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Gliomas are the most frequent primary brain tumours. Treating these tumours is difficult because of the proximity of organs at risk, infiltrating nature, and radioresistance. Clinical prognostic factors such as age, Karnofsky performance status, tumour location, and treatments such as surgery, radiation therapy, and chemotherapy have long been recognized in the management of patients with gliomas. Molecular biomarkers are increasingly evolving as additional factors that facilitate diagnosis and therapeutic decision-making. These practice guidelines aim at helping in choosing the best treatment, in particular radiation therapy.

Gliomas are the most frequent primary brain tumors. Their care is difficult because of the proximity of organs at risk. The treatment of glioblastoma includes surgery followed by chemoradiation with the protocol of Stupp et al. The addition of bevacizumab allows an increase in progression-free survival by 4 months but it does not improve overall survival. This treatment is reserved for clinical trials. Intensity modulation radiotherapy may be useful to reduce the neurocognitive late effects in different types of gliomas. In elderly patients an accelerated radiotherapy 40 Gy in 15 fractions allows a similar survival to standard radiotherapy. O(6)-methylguanine-DNA methyltransferase (MGMT) status may help to choose between chemotherapy and radiotherapy. There is no standard for the treatment of recurrent gliomas. Re-irradiation in stereotactic conditions allows a median survival of 8 to 12.4 months. Anaplastic gliomas with 1p19q mutation have a greater sensibility to chemotherapy by procarbazine, lomustine and vincristine. Chemoradiotherapy in these patients has become the standard treatment. Many studies are underway testing targeted therapies, their place in the therapeutic management and new radiotherapy techniques.

Natural killer (NK)/T-cell lymphoma are part of lymphoproliferative diseases, they are rare in Europe and the United States but relatively common in Asia and South America. Natural killer (NK)/T-cell lymphoma present clinically as destructive lesions of the upper aerodigestive tract with perforation of deep structures of the face, destruction of the palate or an invasion of orbits. Treatment modalities of these lymphomas are still discussed because of the lack of available studies and the rarity of this disease. Radiotherapy provides a rapid control of the disease and is positioned as a major treatment of localized stages of NK/T-cell lymphoma of the nasal cavity. We therefore studied the different forms of radiation therapy in the early stages of nasal NK/T-cell lymphoma.

Central neurocytoma is a rare primary central nervous system tumour of young adults with good prognosis. Typical and atypical forms are described according to various histologic and histopathologic parameters. Central neurocytoma develops in the periventricular areas and is revealed by increased intracranial pressure. The tumour exhibits typical characteristics on CT scan and MRI and a characteristic peak of glycine on spectroscopy-MRI. The main treatment is total resection, which is achievable only in half of the cases. External beam therapy improves local control of partially resected and/or atypical central neurocytoma. Many studies show that stereotactic radiotherapy can be used in the therapeutic management as exclusive treatment, in postoperatives residues and in case of distant recurrence. Chemotherapy is the last line of treatment in refractory forms, especially in the forms with extracranial and/or neuromeningeal spread and in recurrent forms after treatment with surgery and/or radiotherapy.

Many clinical studies have showed the key role of radiotherapy in anticancer treatment strategy. Radiations are delivered alone or in combination with systemic therapies. In recent years, the main goal of all clinical developments has focused on improving clinical benefit, with an increased tumour control and a higher normal tissue protection. This research was designed to reduce local recurrences, to increase recurrence-free or overall survival and to decrease acute and late effects. Technological and biological evolutions (or revolutions) accompanied clinicians to improve clinical benefit, namely with strong progress in radiology and better understanding of radiobiology, particularly at the molecular level. Differences in tumour and normal tissues radiosensitivity are nowadays integrated in daily clinical practice of radiation oncologists. The current report details the last 5-year developments of clinical and translational research in radiation oncology, especially the role of French teams in the development of personalized treatment.

The purpose of this review was to analyze data available on reirradiation for high-grade glioma or brain metastasis. This reirradiation can be 3D conformal or stereotactic. There are no randomized trials. No definitive recommendations can be given but solutions can be proposed. In high-grade gliomas, results of 3D conformal irradiation are fair. Stereotactic irradiation produces more encouraging survival rates but the range of doses delivered is too large for allowing recommendations. However, fractions less than 5Gy seem better tolerated. In brain metastases, total brain irradiation seems useful if metastases are multiple and the patient in good condition. With radiosurgery, local control rates are high and survival encouraging. In a retrospective study, bifractionated irradiation looked interesting when compared to radiosurgery. Overall prospective trials seem to be necessary.

