[Stereotactic radiotherapy of non-tumoral brain pathologies: Arteriovenous malformations and trigeminal neuralgias]. / Radiothérapie stéréotaxique des affections cérébrales non tumorales : malformations artérioveineuses et névralgies trigéminales.

Stereotactic radiotherapy and radiosurgery allow delivery of high irradiation doses in a limited volume. These techniques are specially adapted to brain and nervous pathologies. Indication are not only cancers and tumors but also non tumor tissues such as arteriovenous malformations. In some case purpose of stereotactic radiotherapy is solely functional, for example for trigeminal neuralgia. We detail the questions that raise treatment of these non-tumor pathologies. These pathologies imply a multidisciplinary approach that associate radiation oncologists, neuro-radiologist and neurosurgeons.

[Role of stereotactic radiotherapy in the treatment of oligometastatic colorectal cancer]. / Place de la radiothérapie (cancer primitif, métastases) dans la prise en charge des patients atteints d'un cancer oligométastatique : cancer colorectal.

Stereotactic radiotherapy is used for patients with oligometastases from colorectal cancer. It results in good local tumour control, especially for hepatic and pulmonary metastases, subject to a sufficiently high biologically effective dose, and is well-tolerated. It can be associated with other local treatments such as surgery or radiofrequency as part of combined treatments, in order to increase patient survival.

[Research ethics: French regulations and applications in radiation oncology]. / Éthique de la recherche : réglementations françaises et applications en oncologie radiothérapie.

French regulations about research ethics are based on the so-called Jardé law, which defines researches involving human beings. Researches involving human beings require the submission of research protocols to a committee for protection of persons with a precise list of documents to submit for a favourable opinion. This law describes different categories of researches and determines the ethical procedures to apply before setting up a research protocol. This issue of categorisation is central and must be taken into account by researchers from the beginning of the research process. Researches considered as not involving human beings also require a set of ethical precautions focused on patients' information and the collection of their non-opposition (due to the application of the General Data Protection Regulation adopted by the European Parliament). Thus, many regulations exist and they require a real work for researchers to meet these requirements in research ethics. This article aims to summarise French regulations. Selected examples are specifically taken into the field of radiation oncology research.

Stereotactic radiotherapy in targeted therapy treated oligo-metastatic oncogene-addicted (non-small-cell) lung cancer.

While the prognosis of metastatic non-small-cell lung cancer has shown significant progress these last years, notably with the discovery of oncogen-driven subtypes and the development of targeted therapies, significant improvements are still needed. More recently, numerous authors studied the oligo-metastasis concept, where the metastasis are limited in number and sites involved, and that could benefit from an aggressive approach of these lesions, for instance with the help of stereotactic radiotherapy. Nevertheless, there is no clear consensus existing for the time being for the treatment of these tumors. Three main clinical situations can be distinguished: oligo-metastasis state de novo at diagnosis (synchronous) or as first metastatic event of an initially locally limited affection (metachronous); oligo-progression during systemic treatment of a pluri-metastatic disease; and finally oligo-persistence of some remaining metastatic lesions at the nadir of the systemic therapy effect. In this review, we will discuss the place of stereotactic radiotherapy in the treatment of non-small-cell oligo-metastatic oncogene-addicted cancers treated with targeted therapies, differentiating these three main clinical situations. In all these indications, this technique could provide a benefit in terms of local control, possibly even in specific survival, when associated with targeted therapy continuation, related to local control of the oligo-metastatic cerebral or extracerebral lesions.

[Prevalence and expectations of "alternative and complementary medicine" use during radiotherapy in 2016: A prospective study]. / Prévalence et attentes de l'utilisation des « médecines alternatives et complémentaires ¼ pendant la radiothérapie en 2016 : étude prospective.

