Characterization of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure.

As MOSFET (Metal Oxide Semiconductor Field Effect Transistor) detectors allow dose measurements in real time, the interest in these dosimeters is growing. The aim of this study was to investigate the dosimetric properties of commercially available TN-502RD-H MOSFET silicon detectors (Best Medical Canada, Ottawa, Canada) in order to use them for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure. Reproducibility of the measurements, dose rate dependence, and dose response of the MOSFET detectors have been studied with a Co source. Influence of the dose rate, frequency, and pulse duration on MOSFET responses has also been studied in pulsed x-ray fields. Finally, in order to validate the integrated dose given by MOSFET detectors, MOSFETs and TLDs (LiF:Mg,Cu,P) were fixed on an Alderson-Rando phantom in the conditions of an interventional neuroradiology procedure, and their responses have been compared. The results of this study show the suitability of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of accident, provided a well-corrected energy dependence, a pulse duration equal to or higher than 10 ms, and an optimized contact between the detector and the skin of the patient are achieved.

Potential of hybrid computational phantoms for retrospective heart dosimetry after breast radiation therapy: a feasibility study.

PURPOSE: Current retrospective cardiovascular dosimetry studies are based on a representative patient or simple mathematic phantoms. Here, a process of patient modeling was developed to personalize the anatomy of the thorax and to include a heart model with coronary arteries. METHODS AND MATERIALS: The patient models were hybrid computational phantoms (HCPs) with an inserted detailed heart model. A computed tomography (CT) acquisition (pseudo-CT) was derived from HCP and imported into a treatment planning system where treatment conditions were reproduced. Six current patients were selected: 3 were modeled from their CT images (A patients) and the others were modelled from 2 orthogonal radiographs (B patients). The method performance and limitation were investigated by quantitative comparison between the initial CT and the pseudo-CT, namely, the morphology and the dose calculation were compared. For the B patients, a comparison with 2 kinds of representative patients was also conducted. Finally, dose assessment was focused on the whole coronary artery tree and the left anterior descending coronary. RESULTS: When 3-dimensional anatomic information was available, the dose calculations performed on the initial CT and the pseudo-CT were in good agreement. For the B patients, comparison of doses derived from HCP and representative patients showed that the HCP doses were either better or equivalent. In the left breast radiation therapy context and for the studied cases, coronary mean doses were at least 5-fold higher than heart mean doses. CONCLUSIONS: For retrospective dose studies, it is suggested that HCP offers a better surrogate, in terms of dose accuracy, than representative patients. The use of a detailed heart model eliminates the problem of identifying the coronaries on the patient's CT.

Minimized doses for linear accelerator radiosurgery of brainstem metastasis.

PURPOSE: Treatment of cerebral metastases located inside the brainstem remains a challenge, as the brainstem is considered to be a neurological organ at risk, whatever the treatment strategy. We report a retrospective study of 30 consecutive patients treated in our institution between 2005 and 2007 with micromultileaf linear accelerator (LINAC)-radiosurgery for brainstem metastases, with reduced doses compared to those usually reported in the literature. METHODS AND MATERIALS: Mean follow-up was 311 days (range, 41-1351). Median age was 57 years (range, 37-82), Mean Karnofsky Index (KI) was 80. Primary tumor site was lung (n = 13), breast (n = 4), kidney (n = 4), skin (melanoma; n = 3), and others (n = 6). Primary tumor was controlled in 17 cases; extracranial metastases were controlled in 12 cases. Mean number of metastases was 1.46 (one to three); median volume was 2.82 cc (0.06-18). Dose was delivered by a micromultileaf collimator 6-MV LINAC . RESULTS: Dose administered at the 70% isodose was 13.4 Gy (range, 8.2-15). Median survival was 10 months. Local control rates at 3, 6, and 12 months were 100%, 100%, and 79% respectively. Median neurological control duration was 5 months. Neurological control rates at 3, 6, and 12 months were 73%, 42%, and 25%, respectively. No parameter was found to significantly correlate with survival, local, or cerebral control. No patients had severe side effects (Grade III-IV), according to the Radiation Therapy Oncology Group (RTOG) scale. CONCLUSION: Lower doses than previously reported can achieve the same local control and survival rates in brain metastases, with minimal side effects.

