Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years.

BACKGROUND: Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique. METHODS: Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed. RESULTS: After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups. CONCLUSION: The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.

Craniospinal irradiation with concomitant and adjuvant temozolomide--a feasibility assessment of toxicity in patients with glioblastoma with a PNET component.

There is no standard treatment for glioblastoma with elements of PNET (GBM-PNET). Conventional treatment for glioblastoma is surgery followed by focal radiotherapy with concurrent temozolomide. Given the increased propensity for neuroaxial metastases seen with GBM-PNETs, craniospinal irradiation (CSI) with temozolomide (TMZ) could be a feasible treatment option but little is known regarding its toxicity. The clinical records of all patients treated at two UK neuro-oncology centres with concurrent CSI and TMZ were examined for details of surgery, radiotherapy, chemotherapy and toxicities related to the CSI-TMZ component of their treatment. Eight patients were treated with CSI-TMZ, the majority (6/8) for GBM-PNET. All patients completed radiotherapy to the craniospinal axis 35-40 Gy in 20-24 daily fractions with a focal boost to the tumour of 14-23.4 Gy in 8-13 daily fractions. Concurrent TMZ was administered at 75 mg/m(2) for seven of the cohort, with the other patient receiving 50 mg/m(2). The most commonly observed non-haematological toxicities were nausea and vomiting, with all patients experiencing at least grade 2 symptoms of either or both. All patients had at least grade 3 lymphopaenia. Two patients experience grade 4 neutropaenia and grade 3 thrombocytopaenia. Three of the eight patients required omission of TMZ for part of their chemoradiotherapy and 3/8 required hospital admission at some point during chemoradiotherapy. The addition of TMZ to CSI did not interrupt radiotherapy. Principal toxicities were neutropaenia, lymphopaenia, thrombocytopaenia, nausea and vomiting. Treatment with CSI-TMZ merits further investigation and may be suitable for patients with tumours at high-risk of metastatic spread throughout the CNS who have TMZ-sensitive pathologies.

Practical aspects of pediatric proton radiation therapy.

Many radiotherapy centers desire proton therapy (PrT) because the unique physical dosimetry allows for improved dose distribution in some clinical situations. These benefits are best described in skull base and many pediatric lesions. However, there are significant challenges to PrT that are overlooked or simply ignored when centers embark on the PrT journey particularly as it applies to pediatric patients.In this review, we review the Indiana University Health Proton Therapy Center experience regarding benefits and drawbacks of PrT for pediatric patients. In conclusion, centers aspiring to PrT capacity should be aware not only of the well-described benefits in some clinical scenarios, but also the significant challenges to the modality in its practical clinical application.

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.

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.