Cost–Utility Analysis of Radiation Treatment Modalities for Intermediate-Risk Prostate Cancer

Introduction: Variable costs of different radiation treatment modalities have played an important factor in selecting the most appropriate treatment for patients with intermediate-risk prostate cancer. Methods: Analysis using a Markov model was conducted to simulate 20-year disease trajectory, quality-adjusted life years (QALYs) and health system costs of a cohort of intermediate-risk prostate cancer patients with mean age of 60 years. Clinical outcomes on toxicity and disease recurrence were measured and a probabilistic sensitivity analysis was performed, varying input parameters simultaneously according to their distributions. Results: Among the six radiation treatment modalities, including conventionally fractionated intensity-modulated radiation therapy (IMRT), hypofractionated IMRT, IMRT combined with high-dose-rate (HDR) brachytherapy, HDR brachytherapy monotherapy, low-dose-rate brachytherapy monotherapy, and stereotactic body radiotherapy (SBRT), SBRT was found to be more cost-effective when compared with LDR-b and other treatment modalities, resulting in an incremental cost–utility ratio of $2985 per QALY. Conclusions: Stereotactic body radiotherapy is the most cost-effective radiation treatment modality in treatment of intermediate-risk prostate cancer, while treatment toxicity and cost data are the key drivers of the cost–utility. Further work is required with long-term follow-up for SBRT.     

Cost–utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels

Background

Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost–utility (cu) of this therapy could help to determine its role in clinical practice.

Methods

Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters.

Results

Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained.

Conclusions

Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.     

Cost-effectiveness of lapatinib plus letrozole in her2-positive,hormone receptor–positive metastatic breast cancer in Canada

Background

The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor–positive (hr+), human epidermal growth factor receptor 2–positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives.

Methods

A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib–letrozole, letrozole, anastrozole, or trastuzumab–anastrozole as first-line treatment. Clinical inputs for lapatinib–letrozole and letrozole were taken from the EGF30008 trial ({"type":"clinical-trial","attrs":{"text":"NCT00073528","term_id":"NCT00073528"}}NCT00073528). Clinical inputs for anastrozole and trastuzumab–anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer’s price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan’s Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters.

Results

Quality-adjusted life years gained with lapatinib–letrozole were 0.236 compared with trastuzumab–anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib–letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab–anastrozole. Results from the societal perspective were similar.

Conclusions

In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib–letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab–anastrozole.     

Radiation therapy for pancreatic cancer: eleven year experience at the JCRT

Radiation therapy (XRT) for 41 patients with unresectable pancreatic cancer resulted in a median survival of 7.0 months. There was no difference in median survival for patients receiving external beam alone (3500 to 5600 cGy) (n = 28), intraoperative (IORT) boost plus external beam (5040 to 6750 cGy) (n = 9), or a gold-198 implant +/- external beam radiation (n = 4). A pilot study using orthovoltage IORT boost indicates no acute toxicity with doses of 1250 to 1750 cGy. Serious late damage has not been observed in any patients followed to 2 years. Local recurrence in patients treated post-operatively after "radical" surgery occurred in one of 10 (10%). This adjuvant treatment is safe and appears to improve local control rates compared to historical data, but survival is still poor. The median survival for the post-operative group is 10 months; three patients are alive without disease 8 months to 8.3 years after treatment.     

Cost‐effectiveness of precision diagnostic testing for precision medicine approaches against non‐small‐cell lung cancer: A systematic review