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.

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.

[New devices in radiation oncology]. / Les nouveaux équipements en radiothérapie.

The development of sophisticated conformal radiation techniques, such as intensity-modulated radiation therapy, image-guided radiation therapy, adaptative radiation therapy, and radiosurgery, implies precise and accurate targeting. To achieve this goal, a lot of new devices and techniques have been designed and are now available in radiation therapy departments : modern 3D-imaging systems, sophisticated treatment planning systems, breathing-adapted radiotherapy equipments (for gating and tracking techniques), in-room 3D-imaging systems, tomotherapy, etc. Purpose of this review is to briefly present the new equipments which are now used in radiation therapy departments in conformal therapy.

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.

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.

Linac stereotactic radiosurgery: an effective and safe treatment for elderly patients with brain metastases.

PURPOSE: To evaluate the outcomes of radiosurgery for brain metastases in patients 65 years or older. PATIENTS AND METHODS: Between January 1994 and January 2003, 117 patients (47 women, 70 men), median age 71 years (range, 65-86 years), received radiosurgery for 227 metastases. Sixty-one patients (55%) presented symptoms in relation to the brain metastases. Thirty-eight patients (32%) received whole-brain radiotherapy. Median metastasis diameter and volume were 21 mm (range, 0.5-75 mm) and 1.7 cc (range, 0.02-71 cc), respectively. RESULTS: Median follow-up was 7 months (range, 1-45 months), 9.5 months for alive patients (range, 1-45 months). Median minimum and maximum doses were 14.5 Gy (6.5 Gy, 19.5 Gy), and 20.4 Gy (13.2 Gy, 41.9 Gy), respectively. Median survival was 8 months from the date of radiosurgery. Overall survival rates at 6 and 24 months were 58% +/- 5% and 13% +/- 4%, respectively. According to multivariate analysis, a low Karnofsky performance status was an independent unfavorable prognostic factor for overall survival (p = 0.003; odds ratio [OR] = 0.28; 95% confidence interval [CI], 0.14-0.56). Median brain disease-free survival was 10 months. Brain disease-free survival rates at 6 and 24 months were 67% +/- 6% and 40% +/- 7%, respectively. According to multivariate analysis, a radiosensitive lesion was an independent favorable factor (p = 0.038; OR = 0.42; 95% CI, 0.18-0.95); more than two metastases and a low Karnofsky performance status were independent unfavorable factors for brain disease-free survival (p = 0.046; OR = 2.15; 95% CI, 1.01-4.58 and p = 0.003; OR = 30.4; 95% CI, 3.1-296, respectively). Local control rates were 98% +/- 2% and 91% +/- 8.5% at 6 and 24 months. Out of the 61 patients presenting symptoms before radiosurgery, complete symptomatic response was achieved in 12 patients (20%), partial improvement in 25 (41%), stabilization in 7 (11%), and worsening in 4 (6%) related to a progression of the irradiated metastasis. Seven cases of radionecrosis were described and were related to the margin dose (p = 0.03). CONCLUSION: Radiosurgery for elderly patients was effective and safe. Age alone should not be a criterion for denying radiosurgery to any patient with brain metastases.

Successful combination of local CpG-ODN and radiotherapy in malignant glioma.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) display broad immunostimulating activity and are currently under clinical trial in various malignancies, including recurrent glioblastomas. Combining CpG-ODN with another therapy that could induce antigen release might enhance tumor-specific immune response. We investigated whether radiotherapy (RT) could be associated advantageously to intratumoral injections of CpG-ODN. Fisher rats bearing 9L glioma were treated with various combinations of RT and CpG-28, an oligonucleotide with good immunostimulating activity. RT and CpG-28 induced complete tumor remission in one-third of the animals. When both treatments were combined, complete tumor remission was achieved in two-thirds of the animals (p < 0.001 when compared to non-treated rats, p < 0.03 when compared to CpG-28 alone). Such efficacy was not observed in nude mice, underlying the role of T cells in antitumor effects. The combination of both treatments appeared optimal when the delay between RT and CpG-28 administration was <3 days (from 100% survival for a 3 days delay, to 57% survival for a 21 days delay, p < 0.05). Tumor infiltration by immune cells and expression within tumors of the CpG receptor, TLR9, were not modified by irradiation. These results support an attractive strategy of sequential radiotherapy and immunotherapy by CpG-ODN and have potential implications for future clinical trials with CpG-ODN.

