Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review.

OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

Cost-effectiveness of icotinib versus whole-brain irradiation with or without chemotherapy in EGFR-mutant NSCLC patients with brain metastases.

PURPOSE: Nonsmall cell lung cancer (NSCLC) patients with brain metastases (BM) have a poor prognosis. Despite the traditional methods including radiotherapy and chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) might benefit patients on survival and quality of life. We investigated the cost-effectiveness of icotinib compared with whole-brain irradiation (WBI) with or without chemotherapy for NSCLC patients with BM. MATERIALS AND METHODS: A Markov model was conducted based on the data of BRAIN trial. We compared the economic benefit between icotinib and the combination of WBI and WBI plus chemotherapy group. We considered disease progression as intracranial progression and overall progression separately. Sensitivity analyses were performed to observe the stability of the model. The willingness-to-pay (WTP) was set as 3× per capita gross domestic product ($25929/quality-adjusted life year [QALY]) from the Chinese healthcare perspective. RESULTS: When considering progression as intracranial progression and overall progression, respectively, the incremental cost-effectiveness ratio was $14 882.64/QALY and $13 484.21/QALY between icotinib and WBI/WBI-chemotherapy. Besides, both of the average cost-effective ratio (ACER) and net benefit showed advantage of icotinib (ACER: $34 521.42/QALY for intracranial progression and $36 562.63/QALY for overall progression; net benefit: -$8407.36 for intracranial progression and -$9836.41 for overall progression). One-way sensitivity analyses demonstrated that no thresholds were encountered. The probabilistic sensitivity analyses showed even at a WTP under $18 000/QALY, icotinib could be cost-effective. CONCLUSION: Icotinib was cost-effective compared with WBI with or without chemotherapy.

Whole-brain radiotherapy plus sequential or simultaneous integrated boost for the treatment of a limited number of brain metastases in non-small cell lung cancer: A single-institution study.

BACKGROUND: To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). MATERIALS: Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. RESULTS: The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). CONCLUSIONS: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.

Analysis of the drivers of cost of management when patients with brain metastases are treated with upfront radiosurgery.

OBJECTIVES: We aimed to assess the driving factors for increased cost of brain metastasis management when using upfront stereotactic radiosurgery (SRS). PATIENT AND METHODS: 737 patients treated with upfront SRS without whole brain radiotherapy (WBRT). Patients were evaluated for use of craniotomy, length of hospital stay, need for rehabilitation or facility placement, and use of salvage SRS or salvage WBRT. Costs of care of these interventions were estimated based on 2013 Medicare reimbursements. Multiple linear regression was performed to determine factors that predicted for higher cost of treatment per month of life, as well as highest cumulative cost of care for brain metastasis. RESULTS: Mean cost of brain metastasis management per patient was $42,658, and $4673 per month of life. Upfront SRS represented the greatest contributor of total cost of brain metastasis management over a lifetime (49%), followed by use of any salvage SRS (21%), use of initial surgery (14%), use of salvage surgery (10%), hospitalization (3%) and cost of salvage WBRT (3%). Multiple linear regression identified brain metastasis velocity (BMV) (p < 0.001), use of cavity-directed SRS (<0.001), and CNS symptoms at time of presentation (p = 0.005) as factors that increased costs of care per month of survival. Use of salvage WBRT decreased per month cost of care in patients requiring salvage (p < 0.001). CONCLUSION: The cost of upfront SRS is the greatest contributor to cost of brain metastasis management when using upfront SRS. Higher BMV, progressive systemic disease and presence of symptoms are associated with increased cost of care.

Effect of photobiomodulation on the severity of oral mucositis and molecular changes in head and neck cancer patients undergoing radiotherapy: a study protocol for a cost-effectiveness randomized clinical trial.