PURPOSE: Alternative and complementary medicine is defined as any substance or technique of non-allopathic medicine used to improve health and quality of life. The purpose of this prospective observational study was to evaluate the use of alternative and complementary medicine during radiotherapy. MATERIAL AND METHODS: A questionnaire was given the last week of treatment to all patients treated for breast cancer, prostate cancer or head and neck cancer in our centre in 2016. RESULTS: In 2016, 132 patients were included. Fifty-seven patients (43%) used alternative and complementary medicine during radiotherapy, more women (61%) than men (35%) (P=0.005). The use of alternative and complementary medicine varied according to locations: 44% of head and neck cancers, 57% of breast cancers and 24% of prostate cancers, but sex was the confounding factor. If alternative and complementary medicine was used before radiotherapy, 82% of patients used it during treatment, compared to 30% if they were naive (P<10-7). Healing touch (68%), homeopathy (26%) and magnetisers (21%) were the most used alternative and complementary medicines. Sixty-one percent of patients used alternative and complementary medicine to reduce skin and mucosal side effects of treatments, 28% to improve well-being, and 9% to treat cancer. Seventy-two percent of all patients would advise their loved one to use an alternative and complementary medicine and 87% would like information about them in the hospital. CONCLUSION: Alternative and complementary medicines are used more by women, and by patients who used them before radiotherapy. The desired effects are mainly to reduce the side effects of the treatments. More than 80% of patients, whether or not they use alternative and complementary medicine, demand medical information.

[Adaptive radiation therapy for non-small cell lung cancer]. / Radiothérapie adaptative du carcinome bronchique non à petites cellules.

Anatomical changes and tumor regression during thoracic radiotherapy may alter the treatment volumes. These modifications are not taken into account into set-up or motion margins used for treatment planning. Their dosimetric impact could be significant and a better understanding of the changes occurring during the 6 to 7 weeks of treatment could be useful in order to define quantitative thresholds before a new treatment planning is needed. Margins could also be reduced in order to better spare organs at risk and perform targeted dose escalation. This review assesses the potential of morphologic and metabolic imaging during treatment for adaptive radiotherapy in non-small cell lung cancer.

[Molecular imaging of tumor hypoxia]. / Imagerie moléculaire de l'hypoxie tumorale.

By allowing an earlier diagnosis and a more exhaustive assessment of extension of the disease, the tomography by emission of positrons (TEP) transforms the care of numerous cancers. At present, (18)F-fluorodesoxyglucose ([(18)F]-FDG) imaging appears as the only one available but new molecular markers are being developed. In the next future they would modify the approach of cancers. In this context, the molecular imaging of the hypoxia and especially the (18)Ffluoromisonidazole TEP ([(18)F]-MISO TEP) can give supplementary information allowing the mapping of hypoxic regions within the tumour. Because of the links, which exist between tumour hypoxia and treatment resistance of very numerous cancers, this information can have an interest, for determination of prognosis as well as for the delineation, volumes to be irradiated. Head and neck tumours are doubtless those for which the literature gives the most elements on the therapeutic impact of tumour hypoxia. Targeted therapies, based on hypoxia, already exist and the contribution of the molecular imaging could be decisive in the evaluation of the impact of such treatment. Molecular imaging of brain tumours remains to be developed. The potential contributions of the [(18)F]-MISO TEP for the care of these patients need to be confirmed. In this context, we propose a review of hypoxia molecular imaging taking as examples head and neck tumours and glioblastomas (GB), two tumours for which hypoxia is one of the key factors to overcome in order to increase therapeutics results.

[Volume-effect and radiotherapy [II]. Part II: volume-effect and normal tissue]. / Effet volume en radiothérapie [II]. Deuxième partie : volume et tolérance des tissus sains.

The first part of our work has focused on the relationship between tumor volume and tumor control. Indeed, it is well known that the importance of irradiated volume could be a main parameter of radiation-induced complications. Numerous mathematical models have described the correlation between the irradiated volume and the risk of adverse effects. These models should predict the complication rate of each treatment planning. At the present time late effects have been the most studied. In this report we firstly propose a review of different mathematical models described for volume effect. Secondly, we will discuss whether these theoretical considerations can influence our view of radiation treatment planning optimization.

[Volume-effect in radiation therapy part one: volume-effect and tumour]. / L'effet volume en radiothérapie première partie: effet volume et tumeur.

