A study of the interplay effect for VMAT SBRT using a four-axes motion phantom.

PURPOSE: To assess the accuracy of volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) when treating moving targets (such as lung or liver lesions), focusing on the impact of the interplay effect in the event of complex breathing motion and when a gating window is used. METHODS: A dedicated programmable motion platform was implemented. This platform can carry large quality assurance (QA) phantoms and achieve complex three-dimensional (3D) motion. Volumetric modulated arc therapy SBRT plans were delivered with TrueBeam linac to this moving setup and the measured dose was compared to the computed one. Several parameters were assessed such as breathing period, dose rate, dose prescription, shape of the breathing pattern, the use of a planning target volume (PTV) margin, and the use of a gating window. RESULTS: Loss of dose coverage (D95%) was acceptable in most situations. The doses received by 95% of the CTV, D95% ( C T V m ) ranged from 94 to 101% (mean 98%) and the doses received by 2% of the CTV D2% ( C T V m ) ranged from 94% to 110% of the prescribed dose. A visible interplay effect was observed when no margin was used or when the number of breathing cycles during the treatment delivery was lower than 20. CONCLUSIONS: In our clinical context, treating lung and liver lesions using VMAT SBRT is reasonable. The interplay effect was moderated and acceptable in all simulated situations.

Spatio-spectral regularization to improve magnetic resonance spectroscopic imaging quantification.

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique able to provide the spatial distribution of relevant biochemical compounds commonly used as biomarkers of disease. Information provided by MRSI can be used as a valuable insight for the diagnosis, treatment and follow-up of several diseases such as cancer or neurological disorders. Obtaining accurate metabolite concentrations from in vivo MRSI signals is a crucial requirement for the clinical utility of this technique. Despite the numerous publications on the topic, accurate quantification is still a challenging problem due to the low signal-to-noise ratio of the data, overlap of spectral lines and the presence of nuisance components. We propose a novel quantification method, which alleviates these limitations by exploiting a spatio-spectral regularization scheme. In contrast to previous methods, the regularization terms are not expressed directly on the parameters being sought, but on appropriate transformed domains. In order to quantify all signals simultaneously in the MRSI grid, while introducing prior information, a fast proximal optimization algorithm is proposed. Experiments on synthetic MRSI data demonstrate that the error in the estimated metabolite concentrations is reduced by a mean of 41% with the proposed scheme. Results on in vivo brain MRSI data show the benefit of the proposed approach, which is able to fit overlapping peaks correctly and to capture metabolites that are missed by single-voxel methods due to their lower concentrations. Copyright © 2016 John Wiley & Sons, Ltd.

Virtual bolus for total body irradiation treated with helical tomotherapy.

Intensity-modulated radiation therapy (IMRT) for total body irradiation (TBI) is practiced in several centers using the TomoTherapy System. In this context the planning target volume (PTV) is the entire body including the skin. A safety margin in the air surrounding the body should be added to take into account setup errors. But using inverse planning, over-fluence peak could be generated in the skin region to insure dose homogeneity. This work proposes to study the performance of the use of a virtual bolus (VB). A VB is a material placed on the skin surface during planning, but absent for the real treatment. The optimal VB that compensates large setup errors without introducing a high-dose increase or hot spots for small setup errors was determined. For two cylindrical phantoms, 20VBs with different densities, thicknesses or designs were tested. Dose coverage of the PTV (V95%) in the presence of simulated setup errors was computed to assess the VB performance. A measure of the dose increase in the phantom center due to the absence of the VB during treatment was also achieved. Finally, the fluence peak at the phantom edge was measured in complete buildup conditions using a large phantom and a detector matrix. Using these VBs, simulated setup errors were compensated to a minimum value of 2.6 and 2.1 cm for small and large phantom, respectively (and only 1.2 and 1.7 cm with no VB). An optimal double-layer VB was found with a density of 0.4 kg.m(-3) and a total thickness of 8mm; an inner layer of 5 mm was declared as the target for the treatment planning system and an additional layer of 3 mm was added to avoid the over-fluence peak. Using this VB, setup errors were compensated up to 2.9 cm. The dose increase was measured to be only +1.5% at the phantom center and over-fluence peak was strongly decreased.

A study of the interplay effect in radiation therapy using a Monte-Carlo model.