BACKGROUND: Oral mucositis (OM) is the most frequent and debilitating acute side effect associated with head and neck cancer (HNC) treatment. When present, severe OM negatively impacts the quality of life of patients undergoing HNC treatment. Photobiomodulation is a well-consolidated and effective therapy for the treatment and prevention of severe OM, and is associated with a cost reduction of the cancer treatment. Although an increase in the quality of life and a reduction in the severity of OM are well described, there is no study on cost-effectiveness for this approach considering the quality of life as a primary outcome. In addition, little is known about the photobiomodulation effects on salivary inflammatory mediators. Thus, this study aimed to assess the cost-effectiveness of the photobiomodulation therapy for the prevention and control of severe OM and its influence on the salivary inflammatory mediators. METHODS/DESIGN: This randomized, double-blind clinical trial will include 50 HNC patients undergoing radiotherapy or chemoradiotherapy. The participants will be randomized into two groups: intervention group (photobiomodulation) and control group (preventive oral care protocol). OM (clinical assessment), saliva (assessment of collected samples) and quality of life (Oral Health Impact Profile-14 and Patient-Reported Oral Mucositis Symptoms questionnaires) will be assessed at the 1st, 7th, 14th, 21st and 30th radiotherapy sessions. Oxidative stress and inflammatory cytokine levels will be measured in the saliva samples of all participants. The costs are identified, measured and evaluated considering the radiotherapy time interval. The incremental cost-effectiveness ratio will be estimated. The study will be conducted according to the Brazilian public health system perspective. DISCUSSION: Photobiomodulation is an effective therapy that reduces the cost associated with OM treatment. However, little is known about its cost-effectiveness, mainly when quality of life is the effectiveness measure. Additionally, this therapy is not supported by the Brazilian public health system. Therefore, this study widens the knowledge about the safety of and strengthens evidence for the use of photobiomodulation therapy, providing information for public policy-makers and also for dental care professionals. This study is strongly encouraged due to its clinical relevance and the possibility of incorporating new technology into public health systems. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC, RBR-5h4y4n . Registered on 13 June 2017.

Cost-Effectiveness of Thoracic Radiation Therapy for Extensive-Stage Small Cell Lung Cancer Using Evidence From the Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial (CREST).

PURPOSE: The Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial (CREST) showed that adding thoracic radiation therapy (TRT) to the standard treatment (ST) paradigm of chemotherapy and prophylactic cranial irradiation improves overall survival and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC). We evaluated the cost-effectiveness of adding TRT to ST in ES-SCLC patients. METHODS AND MATERIALS: A cost-utility analysis was performed comparing TRT plus ST versus ST alone. The base-case time horizon was 24 months, consistent with the maximum PFS reported in the CREST. Overall survival was partitioned into 2 health states: PFS and postprogression survival. The proportion of patients in each health state over time was estimated by fitting parametric probability distributions to the CREST survival data. Costs were from a US health care payer perspective, and utilities were derived from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated per quality-adjusted life-year (QALY) using a 3% discount rate. Sensitivity analyses addressed uncertainty in key variables. RESULTS: In the base-case analysis, adding TRT to ST was both cost saving and more effective, thereby strongly dominating ST alone. At willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, TRT was preferred 68%, 81%, and 96% of the time, respectively. In the lifetime scenario analysis, the TRT ICER increased to $194,726/QALY. CONCLUSIONS: By use of the actual follow-up interval reported in the CREST, adding TRT to ST strongly dominates a strategy of ST alone in ES-SCLC patients. Since the long-term survival benefit of TRT is small relative to ongoing costs of progressive metastatic disease, we estimate less favorable ICERs for TRT over a lifetime horizon.

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases.

AIMS: Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. MATERIALS AND METHODS: A Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. RESULTS: In the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. CONCLUSIONS: Based on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS.

Cost-effectiveness of prophylactic cranial irradiation with hippocampal avoidance in limited stage small cell lung cancer.

BACKGROUND AND PURPOSE: Prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) prevents brain metastases and improves survival, with the potential for neurocognitive toxicity. RTOG0933 demonstrated that hippocampal avoidance (HA) during whole brain radiotherapy preserves neurocognition. This study's objective was to evaluate the cost-effectiveness of HA-PCI in LS-SCLC through decision analysis. MATERIALS AND METHODS: A Markov model was developed to simulate the clinical course of LS-SCLC who received HA-PCI or conventional PCI (C-PCI). A willingness-to-pay threshold of $100,000/QALY was used. Incremental cost effectiveness ratio was calculated (ICER). Sensitivity analyses were performed to determine the parameter thresholds and to assess the robustness of the model. RESULTS: In the base case scenario, HA-PCI is more cost-effective than C-PCI, with an ICER of $47,107/QALY. HA-PCI was preferred over C-PCI provided that the risk of developing brain metastases was not increased by at least 14%, or if neurocognitive dysfunction rates were reduced by at least 40%. HA-PCI was the cost-effective strategy in 68% of tested iterations in probabilistic sensitivity analysis. CONCLUSION: This study demonstrates that HA-PCI is more cost-effective than C-PCI in LS-SCLC. Our results support the use of HA-PCI in this patient population, should results from RTOG0933 be confirmed by the ongoing NRGCC003 trial.

Cost-effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for up to 10 brain metastases.

