost per life-year gained with and without quality-of-life adjustments. RESULTS The IFN cohort was projected to have an increased (undiscounted) survival of 0.52 years at 7 years and 1.90 years over a lifetime. The projected incremental cost (in 1996 United States dollars) per life-year gained in the IFN cohort ranged from $13,700 after 35 years to $32,600 at 7 years, the median follow-up of E1684. Using assigned quality-of-life values for IFN and recurrence, the lifetime cost per quality adjusted life-year increased to $15,200. Even if treatment costs for recurrence were excluded, the lifetime incremental cost per life-year gained was $21,600. CONCLUSION The cost and toxicity of IFN must be balanced against its projected benefits in high-risk melanoma. The derived cost-effectiveness and cost-utility ratios for IFN were comparable to other cancer interventions for which cost-effectiveness analysis has been performed.

PURPOSE High-dose chemotherapy (HDC) with peripheral-blood progenitor cell (PBPC) and autologous bone marrow (ABM) transplant (T) has documented survival benefits for relapsed Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Treatment costs associated with HDC and its supportive care have restricted its use both on and off clinical trial. In a prospective randomized clinical trial, filgrastim-mobilized PBPCT resulted in faster recovery of bone marrow function, with less hospitalization and supportive care than ABMT. This study was undertaken to analyze the costs of the two strategies using prospectively collected data from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT. PATIENTS AND METHODS Clinical results and resource utilization from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT following carmustine, etoposide, cytarabine, and melphalan (BEAM) HDC for HD and NHL are presented. The trial was performed in six centers in Germany, the United Kingdom, and Belgium. Resource utilization data were used to project costs and Massay Cancer Center (MCC) in the United States incurred the cost of treating the cohort. Costs were projected to the United States, because the economic implications to United States centers are significant, costs of care vary markedly among countries but resource utilization on this trial did not, and a randomized trial is unlikely to be performed in the United States. RESULTS Fifty-eight patients with relapsed HD or NHL underwent HDC with BEAM. The PBPCT and ABMT groups had similar short-term survival after BEAM. PBPCT patients had a shorter hospitalization (median, 17 v 23 days; P = .002), neutrophil recovery (11 v 14 days; P = .005), platelet recovery to > or = 20 x 10(9)/L (16 v 23 days; P = .02), and days of platelet transfusions (6 v 10; P < .001). Estimated costs were $8,531 for ABM harvest and $5,760 for PBPC collection, including filgrastim mobilization. The total estimated average cost was $59,314 for each ABMT patient versus $45,792 for each PBPCT patient. Cost savings of $13,521 (23%) were due to shorter hospitalizations with less supportive care. CONCLUSION PBPCT is as safe and more effective than ABMT for HD and NHL in the short term. PBPCT represents a significant cost savings due to lower autograft collection costs, shorter hospital stays, and less supportive care. The savings exceed the costs for filgrastim mobilization and PBPC collection. Actual savings will vary depending on local practice patterns, charges, and costs.

In 1993, the Health Services Research Committee of the American Society of Clinical Oncology (ASCO) charged an Outcomes Working Group with defining the outcomes of adult and pediatric cancer treatment to be used for technology assessment and development of cancer treatment guidelines. The Working Group defined by consensus outcomes for technology assessment and guideline development, focusing on cancer treatments. The Working Group considered a variety of perspectives on outcomes, including those of patients, physicians, clinical investigators, ASCO, and policy makers. Because ASCO's guidelines will define what constitutes the best treatment and not whether that treatment should be paid for, the Working Group gave higher priority to the clinical and clinical research perspectives than to the health policy perspective. Survival is the most important outcome of cancer treatment. An improvement in at least disease-free survival is a prerequisite for recommending adjuvant therapy. In the case of metastatic cancer, treatment can be recommended even without an improvement in survival, if it improves quality of life. Quality of life includes global quality of life, as well as its physical, psychologic, and social dimensions. To be an outcome of cancer treatment, quality-of-life measures must be sensitive to clinically meaningful changes produced by treatment; evaluations must control for placebo effects and determinants of quality of life not related to cancer or its treatment. Toxicity, both short and long term, is vitally important, with the latter being particularly critical in children. The value of cancer outcomes like tumor response (eg, complete or partial response) and biomarkers (eg, CA-125) for technology assessment and guideline development depends on their ability to predict patient outcomes (survival and quality of life) or to influence decisions about treatment. Complete response is an important outcome when it predicts survival. Progression is important because it signals the need to change or stop treatment. Cost-effectiveness is an especially important outcome to consider when the benefits of treatment are modest or the costs are high. Patient outcomes (eg, survival and quality of life) should receive higher priority than cancer outcomes (eg, response rate), but both types of outcomes are important in technology assessment and guideline development. Multiple outcomes should be considered because no single outcome adequately describes the results of cancer treatment. In general, there is no minimum benefit above which treatments are justified; rather, benefits should be balanced against toxicity and cost.