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.

LINAC radiosurgery for brain metastasis of renal cell carcinoma.

The purpose of the study was to evaluate the efficacy and toxicity of stereotactic radiotherapy in the treatment of the brain metastasis of renal cell carcinoma. From 1994 to 2001, 28 patients presenting with 65 metastases of renal cell cancer were treated by radiosurgery. Median age was 55 years (35-75), and median Karnofski performance status ranges between 50 and 100. Seven patients had received whole brain radiotherapy (WBRT) before radiosurgery. Twelve patients were treated by radiosurgery for 1 metastasis, 5 patients for two metastases and 6 for three, and 5 for more than three metastases. One procedure was performed in 22 patients and, 2 or 3 procedures for 6 patients. Median metastasis diameter was 19 mm (5-55 mm). Median metastasis volume was 1.28 cc (0.02-28 cc). Irradiation was delivered by linear accelerator. Median minimal dose (on the 70% isodose) was 14.7 Gy (10.8 Gy, 19.5 Gy), median maximal dose (at the isocenter) 20.5 Gy (14.3 Gy, 39.6 Gy). Median follow-up was 14 months (1-33). Two metastases progressed (3%), 2 and 12 months after radiosurgery. Overall, crude local control rate was 97% and 3-, 6- and 12-month local control rates were 98% +/- 2%, 98% +/- 2%, and 93% +/- 5%, respectively. In univariate analysis, no prognostic factor of local control was retrieved. Median brain disease-free survival was 25 months after RS. the 3-, 6- and 12-month distant brain control rates were 91% +/- 4%, 91% +/- 4%, and 70% +/- 12%, respectively. Median survival duration was 11 months. The 3-, 6-, 12- and 24-month overall survival rates were 82% +/- 7%, 67% +/- 9%, 48% +/- 10%, and 33% +/- 10%, respectively. According to univariate analysis, only site of metastasis was overall survival prognostic factor. Radiosurgery for brain metastasis of renal cell carcinoma is an effective and accurate treatment. The use of radiosurgery alone is an appropriate management strategy for many patients with brain metastasis of renal cell carcinoma. Radiosurgery is efficient even after development of new metastasis appearing after WBRT.

[Radiosurgery of brain metastasis: reflexions, controversies and unanswered questions in 2004]. / La radiothérapie en conditions stéréotaxiques des métastases cérébrales : réflexions, controverses et questions sans réponse en 2004.

The quantity of results published since the development of the radiochirurgie does not always lead to consider overall the consequences of the introduction of this treatment into the therapeutic arsenal of the clinician. The role of this treatment in front of the surgery, its association with the whole brain radiation therapy, the impact on the survival of this treatment and the incorporation of the various prognostic factors to the therapeutic decision are some one of the unresolved question. Best indications of radiosurgery concern probably patient with a good performance status, without extra-cranial disease and presenting no more than 4 metastasis. However, in an obviously palliative context, any dogmatism must be avoided. Development of prospective trials is the best solution to well specify the indication of the technique.

Radiation-induced cognitive dysfunction: the protective effect of ethyol in young rats.

PURPOSE: To evaluate the protective learning and memory effect of Ethyol in irradiated young rats. METHODS AND MATERIALS: One hundred twenty-eight 45-day-old Wistar rats received whole brain fractionated radiation (30 Gy), whereas 48 rats received sham irradiation. Four irradiated subgroups were defined: saline, 37.5 mg/kg, 75 mg/kg, and 150 mg/kg Ethyol. Sequential behavioral studies including one-way and two-way avoidance tasks were undertaken before and after radiation. RESULTS: Before radiation, the performances of all groups were similar. For the one-way avoidance task, at 1, 3, and 6 months postradiation, saline-irradiated rats had a lower percentage of avoidance than sham- or Ethyol- (75 or 150 mg/kg) irradiated rats (p

Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer.

