Pencil beam scanning proton therapy for pediatric intracranial ependymoma.

To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n = 46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6 years (range 1.1-15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5 cc and 9 with >1.5 cc residual tumor respectively). Forty-three (86 %) patients received post-operative chemotherapy before PT according to protocols; 44 (88 %) patients younger than 5 years required general anesthesia. Median prescribed dose was 59.4 Gy (RBE) (range 54-60) delivered in 1.8-2 Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4 months (range 8.5-113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5 cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78 ± 7.5 % and 5-year OS rates were 84 ± 6.8 %. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5 years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92 % of the patients and the number of patients with residual tumor ≥1.5 cc. The rates of late effects compare favorably with published photon-treated cohorts.

Proton therapy for uveal melanoma in 43 juvenile patients: long-term results.

PURPOSE: To examine the metastatic and survival rates, eye retention probability, and the visual outcomes of juvenile patients after proton beam radiotherapy (PBRT) for uveal melanoma (UM). DESIGN: Retrospective case-factor matched control study. PARTICIPANTS AND CONTROLS: Forty-three patients younger than 21 years treated with PBRT for UM were compared with 129 matched adult control patients. METHODS: Information on patient demographics and clinical characteristics were recorded before and after treatment from patients' files. The control group was composed of adult patients (>21 years) matched for tumor size (largest tumor diameter, ±2 mm; height, ±2 mm) and anterior margin location (iris, ciliary body, pre-equatorial or postequatorial choroid). For each juvenile patient, 3 adults were selected. MAIN OUTCOME MEASURES: Comparing outcomes of juvenile and adult patients in terms of metastatic and eye retention rates using the log-rank statistic, relative survival using the Hakulinen method, as well as their visual outcomes. RESULTS: Forty-three juvenile and 129 control cases were reviewed. The metastatic rate at 10 years was significantly lower in juvenile UM patients than in adult controls (11% vs. 34%; P <0.01), with an associated relative survival rate of 93% versus 65% (P = 0.02). Six juvenile patients (14%) demonstrated metastases. One patient underwent enucleation because of a presumed local tumor recurrence and 4 additional patients underwent enucleation because of complications (9.3%). In the adult control group, 27% (n = 35) of matched patients demonstrated metastases, there were 2 cases of local recurrence, and 16% (n = 21) underwent enucleation because of complications. A visual acuity of more than 0.10 was maintained in most cases, without any significant differences before or after treatment observed between both groups. CONCLUSIONS: After PBRT, metastatic and survival rates are significantly better for juvenile than for adult patients with UM. Clinically, juvenile and adult eyes react similarly to PBRT, with patients having a comparable eye retention probability and maintaining a useful level of vision in most cases. This is the largest case-control study of proton therapy in juvenile eyes to date and further validates PBRT as an appropriate conservative treatment for UM in patients younger than 21 years.

Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at paul scherrer institute.

PURPOSE: To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. METHODS AND MATERIALS: Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose of 1.8-2.0 Gy (RBE) per fraction. RESULTS: Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. CONCLUSIONS: Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.

Dose to the developing dentition during therapeutic irradiation: organ at risk determination and clinical implications.

PURPOSE: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. METHODS AND MATERIALS: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. RESULTS: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. CONCLUSIONS: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.

Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors.

PURPOSE: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. METHODS AND MATERIALS: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1, 2, and 3 cc of brain volume (D(0.5), D(1), D(2), D(3)) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. RESULTS: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 ± 5 Gy (RBE) for no toxicity to 74 ± 5 Gy (RBE) for Grade 1 and to 76 ± 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of ≥ 64 Gy (RBE) D(3), ≥ 68 Gy (RBE) D(2), ≥ 72 Gy (RBE) D(1), and ≥ 73 Gy (RBE) D(0.5), respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. CONCLUSIONS: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of establishing an organ-at-risk maximally permissible dose for BP.

Spot scanning-based proton therapy for intracranial meningioma: long-term results from the Paul Scherrer Institute.

BACKGROUND: To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 ± 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm(3) (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. RESULTS: Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade ≥3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). CONCLUSIONS: PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.

Spot-scanning-based proton therapy for extracranial chordoma.