OBJECTIVE The JLGK0901 study found that stereotactic radiosurgery (SRS) is a safe and effective treatment option for treating up to 10 brain metastases. The purpose of this study is to determine the cost-effectiveness of treating up to 10 brain metastases with SRS, whole-brain radiation therapy (WBRT), or SRS and immediate WBRT (SRS+WBRT). METHODS A Markov model was developed to evaluate the cost effectiveness of SRS, WBRT, and SRS+WBRT in patients with 1 or 2-10 brain metastases. Transition probabilities were derived from the JLGK0901 study and modified according to the recurrence rates observed in the Radiation Therapy Oncology Group (RTOG) 9508 and European Organization for Research and Treatment of Cancer (EORTC) 22952-26001 studies to simulate the outcomes for patients who receive WBRT. Costs are based on 2015 Medicare reimbursements. Health state utilities were prospectively collected using the Standard Gamble method. End points included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was $100,000 per QALY. One-way and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions. RESULTS In patients with 1 brain metastasis, the ICERs for SRS versus WBRT, SRS versus SRS+WBRT, and SRS+WBRT versus WBRT were $117,418, $51,348, and $746,997 per QALY gained, respectively. In patients with 2-10 brain metastases, the ICERs were $123,256, $58,903, and $821,042 per QALY gained, respectively. On the sensitivity analyses, the model was sensitive to the cost of SRS and the utilities associated with stable post-SRS and post-WBRT states. In patients with 2-10 brain metastases, SRS versus WBRT becomes cost-effective if the cost of SRS is reduced by $3512. SRS versus WBRT was also cost effective at a WTP of $200,000 per QALY on the probabilistic sensitivity analysis. CONCLUSIONS The most cost-effective strategy for patients with up to 10 brain metastases is SRS alone relative to SRS+WBRT. SRS alone may also be cost-effective relative to WBRT alone, but this depends on WTP, the cost of SRS, and patient preferences.

Impact of image guidance during whole-brain radiation therapy.

PURPOSE: Radiation oncologists are rapidly adopting image-guided radiation therapy (IGRT), warranting further evaluation of its role and value. We analyzed the impact of IGRT for one of the most common radiation treatments. METHODS AND MATERIALS: We retrospectively identified patients who received whole-brain radiation therapy (WBRT) with mask immobilization and who underwent routine IGRT with kilovoltage imaging. We calculated IGRT shifts by comparing couch positions before and after imaging. We determined the dosimetric impact of IGRT on lens maximum and dose received by 95% (D95%) of the brain and cribriform region. We calculated episode of care costs using the Medicare Physician Fee Schedule. RESULTS: A total of 206 patients received 2392 image-guided fractions. The median absolute shift was 1 mm, 1 mm, and 2 mm in the vertical, lateral, and longitudinal directions, respectively. Ninety-nine percent of shifts were ≤6 mm, 7 mm, and 9 mm in the vertical, lateral, and longitudinal directions, respectively. For the 22 patients with the largest average shift per fraction, treating without IGRT would have changed D95% brain by a median 3 cGy (interquartile range, 2-9) and D95% cribriform region by a median 39 cGy (interquartile range, 7-116). Without IGRT, lens doses would have increased for 11/22 patients and decreased for 11/22. Using a 700 cGy lens threshold, there was no net change in the proportion of patients above and below the threshold regardless of IGRT use. For a 10-fraction course, daily IGRT accounted for 10% of the total episode of care cost. CONCLUSIONS: IGRT results in small positional corrections during WBRT. Even among cases with the largest shifts, the dosimetric impact is minor for the brain and modest for the cribriform region and lenses. This study suggests mask immobilization alone is sufficient for routine cases, and it may help clinicians make evidence-based decisions about IGRT in this setting.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND: Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN: A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION: ISRCTN71502099 on 19 May 2014.

Prophylactic cranial irradiation revisited: cost-effectiveness and quality of life in small-cell lung cancer.

PURPOSE: To investigate the therapeutic usefulness and cost-effectiveness of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC) who had achieved a complete remission. METHODS: A retrospective chart review was undertaken of all patients diagnosed in Saskatchewan with SCLC between 1987 and 1998 inclusive. Patients who achieved a complete remission were divided into two groups, depending on whether they underwent PCI (PCI+ and PCI-, respectively). The quality-of-life-adjusted survival was estimated by the Q-TWiST method (quality time without symptoms and toxicity). The mean incremental costs per month of incremental OS were calculated in a cost-effectiveness analysis. RESULTS: Among the 98 complete remission patients, the median OS for PCI+ and PCI- patients was 20.0 and 19.0 months, respectively (p > 0.05, nonsignificant). The median disease-free survival was 14.7 and 10.0 months, respectively (p < 0.05). The difference in the mean Q-TWiST survival was significant (p < 0.01). The mean marginal cost was $18,834/PCI+ patient and $17,885/PCI- patient (p > 0.05, nonsignificant). The cost-effectiveness ratio was $70/mo of incremental OS if u(tox) and u(rel) (the utility coefficients to reflect the value of time in health states of toxicity and relapse) were assumed to be 1.0. CONCLUSION: PCI is a cost-effective treatment that improves the quality-of-life-adjusted survival for patients with a complete remission of SCLC.