Volume is an important parameter of radiation therapy. Local control is inversely related to tumor size and the complication rate increases with the importance of the irradiated volume. Although the effect of irradiated volume has been widely reported since the beginning of radiotherapy, it has been less studied than other radiation parameters such as dose, fractionation, or treatment duration. One of the first organ system in which the adverse effect of increased volume was well defined is the skin. Over the last twenty years, numerous mathematical models have been developed for different organs. In this report we will discuss the relation between irradiated volume and tumor control. In a second article we will study the impact of irradiated volume on radiation adverse effects.

Detection of circulating cells expressing chromogranin A gene transcripts in patients with lung neuroendocrine carcinoma.

High grade lung neuroendocrine carcinomas, like small and large cell neuroendocrine carcinomas, pose therapeutic problems. Most initially respond to chemotherapeutic agents, but early relapses are frequent and are resistant to the presently available treatments. Our study reports for the first time the development and evaluation of a test for detecting the presence of circulating tumour cells by measuring chromogranin A gene transcripts with reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting. The test is specific and sensitive (detection of 10 cancer cells/ml blood), and only minimally invasive. Positivity is statistically correlated to high grade neuroendocrine carcinomas and to a poor prognosis with a 3-fold higher lethal risk. The test now needs to be assessed for its usefulness as a tool in the initial staging procedures and follow-up by comparison with the recent immunoradiometric assay (RIA) for detection of chromogranin A in the serum.

[Conformal therapy of locally advanced cholangiocarcinoma of the main bile ducts]. / Radiothérapie conformationnelle des cholangiocarcinomes de la voie biliaire principale localement évolués.

PURPOSE: Retrospective study of 23 patients treated with conformal radiotherapy for a locally advanced bile duct carcinoma. PATIENTS AND METHODS: Eight cases were irradiated after a radical resection (R0), because they were N+; seven after microscopically incomplete resection (R1); seven were not resected (R2). A dose of 45 of 50 Gy was delivered, followed by a boost up to 60 Gy in R1 and R2 groups. Concomitant chemotherapy was given in 15 cases. RESULTS: Late toxicity included a stenosis of the duodenum, and one of the biliary anastomosis. Two patients died from cholangitis, the mechanism of which remains unclear. Five patients are in complete remission, six had a local relapse, four developed a peritoneal carcinosis, and six distant metastases. Actuarial survival rate is 75%, 28% and 7% at 1, 3 and 5 years, respectively (median: 16.5 months). Seven patients are still alive with a 4 to 70 months follow-up. Survival is similar in the 3 small subgroups. The poor local control among R0N+ cases might be related to the absence of a boost to the "tumor bed". In R1 patients, relapses were mainly distant metastases, whereas local and peritoneal recurrences predominated in R2. CONCLUSION: Conformal radiochemotherapy delivering 60 Gy represents a valuable palliative approach in locally advanced biliary carcinoma.

[Fractionated radiotherapy of intracranial meningiomas: 15 years' experience at the Bordeaux University Hospital Center]. / Radiothérapie fractionnée des méningiomes intracrâniens: 15 ans d'expérience au centre hospitalier universitaire de Bordeaux.

PURPOSE: To evaluate the long-term results of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: From January 1981 to December 1996, 156 patients with intracranial meningiomas were treated with external fractionated RT. Median age was 57. Indications for radiation therapy were as follows: (1) completely excised histologically aggressive tumors (12 patients); (2) incomplete surgical resection (37 patients); (3) medically inoperable or basilar tumors where operation would involve considerable danger or permanent neurological damage (77 patients); and, (4) tumor recurrences (30 patients). Most patients were irradiated with 6 to 9 MV photon beams. A three to four-field technique with coned-down portals was used. Since 1993, 71 patients had a three dimensional dosimetry. Doses were calculated on the 95% or 98% isodoses, all fields were treated every day, five days a week, for a median total dose of 50 Gy (1.8 Gy/Fraction). RESULTS: Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent; an early clinical improvement during radiation therapy was noted in 19 patients (17.8%). Clinical improvement or stabilization was observed in 130 patients (83.4%). Radiologically, local control was obtained in 124 cases (79.4%) and tumor recurrences occurred in 21 cases (ten progressions in the treated volume, five borderline, six new locations). Overall and cause specific-survival rates were 75% and 89% at five years, and 45 and 76% at 10 years, respectively. CONCLUSION: These results reassess the role of fractionated RT in the treatment of intracranial meningiomas. Long-term tolerance is excellent for a majority of patients. The study of recurrences confirms the importance of the definition of the target volume, and asks questions about total given doses.