Retrospective analysis of ten cases of germinoma of the central nervous system treated in Pitié-Salpêtrière Hospital, Paris.Ten male patients were treated from 1997 to 2005 for histologically verified primary seminoma of the central nervous system. The median age was 27 years (range 18-40 years). Our option for the treatment was the association of 3-4 cycles of neoadjuvant chemotherapy (cisplatin and etoposide) to radiotherapy. Five patients received a craniospinal radiotherapy of 30 Gy (for one patient 36 Gy) followed by a tumoral boost from 20 to 24 Gy. For five patients, irradiated volume was limited to the tumour, total dose from 24 to 54 Gy (for three patients the total dose was from 24 to 30 Gy). Surgery was used for five patients, but only in one case was macroscopic complete.Six patients were in situation of complete remission after neoadjuvant chemotherapy. All the patients were in situation of complete remission after the irradiation. All the patients were alive free of disease with a median follow-up 46 months (range 13-90 months).In spite of the fact that the intracranial germinal tumours are not the subject of a consensual treatment strategy, this retrospective analysis pleads in favour of chemotherapy followed by limited dose and volume irradiation.

Goal of radiotherapy is to treat patient with the best therapeutic ratio, i.e. the highest local control and the lowest toxicity rates. The conformal approach, three-dimensional conformal radiotherapy or intensity-modulated radiotherapy, is based on imageries, up-dated 3-D treatment planning systems, immobilization systems, restricted quality assurance and treatment verification. The aim is to ensure a high dose distribution tailored to the limits of the target volume, while reducing exposure of normal tissues. The evaluation tools used for optimizing treatment are the visual inspection of the dose distribution in various planes, and the dose-volume histograms, but they do not fully quantify the conformity of dose distributions. The conformal index is a tool for scoring a given plan or for evaluating different treatment plans for the same patient. This paper describes the onset and evolution of conformal index and his potential application field.

Glioblastoma multiform and astrocytoma are the most frequent primary cancer of the central nervous system of adult. Definitions of gross tumor volume (GTV) and clinical target volume (CTV) are based on the confrontation of clinical presentation (age, performance status, neurologic symptoms...), histological type and imaging aspects. For glioblastoma multiform, the GTV can be defined by the area of contrast enhancement observed on the CT scan or MRI. Definition of the CTV can be more difficult and have to take into account the risk of presence of isolated malignant cells in the oedema surrounding the tumor or in the adjacent brain structures. The classical concept of GTV plus a safety margin of 2 cm around is discussed with a CTV containing at least all the oedematous area and eventually adjacent brain structures (nuclei, corpus callosum or other long associative fibers...). For low grade astrocytoma, the definition of GTV can be difficult if the tumoral infiltration is diffuse without nodular visible tumor. CTV corresponds to at least T2 MRI hypersignal area when visible. For postoperative tumor, technical considerations are important for the detection of residual tumor. A safety margin around the resected area is designed according to the risk of presence of isolated cells or involvement of adjacent brain structures.

Cerebral meningiomas account for 15-20% of all cerebral tumours. Although seldom malignant, they frequently recur in spite of complete surgery, which remains the cornerstone of the treatment. In order to decrease the probability of local recurrence, radiotherapy has often been recommended in atypical or malignant meningioma as well as in benign meningioma which was incompletely resected. However, this treatment never was the subject of prospective studies, randomized or not. The purpose of this review of the literature was to give a progress report on the results of different published series in the field of methodology as well as in the techniques of radiotherapy. Proposals for a therapeutic choice are made according to this analysis. For grade I or grade II-III meningiomas, limits of gross tumor volume (GTV) include the tumour in place or the residual tumour after surgery; clinical target volume (CTV) limits include gross tumour volume before surgery with a GTV-CTV distance of 1 and 2 cm respectively. Delivered doses are 55 Gy into CTV and 55-60 Gy and 70 Gy into GTV for grade I and grade II-III meningiomas respectively.