Cost and survival analysis of metastatic cerebral tumors treated by resection and radiation.

The surgical treatment of metastatic brain tumors remains controversial, primarily because of the limited prognosis of patients with metastatic cancer. The cost effectiveness of even standard therapies is of increasing concern to third-party payers. We reviewed the records of patients who had a single metastatic brain tumor resected at the Medical Center Hospital of Vermont (a referral center in a rural state) since cost data recording began. The 32 patients ranged in age from 35 to 77 years, with a 2.2:1 female-to-male ratio. Thirty-four percent of tumors originated in the lung, 15.6% were renal, 12.5% were breast, 12.5% were gynecological, 9.4% were gastrointestinal, and 9.4% were ultimately of unknown origin. Thirty-one tumors were completely resected; 30 patients were irradiated, most after surgery (mean dose, 3,908 +/- 1,250 cGy). Karnofsky scores improved from 80 +/- 11 to 88 +/- 16 postoperatively (P = 0.0038, one-tailed paired t-test). Patients were hospitalized an average of 8.22 +/- 6.26 days postoperatively, with total operative and postoperative charges of $19,190 +/- 5,684, noninclusive of radiotherapy. The expected median survival of all patients was 26 months (Kaplan-Meier estimate). The presence of disseminated disease was not significantly correlated with survival (P = 0.237). The number of postoperative days was more for patients with disseminated disease (P = 0.0274), but not for patients with infratentorial tumors (P = 0.6991). Age higher than the median was not correlated with an increased number of postoperative days (P = 0.1366) nor was a preoperative Karnofsky score of 70 or less (P = 0.1382).(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness of stereotactic radiosurgery with and without whole-brain radiotherapy for the treatment of newly diagnosed brain metastases.

OBJECT: Stereotactic radiosurgery (SRS) alone is increasingly used in patients with newly diagnosed brain metastases. Stereotactic radiosurgery used together with whole-brain radiotherapy (WBRT) reduces intracranial failure rates, but this combination also causes greater neurocognitive toxicity and does not improve survival. Critics of SRS alone contend that deferring WBRT results in an increased need for salvage therapy and in higher costs. The authors compared the cost-effectiveness of treatment with SRS alone, SRS and WBRT (SRS+WBRT), and surgery followed by SRS (S+SRS) at the authors' institution. METHODS: The authors retrospectively reviewed the medical records of 289 patients in whom brain metastases were newly diagnosed and who were treated between May 2001 and December 2007. Overall survival curves were plotted using the Kaplan-Meier method. Multivariate proportional hazards analysis (MVA) was used to identify factors associated with overall survival. Survival data were complete for 96.2% of patients, and comprehensive data on the resource use for imaging, hospitalizations, and salvage therapies were available from the medical records. Treatment costs included the cost of initial and all salvage therapies for brain metastases, hospitalizations, management of complications, and imaging. They were computed on the basis of the 2007 Medicare fee schedule from a payer perspective. Average treatment cost and average cost per month of median survival were compared. Sensitivity analysis was performed to examine the impact of variations in key cost variables. RESULTS: No significant differences in overall survival were observed among patients treated with SRS alone, SRS+WBRT, or S+SRS with respective median survival of 9.8, 7.4, and 10.6 months. The MVA detected a significant association of overall survival with female sex, Karnofsky Performance Scale (KPS) score, primary tumor control, absence of extracranial metastases, and number of brain metastases. Salvage therapy was required in 43% of SRS-alone and 26% of SRS+WBRT patients (p < 0.009). Despite an increased need for salvage therapy, the average cost per month of median survival was $2412 per month for SRS alone, $3220 per month for SRS+WBRT, and $4360 per month for S+SRS (p < 0.03). Compared with SRS+WBRT, SRS alone had an average incremental cost savings of $110 per patient. Sensitivity analysis confirmed that the average treatment cost of SRS alone remained less than or was comparable to SRS+WBRT over a wide range of costs and treatment efficacies. CONCLUSIONS: Despite an increased need for salvage therapy, patients with newly diagnosed brain metastases treated with SRS alone have similar overall survival and receive more cost-effective care than those treated with SRS+WBRT. Compared with SRS+WBRT, initial management with SRS alone does not result in a higher average cost.

