Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer.

PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data. RESULTS: The estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions. CONCLUSIONS: IMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.

Trends in Medicare Reimbursement and Work Relative Value Unit Production in Radiation Oncology.

PURPOSE: Medicare payments to individual physicians are released annually by the CMS. The purpose of this study is to analyze trends in Medicare reimbursement and work relative value unit (wRVU) production to radiation oncologists. MATERIALS AND METHODS: The Medicare Physician Supplier and Other Provider Public Use File and the CMS Physician Fee Schedule Relative Value Files (to calculate wRVUs) for the calendar years 2012 to 2015 were used in this analysis. Medicare reimbursement was aggregated for each calendar year. Using the CMS Physician Fee Schedule Relative Value Files, the number of Medicare wRVUs was calculated for each radiation oncologist. RESULTS: In 2015, 4,323 radiation oncologists produced 12,895,298 wRVUs compared with 11,352,286 wRVUs produced in 2012. These datasets include only Medicare reimbursements and do not include wRVUs from private insurance or other payers. In 2015, radiation oncologists produced a median of 2,486 wRVUs from Medicare (range 3 to 24,349). Billing to Healthcare Common Procedure Coding System Code 77427 (radiation treatment management, five treatments), a proxy for total radiation treatments, fell from 1,111,670 in 2012 to 1,039,403 in 2015, a decline of 7%. CONCLUSION: The total number of wRVUs produced by radiation oncologists has risen by 14% from 2012 to 2015. However, the number of external beam radiation fractions has declined by approximately 7% over this same period, likely due to a trend toward hypofractionated courses of treatment and use of special treatment modalities such as proton beam therapy or stereotactic body radiation therapy.

Early Results From the Implementation of a Lung Cancer Screening Program: The Beaumont Health System Experience.

PURPOSE: In 2010, a new study published by the National Lung Screening Trial showed a 20% reduction in mortality for those patients screened with low-dose computed topography (CT) versus x-ray. Recently, the Centers of Medicare and Medicaid have agreed to cover this service for those patients who meet the screening criteria. We compare the outcomes and costs associated with developing and implementing a lung cancer screening program. MATERIALS AND METHODS: One thousand sixty-five patients were screened from January 2014 to December 2014. These patients were screened on a low-dose CT screening protocol throughout Beaumont Health System. The American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) were used to assign the score for each patient. Screening eligibility criteria were based on the National Comprehensive Cancer Network guidelines. Downstream activity and revenue was determined after initial low-dose CT screening. RESULTS: At 1 year, 20 patients (1.6%) were diagnosed with lung cancer and another 15 patients were diagnosed with another form of cancer after screening. The median age, packs per day, and pack years smoked for all patients was 63, 1.0, and 39.0 years, respectively. Lung-RADS scores for all patients was 18% (1), 24.1% (2), 6.3% (3), and 5.4% (4). The net revenue for all activity after screening was $3.2 million. CONCLUSIONS: The establishment of a low-dose CT lung cancer screening program improved the ability to screen patients as demonstrated by the number of patients screened and those diagnosed with a malignancy. These findings were also consistent with the findings from the National Lung Screening Trial study.

Variations in Medicare Reimbursement in Radiation Oncology: An Analysis of the Medicare Provider Utilization and Payment Data Set.