Gliomas are moderately radiosensitive. The main prognostic factors are the anatomicopathological type and grade of glioma, the performance status, age of the patient and the extent of the surgery. According to data from the literature, high-grade gliomas should be given 60 Gy in five weekly fractions of 1.7 to 2 Gy in a volume including tumor or tumor bed, edema and a 2- to 3-cm margin. A dose of 45 Gy would be sufficient for low-grade gliomas, according to the results of a recent randomized EORTC trial. Brachytherapy and radiosurgery techniques may be indicated in selected cases.

Conformal irradiation of brain tumours is based on the three-dimensional reconstruction of the targeted volumes and at-risk organ images, the three-dimensional calculation of the dose distribution and a treatment device (immobilisation, beam energy, collimation, etc.) adapted to the high precision required by the procedure. Each step requires an appropriate methodology and a quality insurance program. Specific difficulties in brain tumour management are related to GTV and CTV definition depending upon the histological type, the quality of the surgical resection and the medical team. Clinical studies have reported dose escalation trials, mostly in high-grade gliomas and tumours at the base of the skull. Clinical data are now providing a better knowledge of the tolerance of normal tissues. As for small tumours, the implementation of beam intensity modulation is likely to narrow the gap between conformal and stereotaxic radiotherapy.

About 30% of patients who underwent percutaneous transluminal coronary angioplasty show evidence of restenosis, which appears to be independent of the angioplasty method used. The restenosis is due of two factors, firstly migration of smooth vascular muscle cells of the vascular media to the intima and multiplication which lead to the formation of a neo-intima. Irradiation limits the proliferation by acting of the cells in the mitotic stage. The vascular target volume is not very thick and is difficult to define it, that why brachytherapy seems to be the best procedure to prevent restenosis. However, the development of this treatment present many difficulties. Different irradiation techniques have been studied. Such techniques include catheter containing radioactive sealed source, radioactive stent, or balloon containing radioactive liquid inside. Each of these methods have their own advantages, inconveniences, problems and risks. Radioisotope may be either beta or gamma emitters. Gamma emitter presents problems for radioprotection but the satisfactory dose distribution may be difficult to obtain using beta emitter. Choice of dose, dose rate and delay between the end of angioplasty and the beginning of brachytherapy is subject to some discuss. Animal experiments using radioisotope have shown reduction in cell proliferation. Human trials showed feasibility, safety of the method and real impact on restenosis prevention. However, long-term efficacy has not been proved because the follow-up of the patients is too short. A randomized trial of 192Ir brachytherapy for prevention of restenosis has recently shown the efficacy in short and median term. However, long term efficiency and secondary effects have not yet been established as the follow up time of this study is still too short. That is why, collaboration between cardiologists and radiotherapists and physicists is indispensable to enable the development of an optimal technique.

We have looked for trials which are in progress in the field of stereotactic radiotherapy (radiosurgery) of malignant brain tumors. Most randomized trials are conducted by the Radiation Therapy Oncology Group (RTOG) or the European Organization for Research and Treatment of Cancer (EORTC) and assess the role of radiosurgery in treatment of high grade glioma and brain metastasis.

Glioblastoma cells appear to be inherently radioresistant and to present a significant fraction of hypoxic cells. The most significant prognostic factors to compare results achieved in several series of patients are the age, performance status and quality of surgical resection. Several randomized trials have provided evidence supporting the efficacy of radiation therapy in the treatment of glioblastoma. Prescription of a 60-Gy dose delivered according to a conventional dose-fractionation scheme (single daily fractions of 1.7 to 2 Gy five times per week) in a target volume with a 2-3 cm margin of tissue surrounding the perimeter of the contrast enhancing lesion on computerized tomography and magnetic resonance imaging is derived from observations made in several retrospective and prospective studies. Evidence of improvement in survival was observed neither in patients receiving hyperfractioned and accelerated radiotherapy, nor in patients for whom radiation sensitizers such as nitroimidazole compounds or halogenated pyrimidine analogs were associated to radiation therapy. The addition of nitrosourea to radiotherapy increases the 2-year survival rate by about 10%. Combination of full-dose external beam radiotherapy and brachytherapy or radiosurgery boost in selected patients with glioblastoma leads to an increase in the median survival, while external beam radiation alone in patients with similar prognosis does not.

