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Georges Noël

Publications and source records attributed to Georges Noël.

At least 19 recordsLinked to original sources

Conformity index: a review.

We present a critical analysis of the conformity indices described in the literature and an evaluation of their field of application. Three-dimensional conformal radiotherapy, with or without intensity modulation, is based on medical imaging techniques, three-dimensional dosimetry software, compression accessories, and verification procedures. It consists of delineating target volumes and critical healthy tissues to select the best combination of beams. This approach allows better adaptation of the isodose to the tumor volume, while limiting irradiation of healthy tissues. Tools must be developed to evaluate the quality of proposed treatment plans. Dosimetry software provides the dose distribution in each CT section and dose-volume histograms without really indicating the degree of conformity. The conformity index is a complementary tool that attributes a score to a treatment plan or that can compare several treatment plans for the same patient. The future of conformal index in everyday practice therefore remains unclear.

Algorithms↗

Radiosensitization by the poly(ADP-ribose) polymerase inhibitor 4-amino-1,8-naphthalimide is specific of the S phase of the cell cycle and involves arrest of DNA synthesis.

Radiosensitization caused by the poly(ADP-ribose) polymerase (PARP) inhibitor 4-amino-1,8-naphthalimide (ANI) was investigated in 10 asynchronously growing rodent (V79, CHO-Xrs6, CHO-K1, PARP-1+/+ 3T3, and PARP-1-/- 3T3) or human (HeLa, MRC5VI, IMR90, M059J, and M059K) cell lines, either repair proficient or defective in DNA-PK (CHO-Xrs6 and M059J) or PARP-1 (PARP-1-/- 3T3). Pulse exposure to ANI (1-hour contact) potentiated radiation response in rodent cells except in PARP-1(-/-) 3T3 fibroblasts. In contrast, ANI did not significantly enhance radiation susceptibility in asynchronously dividing human cells; yet, single-strand break rejoining was lengthened by ca. 7-fold in all but mouse PARP-1-/- 3T3s. Circumstantial evidence suggested that radiosensitization by ANI occurs in rapidly dividing cells only. Experiments using synchronized HeLa cells consistently showed that ANI-induced radiosensitization is specific of the S phase of the cell cycle and involves stalled replication forks. Under these conditions, prolonged contact with ANI ended in the formation of de novo DNA double-strand breaks hours after irradiation, evoking collision with uncontrolled replication forks of DNA lesions whose repair was impaired by inhibition of the PARP catalytic activity. The data suggest that increased response to radiotherapy by PARP inhibitors may be achieved only in rapidly growing tumors with a high S-phase content.

1-Naphthylamine↗

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.

Adolescent↗

Chondromyxoid fibroma of the skull base: differential diagnosis and radiotherapy: two case reports and a review of the literature.

Chondromyxoid fibromas are uncommon tumours mostly arising in long bones of young males. Involvement of the skull base is extremely rare. We describe two new cases of base of the skull chondromyxoid fibromas. The tumours were incompletely excised and irradiated with protons because of the high risk of complications of another surgical procedure. The rationale for proton therapy was based on the intimate relations between the tumour and the organs at risk. Skull base chondromyxoid fibroma is a very rare, slowly growing benign tumour that can cause severe disabilities due to tumour compression of critical structures. Only surgical resection has been shown to be relatively effective. We report two cases of incompletely excised lesions treated by postoperative high-dose radiation including proton therapy with no active disease and complication. Our review of the literature allows us to conclude that histological diagnosis of lesions in this site is a trap for pathologists and that radiotherapy is not contraindicated.

Adolescent↗

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.

Adolescent↗

[Biological basis for concomitant chemoradiotherapy in carcinomas].

Clinical trials carried out during the last decade have shown that chemo-radiotherapeutic combinations can be used to improve the treatment of locally advanced carcinomas in a range of localisations. A small number of drugs only, among which platinum salts are the most frequently used, was selected on the basis of randomized trials. The rationale for these combinations relies on spatial cooperation for the control of metastases and on interaction at the level of the primary tumour. Such interaction may take place at the molecular level, with altered DNA repair or modification of the lesions induced by drugs or radiation; at the cellular level, notably through cytokinetic cooperation arising from differential sensitivity of the various compartments of the cell cycle to drug or radiation; and at the tissular level including reoxygenation, increased drug uptake or inhibition of repopulation or angiogenesis. Further improvements aiming at an increased therapeutic index, should come from studies on the mode of action of drugs and on the mechanisms of acute toxicity of drugs and radiation.

Antineoplastic Agents↗

Chondrosarcomas of the base of the skull in Ollier's disease or Maffucci's syndrome--three case reports and review of the literature.