PURPOSE: To evaluate effectiveness and safety of spot-scanning-based proton-radiotherapy (PT) for extracranial chordomas (ECC). METHODS AND MATERIAL: Between 1999-2006, 40 patients with chordoma of C-, T-, and L-spine and sacrum were treated at Paul Scherrer Institute (PSI) with PT using spot-scanning. Median patient age was 58 years (range, 10-81 years); 63% were male, and 36% were female. Nineteen patients (47%) had gross residual disease (mean 69 cc; range, 13-495 cc) before PT, and 21 patients (53%) had undergone prior titanium-based surgical stabilization (SS) and reconstruction of the axial skeleton. Proton doses were expressed as Gy(RBE). A conversion factor of 1.1 was used to account for higher relative biological effectiveness (RBE) of protons compared with photons. Mean total dose was 72.5 Gy(RBE) [range, 59.4-75.2 Gy(RBE)] delivered at 1.8-2.0 Gy(RBE) dose per fraction. Median follow-up time was 43 months. RESULTS: In 19 patients without surgical stabilization, actuarial local control (LC) rate at 5 years was 100%. LC for patients with gross residual disease but without surgical stabilization was also 100% at 5 years. In contrast, 12 failures occurred in 21 patients with SS, yielding a significantly decreased 5-year LC rate of 30% (p = 0.0003). For the entire cohort, 5-year LC rates were 62%, disease-free survival rates were 57%, and overall survival rates were 80%. Rates were 100% for patients without SS. No other factor, including dosimetric parameters (V95, V80) were predictive for tumor control on univariate analysis. CONCLUSION: Spot-scanning-based PT at PSI delivered subsequently to function-preserving surgery for tumor debulking, decompression of spinal cord, or biopsy only is safe and highly effective in patients with ECC without major surgical instrumentation even in view of large, unresectable disease.

Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements?

PURPOSE: To study the potential reduction of dose to organs at risk (OARs) with intensity-modulated proton radiotherapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) photon radiotherapy for left-sided breast cancer patients. METHODS AND MATERIALS: Comparative treatment-planning was performed using planning computed tomography scans of 20 left-sided breast cancer patients. For each patient, three increasingly complex locoregional volumes (planning target volumes [PTVs]) were defined: whole breast (WB) or chest wall (CW) = (PTV1), WB/CW plus medial-supraclavicular (MSC), lateral-supraclavicular (LSC), and level III axillary (AxIII) nodes = (PTV2) and WB/CW+MSC+LSC+AxIII plus internal mammary chain = (PTV3). For each patient, 3D-CRT, IMRT, and IMPT plans were optimized for PTV coverage. Dose to OARs was compared while maintaining target coverage. RESULTS: All the techniques met the required PTV coverage except the 3D-CRT plans for PTV3-scenario. All 3D-CRT plans for PTV3 exceeded left-lung V20. IMPT vs. 3D-CRT: significant dose reductions were observed for all OARs using IMPT for all PTVs. IMPT vs. IMRT: For PTV2 and PTV3, low (V5) left lung and cardiac doses were reduced by a factor >2.5, and cardiac doses (V22.5) were by a factor of >20 lower with IMPT compared with IMRT. CONCLUSIONS: When complex-target irradiation is needed, 3D-CRT often compromises the target coverage and increases the dose to OARs; IMRT can provide better results but will increase the integral dose. The benefit of IMPT is based on improved target coverage and reduction of low doses to OARs, potentially reducing the risk of late-toxicity. These results indicate a potential role of proton-radiotherapy for extended locoregional irradiation in left breast cancer.

Proton spot scanning radiotherapy of spontaneous canine tumors.

Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanning technique to evaluate the safety and efficacy of the system, and to study the acute and late radiation reactions. Nasal tumors, soft tissue sarcomas, and miscellaneous tumors of the head were treated with a median total dose of 52.5 Gy given in 3.5 Gy fractions. Acute effects, late effects, tumor response, and outcome were analyzed. No unexpected radiation reactions were seen, however two dogs did develop in-field osteosarcoma, and one dog developed in-field bone necrosis. Complete response to therapy was seen in 40% (12/30), partial response in 47% (14/30), and no response in 13% (4/30). Median survival for all dogs was 385 days (range of 14-4583 days). Dogs with nasal cavity tumors had a median survival of 385 days (range of 131-1851 days) and dogs with soft tissue sarcomas had a median survival time of 612 days (range of 65-4588 days). Treatment outcome was similar to historical controls. This new proton spot scanning technique proved to be safe and reliable.

Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report.

PURPOSE: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. METHODS AND MATERIALS: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. RESULTS: Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. CONCLUSIONS: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

Experiences at the Paul Scherrer Institute with a remote patient positioning procedure for high-throughput proton radiation therapy.

PURPOSE: To describe a remote positioning system for accurate and efficient proton radiotherapy treatments. METHODS AND MATERIALS: To minimize positioning time in the treatment room (and thereby maximize beam utility), we have adopted a method for remote patient positioning, with patients positioned and imaged outside the treatment room. Using a CT scanner, positioning is performed using orthogonal topograms with the measured differences to the reference images being used to define daily corrections to the patient table in the treatment room. Possible patient movements during transport and irradiation were analyzed through periodic acquisition of posttreatment topograms. Systematic and random errors were calculated for this daily positioning protocol and for two off-line protocols. The potential time advantage of remote positioning was assessed by computer simulation. RESULTS: Applying the daily correction protocol, systematic errors calculated over all patients (n = 94) were below 0.6 mm, whereas random errors were below 1.5 mm and 2.5 mm, respectively, for bite-block and for mask immobilization. Differences between pre- and posttreatment images were below 2.8 mm (SD) in abdominal/pelvic region, and below 2.4 mm (SD) in the head. Retrospective data analysis for a subset of patients revealed that off-line protocols would be significantly less accurate. Computer simulations showed that remote positioning can increase patient throughput up to 30%. CONCLUSIONS: The use of a daily imaging and correction protocol based on a "remote" CT could reduce positioning errors to below 2.5 mm and increase beam utility in the treatment room. Patient motion between imaging and treatment were not significant.

Adjuvant intra-arterial hepatic fotemustine for high-risk uveal melanoma patients.

Uveal melanoma metastases occur most commonly in the liver. Given the 50% mortality rate in patients at high risk of developing liver metastases, we tested an adjuvant intra-arterial hepatic (i.a.h.) chemotherapy with fotemustine after proton beam irradiation of the primary tumour. We treated 22 high-risk patients with adjuvant i.a.h. fotemustine. Planned treatment duration was 6 months, starting with four weekly doses of 100 mg/m(2), and after a 5-week rest, repeated every 3 weeks. The survival of this patient group was compared with that of a 3 : 1 matched control group randomly selected from our institutional database. Half of the patients experienced > or =grade 3 hepatotoxicity (one patient developing cholangitis 8 years later). Catheter-related complications occurred in 18%. With a median follow-up of 4.6 years for the fotemustine group and 8.5 years for the control group, median overall survival was 9 years [95% confidence interval (CI) 2.2-12.7] and 7.4 years (95% CI 5.4-12.7; P=0.5), respectively, with 5-year survival rates of 75 and 56%. Treatment with adjuvant i.a.h. fotemustine is feasible. However, toxicities are important. Although our data suggest a survival benefit, it was not statistically significant. Confirming such a benefit would require a large, internationally coordinated, prospective randomized trial.

New developments in external beam radiotherapy for retinoblastoma: from lens to normal tissue-sparing techniques.

Historically, retinoblastoma was treated with external beam radiotherapy (EBR) and for many years this was the accepted standard of care. With greater knowledge of radiation-induced morbidity and mortality, the trend over the past decade has shifted towards primary chemotherapy for most globe conservative treatments. Such a radical change in treatment modalities has restrained EBR to second-line and salvage indications with little consensus regarding dose, timing and techniques. New radiotherapy options now allow for more focused radiation to the globe with further sparing of adjacent structures in such a way that their role in the management of retinoblastoma need to be reappraised. In this perspective paper, first the historical techniques of using EBR primarily with linear accelerated photons are reviewed. Then modern approaches are described, such as stereotactic conformal radiotherapy using a micromultileaf collimator, and proton therapy using a fixed horizontal beam and tantalum localization, or a rotating ganthry with spot scanning. For the first time, to the authors' knowledge, the benefits of these new irradiation modalities over conventional EBR are illustrated with six successfully treated pilot cases. Finally, some guidelines are provided regarding indications to modern radiation therapy in patients requiring second-line or salvage treatment for intraocular retinoblastoma, as well as adjuvant therapy for orbital involvement.