To determine the efficacy and safety of induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of stage III non-small cell lung cancer and whether the response to induction chemotherapy can predict the response to subsequent chemoradiotherapy and survival.Between December 1987 and June 1993, 46 patients with previously untreated stage III non-small cell lung cancer received every 21 days induction chemotherapy (ICT) including three cycles of 5-fluorouracil (600 mg/m2/d in short infusion from d1 to d5), cisplatin (15 mg/m2/d from d1 to d5), etoposide (50 mg/m2/d from d1 to d5) and hydroxyurea (1,500 mg/d from d1 to d5). The first 21 patients also received bleomycin (3 mg/m2/d from d1 to d5). All patients received concomitant chemotherapy and had chest radiotherapy (CCRT). Patients received irradiation (65 Gy/33-6 fractions/7 weeks) on d25 after the third cycle of chemotherapy. Concomitant chemotherapy was composed of cisplatin (20 mg/m2) and 5-fluorouracil (500 mg/m2) that were administered each Monday and Thursday during radiotherapy. Maintenance chemotherapy consisted of thiotepa (10 mg/m2) and methotrexate (10 mg/m2) that were administered every 2 weeks for 6 months.Pulmonary toxicity was observed in four out of 21 patients who had received bleomycin and subsequently developed pulmonary fibrosis, leading to death for two of them. ICT alone produced five complete responses (11%) and 13 partial responses (28%). The combination of chemotherapy and radiotherapy led to 19 complete responses (41%) and 14 partial responses (30%). Eighteen of the 18 responders (100%) to ICT responded to subsequent CCRT, of whom 13 (72%) became complete responders. Fifteen of the 28 non-responders to ICT (53%) responded to CCRT, six of them being complete responders (21%) (P0.001). The median overall survival rate was 17 months when considering all patients, 25 months in patients responding to ICT and 13 months in non-responders. The 2-year survival rates were 28, 55 and 11%, respectively (P0.05). ICT did not influence the rate of subsequent metastatic events. However, locoregional reprogression was lower in responders to ICT. The number of metastatic events was not significantly related to response to ICT. By contrast, the rate of local failure was higher when there was resistance to ICT (75% versus 39%). Out of the 19 complete responders to CCRT (13 responders to ICT and six non-responders to ICT), four developed secondary locoregional reprogression (21%) and six developed metastatic disease (31%). In complete responders to CCRT, the rate of locoregional failure was 15% in responders to ICT (2/13) and 33% (2/6) in non-responders to ICT. Four out of the 13 responders to CCRT after response to ICT (31%) and two out of the six complete responders to CCRT developed metastatic disease after non-response to ICT.There is a statistically significant relationship not only between the response to ICT and the response to CCRT, but also between the response to ICT and the local outcome and survival.

Radical prostatectomy after pelvic lymphadenectomy is an effective treatment for patients with T1-2 pN0 adenocarcinoma of the prostate. However, pathologic analysis of resected tissue reveals that in 20 to 40% of clinical stage B lesions, the tumour has extended locally beyond the prostate. This infra-clinical disease may be the origin of local relapse. Radiation oncologists are often asked to deliver post-operative irradiation. There is sufficient evidence in the literature that postoperative radiation therapy can improve local control rate for patients with pT3 pN0 adenocarcinoma of the prostate; however, the effect of this radiotherapy on survival in this category of patients remains unclear. It is the reason why randomised clinical trials have been implemented for investigating the role of pelvic external irradiation with respect to the effects on local control, acute and late morbidity, overall survival and cancer-related survival, and for better defining the selective indications of radiotherapy, regarding pathological data.

Standard treatment for limited stage adenocarcinoma of the breast includes lumpectomy (or a quadrantectomy), axillary node dissection, regional radiation therapy and, if the prognostic factors are unfavourable, chemotherapy and/or hormone therapy. This is supported by the results of American and European randomised trials. There have been many attempts at improving the modalities of conservative surgery and postoperative radiation therapy in order to maximize local control and minimize late sequellae. It is also likely that induction chemotherapy and external beam radiotherapy applied in selected cases increase the proportion of patients who can be offered conservative surgery.