Ollier's disease is a rare disease characterized by constitutional bone dysplasia with multiple enchondromas. The combination of haemangioma and chondromatoses is known as Maffucci's syndrome. Malignant degeneration of bone dysplasia into chondrosarcoma is a well-known complication, but a lesion of the base of the skull is exceptional. It is a slowly growing low-grade malignant tumour. Three new cases of chondrosarcoma of the base of the skull occurring in one patient with Marfucci's syndrome and two patients with Ollier's disease are reported and these cases are discussed in the light of the literature. A multidisciplinary approach, comprising surgery and radiotherapy, achieved good results.

Adult↗

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.

Adolescent↗

[Radiosurgery of brain metastasis: reflexions, controversies and unanswered questions in 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.

Brain Neoplasms↗

Poly(ADP-ribose) polymerase (PARP-1) is not involved in DNA double-strand break recovery.

BACKGROUND: The cytotoxicity and the rejoining of DNA double-strand breaks induced by gamma-rays, H2O2 and neocarzinostatin, were investigated in normal and PARP-1 knockout mouse 3T3 fibroblasts to determine the role of poly(ADP-ribose) polymerase (PARP-1) in DNA double-strand break repair. RESULTS: PARP-1-/- were considerably more sensitive than PARP-1+/+ 3T3s to induced cell kill by gamma-rays and H2O2. However, the two cell lines did not show any significant difference in the susceptibility to neocarzinostatin below 1.5 nM drug. Restoration of PARP-1 expression in PARP-1-/- 3T3s by retroviral transfection of the full PARP-1 cDNA did not induce any change in neocarzinostatin response. Moreover the incidence and the rejoining kinetics of neocarzinostatin-induced DNA double-strand breaks were identical in PARP-1+/+ and PARP-1-/- 3T3s. Poly(ADP-ribose) synthesis following gamma-rays and H2O2 was observed in PARP-1-proficient cells only. In contrast neocarzinostatin, even at supra-lethal concentration, was unable to initiate PARP-1 activation yet it induced H2AX histone phosphorylation in both PARP1+/+ and PARP-1-/- 3T3s as efficiently as gamma-rays and H2O2. CONCLUSIONS: The results show that PARP-1 is not a major determinant of DNA double-strand break recovery with either strand break rejoining or cell survival as an endpoint. Even though both PARP-1 and ATM activation are major determinants of the cell response to gamma-rays and H2O2, data suggest that PARP-1-dependent poly(ADP-ribose) synthesis and ATM-dependent H2AX phosphorylation, are not inter-related in the repair pathway of neocarzinostatin-induced DNA double-strand breaks.

Animals↗

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.

Adolescent↗

Radiotherapy and chemotherapy with or without carbogen and nicotinamide in inoperable biopsy-proven glioblastoma multiforme.

BACKGROUND: Nicotinamide and carbogen have been shown to enhance the radiation effect in tumour models. PURPOSE: Prospective evaluation of the toxicity and efficacy of carbogen and nicotinamide with external beam radiotherapy in the management of inoperable glioblastoma. PATIENTS AND METHODS: From April 1995 to December 1997, 33 patients with inoperable biopsy-proven glioblastoma multiforme (GBM) were enrolled in a phase II trial, to undergo radiotherapy (59.4 Gy in 1.8 Gy/fraction), intra-arterial cerebral chemotherapy (ACNU 100 mg/m(2), three cycles), carbogen breathing (15 l/min), and nicotinamide (85 mg/kg). This experimental group was compared to a control group of 38 patients with inoperable GBM treated with radiotherapy and three cycles of nitrosourea-based chemotherapy from January 1990 to March 1995, in our institution. RESULTS: In the experimental group, carbogen breathing was well tolerated, but only 51.5% of patients completed daily nicotinamide over the 6.5-week treatment period. Nausea and vomiting were the most frequent side effects of nicotinamide. No significant difference in overall survival was observed among the two treatment groups: median survival times were 36.7 and 35.3 weeks for patients treated with carbogen and nicotinamide, and for those treated in the control group, respectively. CONCLUSION: The association of carbogen and nicotinamide with radiotherapy is feasible, but tolerable only in 51.5% of patients with GBM. Carbogen and nicotinamide did not appear to modify the evolution of glioblastoma.

Adult↗

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.

Adenocarcinoma↗

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.

Adult↗

[Chemoradiotherapy of solid tumours in the adult: current views and perspectives].

Clinical trials carried out during the last decade have given clear indication on the potential of concomitant association of radiotherapy and chemotherapy for improving local control and survival rates in the management of locally advanced solid tumours. In most trials, cisplatin was used alone or in combination with other drugs. Meta-analysis pointed to the potential of these combinations in head and neck, lung, cervical and oesophagus cancers. The interaction of radiotherapy with chemotherapy for these solid tumours appears to depend primarily on the time-scheduling of radiation versus drug exposure and on radiation fractionation. Major improvements aiming at increasing therapeutic index, are expected from studies on the mode of action of drugs and on the mechanisms of acute toxicity of drugs and radiation.

Adult↗

[Stereotaxic irradiation of brain metastasis in elderly patients].

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.

Aged↗

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.

Adolescent↗