PURPOSE: In modulated radiotherapy, breathing motion can lead to Interplay (IE) and Blurring (BE) effects that can modify the delivered dose. The aim of this work is to present the implementation, the validation and the use of an open-source Monte-Carlo (MC) model that computes the delivered dose including these motion effects. METHODS: The MC model of the Varian TrueBeam was implemented using GATE. The dose delivered by different modulated plans is computed for several breathing patterns. A validation of these MC predictions is achieved by a comparison with measurements performed using a dedicated programmable motion platform, carrying a quality assurance phantom. A specific methodology was used to separate the IE and the BE. The influence of different motion parameters (period, amplitude, shape) and plan parameters (volume margin, dose per fraction) was also analyzed. RESULTS: The MC model was validated against measurement performed with motion with a mean 3D global gamma index pass rate of 97.5% (3%/3 mm). A significant correlation is found between the IE and the period and the antero-posterior amplitude of the motion but not between the IE and the CTV margin or the shape of motion. The results showed that the IE increases D2% and decreases the D98% of CTV with mean values of +6.9% and -3.3% respectively. CONCLUSIONS: We validated the feasibility to assess the IE using a MC model. We found that the most important parameter is the number of breathing cycles that must be greater than 20 for one arc to limit the IE.

Technical note: GAMMORA, a free, open-source, and validated GATE-based model for Monte-Carlo simulations of the Varian TrueBeam.

PURPOSE: Monte Carlo (MC) is the reference computation method for medical physics. In radiotherapy, MC computations are necessary for some issues (such as assessing figures of merit, double checks, and dose conversions). A tool based on GATE is proposed to easily create full MC simulations of the Varian TrueBeam STx. METHODS: GAMMORA is a package that contains photon phase spaces as a pre-trained generative adversarial network (GAN) and the TrueBeam's full geometry. It allows users to easily create MC simulations for simple or complex radiotherapy plans such as VMAT. To validate the model, the characteristics of generated photons are first compared to those provided by Varian (IAEA format). Simulated data are also compared to measurements in water and heterogeneous media. Simulations of 8 SBRT plans are compared to measurements (in a phantom). Two examples of applications (a second check and interplay effect assessment) are presented. RESULTS: The simulated photons generated by the GAN have the same characteristics (energy, position, and direction) as the IAEA data. Computed dose distributions of simple cases (in water) and complex plans delivered in a phantom are compared to measurements, and the Gamma index (3%/3mm) was always superior to 98%. The feasibility of both clinical applications is shown. CONCLUSIONS: This model is now shared as a free and open-source tool that generates radiotherapy MC simulations. It has been validated and used for five years. Several applications can be envisaged for research and clinical purposes.

Positioning accuracy of a single-isocenter multiple targets SRS treatment: A comparison between Varian TrueBeam CBCT and Brainlab ExacTrac.

PURPOSE: This study compared the positioning accuracy between cone-beam CT (CBCT) and ExacTrac (ETX) for a single-isocenter multiple target stereotactic radiosurgery (SRS) on two TrueBeam STx systems. METHODS: A single-isocenter treatment plan was simulated on an anthropomorphic head phantom with six spherical steel ball bearings (BBs). One of the BBs was chosen to be the isocenter. The five off-isocenter targets were located at various distances from the isocenter. MV portal images were generated to evaluate the deviations between the expected and the real center of the targets after CBCT and ETX positioning, respectively. RESULTS: The evaluation of the positioning accuracy for the isocenter target showed that CBCT and ETX positioning provided comparable, sub-millimetric results. Deviations in positioning accuracy were also calculated for all other targets, also showing comparable results for CBCT and ETX. Moreover, our study showed that the deviation between CBCT and ETX positioning were in better agreement for TBSTx1 and deviated slightly higher on TBSTx2 (maximum: 1.23 mm at S/I direction), due to a less perfect alignment between the CBCT coordinate system and the ETX coordinate system on TBSTx2 compared to TBSTx1. This study also showed a correlation between the target positioning accuracy and the distance to the isocenter. CONCLUSION: The positioning accuracy of ETX and CBCT for targets located at isocenter and off-isocenter locations was compared on two treatment machines and found comparable. Our study highlights the importance of a proper calibration procedure, to ensure correct alignment between the CBCT, ETX and machine coordinate systems.

Dosimetric performance of continuous EPID imaging in stereotactic treatment conditions.