PURPOSE: The purposes of this study were to summarize recently published data on Medicare reimbursement to individual radiation oncologists and to identify the causes of variation in Medicare reimbursement in radiation oncology. METHODS AND MATERIALS: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF), which details nearly all services provided by radiation oncologists in 2012, was used for this study. The data were filtered and analyzed by physician and by billing code. Statistical analysis was performed to identify differences in reimbursements based on sex, rurality, billing of technical services, or location in a certificate of need (CON) state. RESULTS: There were 4135 radiation oncologists who received a total of $1,499,625,803 in payments from Medicare in 2012. Seventy-five percent of radiation oncologists were male. The median reimbursement was $146,453. The code with the highest total reimbursement was 77418 (radiation treatment delivery intensity modulated radiation therapy [IMRT]). The most commonly billed evaluation and management (E/M) code for new visits was 99205 (49%). The most commonly billed E/M code for established visits was 99213 (54%). Forty percent of providers billed none of their new office visits using 99205 (the highest E/M billing code), whereas 34% of providers billed all of their new office visits using 99205. For the 1510 radiation oncologists (37%) who billed technical services, median Medicare reimbursement was $606,008, compared with $93,921 for all other radiation oncologists (P<.001). On multivariate analysis, technical services billing (P<.001), male sex (P<.001), and rural location (P=.007) were predictive of higher Medicare reimbursement. CONCLUSIONS: The billing of technical services, with their high capital and labor overhead requirements, limits any comparison in reimbursement between individual radiation oncologists or between radiation oncologists and other specialists. Male sex and rural practice location are independent predictors of higher total Medicare reimbursements.

Cost analysis of adjuvant management strategies in early stage (stage I) testicular seminoma.

BACKGROUND: Acceptable post-orchiectomy adjuvant therapy strategies for stage I seminoma patients include surveillance, para-aortic radiation therapy (RT), dog-leg RT, and a single cycle of carboplatin. The required follow-up recommendations were amended by the National Comprehensive Cancer Network (NCCN) in 2012. Given a cause-specific survival of nearly 100%, a closer analysis of the reimbursement for each treatment strategy is warranted. METHODS: NCCN guidelines were used to design treatment plans for each acceptable adjuvant treatment strategy. Follow-up charges were generated for 10 years based on 2012 (version 1.2012; unchanged in current version 1.2013) and 2011 NCCN (version 2.2011) surveillance recommendations. The 2012 Medicare reimbursement rates were used to calculate each treatment strategy and incremental cost-effectiveness ratios to compare the treatment options. RESULTS: Under the current NCCN follow-up recommendations, the total reimbursements generated over 10 years of surveillance, para-aortic RT, dog-leg RT, and carboplatin were $10,643, $11,678, $9,662, and $10,405, respectively. This is compared with the reimbursements as per the 2011 NCCN recommendations: $20,986, $11,517, $9,394, and $20,365 respectively. Factoring the rates of relapse into a salvage model, observation was found to be more costly and less effective ($-1,831, $-7,318, $-7,010) in the adjuvant management of stage I seminoma patients. CONCLUSION: Based on incremental cost-effectiveness ratios, para-aortic RT, dog-leg RT, and carboplatin are cost-effective options for the treatment of stage I seminoma when compared with observation; however, surveillance could potentially spare as many as 80%-85% of men diagnosed with stage I seminoma from additional therapy after radical inguinal orchiectomy. Such cost and reimbursement analyses are becoming increasingly relevant, but are not meant to usurp sound clinical judgment. Further studies are required to validate these findings.

Implementation of an oncology exercise and wellness rehabilitation program to enhance survivorship: the Beaumont Health System experience.

We developed a multidisciplinary approach to oncology rehabilitation by setting up a physical therapy screening program in a dedicated multidisciplinary clinic to improve survivorship care in the community oncology setting. In June 2011, an oncology rehabilitation program was launched as part of the overall survivorship program to provide patients with an introduction to cancer services, consultation with multiple clinicians, education about their diagnoses, and recommendation for rehabilitation services during or after treatment. The consultation was in conjunction with specialists at the multidisciplinary clinics that were already established within the organization. A dedicated and trained oncology physical therapist participated in the comprehensive multidisciplinary discussion. From the beginning of the program in June 2011 until December 2012, 288 patients (231 women and 57 men) entered the oncology exercise and wellness rehabilitation program. The establishment of the program improved the quality of care for cancer patients as demonstrated by the number of patients screened before treatment recommendations. The program also served the need for continued health and wellness for those in survivorship.

Evaluating radiotherapy options in breast cancer: does intraoperative radiotherapy represent the most cost-efficacious option?

