Cost-Effectiveness of Proton Versus Photon Therapy in Pediatric Medulloblastoma Treatment: A Patient Volume-Based Analysis.

BACKGROUND: Proton radiation therapy offers advantages over photon therapy, assisting with severe side effect avoidance. Pediatric patients with medulloblastoma have demonstrated benefit from this technology in recently published cohort studies. OBJECTIVES: To compare the costs and benefits between proton and photon therapy in treating pediatric medulloblastoma. METHODS: The model was built with a lifetime horizon from the Brazilian health system perspective using a 3% discount rate. A microsimulation model was developed after a literature search, comparing scenarios of equipment life span and number of patients treated per year (50, 100, and 150 patients with 10, 25, and 20 years of equipment life span). The baseline parameters were 50 patients treated annually and 20 years of equipment life span. RESULTS: The quality-adjusted life-year gain was 2.71, and the average incremental cost-effectiveness ratio was $34 590.54 per quality-adjusted life-year. For the willingness-to-pay threshold of 1 gross domestic product per capita, it was observed that the incorporation of the technology would be cost-effective if more than 150 patients were treated per year. The weight of the equipment life span and other variables was limited when it varied in the sensitivity analysis, without significant changes to the model results. CONCLUSIONS: Proton therapy is not cost-effective for pediatric medulloblastoma treatment from the Brazilian health system perspective. The investment is not worth when considering the number of potential patients and the country dimensions.

Computerized assessment of cognitive impairment among children undergoing radiation therapy for medulloblastoma.

PURPOSE: Advantages to computerized cognitive assessment include increased precision of response time measurement and greater availability of alternate forms. Cogstate is a computerized cognitive battery developed to monitor attention, memory, and processing speed. Although the literature suggests the domains assessed by Cogstate are areas of deficit in children undergoing treatment for medulloblastoma, the validity of Cogstate in this population has not been previously investigated. METHODS: Children participating in an ongoing prospective trial of risk-adapted therapy for newly diagnosed medulloblastoma (n = 73; mean age at baseline = 12.1 years) were administered Cogstate at baseline (after surgery, prior to adjuvant therapy) and 3 months later (6 weeks after completion of radiation therapy). Gold-standard neuropsychological measures of similar functions were administered at baseline. RESULTS: Linear mixed models revealed performance within age expectations at baseline across Cogstate tasks. Following radiation therapy, there was a decline in performance on Cogstate measures of reaction time (Identification and One Back). Females exhibited slower reaction time on One Back and Detection tasks at baseline. Higher-dose radiation therapy and younger age were associated with greater declines in performance. Pearson correlations revealed small-to-moderate correlations between Cogstate reaction time and working memory tasks with well-validated neuropsychological measures. CONCLUSIONS: Cogstate is sensitive to acute cognitive effects experienced by some children with medulloblastoma and demonstrates associations with clinical predictors established in the literature. Correlations with neuropsychological measures of similar constructs offer additional evidence of validity. The findings provide support for the utility of Cogstate in monitoring acute cognitive effects in pediatric cancer.

Quality of life in patients with proton-treated pediatric medulloblastoma: Results of a prospective assessment with 5-year follow-up.

BACKGROUND: To the authors' knowledge, health-related quality of life (HRQOL) outcomes are not well described in patients with medulloblastoma. The use of proton radiotherapy (RT) may translate into an improved HRQOL. In the current study, the authors report long-term HRQOL in patients with proton-treated pediatric medulloblastoma. METHODS: The current study was a prospective cohort HRQOL study of patients with medulloblastoma who were treated with proton RT and enrolled between August 5, 2002, and October 8, 2015. Both child report and parent-proxy report Pediatric Quality of Life Inventory (PedsQL) surveys were collected at baseline during RT and annually thereafter (score range on surveys of 0-100, with higher scores indicating better HRQOL). Patients were dichotomized by clinical/treatment variables and subgroups were compared. Mixed-model analysis was performed to determine the longitudinal trajectory of PedsQL scores. The Student t test was used to compare long-term HRQOL measures with published means from a healthy child population. RESULTS: Survey data were evaluable for 116 patients with a median follow-up of 5 years (range, 1-10.6 years); the median age at the time of diagnosis was 7.6 years (range, 2.1-18.1 years). At baseline, children reported a total core score (TCS) of 65.9, which increased by 1.8 points annually (P<.001); parents reported a TCS of 59.1, which increased by 2.0 points annually. Posterior fossa syndrome adversely affected baseline scores, but these scores significantly improved with time. At the time of last follow-up, children reported a TCS of 76.3, which was 3.3 points lower than that of healthy children (P = .09); parents reported a TCS of 69, which was 11.9 points lower than that of parents of healthy children (P<.001). Increased follow-up time from diagnosis correlated with improved HRQOL scores. CONCLUSIONS: HRQOL scores appear to increase over time after treatment in children treated with proton RT for medulloblastoma but remain lower compared with those of parent-proxy reports as well as published means from a healthy normative sample of children. Additional follow-up may translate into continued improvements in HRQOL. Cancer 2018. © 2018 American Cancer Society.

