Michael L. Steinberg

Delivering affordable cancer care in high-income countries

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US

American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of stereotactic body radiation therapy.

895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.

Stereotactic body radiotherapy for localized prostate cancer: Pooled analysis from a multi-institutional consortium of prospective phase II trials

These guidelines are an educational tool designed to assist practitioners in providing appropriate radiologic care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the developers of this guideline cautions against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, an approach that differs from the

Lay patient navigator program implementation for equal access to cancer care and clinical trials: essential steps and initial challenges.

PURPOSE The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested. METHODS AND MATERIALS A total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003-11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4-5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2ng/ml above nadir was analyzed with the Kaplan Meier method. RESULTS With a median follow-up of 36months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ⩽6, 7 and ⩾8, respectively (p=0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p<0.001). No differences were observed with ADT (p=0.71) or as a function of total dose (p=0.17). A PSA bounce of >0.2ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively. CONCLUSION PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients.

Health-Related Quality of Life After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: Results From a Multi-institutional Consortium of Prospective Trials

Disparities in cancer detection, treatment, and outcomes among racial/ethnic minorities and low‐income patients are well documented. One way to reduce these disparities is to use patient navigators to address barriers to care. However, little information about optimal characteristics of navigator programs or considerations for those interested in setting up such programs is available.

Quality-of-Care Indicators for Early-Stage Prostate Cancer

PURPOSE To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS Patient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients. RESULTS Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age. CONCLUSION Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.

Stereotactic body radiation therapy and 3-dimensional conformal radiotherapy for stage I non-small cell lung cancer: A pooled analysis of biological equivalent dose and local control

PURPOSE Decisions regarding treatment for early-stage prostate cancer are frustrated not only by inadequate evidence favoring one treatment modality but also by the absence of data comparing quality among providers. In fact, the choice of provider may be as important as the choice of treatment. We undertook this study to develop an infrastructure to evaluate variations in quality of care for men with early-stage prostate cancer. METHODS We enlisted several sources to develop a list of proposed quality-of-care indicators and covariates. After an extensive structured literature review and a series of focus groups with patients and their spouses, we conducted structured interviews with national academic leaders in prostate cancer treatment. We then convened an expert panel using the RAND consensus method to discuss and rate the validity and feasibility of the proposed quality indicators and covariates. RESULTS The panel endorsed 49 quality-of-care indicators and 14 covariates, which make up our final list of candidate measures. Several domains of quality are represented in the selected indicators, including patient volume, pretreatment referrals, preoperative testing, interpretation of pathology specimens, and 10-year disease-free survival. Covariates include measures of case-mix, such as patient age and comorbidity. CONCLUSION This study establishes a foundation on which to build quality-of-care assessment tools to evaluate the treatment of early-stage prostate cancer. The next step is to field-test the indicators for feasibility, reliability, validity, and clinical utility in a population-based sample. This work will begin to inform medical decision-making for patients and their physicians.

Utilizing time-driven activity-based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer.

PURPOSE To determine the relationship between tumor control probability (TCP) and biological effective dose (BED) for radiation therapy in medically inoperable stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS Forty-two studies on 3-dimensional conformal radiation therapy (3D-CRT) and SBRT for stage I NSCLC were reviewed for tumor control (TC), defined as crude local control ≥ 2 years, as a function of BED. For each dose-fractionation schedule, BED was calculated at isocenter using the linear quadratic (LQ) and universal survival curve (USC) models. A scatter plot of TC versus BED was generated and fitted to the standard TCP equation for both models. RESULTS A total of 2696 patients were included in this study (SBRT: 1640; 3D-CRT: 1056). Daily fraction size was 1.2-4 Gy (total dose: 48-102.9) with 3D-CRT and 6-26 (total dose: 20-66) with SBRT. Median BED was 118.6 Gy (range, 68.5-320.3) and 95.6 Gy (range, 46.1-178.1) for the LQ and USC models, respectively. According to the LQ model, BED to achieve 50% TC (TCD50) was 61 Gy (95% confidence interval, 50.2-71.1). TCP as a function of BED was sigmoidal, with TCP ≥ 90% achieved with BED ≥ 159 Gy and 124 Gy for the LQ and USC models, respectively. CONCLUSIONS Dose-escalation beyond a BED 159 by LQ model likely translates into clinically insignificant gain in TCP but may result in clinically significant toxicity. When delivered with SBRT, BED of 159 Gy corresponds to a total dose of 53 Gy in 3 fractions at the isocenter.

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study

Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time‐driven activity‐based costing (TDABC) for competing treatments of low‐risk prostate cancer.

Clinical Outcomes for Patients with Gleason Score 9–10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis

BACKGROUND Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING University of California.