[Central nervous system. Experience of the Bordeaux University Hospital Center and review of the literature]. / Les dysgerminomes du système nerveux central. Expérience du Centre Hospitalier Universitaire de Bordeaux et analyse de la littérature.

PURPOSE: Retrospective analysis of 17 patients with intracranial germ cell tumors treated in a multidisciplinary consultation at the Bordeaux University Hospital a and literature review. MATERIALS AND METHODS: Seventeen consecutive patients were treated from 1978 to 1995 for a primary intracranial germ cell tumor. Median age was 14 (range 3-29 years). There were two malignant teratoma, six proved germinoma and nine presumed germinoma (diagnostic based on biological, radiological and treatment criteria). All received radiotherapy from 30 to 60 Gy (median 40 Gy) in different volumes. Chemotherapy was administered in 15 cases, three after surgery and 12 after radiotherapy. RESULTS: All tumours were in complete remission after initial treatment. The two malignant teratomas recurred in non-irradiated area after nine and 48 months, and the patients died. None of the germinoma recurred within a follow-up period of two to 17 years (median 65 months). Five and 10 year actuarial overall survival rates were the same: 84% for all histologies and 100% for germinomas. Only two patients developed school difficulties and six presented an hypopituitarism, of which one was consecutive to radiotherapy. Chemotherapy was well tolerated. CONCLUSION: This retrospective study and literature analysis are in favor of limited dose and volume of radiation therapy associated with chemotherapy.

[Fractionated irradiation of cerebellopontine angle neurinoma: 12 years' experience of the Bordeaux University Hospital Center]. / Irradiation fractionnée des neurinomes de l'angle pontocérébelleux: 12 ans d'expérience au centre hospitalier universitaire de Bordeaux.

PURPOSE: To evaluate retrospectively the long-term results of fractionated radiation therapy (RT) in cerebello-pontine angle neurinomas (CPA). METHODS AND MATERIAL: From January 1986 to October 1995, 29 patients with stage III and IV neurinomas were treated with external fractionated RT. One patient was irradiated on both sides and indications for RT were as follows: (1) general contraindications for surgery (16 patients); (2) hearing preservation in bilateral neurinomas after controlateral tumor exeresis (six patients); (3) partial tumor removal (five patients); and, (4) non-surgical recurrence (three patients). A three to four fields technique with coplanar static beams and conformal cerobend blocks was used; doses were calculated on a 95 to 98% isodoses and were given five days a week for a median total dose of 51 Gy (1.8 Gy/fraction). Most patients were irradiated with 6 to 10 MV photons). RESULTS: Median follow-up was 66 months (seven to 120 months). Seven patients died, two with progressive disease, five from non-tumoral causes. Tumor shrinkage was observed in 13 patients (43.3%), stable disease in 14 (46.6%), and tumor progression in three. Two patients underwent total tumor removal after RT (one stable and one growing tumor). Hearing was preserved in four out of six patients. No patient experienced facial or trigeminal neuropathy. CONCLUSION: Fractionated RT is a well tolerated and efficacious treatment of large non-surgical CPA neurinomas.

[Practice of virtual simulation at the Saint-André hospital]. / Pratique de la simulation virtuelle à l'hôpital Saint-André.

PURPOSE: Prospective evaluation of a virtual simulation technique. PATIENTS AND METHODS: From September 1993 to February 1997, 343 patients underwent radiation therapy using this technique. Treated sites were mostly: brain (132), rectum (59), lung (43), and prostate (28). A CT-scan was performed on a patient in treatment position. Twenty-five to 70 jointive slices widely encompassed the treated volume. The target volume (CTV according to ICRU 50) and often critical organs were controured, slice by slice, by the radiation oncologist. Beams covering the CTV plus a security margin (PTV) were placed on the "virtual patient". Digital radiographs were reconstructed (DRR) as simulator radiographs for each field. Thus, the good coverage of PTV was assessed. Fields and beam arrangements were further optimized. Definitive isocenter was then placed using a classical simulator. Perfect matching of DRR and actual simulator radiographs had to be obtained. RESULTS: Nineteen patients presented grade 3, and 1 grade 4 acute radiation effects. With a median follow-up of 18 months, five patients suffered from grade 3, and one from grade 4 complications. Fifty-five patients had tumor recurrence in the treated volume, and 19 had marginal relapse. CONCLUSION: In our department, virtual simulation has become a routine technique of treatment planning for deep-seated tumors. This technique remains time-consuming for radiation oncologists: about 2 hours. But it stimulates reflexion on anatomy, tumor extension pathways, target volumes; and is becoming an excellent pedagogical tool.