PURPOSE: To determine local control and survival rates in 92 patients with 145 brain metastases treated with three options of radiotherapy including stereotactic radiosurgery (SR). METHODS: Between July 1994 and August 2002, 92 consecutive patients with 145 metastases were treated with a SR, 34 with initially SR alone, 22 initially with an association of whole-brain radiotherapy (WBRT) and 36 with SR alone for recurrent new brain metastasis after WBRT. At time of treatment, extracranial disease was controlled in 46 (50%) and uncontrolled in 46 (50%). Pathologies were adenocarcinoma in 54 cases (59%), squamous cell carcinoma in 14 cases (15%), small cell carcinoma in 10 cases (11%) and miscellaneous in 14 cases (15%). All patients underwent only one treatment fraction for 1 or 2 metastases in 73 cases (83%) and for more than 2 metastases for the others. RESULTS: The characteristics of patients and metastases in the group treated initially with SR alone and in the group treated initially with WBRT+SR were comparable. Median follow-up was 29 months (18-36). Overall, the median and the 1- and 2-year rates of overall survival were, respectively, 9 months, 37 and 20%. A controlled extracranial disease, a high Karnofsky index and a low number of metastasis were independent prognostic factor of overall survival, respectively, HR 0.53 (95% CI 0.31-0.90, P=0.01), HR 0.95 (95% CI 0.92-0.97, P=0.0002), and HR 0.48 (95% CI 0.25-0.90, P=0.02). Thirteen metastases were not controlled (9%). Six-month and 1-year local control rate were, respectively, 93 and 86%. High delivered dose was an independent prognostic factor of local control, HR 0.41 (95% CI 0.18-0.95, P=0.03). A controlled extracranial disease was favourable independent prognostic factor of brain free-disease free survival, HR 0.47 (95% CI 0.2-0.98, P=0.04). Although there was a trend of a better local control, overall and brain disease free survivals rates in the WBRT+SR group compared to SR alone one, the difference were not statistically different. CONCLUSION: Local control and survival rates are acceptable for a palliative treatment for the three option of treatment. In this series, the number of patients is not enough great to conclude to the necessity of the association of WBRT to SR. Re-irradiation is a safe treatment after new metastases appeared in previously irradiated area.

Radiosurgery for brain metastasis: impact of CTV on local control.

PURPOSE: The purpose of the present analysis was to assess whether adding a 1 mm margin to the gross tumour volume (GTV) improves the control rate of brain metastasis treated with radiosurgery (RS). PATIENTS AND METHODS: All the patients had one or two brain metastases, 30 mm or less in diameter, and only one isocentre was used for RS. There were 23 females and 38 males. The median age was 54 years (34-76). The median Karnofsky performance status was 80 (60-100). At the time of RS, 23 patients had no evidence of extracranial disease and 38 had a progressive systemic disease. Thirty-eight patients were treated up-front with only RS. Twenty-three patients were treated for relapse or progression more than 2 months after whole brain radiotherapy. From January 1994 to July 1995, clinical target volume (CTV) was equal to GTV without any margin (33 metastases). From August 1995 to August 2000, CTV was defined as GTV plus a 1 mm margin (45 metastases). A dose of 20Gy was prescribed to the isocentre and 14Gy at the margin of CTV. RESULTS: The median follow-up was 10.5 months (1-45). The mean minimum dose delivered to GTV was 14.6Gy in the group without a margin and 16.8Gy in the group with a 1 mm margin (P<0.0001). The response of 11 metastases was never assessed because patients died before the first follow-up. Ten metastases recurred, eight in the group treated without a margin and two in the group treated with a 1 mm margin (P=0.01). Two-year local control rates were 50.7+/-12.7% and 89.7+/-7.4% (P=0.008), respectively. Univariate analysis showed that the treatment group (P=0.008) and the tumour volume (P=0.009) were prognostic factors for local control. In multivariate analysis, only the treatment group with a 1 mm margin was an independent prognostic factor for local control (P=0.04, RR: 5.8, 95% CI [1.08-31.13]). There were no significant differences, either in overall survival rate or in early and late side effects, between the two groups. CONCLUSION: Adding a 1 mm margin to the GTV in patients treated with RS significantly improves the probability of metastasis control without increasing the side effects.