Sensitivity of intensity modulated proton therapy plans to changes in patient weight.

PURPOSE: A retrospective study to investigate the sensitivity of intensity modulated proton therapy (IMPT) to changes in body weight occurring during the course of radiotherapy for patients treated in the sacral region. MATERIALS AND METHODS: During therapy, important weight gain and loss were observed for two patients treated to para-spinal tumors, which resulted in both patients being re-scanned and re-planned. Both patients were treated as part of their therapy, with a narrow-angle IMPT (NA-IMPT) plan delivering a 'dose hole' around the cauda equina (CE), which was mainly formed through modulation of Bragg peaks in depth. To investigate the impact of these weight changes on the proton range and delivered dose, the nominal fields were re-calculated on the new CT data sets. Results were analyzed by comparing these new plans with those originally delivered and by calculating changes in range and delivered doses in target volumes and normal tissues. RESULTS: Maximum differences in proton range in the CE region of up to +8 mm and -13 mm, respectively, for the patient who gained weight and for the patient who lost weight, increased the maximum dose to the CE by only 2%. This indicates that both IMPT plans were relatively insensitive to substantial range uncertainties. Even greater differences in range (16 mm) in the planning target volume only slightly affected its dose homogeneity (differences in V(90%) of 6% in the worst case). Nevertheless, some large undesired local dose differences were observed. CONCLUSIONS: We demonstrated, that, at least for the two analyzed cases, NA-IMPT plans are less sensitive to weight variations than one may expect. Still, we would advise to calculate new plans in case of substantial change in weight for patients treated in the sacral region, primarily due to the presence of new hot/cold area.

Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute.

PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.

Novel technique of craniospinal axis proton therapy with the spot-scanning system: avoidance of patching multiple fields and optimized ventral dose distribution.

BACKGROUND AND PURPOSE: Conventional craniospinal irradiation (CSI) is a complex procedure carrying a high risk of adverse side effects. Still, it is indispensable for cure in a number of pediatric brain tumors. In this study, the feasibility and the potential advantage of spot-scanning proton therapy for CSI are investigated. MATERIAL AND METHODS: A boy (5.5 years of age) with a recurrent medulloblastoma received CSI with a single posterior field using the spot-scanning system at Paul Scherrer Institute. Dose distribution to the targets and the organs at risk, treatment time, reproducibility of patient positioning, toxicity (according to EORTC/RTOG score), and treatment outcome were evaluated. RESULTS: The plan achieved a homogeneous coverage of the target volume, even using a single field. The doses to the organs ventral to the target were minimized. During treatment, grade 1 skin reaction and grade 2 central nervous system toxicity were observed. After 2 months, the boy presented with a transitory fatigue. After 24 months, he is alive and free of disease. Growth hormones and thyroid hormones are reduced. CONCLUSION: These results, based on a single patient, suggest that spot-scanning proton therapy for craniospinal treatment is feasible and safe. By applying a single dorsal field, difficulties of multiple-field patching can be avoided and the ventral dose spread can be minimized.

Deep propofol sedation for vacuum-assisted bite-block immobilization in children undergoing proton radiation therapy of cranial tumors.

BACKGROUND: Vacuum-assisted bite-block immobilization of the head is a reliable technique for reproducible precise head positioning as used for proton radiation in adults. We report preliminary experience using deep propofol sedation without an artificial airway in children undergoing proton radiation of cranial tumors requiring vacuum-assisted bite-block immobilization. METHODS: Sedation was started with a bolus of i.v. midazolam followed by repeated small boluses of propofol as required to tolerate bite-block insertion and patient positioning. Sedation was maintained by continuous propofol infusion until removal of the bite block. Oxygen was administered by a nasal cannula. SpO2, endtidal CO2 taken at the nose and respiratory adverse events such as coughing, bucking, airway obstruction, regurgitation or aspiration were recorded. Data are mean+/-sd. RESULTS: Ten children aged 2.6+/-0.8 years were treated to date. For each child, cumulative 26.7+/-1.9 radiation fractions were administered. Propofol dose administered for induction, bite-block insertion and patient positioning was 3.9+/-0.5 mg.kg(-1). Time from insertion to removal of the bite block lasted 48.3+/-6.2 min. Endtidal CO2 values were 5.6+/-0.8 kPa (43+/-7 mmHg) and SpO2 values were 98.3+/-1.9% with spontaneous breathing, supplemental oxygen and bite block inserted. No respiratory adverse events occurred during the 267 sedation procedures performed. CONCLUSION: Deep propofol sedation without the use of an artificial airway is an interesting technique for vacuum-assisted bite-block immobilization in young children undergoing precise radiation therapy of cranial tumors. However, simultaneous individual anesthetic challenges require pediatric anesthesiologists highly experienced with the pediatric airway, clinical alertness and closed monitoring.