Fractionated radiation therapy in the treatment of intracranial meningiomas: local control, functional efficacy, and tolerance in 91 patients.

PURPOSE: To evaluate efficacy and tolerance of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. METHODS AND MATERIALS: From January 1981 to September 1993, 91 patients with intracranial meningiomas were treated with fractionated RT. Indications were as follows: (a) incomplete surgical resection, 29 patients; (b) tumor recurrences without considering the amount of the second resection, if performed, 14 patients; (c) completely excised angioblastic, aggressive benign, and anaplastic tumors, 8 patients; (d) medically inoperable and basilar tumors where operation would involve considerable danger or permanent neurological damage, 44 patients. Most patients were irradiated with 6 to 9 MV photon beams. A three- to four-field technique with coned-down portals was used. Doses were calculated on the 95% isodose and were given 5 days a week for a median total dose of 52 Gy (1.80 Gy/fraction). RESULTS: Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent, but there were six late delayed injuries. Tumor recurrences occurred in six cases. Six patients died from their tumor or RT complications, 19 from nontumoral reasons. Three, 5- and 10-year survival rates were 82, 71, and 40%, respectively. The most significant prognostic factor was age: 5-year survival rate was 86% for patients less than 65 years and 37% for patients more than 65. However, there were no differences in recurrence-free survival rates between patients younger than 65 and the oldest ones. Of 60 symptomatic patients with neurological deficits, 43 had neurological improvement (72%), beginning in some cases within 15 to 20 days after starting RT. CONCLUSION: These results reassess the role of fractionated RT in the treatment of meningiomas, and stress on its efficacy, especially on cranial nerves palsies, without severe toxicity in most cases.

Fractionated radiation therapy in the treatment of stage III and IV cerebello-pontine angle neurinomas: long-term results in 24 cases.

PURPOSE: To reevaluate long-term results of fractionated radiation therapy (RT) in a previously published series of cerebello-pontine angle neurinomas (CPA). METHODS AND MATERIALS: From January 1986 to May 1992, 24 patients with Stage III and IV CPA neurinomas were treated with external fractionated RT; 7 patients had phacomatosis. One patient was irradiated on both sides and indications for radiotherapy were as follows: (a) poor general condition or old age contraindicating surgery, 14 cases; (b) hearing preservation in bilateral neurinomas after contralateral tumor removal, 5 cases; (c) partial resection or high risk of recurrence after subsequent surgery for relapse, 4 cases; (d) nonsurgical relapse, 2 cases. Most patients were irradiated with 9 MV photons. A three- to four-field technique with coned-down portals was used. Doses were calculated on a 95% isodose and were given 5 days a week for a mean total dose of 51 Gy (1.80 Gy/fraction). RESULTS: Median follow-up from RT was 60 months (7 to 84); five patients died, two with progressive disease. Two patients underwent total tumor removal after RT (one stable and one growing tumor). On the whole, tumor shrinkage was observed in 9 patients (36%), stable disease in 13 (52%), and tumor progression in 3. Hearing was maintained in 3 out of 5 hearing patients with phacomatosis. CONCLUSION: Fractionated RT appears to be an effective and well-tolerated treatment for Stage III and IV CPA neurinomas. Hearing can be preserved for a long time.

[Routine use of electronic portal imaging. Positioning verification in 922 successive pelvic fields]. / Utilisation en routine du portal imaging électronique. Vérification de mise en place de 922 champs pelviens successifs.