Our aim was to analyse feasibility and preliminary results obtained with iridium 192 re-irradiation of recurrent high grade gliomas.a technique for implanting rigid plastic tubes afterloaded with iridium 192 wires was developed that utilised a stereotactic Leksell frame. Nineteen glioblastomas and one anaplastic glioma (12 males and 8 females: age: 20-69 years, median: 50) were implanted between January 1993 and December 1994. Previous treatments included surgery (18/20). 55-60 Gy external beam radiotherapy (20/20), and chemotherapy (16/20); interval between initial treatment and retreatment with iridium 192 was 6 to 39 months (median: 10). Maximum diameter of the tumour at the moment of implantation was 2.1-10.1 cm (median: 6.4 cm) and tumour volume 2.122 cm3 (median: 22 cm3). All tumours were supra-tentorial (right hemisphere: 9; left hemisphere: 11). Karnofsky index was 60-100 (median: 80). Implantation was carried out under local anaesthesia; tumour contours were visualised using either a CT-scan (16/20) or a MRI (4/20). Dosimetry was carried out using two orthogonal films and CT-scan images. Total dose on the reference isodose was 40-60 Gy (60 Gy: 9; 50 Gy: 7; 40 Gy: 4); dose-rate was 0.24-0.73 Gy/h (median: 0.38).probability of overall survival is 90% at 6 months, 55% at one year, and 26% at two years. Median survival is 56 weeks. Eleven patients died from local failure, and three from leptomeningeal metastasis. Six patients are alive, 15-30 months after the implantation. Two were reoperated for brain necrosis. Three patients showed evidence of bacterial meningitis, and three others of skin necrosis.according to this preliminary analysis, results obtained after reirradiation of high grade gliomas with iridium 192 are encouraging. More patients and longer follow-up are needed to draw definitive conclusions.

The pulse dose rate (PDR) afterloading system is a new afterloading system which operates on the pulsed brachytherapy principle. A typical pulse length is 10 minutes, increasing to approximately 30 minutes three months later as the iridium 192 source decays. The pulse treatment is repeated each hour. The source activity is 1 Ci or less and thus the system can be installed in shielded rooms suitable for low dose rate implants. The PDR afterloading system enables equivalent continuous low dose rate treatments to be given with all the advantages of a stepping source: only one source to replace once every three months (no source inventory required), no source preparation, programmable low dose rate, optimization of dose distribution, radiation protection, patient can be disconnected between pulses, intracavitary, interstitial, intraoperative, and intralumenal treatments feasible using a single afterloader.

Experimental evidence exists of a dose-rate effect relationship in low dose continuous irradiation of cell population. In 1952, Paterson drew from his clinical experience on radium 226 implant, a dose-time iso-effect curve. Several authors, reviewing series of squamous cell carcinomas of the mobile tongue, implanted by radium 226 or iridium 192, did not confirm Paterson's hypothesis. Recently, a retrospective analysis of T1 and T2 squamous cell carcinomas, all treated exclusively by iridium 192 at the Henri-Mondor Hospital (Créteil, France), suggested a possible dose-rate effect relationship below 1 Gy/h. However, the role of dose-rate remains unclear. Further experience is needed before definitive conclusions can be drawn.

Between February 1979 and January 1982, a Phase II study of misonidazole as a radiosensitizer was performed in 34 patients with advanced carcinoma of the uterine cervix. Twenty-nine patients were treated with conventional fractionated radiation and five patients with a twice daily fractionation schedule, 3 days a week. The total dose to the whole pelvis was 5000 cGy delivered in 5.5 weeks. Intracavitary curietherapy delivered an additional boost to the tumor. Misonidazole was given to all patients during external radiation and to 25 patients during intracavitary treatment for a total dose of 11 to 14 g/m2. All patients were followed for at least 28 months after treatment with a median follow-up of 52 months. Misonidazole toxicity included peripheral neuropathy (18%) and central nervous system toxicity (3%). The 3-year survival rate is 74% and the 3-year disease-free survival is 57%. When compared to our historical group survival, 42 and 12% for Stage III and IV, respectively, our data suggest that there is a probable advantage from using misonidazole in advanced carcinoma of the cervix.

From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90%, respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated.

With a minimum follow-up period of 10 years, the incidence of sequelae after loco-regional treatment of 349 breast cancers remains low, being dominated by lymphoedema. Rare after treatment by irradiation alone, lymphoedema appears more frequently in patients treated by radio-surgical association, in spite of a moderate dose of radiation. If a rigorous technique is carried out, the possibility of achieving satisfactory local control in the axilla with radiation alone without neurological sequelae, therefore brings into question the need for axillary dissection without clinically significant adenopathy.