Spot scanning proton therapy in the curative treatment of adult patients with sarcoma: the Paul Scherrer institute experience.

PURPOSE: To assess the safety and efficacy of spot scanning proton beam therapy (PT) in the curative treatment of soft-tissue sarcoma (STS) in adults patients. PATIENTS AND METHODS: We identified 13 STS patients treated with PT between July 1998 and May 2005 in our institutional database. Tumor histology varied with the most common histologic subtypes including liposarcoma and peripheral nerve sheet tumor. All tumors were located in vicinity of critical structures, such as the spinal cord, optic apparatus, bowel, kidney, or bowel. Of the patients, 6 and 5 patients received PT either as adjuvant therapy for non-R0 resection or for recurrence, respectively. Two patients received radical PT for unresectable disease. The median prescribed dose was 69.4 CGE (CGE = proton Gy x 1.1)-Gy (range, 50.4-76.0) at 1.8 to 2 CGE-Gy (median, 1.9) per fraction. Pre-PT anthracycline-based chemotherapy was delivered to 3 patients only. No patient has been lost to follow-up (median 48.1 months, range, 19.1-100.7 months). RESULTS: Of the 13 patients, all but 2 patients were alive. Local recurrence developed in 3 (23%) patients. The administered dose to these patients was < or =60 Gy-CGE. Distant control was achieved in all but 2 patients (lung metastasis), 1 of whom presented with a concomitant local recurrence. The 4-year local control and metastasis-free survival rates were 74.1% and 84.6%, respectively. Late grade > or =2 toxicity was observed in only 2 patients. CONCLUSIONS: Spot scanning PT is an effective and safe treatment for patient with STS in critical locations. The observed toxicity rate was acceptable.

Extracranial chordoma: Outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation.

PURPOSE: To evaluate the use of postoperative proton therapy (PT) in extracranial chordoma. PATIENTS AND METHODS: Twenty-six patients were treated. Gross total resection was achieved in 18 patients. Nine patients had cervical, 2 had thoracic, 8 had lumbar, and 7 had sacro-coccygeal chordomas. Thirteen patients had implants. PT was administered after function-preserving surgery, using a gantry and spot scanning, without or with intensity modulation (IMPT; 6 patients), and/or photon-based radiotherapy (RT, 6 patients). Median total dose was 72 cobalt Gray equivalent (CGE; range, 59.4-74.4), with means of 70.5 and 73.2 CGE for patients with and without implants. Median follow-up time was 35 months (range, 13-73 months). Adverse events were scored using the Common Terminology Criteria for Adverse Events grading system (version 3.0). RESULTS: At 3 years, actuarial overall survival (OS) and progression-free survival (PFS) rates were 84% and 77%, respectively. One patient each died of local failure (LF), distant failure (DF), suicide, and secondary tumor. We observed 5 LFs and 3 DFs; 3-year LF-free and DF-free survival rates were 86%. We observed four radiation-induced late adverse events (Grade 2 sensory neuropathy; Grade 3 subcutaneous necrosis, and osteonecrosis; and Grade 5 secondary cancer). In univariate analysis, implants were associated with LF (p = 0.034). Gross residual tumor above 30 mL was negatively associated with OS (p = 0.013) and PFS (p = 0.025). CONCLUSIONS: Postoperative PT for extracranial chordomas delivered with spot scanning offers high local control rates. Toxicity was acceptable. Implants were significantly associated with LF. Residual tumor above 30 mL impacted negatively on OS and PFS.