Selecting patients for exclusive permanent implant prostate brachytherapy: the experience of the Paris Institut Curie/Cochin Hospital/Necker Hospital group on 809 patients.

PURPOSE: The aim of this study was to analyze overall and relapse-free survival in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than American Brachytherapy Society (ABS) criteria. METHODS AND MATERIALS: Between January 1999 and September 2004, 809 patients were treated with permanent loose 125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809 patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between 10 and 15, or a Gleason score of 7, or both (non-ABS group). RESULTS: Overall 5-year survival was 98%, with no difference between the ABS group and the non-ABS patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS group; it was significantly lower (p = 0.001) in the non-ABS group but remained satisfactory at 94%. On subgroup analysis, the results appeared to be better for the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason score of 7. CONCLUSIONS: Our results suggest that selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed as recipients of permanent implant brachytherapy as monotherapy.

McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients.

BACKGROUND: Acromegaly, which may be present in patients with McCune-Albright syndrome (MCAS), in association with café-au-lait spots, precocious puberty, and fibrous dysplasia, is often difficult to treat surgically because skull base bone dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs (SAs) generally give only partial responses. The use of radiotherapy (RT) is controversial because of a possible risk of bone sarcomatous transformation. AIM: This study was a retrospective analysis of the efficacy and adverse effects of different treatment modalities in six patients with both MCAS and acromegaly. PATIENTS AND METHODS: Because surgery was impossible and SA failed to normalize GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45-55 Grays). Three patients (two with previous RT) were also prescribed pegvisomant. We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and bone radiological features. RESULTS: GH and IGF-I concentrations fell after RT (median follow-up, 5 yr; range, 0.5-9 yr). Symptoms of acromegaly improved in parallel. Bone sarcomatous transformation was only noted in one patient in a region (the mandible) outside the radiation field. RT alone and/or combined with SA failed to normalize GH/IGF-I levels in the five patients concerned. In contrast, IGF-I levels normalized very rapidly (5-9 months) in the three patients receiving pegvisomant (10-20 mg/d). CONCLUSION: RT may be an option for the treatment of acromegaly in patients with MCAS when surgery is impossible and SA therapy is ineffective. However, although no bone sarcomatous transformation was observed within the radiation field in this series, this risk cannot be ruled out. As shown in this small series of severely affected patients, pegvisomant therapy may thus be useful to normalize IGF-I levels rapidly.

[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.

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.

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.