PURPOSE: This study aims at investigating the dosimetric characteristics of a Varian aS1000 EPID, focusing on its continuous acquisition mode under the challenging conditions that can be met in stereotactic radiotherapy verification. METHODS: An aS1000 EPID installed on a Varian TrueBeamSTx was irradiated with 6 and 10 MV unflattened and flattened photon beams. In order to avoid detector saturation, the source-to-detector distance (SDD) was set to 150 or 180 cm depending on the dose rate. EPID image sets were acquired in continuous mode (CM) and also in the commonly used integrated mode (IM) for comparison, to evaluate dose linearity (including dose rate dependence), repeatability, reproducibility, stability, ghosting effect and field size dependence. RESULTS: CM response linearity was found to be within 0.8% of IM and independent of dose rate. Response repeatability was slightly better for IM and FF beams, being in all cases within 0.9%. Reproducibility was within 0.6% for both modes and all beam qualities. Response stability between continuous frames varied within 1% for dynamic and static irradiations and for all the beam qualities, showing its independence from these parameters. Ghosting effect was not significant, being comparable to signal variations between continuous frames (±1%). Field size dependence in both modes agreed within 1%. CONCLUSIONS: The dosimetric response of the aS1000 EPID in CM with FFF beams and high dose rates is comparable to that in IM and for flattened beams provided that the appropriate SDD is used. aS1000 EPID in continuous acquisition mode is therefore suitable for stereotactic applications.

The GIRAFE phase II trial on MVCT-based "volumes of the day" and "dose of the day" addresses when and how to implement adaptive radiotherapy for locally advanced head and neck cancer.

During exclusive curative radiotherapy for head and neck tumors, the patient's organs at risk (OAR) and target volumes frequently change size and shape, leading to a risk of higher toxicity and lower control than expected on planned dosimetry. Adaptive radiotherapy is often necessary but 1) tools are needed to define the optimal time for replanning, and 2) the subsequent workflow is time-consuming. We designed a prospective study to evaluate 1) the validity of automatically deformed contours on the daily MVCT, in order to safely use the "dose-of the day" tool to check daily if replanning is necessary; 2) the automatically deformed contours on the replanning CT and the time gained in the replanning workflow. Forty-eight patients with T3-T4 and/or involved node >2 cm head and neck squamous cell carcinomas, planned for curative radiotherapy without surgery, will be enrolled. They will undergo treatment with helical IMRT including daily repositioning MVCTs. The contours proposed will be compared weekly on intermediate planning CTs (iCTs) on weeks 3, 4, 5 and 6. On these iCTs both manual recontouring and automated deformable registration of the initial contours will be compared with the contours automatically defined on the MVCT. The primary objective is to evaluate the Dice similarity coefficient (DSC) of the volumes of each parotid gland. The secondary objectives will evaluate, for target volumes and all OARs: the DSC, the mean distance to agreement, and the average surface-to-surface distance. Time between the automatic and the manual recontouring workflows will be compared.

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma.

Background and purpose: Pediatric ependymoma carries a dismal prognosis, mainly owing to local relapse within RT fields. The current prospective European approach is to increase the radiation dose with a sequential hypofractionated stereotactic boost. In this study, we assessed the possibility of using a simultaneous integrated boost (SIB), comparing VMAT vs. IMPT dose delivery. Material and methods: The cohort included 101 patients. The dose to planning target volume (PTV59.4) was 59.4/1.8 Gy, and the dose to SIB volume (PTV67.6) was 67.6/2.05 Gy. Gross tumor volume (GTV) was defined as the tumor bed plus residual tumor, clinical target volume (CTV59.4) was GTV + 5 mm, and PTV59.4 was CTV59.4 + 3 mm. PTV67.6 was GTV+ 3 mm. After treatment plan optimization, quality indices and doses to target volume and organs at risk (OARs) were extracted and compared with the standard radiation doses that were actually delivered (median = 59.4 Gy [50.4 59.4]). Results: In most cases, the proton treatment resulted in higher quality indices (p < 0.001). Compared with the doses that were initially delivered, mean, and maximum doses to some OARs were no higher with SIB VMAT, and significantly lower with protons (p < 0.001). In the case of posterior fossa tumor, there was a lower dose to the brainstem with protons, in terms of V59 Gy, mean, and near-maximum (D2%) doses. Conclusion: Dose escalation with intensity-modulated proton or photon SIB is feasible in some patients. This approach could be considered for children with unresectable residue or post-operative FLAIR abnormalities, particularly if they have supratentorial tumors. It should not be considered for infratentorial tumors encasing the brainstem or extending to the medulla.

Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies.

PURPOSE: To evaluate outcomes and tolerance of high-dose photon and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. PATIENTS AND METHODS: Thirty children were treated postoperatively with high-dose photon-proton (29 patients) or protons-only (1 patient) radiotherapy. Twenty-six patients had chordomas (CH), 3 had low-grade chondrosarcomas (CS), and 1 had an aggressive chondroma (AC). The mean age was 12.8 years. At the time of radiation, all but 1 patient had a gross residue. The anatomic sites affected were skull base (n = 16), cervical canal (n = 1), or both (n = 13). Mean total dose was 68.4 cobalt Gray equivalents, conventionally fractionated. RESULTS: With a mean follow-up of 26.5 months, 5 of 30 children failed locally: 5 of 5 lesions were CH, 5 of 5 patients had experienced pain at presentation (p = 0.03), and 4 of 5 had cervical extension (p = 0.07). The 5-year overall survival/progression-free survival rates for CS and CH were 100%/100% and 81%/77%, respectively. Side effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Acute toxicity ranged between 0 and 2. Late toxicity of radiotherapy was severe in 1 patient (Grade 3 auditory) and minor or mild in the rest of the population (7 patients with Grade 2 pituitary dysfunction). CONCLUSIONS: High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.

A treatment planning comparison of combined photon-proton beams versus proton beams-only for the treatment of skull base tumors.

PURPOSE: To compare treatment planning between combined photon-proton planning (CP) and proton planning (PP) for skull base tumors, so as to assess the potential limitations of CP for these tumors. METHODS AND MATERIALS: Plans for 10 patients were computed for both CP and PP. Prescribed dose was 67 cobalt Gray equivalent (CGE) for PP; 45 Gy (photons) and 22 CGE (protons) for CP. Dose-volume histograms (DVHs) were calculated for gross target volume (GTV), clinical target volume (CTV), normal tissues (NT), and organs at risk (OARs) for each plan. Results were analyzed using DVH parameters, inhomogeneity coefficient (IC), and conformity index (CI). RESULTS: Mean doses delivered to the GTVs and CTVs with CP (65.0 and 61.7 CGE) and PP (65.3 and 62.2 Gy CGE) were not significantly different (p > 0.1 and p = 0.72). However, the dose inhomogeneity was drastically increased with CP, with a mean significant incremental IC value of 10.5% and CP of 6.8%, for both the GTV (p = 0.01) and CTV (p = 0.04), respectively. The CI(80%) values for the GTV and CTV were significantly higher with PP compared with CP. Compared with CP, the use of protons only led to a significant reduction of NT and OAR irradiation, in the intermediate-to-low dose (< or =80% isodose line) range. CONCLUSIONS: These results suggest that the use of CP results in levels of target dose conformation similar to those with PP. Use of PP significantly reduced the tumor dose inhomogeneity and the delivered intermediate-to-low dose to NT and OARs, leading us to conclude that this treatment is mainly appropriate for tumors in children.

[Observational study of outpatient unit duration of stay depending on the route of administration (intravenous vs subcutaneous) for a targeted therapy]. / Étude observationnelle du temps passé en hôpital de jour selon la voie d'administration (intraveineuse vs sous-cutanée) d'une thérapie ciblée.

New routes of administration available for some targeted therapies, especially subcutaneous injections, have an impact not only on the patients' daycare experience, but also on the unit's organization. This observational study conducted on 48 voluntary patients at the Institut universitaire du cancer Toulouse-Oncopole shows that the mean duration of the outpatient unit stay is diminished by one hour when a subcutaneous injection is used instead of an intravenous route. This duration decrease is mainly caused by an 82% average reduction in treatment duration. However, the waiting times before and after the treatment itself are not significantly impacted. Organizational methods related to the treatment prescription and preparation remain indeed the same. Anticipated prescription is not noticeably impacted either. This reduction of the duration of stay will truly be obtained if the whole unit's organization is adapted.

Functional outcome of patients with benign meningioma treated by 3D conformal irradiation with a combination of photons and protons.