BACKGROUND Oncologists face ethical dilemmas every day in deciding about choice of treatment, continuation of treatments, events near the end of life, conflicts of interest, and risk management. Yet, many oncologists have limited training in ethics. METHODS Review of existing studies and definitions of useful terms. Case studies analyzed according to ethical principles. RESULTS Individual oncology cases can be analyzed according to ethical principles with benefit to the patient, physician, and possibly society. Ethics cannot resolve many of the thorny questions about allocation of resources, justice, or possible conflict of interest. CONCLUSION Oncology decision-making fits into formal ethical frameworks, and understanding both can help doctors and patients make difficult choices. Understanding of ethical principles can help daily practice, but does not solve current dilemmas of allocation of resources, unrealistic demands, etc. More formal collaboration between hospital ethics committees or personnel and clinical oncologists is recommended for the day-to-day decision-making process.

PURPOSE This study determines the survival benefit and cost-effectiveness of adjuvant chemotherapy in elderly women with breast cancer. In addition, the analysis measures the impact of substituting active life expectancy for survival in the clinical decision. PATIENTS AND METHODS Two cohorts of women with estrogen receptor (ER)-negative, stage I breast cancer from age 60 to 80 years were monitored using a Markov process. One group received standard chemotherapy following primary therapy, and the other had no postoperative treatment. Data were derived from recently published clinical trials and a major meta-analysis. Outcome included the average survival, active life-expectancy, and incremental cost/quality-adjusted life-year (cost/QALY). RESULTS Adjuvant chemotherapy prolongs survival in older women, but to a lesser extent compared with younger women. The average gain in quality-adjusted months was 1.8 months in a 75-year-old cohort at a cost/QALY of $4,400. These small benefits were not substantially altered when univariate changes were made in toxicity, recurrence risk, or effectiveness of chemotherapy. When active life expectancy replaced survival as an end point, the benefit for 75-year-old women decreased to 2 weeks at a cost of more than $96,000/QALY. CONCLUSION There is a small survival benefit for adjuvant chemotherapy in elderly patients. The cost of this benefit is high, but within the range of commonly reimbursed procedures until a point between 75 and 80 years old. The use of active life expectancy as the primary outcome reduces the benefit and adds to the cost. If physicians and policymakers agree that active life expectancy is a relevant outcome, withholding chemotherapy for patients > or = 70 years old is a reasonable approach.

PURPOSE AND METHODS We used decision analysis to model the natural history of breast cancer in hypothetical cohorts of 45-year-old women receiving tamoxifen, chemotherapy, or combined therapy. We used recurrence and efficacy data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), utility values from focus groups, and costs from clinic charges and Medicare data. RESULTS Tamoxifen alone provides minimal benefit in estrogen receptor-negative (ER-; 0.2 to 0.4 months) and modest benefit in receptor-positive (ER+; 3.5 to 5.2 months) cancer. Chemotherapy adds substantial benefit independent of receptor status (4.9 to 10.7 quality-adjusted months). In ER+ cancer, combined therapy adds an additional benefit (1.2 to 2.1 months) compared with chemotherapy alone. The incremental costs (United States dollars) necessary to add an additional year of life to the average woman ranged from $4,300 to $11,400 for tamoxifen alone for ER+ cancer, $4,900 to $11,400 for chemotherapy alone, and $14,800 to $33,100 for combined therapy. CONCLUSION In premenopausal early-stage breast cancer, chemotherapy adds substantial clinical benefit at a modest cost. Tamoxifen alone adds meaningful benefit only in ER+ cancer. Combined therapy is effective for all women, but is most beneficial and only cost-effective in ER+ women. If secondary effects of tamoxifen in reduction of cardiovascular and osteoporosis mortality are confirmed, then combined treatment may be optimal for all premenopausal women.

Cytosine arabinoside is known to cause severe gastrointestinal side effects in an already very ill patient population. Three cases are reviewed in which apparent surgical peritonitis was managed conservatively, with very careful clinical monitoring. Two of the patients recovered completely, and one died of systemic fungal infection. No patient had a surgically remediable condition, and all were extremely poor surgical risks. A review of our experience and the literature leads us to recommend careful conservative management in patients receiving cytosine arabinoside who appear to have a "surgical abdomen," but in whom a definitive surgical diagnosis cannot be made.