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients.

PURPOSE: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. METHODS AND MATERIALS: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. RESULTS: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. CONCLUSIONS: Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children.

Socioeconomic factors affect the selection of proton radiation therapy for children.

BACKGROUND: Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. METHODS: This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy. RESULTS: Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001). CONCLUSIONS: Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017;123:4048-56. © 2017 American Cancer Society.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

BACKGROUND: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. METHODS AND MATERIALS: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. RESULTS: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). CONCLUSIONS: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation.

BACKGROUND: To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams. METHODS: The dosimetry and alopecia outcomes of 12 children with medulloblastoma (ages 4-15 years) comprise the study cohort. Permanent alopecia was assessed and graded after completion of the entire therapy. Skin threshold doses of permanent alopecia were calculated based on the skin dose from the craniospinal irradiation (CSI) plan using the concept of generalized equivalent uniform dose (gEUD) and accounting for chemotherapy intensity. Monte Carlo simulations were employed to accurately assess uncertainties due to beam range prediction and secondary particles. RESULTS: Increasing the dose of the CSI field or the dose given by the boost field to the posterior fossa increased total skin dose delivered in that region. It was found that permanent alopecia could be correlated with CSI dose with a threshold of about 21 Gy (relative biological effectiveness, RBE) with high dose chemotherapy and 30 Gy (RBE) with conventional chemotherapy. CONCLUSIONS: Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. The alopecia risk as assessed with gEUD could be predicted based on the treatment plan information.

A comparative study on the risks of radiogenic second cancers and cardiac mortality in a set of pediatric medulloblastoma patients treated with photon or proton craniospinal irradiation.

PURPOSE: To compare the risks of radiogenic second cancers and cardiac mortality in 17 pediatric medulloblastoma patients treated with passively scattered proton or field-in-field photon craniospinal irradiation (CSI). MATERIAL/METHODS: Standard of care photon or proton CSI treatment plans were created for all 17 patients in a commercial treatment planning system (TPS) (Eclipse version 8.9; Varian Medical Systems, Palo Alto, CA) and prescription dose was 23.4 or 23.4 Gy (RBE) to the age specific target volume at 1.8 Gy/fraction. The therapeutic doses from proton and photon CSI plans were estimated from TPS. Stray radiation doses were determined from Monte Carlo simulations for proton CSI and from measurements and TPS for photon CSI. The Biological Effects of Ionization Radiation VII report and a linear model based on childhood cancer survivor data were used for risk predictions of second cancer and cardiac mortality, respectively. RESULTS: The ratios of lifetime attributable risk (RLARs) (proton/photon) ranged from 0.10 to 0.22 for second cancer incidence and ranged from 0.20 to 0.53 for second cancer mortality, respectively. The ratio of relative risk (RRR) (proton/photon) of cardiac mortality ranged from 0.12 to 0.24. The RLARs of both cancer incidence and mortality decreased with patient's age at exposure (e), while the RRRs of cardiac mortality increased with e. Girls had a significantly higher RLAR of cancer mortality than boys. CONCLUSION: Passively scattered proton CSI provides superior predicted outcomes by conferring lower predicted risks of second cancer and cardiac mortality than field-in-field photon CSI for all medulloblastoma patients in a large clinically representative sample in the United States, but the magnitude of superiority depends strongly on the patients' anatomical development status.

Patterns of failure after proton therapy in medulloblastoma; linear energy transfer distributions and relative biological effectiveness associations for relapses.

PURPOSE: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. METHODS AND MATERIALS: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. RESULTS: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. CONCLUSIONS: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. RESULTS: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. CONCLUSIONS: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma.