PURPOSE: To evaluate efficacy and tolerance of external fractionated combination of photon and proton radiation therapy (RT) for intracranial benign meningiomas. METHODS AND MATERIALS: Between 1994 and 2002, 51 patients with intracranial meningiomas of the base of the skull were treated with a combination of photon and proton RT. Median total dose was 60.6 cobalt Gy equivalent (54-64). One hundred eight eye-related symptoms were collected; 80 other symptoms were noted and followed up. RESULTS: Mean follow-up was 25.4 months. Acute tolerance was excellent. Out of the 108 eye-related symptoms, 106 (96%) were evaluated. Improvements were reported for 73 (68.8%) of them. Out of the 88 other miscellaneous symptoms, 81 (92%) were evaluated. Improvements were reported in 54 cases (67%). Median time to improvement ranged from 1 to 24 months after completion of the radiotherapy, depending on the symptom. We did not observe any worsening of primary clinical signs. Radiologically, 1 patient relapsed 4 months after the end of irradiation. Pathology revealed a malignant (Grade 3) transformation of the initial Grade 1 meningioma. Four-year local control and overall survival rates were, respectively, 98% and 100%. Stabilization of the tumor was observed in 38 cases (72%), volume reduction in 10 cases (20%), and intratumor necrosis in 3 cases. Two patients complained of Grade 3 side effects: 1 unilateral hearing loss requiring aid and 1 case of complete pituitary deficiency. CONCLUSION: These results stressed the clinical efficacy of fractionated-associated photon-proton RT in the treatment of meningiomas, especially on cranial nerve palsies, without severe toxicity in almost all patients.

Gamma index comparison of three VMAT QA systems and evaluation of their sensitivity to delivery errors.

PURPOSE: To compare detectors for dosimetric verification before VMAT treatments and evaluate their sensitivity to errors. METHODS AND MATERIALS: Measurements using three detectors (ArcCheck, 2d array 729 and EPID) were used to validate the dosimetric accuracy of the VMAT delivery. Firstly, performance of the three devices was studied. Secondly, to assess the reliability of the detectors, 59 VMAT treatment plans from a variety of clinical sites were considered. Thirdly, systematic variations in collimator, couch and gantry angle plus MLC positioning were applied to four clinical treatments (two prostate, two head and neck cases) in order to establish the detection sensitivity of the three devices. Measurements were compared with TPS computed doses via gamma analysis (3%/3 mm and 2%/2 mm) with an agreement of at least 95% and 90% respectively in all pixels. Effect of the errors on the dose distributions was analyzed. RESULTS: Repeatability and reproducibility were excellent for the three devices. The average pass rate for the 59 cases was superior to 98% for all devices with 3%/3 mm criteria. It was found that for the plans delivered with errors, the sensitivity was quite similar for all devices. Devices were able to detect a 2 mm opened or closed MLC error with 3%/3 mm tolerance level. An error of 3° in collimator, gantry or couch rotation was detected by the three devices using 2%/2 mm criteria. CONCLUSIONS: All three devices have the potential to detect errors with more or less the same threshold. Nevertheless, there is no guarantee that pretreatment QA will catch delivery errors.

Practicability of protontherapy using compact laser systems.

Protontherapy is a well-established approach to treat cancer due to the favorable ballistic properties of proton beams. Nevertheless, this treatment is today only possible with large scale accelerator facilities which are very difficult to install at existing hospitals. In this article we report on a new approach for proton acceleration up to energies within the therapeutic window between 60 and 200 MeV by using modern, high intensity and compact laser systems. By focusing such laser beams onto thin foils we obtained on target intensities of 6 x 10(19) W/cm2, which is sufficient to produce a well-collimated proton beam with an energy of up to 10 MeV. These results are in agreement with numerical simulations and indicate that proton energies within the therapeutic window should be obtained in the very near future using such economical and very compact laser systems. Hence, this approach could revolutionize cancer treatment by bringing the "lab to the hospital-rather than the hospital to the lab".

[Radiation therapy for chordomas and chondrosarcomas of the base of the skull and cervical spine]. / Irradiation par association de photons et de protons des chordomes et des chondrosarcomes de la base du crâne et du rachis cervical.