INTRODUCTION: This study analyzed the cost-efficacy of intraoperative radiation therapy (IORT) compared with whole-breast irradiation (WBI) and accelerated partial-breast irradiation (APBI) for early-stage breast cancer. MATERIALS AND METHODS: Data for this analysis came from 2 phase III trials: the TARGIT (Targeted Intraoperative Radiotherapy) trial and the ELIOT (Electron Intraoperative Radiotherapy) trial. Cost analyses included a cost-minimization analysis and an incremental cost-effectiveness ratio analysis including a quality-adjusted life-year (QALY) analysis. Cost analyses were performed comparing IORT with WBI delivered using 3-dimensional conformal radiotherapy (3D-CRT), APBI 3D-CRT, APBI delivered with intensity-modulated radiotherapy (IMRT), APBI single-lumen (SL), APBI multilumen (ML), and APBI interstitial (I). RESULTS: Per 1000 patients treated, the cost savings with IORT were $3.6-$4.3 million, $1.6-$2.4 million, $3.6-$4.4 million, $7.5-$8.2 million, and $2.8-$3.6 million compared with WBI 3D-CRT, APBI IMRT, APBI SL, APBI ML, and APBI I, respectively, with a cost decrement of $1.6-$2.4 million compared with APBI 3D-CRT based on data from the TARGIT trial. The costs per QALY for WBI 3D-CRT, APBI IMRT, APBI SL, APBI ML, and APBI I compared with IORT were $47,990-$60,002; $17,335-$29,347; $49,019-$61,031; $108,162-$120,173; and $36,129-$48,141, respectively, based on data from the ELIOT trial. These results are consistent with APBI and WBI being cost-effective compared with IORT. CONCLUSION: Based on cost-minimization analyses, IORT represents a potential cost savings in the management of early-stage breast cancer. However, absolute reimbursement is misleading, because when additional medical and nonmedical costs associated with IORT are factored in, WBI and APBI represent cost-effective modalities based on cost-per-QALY analyses. They remain the standard of care.

Toxicities and costs of placing prophylactic and reactive percutaneous gastrostomy tubes in patients with locally advanced head and neck cancers treated with chemoradiotherapy.

BACKGROUND: We compared dependence rates, complications, toxicities, and costs associated with prophylactic versus reactive percutaneous endoscopic gastrostomy (PEG) tube placement. METHODS: One hundred ninety-three patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy were retrospectively reviewed. RESULTS: The 1-year and 2-year actuarial PEG tube dependence rate of the entire cohort was 24% and 13%, respectively. There was no difference in the PEG tube dependence rates between those placed prophylactically versus reactively. Patients who received a PEG tube reactively had a significantly higher stricture rate (p = .03) and aspiration rate (p < .001) compared to the prophylactic group. There were significantly fewer hospitalizations in the prophylactic group compared to the reactive group (p = .003). When accounting for both PEG placement and hospitalizations, the prophylactic approach was found to be more cost effective. CONCLUSION: PEG tubes placed prophylactically were associated with lower rates of strictures, aspirations, hospitalizations, and costs compared to those placed reactively.

Cost-efficacy of acceleration partial-breast irradiation compared with whole-breast irradiation.

The purpose of this study was to analyze the cost-efficacy of multiple accelerated partial-breast irradiation (APBI) techniques compared with whole breast irradiation (WBI) delivered utilizing 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT). A previously reported matched-pair analysis consisting of 199 patients receiving WBI and 199 patients receiving interstitial APBI formed the basis of this analysis. Cost analyses included a cost minimization analysis, incremental cost- effectiveness ratio (ICER) analysis, and cost per quality adjusted life year (QALY) analysis. Per 1,000 patients treated, the cost savings with the utilization of APBI compared to WBI IMRT is $14.9 million, $10.9 million, $8.8 million, $5.0 million, and $9.7 million for APBI 3D-CRT, APBI IMRT, APBI single-lumen (SL), APBI multi-lumen (ML), and APBI interstitial, respectively. Per 1,000 patients treated, the cost savings with the utilization of APBI compared to WBI 3D-CRT is $6.0 million, $2.0 million, and $0.7 million for APBI 3D-CRT, APBI IMRT, and APBI interstitial, respectively. The cost per QALY for APBI SL, APBI ML, and APBI interstitial compared with APBI 3D-CRT are $12,273, $66,032, and $546, respectively. When incorporating non-medical costs and cost of recurrences the cost per QALY was $54,698 and $49,009 for APBI ML compared with APBI 3D-CRT. When compared to WBI IMRT, all APBI techniques are cost-effective based on cost minimization, ICER, and QALY analyses. When compared to WBI 3D-CRT, external beam APBI techniques represent a more cost-effective approach based on cost minimization with brachytherapy representing a cost-effective approach based on cost per QALY.

Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer.

PURPOSE: To evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer. METHODS AND MATERIALS: One thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n=207), HDR with four fractions (n=252), or IMRT (n=869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42-44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival. RESULTS: Overall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was $9,938; $17,514; and $29,356, respectively. HDR and LDR brachytherapy were statistically less costly to Medicare and the institution than IMRT (p<0.001), and LDR brachytherapy was less costly than HDR brachytherapy (p=0.01 and p<0.001). Incremental cost-effectiveness ratios for cost to Medicare for BC with IMRT were $4045 and $2754 per percent of BC for LDR and HDR brachytherapy, respectively. Incremental cost-effectiveness ratio using institutional cost comparing IMRT with LDR and HDR brachytherapy was $4962 and $4824 per 1% improvement in BC. CONCLUSIONS: In this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.

Stereotactic radiotherapy reduces treatment cost while improving overall survival and local control over standard fractionated radiation therapy for medically inoperable non-small-cell lung cancer.

PURPOSE: Radiation therapy (RT) is the standard alternative curative treatment option for medically inoperable early stage non-small-cell lung cancer (NSCLC). Recently, stereotactic body radiotherapy (SBRT) has shown substantial promise to improve local control rates as compared with conventional fractionated RT [external beam RT (EBRT)]. We compare treatment outcomes and costs between SBRT and EBRT in this patient population. MATERIALS AND METHODS: A total of 86 patients with Stage I (Tl-2 N0) NSCLC were treated with either EBRT (n=41) or SBRT (n=45) between January 2002 and April 2008. EBRT patients were treated to a median dose of 70 Gy with 3-dimensional conformal RT (n=39) or intensity-modulated radiation therapy (n=2). SBRT was delivered in 4 or 5 fractions to 48 (Tl, n=44) or 60 (T2, n=1) Gy. The actual cost was calculated using 2010 Medicare hospital-based Ambulatory Payment Classification and hospital-based physician fee screen reimbursement rates for both the technical and professional components. RESULTS: On the basis of a median number of fractions for this patient population, SBRT was significantly less expensive ($13,639 EBRT vs. $10,616 SBRT, P < 0.01). Survival analysis demonstrated superior 36-month overall survival using SBRT, 71% versus 42% for EBRT (P < 0.05). SBRT also reduced local failure by nearly 3 times compared with EBRT (12% vs. 34%, P=0.10). CONCLUSION: In this study of Stage I NSCLC patients, SBRT was found to be less expensive than standard fractionated EBRT, with the cost savings highly dependent on the number of SBRT fractions and EBRT technique (3-dimensional conformal RT vs. intensity-modulated radiation therapy). SBRT was also associated with superior local control and overall survival.

Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.

The Type 1 PI3Kinases comprise a family of enzymes, which primarily phosphorylate PIP2 to give the second messenger PIP3, a key player in many intracellular signaling processes [Science, 2002, 296, 1655; Trends Pharmacol. Sci.2003, 24, 366]. Of the four type 1 PI3Ks, the gamma-isoform, which is expressed almost exclusively in leukocytes [Curr. Biol., 1997, 7, R470], is of particular interest with respect to its role in inflammatory diseases such as rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) [Mol. Med. Today, 2000, 6, 347]. Investigation of a series of 4,6-disubstituted-4H-benzo[1,4]oxazin-3-ones has led to the identification of single-digit nanomolar inhibitors of PI3Kgamma, several of which had good cell based activity and were shown to be active in vivo in an aspectic peritonitis model of inflammatory cell migration.