Cost-effectiveness analysis of a randomized study comparing radiosurgery with radiosurgery and whole brain radiation therapy in patients with 1 to 3 brain metastases.

BACKGROUND: In this study, we compare 2 treatment options and determine cost-effectiveness and cost-utility. METHODS: We carried out a decision analysis populated with data from patients with brain metastasis in a concurrent trial randomized to either stereotactic radiosurgery (SRS) and observation or SRS and whole brain radiation therapy. Outcomes included actual life years saved (LYS), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Costs used were from the healthcare perspective and utilities were captured through a time-trade-off method, using 10-year, 5-year, and 1-year time horizons. One-way sensitivity analyses were carried out to determine robustness of the decision analysis model. RESULTS: Compared with SRS and whole brain radiation therapy, SRS and observation not only had a higher average cost ($74,000 vs $119,000, respectively) but also a higher average effectiveness (0.60 LYS vs 1.64 LYS, respectively) with an ICER of $44,231/LYS or $41,783/QALY (with utilities captured using a 10-year horizon). Slightly higher ICER estimates were achieved with utilities captured using the other time horizons ($43,280/QALY and $44,064/QALY, respectively). Sensitivity analysis showed that the following variables had the highest impact on the ICER: probability of no recurrence in recursive-partitioning analysis class 2 after SRS and observation; probability of being alive after SRS and observation in recursive-partitioning analysis class 2 and being treated for recurrence. CONCLUSIONS: Compared with other interventions in the $50,000 to $100,000/QALY cost-effectiveness range, the application of SRS and observation, with subsequent neurosurgical management of recurrences, is shown to be a reasonable treatment modality for brain metastases.

Dose escalation beyond 30 grays in 10 fractions for patients with multiple brain metastases.

BACKGROUND: Whole-brain radiotherapy (WBRT) to 30 grays (Gy) in 10 fractions is the standard treatment in patients with multiple brain metastases in the majority of treatment centers worldwide. The current study investigated the potential benefit of dose escalation beyond 30 Gy. METHODS: Data regarding 416 patients who were treated with WBRT for multiple brain metastases were evaluated retrospectively. Survival and freedom from recurrent brain metastasis (local control) of 257 patients who were treated with 10 fractions of 3 Gy each for 2 weeks were compared with those of 159 patients treated with 45 Gy in 15 fractions for 3 weeks or 40 Gy in 20 fractions for 4 weeks. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), tumor type, interval between tumor diagnosis and RT, number of metastases, extracranial metastases, and Recursive Partitioning Analysis (RPA) class. RESULTS: On multivariate analysis, improved survival was found to be associated with lower RPA class (P < .001), age <60 years (P = .026), KPS >or=70 (P < .001), and absence of extracranial metastases (P = .003). A trend was observed for number of metastases (2-3 vs >or=4; P = .07). Improved local control was associated with a KPS >or=70 (P < .001) and breast cancer (P < .001). A trend was observed for number of metastases (P = .059). The RT schedule did not appear to have any significant impact on survival (P = .86) or local control (P = .61). The subgroup analyses, performed for each of the 3 RPA classes, did not demonstrate a significantly better outcome with dose escalation. CONCLUSIONS: Dose escalation beyond 30 Gy in 10 fractions does not appear to improve survival or local control in patients with multiple brain metastases but does increase the treatment time and cost of therapy.

Intracavity fractionated balloon brachytherapy in glioblastoma.

In order to reduce hospitalisation time for patients receiving postoperative radiotherapy a phase I-II study of intracavity balloon brachytherapy was instituted. An indwelling balloon catheter was implanted during the closing phase of the initial operation. Starting on the second or third postoperative day the catheter was afterloaded with a high dose rate isotope via a remotely controlled afterloading system. The treatment consisted of 10-12 fractions over a period of 5-6 days, with each treatment session requiring approximately 15 minutes. No external beam radiation was given. Forty-four newly diagnosed patients were treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was given. The overall median survival was 11.7 months, (range 2.7-50.9). The treatment was well tolerated and none of the applicators were removed prematurely. The total median hospital stay for this group of patients was significantly reduced compared to more conventional protocols. This study indicates that intracavity high dose rate balloon brachytherapy can achieve survival rates equivalent to those of conventional radiotherapy and is both cost and time efficient.