Radiation therapy for chordoma and chondrosarcoma of the skull base and the cervical spine. Prognostic factors and patterns of failure.

BACKGROUND: Prospective analysis of local tumor control, survival and treatment complications in 67 consecutive patients treated with fractionated photon and proton radiation for chordoma or chondrosarcoma of the base of the skull and the cervical spine. PATIENTS AND METHODS: Between December 1995 and January 2000, 67 patients with a median age of 52 years (range: 14-85 years), were treated at the Centre de Protonthérapie d'Orsay (CPO), France, using the 201-MeV proton beam, 49 for chordoma and 18 for chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two thirds of the total dose and protons one third. The median total dose delivered within gross tumor volume (GTV) was 67 Cobalt Gray Equivalents (CGE; range: 60-70 CGE). RESULTS: Within a median follow-up of 29 months (range: 4-71 months), the 3-year local control rates were 71% and 85% for chordomas and chondrosarcomas, respectively, and the 3-year overall survival rates 88% and 75%, respectively. 14 tumors (21.5%) failed locally (eight within the GTV, four within the clinical target volume [CTV], and two without further assessment). Seven patients died from their tumor and another one from a nonrelated condition (pulmonary embolism). The maximum tumor diameter and, similarly, the GTV were larger in relapsing patients, compared with the rest of the population: 56 mm vs 44 mm (p = 0.024) and 50 ml vs 22 ml (p = 0.0083), respectively. In univariate analysis, age < or = 52 years at the time of radiotherapy (p = 0.002), maximum diameter < 45 mm (p = 0.02), and GTV < 28 ml (p = 0.02) impacted positively on local control. On multivariate analysis, only age was an independent prognostic factor of local control. CONCLUSION: In chordomas and chondrosarcomas of the skull base and cervical spine, combined photon and proton radiation therapy offers excellent chances of cure. In two thirds of the cases, relapses are located in the GTV. Maximum diameter, GTV, and age are prognostic indicators of local control. These results should be confirmed during a longer follow-up.

Predictive factors of radiation necrosis after radiosurgery for cerebral metastases.

The aim of this study was to determine if the risk of radiation necrosis after radiosurgery is related to the presence of normal tissue included in the prescription volume. Between 1994 and 2001, 377 patients representing 760 lesions were treated by radiosurgery in our center with a 10-MV LINAC. The median age of the patients was 57 years (range 30-86 years), median tumor volume was 4.9 cm(3), median peripheral dose (70%) was 15.6 Gy and median dose at the isocenter was 21.6 Gy. Karnofsky index, disease control and number of lesions were the only parameters significantly influencing survival (median 8.6 months), while disease-free survival was correlated with the number of isocenters. Seven percent of the patients presented severe complications, including nine episodes of radiation necrosis. The only parameter influencing the risk of radiation necrosis was the conformity index (p = 0.001). These findings emphasize the importance of reducing falsely irradiated normal tissue during radiosurgery to prevent radiation necrosis.

[Stereotaxic irradiation of brain metastasis in elderly patients]. / Irradiation en conditions stéréotaxiques des métastases cérébrales chez les patients âgés.