BACKGROUND: Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modality's ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma. METHODS: A cost-effective analysis was performed from the societal perspective using a Monte Carlo simulation model. A population of pediatric medulloblastoma survivors aged 18 years was studied who had received treatment at age 5 years and who were at risk of developing 10 adverse events, such as growth hormone deficiency, coronary artery disease, ototoxicity, secondary malignant neoplasm, and death. Costing data included the cost of investment and the costs of diagnosis and management of adverse health states from institutional and Medicare data. Longitudinal outcomes data and recent modeling studies informed risk parameters for the model. Incremental cost-effectiveness ratios were used to measure outcomes. RESULTS: Results from the base case demonstrated that proton therapy was associated with higher quality-adjusted life years and lower costs; therefore, it dominated photon therapy. In 1-way sensitivity analyses, proton therapy remained the more attractive strategy, either dominating photon therapy or having a very low cost per quality-adjust life year gained. Probabilistic sensitivity analysis illustrated the domination of proton therapy over photon therapy in 96.4% of simulations. CONCLUSIONS: By using current risk estimates and data on required capital investments, the current study indicated that proton therapy is a cost-effective strategy for the management of pediatric patients with medulloblastoma compared with standard of care photon therapy.

Modeling freedom from progression for standard-risk medulloblastoma: a mathematical tumor control model with multiple modes of failure.

PURPOSE: As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. METHODS AND MATERIALS: Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. RESULTS: The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. CONCLUSIONS: Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.

Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient.

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation.

The purpose of this study was to compare the predicted risks of second malignant neoplasm (SMN) incidence and mortality from secondary neutrons for a 9-year-old girl and a 10-year-old boy who received proton craniospinal irradiation (CSI). SMN incidence and mortality from neutrons were predicted from equivalent doses to radiosensitive organs for cranial, spinal and intracranial boost fields. Therapeutic proton absorbed dose and equivalent dose from neutrons were calculated using Monte Carlo simulations. Risks of SMN incidence and mortality in most organs and tissues were predicted by applying risks models from the National Research Council of the National Academies to the equivalent dose from neutrons; for non-melanoma skin cancer, risk models from the International Commission on Radiological Protection were applied. The lifetime absolute risks of SMN incidence due to neutrons were 14.8% and 8.5%, for the girl and boy, respectively. The risks of a fatal SMN were 5.3% and 3.4% for the girl and boy, respectively. The girl had a greater risk for any SMN except colon and liver cancers, indicating that the girl's higher risks were not attributable solely to greater susceptibility to breast cancer. Lung cancer predominated the risk of SMN mortality for both patients. This study suggests that the risks of SMN incidence and mortality from neutrons may be greater for girls than for boys treated with proton CSI.

Mapping radiation dose distribution on the fractional anisotropy map: applications in the assessment of treatment-induced white matter injury.

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. DeltaFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean DeltaFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean DeltaFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors.

Radiotherapy in pediatric medulloblastoma: quality assessment of Pediatric Oncology Group Trial 9031.

PURPOSE: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients. METHODS AND MATERIALS: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates were calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure. RESULTS: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival. CONCLUSIONS: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival.

The potential of proton beam therapy in paediatric cancer.

A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. It is estimated that in paediatric cancers, proton beams are of potential importance in 80-100 children annually in Sweden. About 20 of the patients have medulloblastoma. The main purpose is to reduce late sequelae, but these are also increased chances to avoid myelosupression during e.g. concomitant chemo-radiation and to further intensify the chemotherapy.

Investigation of using a power function as a cost function in inverse planning optimization.

The purpose of this paper is to investigate the use of a power function as a cost function in inverse planning optimization. The cost function for each structure is implemented as an exponential power function of the deviation between the resultant dose and prescribed or constrained dose. The total cost function for all structures is a summation of the cost function of every structure. When the exponents of all terms in the cost function are set to 2, the cost function becomes a classical quadratic cost function. An independent optimization module was developed and interfaced with a research treatment planning system from the University of North Carolina for dose calculation and display of results. Three clinical cases were tested for this study with various exponents set for tumor targets and sensitive structures. Treatment plans with these exponent settings were compared, using dose volume histograms. The results of our study demonstrated that using an exponent higher than 2 in the cost function for the target achieved better dose homogeneity than using an exponent of 2. An exponent higher than 2 for serial sensitive structures can effectively reduce the maximum dose. Varying the exponent from 2 to 4 resulted in the most effective changes in dose volume histograms while the change from 4 to 8 is less drastic, indicating a situation of saturation. In conclusion, using a power function with exponent greater than 2 as a cost function can effectively achieve homogeneous dose inside the target and/or minimize maximum dose to the critical structures.