Precision diagnostic testing (PDT) employs appropriate biomarkers to identify cancer patients that may optimally respond to precision medicine (PM) approaches, such as treatments with targeted agents and immuno‐oncology drugs. To date, there are no published systematic appraisals evaluating the cost‐effectiveness of PDT in non‐small‐cell lung cancer (NSCLC). To address this gap, we conducted Preferred Reporting Items for Systematic Reviews and Meta‐Analyses searches for the years 2009–2019. Consolidated Health Economic Evaluation Reporting Standards were employed to screen, assess and extract data. Employing base costs, life years gained or quality‐adjusted life years, as well as willingness‐to‐pay (WTP) threshold for each country, net monetary benefit was calculated to determine cost‐effectiveness of each intervention. Thirty‐seven studies (50%) were included for analysis; a further 37 (50%) were excluded, having failed population‐, intervention‐, comparator‐, outcomes‐ and study‐design criteria. Within the 37 studies included, we defined 64 scenarios. Eleven scenarios compared PDT‐guided PM with non‐guided therapy [epidermal growth factor receptor (EGFR), n = 5; programmed death‐ligand 1 (PD‐L1), n = 6]. Twenty‐eight scenarios compared PDT‐guided PM with chemotherapy alone (anaplastic lymphoma kinase, n = 3; EGFR, n = 17; PD‐L1, n = 8). Twenty‐five scenarios compared PDT‐guided PM with chemotherapy alone, while varying the PDT approach. Thirty‐four scenarios (53%) were cost‐effective, 28 (44%) were not cost‐effective, and two were marginal, dependent on their country’s WTP threshold. When PDT‐guided therapy was compared with a therapy‐for‐all patients approach, all scenarios (100%) proved cost‐effective. Seven of 37 studies had been structured appropriately to assess PDT‐PM cost‐effectiveness. Within these seven studies, all evaluated scenarios were cost‐effective. However, 81% of studies had been poorly designed. Our systematic analysis implies that more robust health economic evaluation could help identify additional approaches towards PDT cost‐effectiveness, underpinning value‐based care and enhanced outcomes for patients with NSCLC.     

Ovarian function after ovarian transposition and additional pelvic radiotherapy: A systematic review

ObjectiveTo investigate the ovarian survival (OS) after ovarian transposition (OT) and pelvic radiation.DesignSystematic review.Electronic databases were searched to identify studies on OT prior to external beam radiation therapy (EBRT, to the pelvic). Primary outcome was the ovarian function after radiotherapy and ovarian transposition. Secondary outcomes were complication-rate. Only studies in English, German or French were included.SettingNot applicable.PatientsFertile women undergoing ovarian transposition prior to pelvic radiation therapy.InterventionsWe included all studies, containing >5 patients, treated with OT prior to radiation therapy.Main outcome measureOvarian function.ResultsOur search yielded a total of 1130 studies of which 38 were eligible with a total of 765 patients. All studies were cohort studies or case-series. Heterogeneity among studies could not be rejected hence meta-analysis could not be performed.OS after OT and EBRT ranged from 20% to 100%. The median follow-up ranged from 7 to 102 months. OS was higher after OT and brachytherapy (OS 63.6–100%) when compared to OT and EBRT (20–100%) and OT concomitant chemoradiotherapy (0–69.2%).Only 22 studies (with 112 patients) reported on complications: among these studies the complication-rate was 0%–28.6%.ConclusionFrom our systematic review of literature we conclude that the preservation of ovarian function after OT prior to EBRT is successful in 20–100% of patients. Most favorable outcome with regard to preservation of ovarian function is seen in patients after OT and BT, followed by OT and EBRT and OT and RT combined with chemotherapy.     

Lack of toxicity in a patient with germline TP53 mutation treated with radiotherapy

Li–Fraumeni syndrome is an autosomal dominant disorder characterized by germline TP53 mutation and increased susceptibility to cancer. Despite certain in vitro findings and a theoretical rationale for patients with TP53 mutation to be more radiosensitive and more prone to developing radiotherapy (rt)–induced secondary malignancies, corresponding clinical data remain elusive. Here, we report the case of a woman with TP53 mutation who was treated with adjuvant pelvic rt for stage ib uterine leiomyosarcoma in 2000, with radioactive iodine for papillary thyroid cancer in 2001, and with palliative rt to the humerus in 2010 for metastatic uterine leiomyosarcoma. She has not developed any acute or late rt-related toxicity, nor any secondary malignancies, since her first rt treatment. The literature review describes the potential risks and benefits of using irradiation in patients with TP53 mutation.     

Radiation induced failures of complementary metal oxide semiconductor containing pacemakers: a potentially lethal complication

New multi-programmable pacemakers frequently employ complementary metal oxide semiconductors (CMOS). This circuitry appears more sensitive to the effects of ionizing radiation when compared to the semiconductor circuits used in older pacemakers. A case of radiation induced runaway pacemaker in a CMOS device is described. Because of this and other recent reports of radiation therapy-induced CMOS type pacemaker failure, these pacemakers should not be irradiated. If necessary, the pacemaker can be shielded or moved to a site which can be shielded before institution of radiation therapy. This is done to prevent damage to the CMOS circuit and the life threatening arrythmias which may result from such damage.     

Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis

Using a decision-analytic model, we evaluated the effectiveness and cost-effectiveness of surveillance for hepatocellular carcinoma (HCC) in individuals with cirrhosis. Separate cohorts with cirrhosis due to alcoholic liver disease, hepatitis B and hepatitis C were simulated. Results were also combined to approximate a mixed aetiology population. Comparisons were made between a variety of surveillance algorithms using alpha-foetoprotein (AFP) assay and/or ultrasound at 6- and 12-monthly intervals. Parameter estimates were obtained from comprehensive literature reviews. Uncertainty was explored using one-way and probabilistic sensitivity analyses. In the mixed aetiology cohort, 6-monthly AFP+ultrasound was predicted to be the most effective strategy. The model estimates that, compared with no surveillance, this strategy may triple the number of people with operable tumours at diagnosis and almost halve the number of people who die from HCC. The cheapest strategy employed triage with annual AFP (incremental cost-effectiveness ratio (ICER): 20,700 pounds per quality-adjusted life-year (QALY) gained). At a willingness-to-pay threshold of 30,000 pounds per QALY the most cost-effective strategy used triage with 6-monthly AFP (ICER: 27,600 pounds per QALY gained). The addition of ultrasound to this strategy increased the ICER to 60,100 pounds per QALY gained. Surveillance appears most cost-effective in individuals with hepatitis B-related cirrhosis, potentially due to younger age at diagnosis of cirrhosis. Our results suggest that, in a UK NHS context, surveillance of individuals with cirrhosis for HCC should be considered effective and cost-effective. The economic efficiency of different surveillance strategies is predicted to vary markedly according to cirrhosis aetiology.     

中国大陆地区鼻咽癌放疗后放射性脑病的系统评价

目的：了解中国大陆地区鼻咽癌放射治疗后放射性脑病的整体情况。方法：应用系统评价的方法,经过计算机检索,确定文献的入选与排除标准以及资料摘录等过程,对描述该病临床特征和与发病相关因素的数据进行统计学处理。结果：共有16家医院,18篇文献,累计病例数为553例的资料进入研究,在CT或MRI检查的条件下,放射性脑损伤的发生率平均为1．9％,病变部位位于颞叶和脑干;首程常规后脑病患者鼻咽和颅底区放疗总剂量的均数为72．9Gy;发病的潜伏期平均为3．6年,结论：为了准确地掌握鼻咽癌放射性脑病的临床特征,必须组织多中心的病例对照研究或队列研究。     

Soft tissue sarcomas of the buttock: A systematic review and meta-analysis

BackgroundSoft tissue sarcomas of the buttock (BSTS) are historically associated with a poor prognosis. The literature includes retrospective studies with small sample size. It is difficult to estimate the rate of local recurrence (LR), distant metastasis (DM) and overall survival (OS). A systematic review and meta-analysis was deployed to summarize the available information on BSTS patients that underwent surgical treatment.MethodsThe PubMed, EMBASE, Scopus and Google Scholar databases were reviewed for eligible studies following PRISMA guidelines. Inclusion criteria: (1) primary BSTS confirmed by pathological biopsy (2) indication for surgical treatment (3) reporting either the rate of LR, DM, or OS at 5-year (4) articles published up to December 2021 (5) english language. The Methodological Index for Non-Randomized Studies (MINORS) was applied for the quality appraisal.ResultsSix eligible studies with 216 BSTS patients were identified. Most patients underwent surgical resection, associated with radiation therapy. The most represented histological types were liposarcoma (n = 43, 19,9%), rhabdomyosarcoma (n = 27, 12.5%), and undifferentiated pleomorphic sarcoma (n = 23, 10.6%). High-grade tumor rates ranged from 37% to 88.2%, marginal resection rates from 20.3% to 50%, LR rates from 0% to 62.5%, DM rates from 37.5% to 62.5%. The pooled 5-year OS from 1941 to 2002 was 41% (IC95%: 33%–49%). The average MINORS score was 9.3 (range: 6 to 11).ConclusionsSurgical resection of BSTS had on average dissatisfactory outcomes, and the 5-year overall survival was poor, with high rates of local recurrence and distant metastasis. An effort to collect new data with a higher level of evidence is warranted.     

Radiation-induced sarcoma of the breast: a systematic review

Introduction.

Radiation-induced sarcoma (RIS) is a rare, aggressive malignancy. Breast cancer survivors treated with radiotherapy constitute a large fraction of RIS patients. To evaluate evidenced-based practices for RIS treatment, we performed a systematic review of the published English-language literature.

Methods.