AIMS: Analysis of results of stereotactic irradiation for brain metastases for patients older than 70 years. PATIENTS AND METHODS: From January 1994 to January 2002, 53 patients received stereotactic irradiation for a total of 105 brain metastases. There were 26 females and 27 males. Median age was 73 years (70-86). Median interval between cancer diagnosis and brain metastases was 18 months (0-216). Metastases were diagnosed after development of related clinical symptoms in 34 patients (64.1%). Patients were irradiated for one to 6 metastases. Twenty-nine patients (54.7%) were treated for only one metastasis. Median metastasis diameter and volume were respectively 24 mm (5-74.9 mm) and 2.1 cc (0.02-71.3). Eighty-three metastases were supratentorial (79%), and 22 subtentorial (21%). Forty-five underwent only one procedure (85%) and 8 patients underwent a second procedure for one or several new metastases. Three patients were irradiated with whole brain radiotherapy (WBRT) concomitantly of radiosurgery and three patients received WBRT after radiosurgery for development of more than four metastases or for carcinomatous meningitis. RESULTS: The median follow-up was 8 months (1-33). Median minimum and maximum doses delivered to the metastases were respectively, 16.42 Gy (6.5-20.5) and 20.36 Gy (13.2-41.9). The median overall survival duration was 9 months. Three-, 6-, 12- and 18-month overall survival rates were respectively, 85.6% +/- 5, 65.2% +/- 7.1, 35.5% +/- 7.8 and 26.6% +/- 8. According to unifactorial analysis, two prognostic factors of overall survival were retrieved, extra-cranial disease status and RPAa (Recursive Partitioning Analysis for aged patients) separated in three classes including Karnofsky index performance status and extra-cranial disease status, respectively p = 0.043 et p = 0.016. According to multifactorial analysis only RPAa was an independent prognostic factor of overall survival (p = 0.019, RR: 0.89, 95% confidence interval [0.017-0.47]). Median brain disease-free survival was 12 months. Three-, 6-, 12- and 18-month free-brain disease survival rates were, 81.5% +/- 6.4, 68.7% +/- 8, 47.2% +/- 9.9 and 35.4% +/- 12.6, respectively. No prognostic factor of free-brain disease survival was retrieved. Crude local control rate was 97%. Only three metastases relapsed. Six and 12-month local control rates were 98.6% +/- 1.4 and 88.5% +/- 7.6. Among 34 patients with initial clinical symptoms, one patient presented an aggravation, 9 improved up to complete response (26.5%), 13 patients presented a partial remission (38.2%) and 5 were stabilized (14.7%). For 6 patients, data were not available. We observed 3 radionecroses and 1 hemorrhage of the metastases. CONCLUSION: Radiosurgery in the elderly was efficient and well tolerated. Age alone should not be used to deny potentially beneficial radiosurgery to any patient with brain metastases.

Highly conformal therapy using proton component in the management of meningiomas. Preliminary experience of the Centre de Protonthérapie d'Orsay.

AIMS: To evaluate the efficacy and the tolerance of an escalated dose of external conformal fractionated radiation therapy combining photons and protons in the treatment of intracranial meningiomas. PATIENTS AND METHODS: Between December 1995 and December 1999, 17 patients received a treatment by 201-MeV proton beam at the Centre de Protonthérapie d'Orsay (CPO) for a meningioma. Five patients presented a histologically atypical or malignant meningioma, twelve patients a benign one that was recurrent or rapidly progressive. In two cases radiotherapy was administered in the initial course of the disease and in 15 cases at the time of relapse. A highly conformal approach was used combining high-energy photons and protons for approximately 2/3 and 1/3 of the total dose. The median total dose delivered within gross tumor volume was 61 Cobalt Gray Equivalent CGE (25-69). RESULTS: Median follow-up was 37 months (17-60). The 4-year local control and overall survival rates were 87.5 +/- 12% and 88.9 +/- 11%, respectively. One patient failed locally within the clinical tumor volume. One patient died of intercurrent disease. A complete or partial clinical improvement was seen in most of patients. Radiologically, there were eleven stable diseases and five partial responses. In 12/15 recurrent cases, the free interval after radiotherapy is longer than that achieved by the initial surgery. This radiotherapy was well tolerated. CONCLUSIONS: In both benign and more aggressive meningiomas, the combination of conformal photons and protons with a dose escalated by 10-15% offers clinical improvements in most patients as well as radiological long-term stabilization.