PURPOSE: Prospective analysis of local tumour control, survival and treatment complications in 67 consecutive patients treated with fractionated photon and proton radiation for a chordoma or a chondrosarcoma of the base of the skull and of the cervical spine. PATIENTS AND METHODS: Between December 1995 and January 2000, 67 patients with a median age of 52.3 years (14-85), were treated using 201 MeV proton beam of the centre de protonthérapie d'Orsay (CPO), 49 for a chordoma and 18 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented 2/3 of the total dose and protons 1/3. The median total dose delivered within gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (60-70). RESULTS: With a mean follow-up of 32 months (4-71), the 3-year local control rates were for chordomas and chondrosarcomas of 70.8% and 85.2%, respectively and 4-year overall survival rates of 87.7% and 75%, respectively. Fourteen tumours (21.5%) failed locally (eight within the gross tumor volume, four into the CTV and 2 in an unknown site). Seven patients died of tumour and one of intercurrent disease. In univariate analysis, age inférieur ou égal à 52.3 years (p = 0.002), maximum tumoral diameter < 44.7 mm (p = 0.02) and GTV < 28.4 mL (0.02), at time of radiotherapy, influenced positively the local control. According to multivariate analysis, only age was an independent prognostic factor of local control. Only five (7.7%) patients presented grade 3 or 4 complications. CONCLUSION: In base of skull chordomas and chondrosarcomas, the combined photon and proton therapy offers excellent chances of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

Positron emission tomography/computed tomography imaging of residual skull base chordoma before radiotherapy using fluoromisonidazole and fluorodeoxyglucose: potential consequences for dose painting.

PURPOSE: To detect the presence of hypoxic tissue, which is known to increase the radioresistant phenotype, by its uptake of fluoromisonidazole (18F) (FMISO) using hybrid positron emission tomography/computed tomography (PET/CT) imaging, and to compare it with the glucose-avid tumor tissue imaged with fluorodeoxyglucose (18F) (FDG), in residual postsurgical skull base chordoma scheduled for radiotherapy. PATIENTS AND METHODS: Seven patients with incompletely resected skull base chordomas were planned for high-dose radiotherapy (dose ≥70 Gy). All 7 patients underwent FDG and FMISO PET/CT. Images were analyzed qualitatively by visual examination and semiquantitatively by computing the ratio of the maximal standardized uptake value (SUVmax) of the tumor and cerebellum (T/C R), with delineation of lesions on conventional imaging. RESULTS: Of the eight lesion sites imaged with FDG PET/CT, only one was visible, whereas seven of nine lesions were visible on FMISO PET/CT. The median SUVmax in the tumor area was 2.8 g/mL (minimum 2.1; maximum 3.5) for FDG and 0.83 g/mL (minimum 0.3; maximum 1.2) for FMISO. The T/C R values ranged between 0.30 and 0.63 for FDG (median, 0.41) and between 0.75 and 2.20 for FMISO (median,1.59). FMISO T/C R >1 in six lesions suggested the presence of hypoxic tissue. There was no correlation between FMISO and FDG uptake in individual chordomas (r = 0.18, p = 0.7). CONCLUSION: FMISO PET/CT enables imaging of the hypoxic component in residual chordomas. In the future, it could help to better define boosted volumes for irradiation and to overcome the radioresistance of these lesions. No relationship was founded between hypoxia and glucose metabolism in these tumors after initial surgery.

Combined proton and photon conformal radiotherapy for intracranial atypical and malignant meningioma.

PURPOSE: To evaluate retrospectively the efficacy of conformal fractionated radiotherapy combining proton and photon beams after primary surgery for treatment of atypical and malignant meningiomas. PATIENTS AND METHODS: Between September 1999 and October 2006, 24 patients (12 male, 12 female) with histopathologically proven meningioma (atypical 19, malignant 5) received postoperative combined radiotherapy with a 201-MeV proton beam at the Centre Protontherapie d'Orsay and a high-energy photon beam. Six patients underwent gross total resection and 18 a subtotal resection. Median gross tumor volume and clinical target volume were 44.7 cm(3) and 153.3 cm(3), respectively. Mean total irradiation dose was 65.01 CGE (cobalt gray equivalent), with a mean proton total dose of 34.05 CGE and a mean photon total dose 30.96 CGE. RESULTS: The median (range) follow-up interval was 32.2 (1-72) months. The overall mean local relapse-free interval was 27.2 (10-50) months, 28.3 (10-50) months for atypical meningioma and 23 (13-33) months for malignant meningioma. Ten tumors recurred locally. One-, 2-, 3-, 4-, 5-, and 8- year local control rates for the entire group of patients were 82.9% +/- 7.8%, 82.9% +/- 7.8%, 61.3% +/- 11%, 61.3% +/- 11%, 46.7% +/- 12.3%, and 46.7% +/- 12.3%, respectively. One-, 2-, 3-, 4-, 5-, and 8- year overall survival rates were 100%, 95.5% +/- 4.4%, 80.4% +/- 8.8%, 65.3% +/- 10.6%, 53.2% +/- 11.6%, and 42.6% +/- 13%, respectively. Survival was significantly associated with total dose. There was no acute morbidity of radiotherapy. One patient developed radiation necrosis 16 months after treatment. CONCLUSIONS: Postoperative combination of conformal radiotherapy with protons and photons for atypical and malignant meningiomas is a well-tolerated treatment producing long-term tumor stabilization.