Treatment reproducibility is a major criterion of quality assurance in radiation therapy. During each course, the same dose should be delivered in the same volume of irradiation. Today, portal imaging devices can be used routinely to check and correct patient positioning before much of the daily irradiation has been delivered. In this study we used the Portal Vision Varian (PVV) system during pelvic irradiation in 16 patients. This device can automatically acquire portal images in the first seconds of each course. Observed discrepancies are directly classified by the radiation oncologist according to their type (cranio-caudal, lateral, antero-posterior) and severity (correction of patient positioning is necessary or not). In case of error, patient positioning is corrected before the end of irradiation. Of the 922 portals analysed with PVV, 901 could be analysed (97%). Two hundred and ninety-nine positioning discrepancies were observed (33%) with 59 of them leading to correction (6%). Most of the time, these errors concerned antero-posterior portals. Finally, each patient had an average of 18 to 19 discrepancies which were mainly of no importance for treatment quality. Nevertheless, real errors leading to correction were observed in 14 patients (88%) with an average of four per patient. In some patients many errors occurred, while in others only a few. These shifts were not related to patient weight and thickness but probably a portal dimension. In summary, we think that during pelvic irradiation a portal imaging device should be used daily to improve treatment quality. This system can help the radiation oncologist to discover many positioning errors (an average of four) in the majority of patients (88%) and to correct them before the end of irradiation.

Radiotoxic model for three-dimensional treatment planning. Part 1: Theoretical basis.

Since recent treatment planning systems calculate volumetric dose distribution, an objective evaluation of potential toxicity in the main critical organs may be helpful in treatment optimization. Modeling the toxicity of radiotherapy must at least account for: (a) specific risks in every critical organ; (b) total dose and dose per fraction; (c) partial irradiation of critical organs; (d) heterogeneous dose distribution. The Radiation Damage Factor formula is aimed at estimating the delayed toxicity of a given treatment plan on every critical organ concerned. The formulation uses a double exponential function: RDF = 100 e-Ke-(a+bd)DVc, where: D is the total dose, and d the dose per fraction; a and b are coefficients representing the radiosensitivity of the critical organ, according to the linear-quadratic model, with a/b = alpha/beta. K represents the theoretical critical unit content of the organ, these critical units being groups of functionally related stem cells. The avoidance of a complication depends on the ability of surviving critical units to preserve organ function. V is the ratio:irradiated volume/total volume of the organ. Exponent c accounts for tissue organization: c is equal to or near 1 in "parallel organs" like the liver or the lung, where localized hot spots are tolerated; c is lower in "series organs" like the spinal cord where hot spots, even in a small portion, are dangerous. Heterogeneous irradiation, summarized by dose cumulative-volume histograms, is accounted for by calculating step by step the dose D' considered as having an equivalent effect when given in the largest irradiated volume ratio. Preliminary calibration of the RDF formula is attempted for radiation myelitis and radiation hepatitis.

Regimen-related toxicity in patients undergoing BMT with total body irradiation using a sweeping beam technique.

In our institution, total body irradiation (TBI) is performed by means of a sweeping beam technique. Toxicity of the procedure was evaluated according to the only grading system designed for high dose chemoradiotherapy. One hundred patients undergoing TBI and conditioned with a standard cyclophosphamide regimen before BMT were evaluated. Regimen-related toxicity was graded according to the Seattle transplantation toxicity system, from 0 to IV (fatal toxicity), in eight organs on days 0, 7, 14, 28 and 100 for lungs. Eighteen patients did not develop any toxicity. Grades III, IV toxicities were uncommon (9%) and were not influenced by dose of TBI, GVHD prophylaxis, disease status and allogenicity although no grade IV toxicity was observed among autologous marrow recipients. However, grade II toxicity was more common in patients receiving allogeneic vs autologous grafts (p < 0.01) because of increased mucosal (p = 0.002) and liver (p = 0.12) toxicities. Renal toxicity was unevaluable. When cumulative toxicity was equal or higher than 4, day 100 survival was worse (p = 0.05). These data confirm the safety of our TBI procedure and the validity of the grading system except for renal toxicity. We suggest that a more aggressive conditioning regimen may be tolerated by patients receiving autologous grafts.