We performed a systematic keyword search of PubMed for original research articles pertaining to RIS of the breast. We classified and evaluated the articles based on hierarchal levels of scientific evidence.

Results.

We identified 124 original articles available for analysis, which included 1,831 patients. No randomized controlled trials involving RIS patients were found. We present the best available evidence for the etiology, comparative biology to primary sarcoma, prognostic factors, and treatment options for RIS of the breast.

Conclusion.

Although the evidence to guide clinical practice is limited to single institutional cohort studies, registry studies, case–control studies, and case reports, we applied the available evidence to address clinically relevant questions related to best practice in patient management. Surgery with widely negative margins remains the primary treatment of RIS. Unfortunately, the role of adjuvant and neoadjuvant chemotherapy remains uncertain. This systematic review highlights the need for additional well-designed studies to inform the management of RIS.     

The cost of the inpatient management of febrile neutropenia in cancer patients – a micro‐costing study in the Irish healthcare setting

The objective was to evaluate the resource use and cost of hospitalisation for febrile neutropenia (FN) from the health‐payer's perspective. This was a single centre study. Adults undergoing chemotherapy, who were admitted for FN, were identified prospectively. Patient medical records were reviewed retrospectively. Demographics and resource utilisation data were obtained from a cohort of 32 patients (69% female, mean age = 58.8 years). Twenty‐five per cent of patients had more than one FN episode. In total, 42 FN episodes were captured; 60% of episodes had occurred within the first two cycles of chemotherapy. The bootstrap estimation was used to determine mean hospital length of stay (LOS) with standard deviation (±SD) and mean costs ± SD. The mean LOS was 7.3 ± 0.5 days. The mean cost per FN episode was €8915 ± 718. The major cost driver was hospital bed‐stay (mean cost of €6851 ± 549). Other cost drivers included antibacterial treatment at €760 ± 156, laboratory investigations at €538 ± 47 and the requirement for blood bank products at €525 ± 189. To our knowledge, this is the first investigation of the cost of chemotherapy induced FN within the context of the Irish healthcare setting.     

Economic outcomes of breast cancer survivorship: CALGB study 79804

Background. Over 80 of women diagnosed with breast cancer will be survivors. We sought to determine the economic consequences of surviving breast cancer.Methods. Disease-free survivors who had received adjuvant chemotherapy for stage II breast cancer on CALGB study 8541 participated in a study of long-term outcomes. Survey responses were used to determine the types and frequency of medical resources used in follow-up, annual direct medical costs, and survivor perceptions of the personal economic impact of breast cancer.Results. 245 of 314 (78%) invited breast cancer survivors (median follow-up 12.2 years, range 9.3–16.4) completed the surveys. Eighty-seven percent reported having cancer specialist follow-up in the past year. The following percentages of survivors reported having had, for breast cancer follow-up, at least once in the past year: breast examination 92%, mammogram 88, bone scan 18%, chest radiograph 59%, tumor marker studies 37%. When follow-up care included a medical oncologist, resources were more likely to be used at least according to published follow-up guidelines, or over-used. Median annual cost of follow-up per survivor was $630 (range $0–10,817) with higher costs associated with medical oncology follow-up, lower income, and younger age. Few women reported a negative impact of breast cancer on employment, but 16% reported being denied life insurance.Conclusions. Among long-term breast cancer survivors, patient self-report data suggest that over-use of medical resources for follow-up appears common. When follow-up care included a medical oncologist, resources were more likely to be used appropriately, or over-used. Costs of follow-up are higher with medical oncology follow-up, lower income and among younger survivors. The annual cost of follow-up varies widely and may be driven by over-use of follow-up tests.     

Cost-effectiveness of breast cancer screening: Preliminary results of a systematic review of the literature

Summary There is now considerable concern that universal access to health care within realistic resource constraints requires some sort of cost-effectiveness analysis of given medical procedures and interventions. One such intervention is routine mammographic screening for breast cancer. Here, we report preliminary results from an ongoing project to conduct a systematic and comprehensive review and comparison of the published cost-effectiveness analyses of screening for the early detection of breast cancer. We examine 16 such studies, and compare two studies in detail to explain how differences in assumptions and in consideration of down-stream effects have caused the published results for apparently comparable breast cancer screening programs to span a broad range.This minisymposium was presented December 8, 1992, at the annual San Antonio Breast Cancer Symposium, and was sponsored by educational grants from Amgen and from Bristol-Myers Oncology Division.