Chordomas of the base of the skull and upper cervical spine. One hundred patients irradiated by a 3D conformal technique combining photon and proton beams.

To define the prognostic factors for local control and overall survival among 100 consecutive patients with chordoma of the base of skull or upper cervical spine treated by fractionated irradiation combining proton and photon beams. Between December 1993 and August 2002, 100 patients (median age: 53 years [8 - 85], M/F sex ratio: 3/2) were treated by a combination of high-energy photons and protons. The proton component was delivered at the Centre de Protonthérapie d'Orsay (CPO) by a 201 MeV beam. The median total dose delivered to the tumor volume was 67 GyECo. With a median follow-up of 31 months [range: 0 - 87], 25 tumours relapsed locally. The 2- and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, at least 95% of the tumor volume encompassed by the 95% isodose (p = 0.048; RR: 3.4 95%CI [1.01 - 11.8]) and a minimal dose delivered into the tumor volume <56 GyECo (p = 0.042; RR: 2.3 95%CI [1.03 - 5.2]) were independent prognostic factors of local control. Ten patients died. The 2- and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%), respectively. According to multivariate analysis, local tumor control (p = 0.005; RR: 21 95%CI [2.2 - 200]) was a prognostic factor of overall survival. For chordomas of the base of the skull and upper cervical spine treated by surgery and irradiation combining photons and protons, the quality of irradiation, reflected by homogeneity of the dose into the tumor volume, is a major factor of local control. Close attention must be paid to minimize the underdosed areas close to critical organs. The role of surgical resection remains paramount, and a trial of dose escalation would have to consider an increase in the dose to critical organs, especially as current results indicate the low toxicity of this treatment.

Radiotherapeutic factors in the management of cervical-basal chordomas and chondrosarcomas.

OBJECTIVE: To define prognostic factors for local control and survival in 90 consecutive patients treated by fractionated photon and proton radiation for chordoma or chondrosarcoma of the cranial base and upper cervical spine. METHODS: Between December 1995 and December 2000, 90 patients (median age, 51.3 yr; range, 10-85 yr; male/female ratio, 3:2) were treated by a combination of high-energy photons and protons. Sixty-four patients had a chordoma, and 26 had a chondrosarcoma. The proton component was delivered by the 201-MeV proton beam of the Centre de Protontherapie d'Orsay. The median total dose delivered to the gross tumor volume (GTV) was 67 cobalt Gray equivalents (range, 22-70 cobalt Gray equivalents). RESULTS: With a median follow-up of 34 months (range, 3-74 mo), treatment of 25 tumors failed locally. The 3-year local control rates were 69.2% (+/-6.0%) and 91.6% (+/-8.4%) for chordomas and chondrosarcomas, respectively. According to multivariate analysis, a small tumor volume excluded from the 95% isodose line (P = 0.032; relative risk [RR], 0.098; 95% confidence interval [CI], 0.01-0.81) and a controlled tumor (P = 0.049; RR, 0.19; 95% CI, 0.04-0.99) were independent favorable prognostic factors for overall survival. On multivariate analysis, a high minimum dose (P = 0.02; RR, 2.8; 95% CI, 1.2-6.6), a high tumor control probability (P = 0.02; RR, 3.8; 95% CI, 1.2-12.5), a high dose delivered to 95% of the GTV (P = 0.03; RR, 3.4; 95% CI, 1.15-10.2), a high GTV encompassed by the 90% isodose line (P = 0.01; RR, 3.29; 95% CI, 1.29-8.44), and a small GTV excluded from the 90% isodose line (P = 0.036; RR, 0.4; 95% CI, 0.1-0.9) were independent favorable prognostic factors for local control. CONCLUSION: In chordomas and chondrosarcomas of the cranial base and cervical spine treated by surgical resection and then by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose uniformity within the GTV. Special attention must be paid to minimize underdosed areas because of the close proximity of critical structures and to redefine and possibly escalate dose constraints to tumor targets in future studies in view of the low toxicity observed to date.