[Intensity modulated radiotherapy for head and neck cancer, dose constraint for normal tissue: Cochlea vestibular apparatus and brainstem]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures, dose de tolérance des tissus sains : appareil cochléovestibulaire et tronc cérébral.

Modern techniques such as intensity modulated radiation therapy (IMRT) have been proven to significantly decrease the dose delivered to the cochleovestibular apparatus, limiting consecutive toxicity especially for sensorineural hearing loss. However, recent data still report a 42% rate of radio-induced hypoacusia underscoring the need to protect the cochleovestibular apparatus. Due to the small size of the cochlea, a precise dose-volume analysis could not be performed, and recommendations only refer to the mean dose. Confusing factors such as age, concomitant chemotherapy, primary site and tumor stage should be taken into account at the time of treatment planning. (Non-coplanar) VMAT and tomotherapy have been proven better at sparing the cochlea in comparison with 3D CRT. Brainstem radio-induced injuries were poorly studied because of their infrequency and the difficulty of distinguishing between necrosis and tumor progression in the case of a primary tumor located at the base of skull. The following toxicities have been described: brainstem focal radionecrosis, cognitive disorders without dementia, cranial nerve injuries and sensori motor disability. Maximal dose to the brainstem should be kept to < 54Gy for conventional fractionation. This dose could be exceeded (no more than 10mL should receive more than 59Gy), provided this hot spot is located in the peripheral area of the organ.

[Nasopharyngeal cancer]. / Cancers du cavum de l'adulte.

The main objective of this work was to propose recommendations concerning the delineation of the target volume of the nasopharyngeal cancers, the planification of the treatment, and describe the expected results about the efficacity and the toxicities. Theses recommendations are based upon anatomy, natural history of theses tumors, and upon published experiences from different teams working with IMRT.

[Comparison between external radiotherapy and laser microsurgery for the treatment of TisT1N0 glottic carcinoma: Clinical modelling and cost-minimization study from the French national health insurance payer's point of view]. / Place de l'analyse médico-économique dans la décision thérapeutique en cancérologie ORL. L'exemple du cancer limité de la corde vocale (Tis, Tla). Comparaison entre la radiothérapie externe et l'exérèse laryngoscopique laser CO2. Création d'un modèle clinique et étude de minimisation de coûts suivant la perspective de l'Assurance Maladie.

OBJECTIVES: The excellent effectiveness of both treatment modalities (radiotherapy, endoscopic laser surgery) for early glottic carcinoma (Tis, TlaN0) is similar (carcinologic, functional and QoL results). This is part of an evidence-based medicine policy, which is to choose the cheapest of various treatment modalities known as equally effective and equally morbid. Is analytical economic approach useful and efficient to guide decision making? The aim of this study is to perform a costminimization analysis using an objective clinical modeling. MATERIAL AND METHODS: For each modality, probabilities of various events were recorded from review of literature. Only local recurrences which constitute the major end-point affecting survival were considered. French national Health insurance's point of view (as the payer's point of view), with a 100% case-mix based payment system was used. Results of cost-minimization between laser endoscopic surgery and external radiation therapy are: Global Cost of laser endoscopic surgery is about 2613.01 euro. Without (90% of cases) and with recurrence it is about 1700.36 euro and 10826.87 euro respectively. Global Cost of external radiation therapy is about 4490.88 euro. Without (90% of cases) and with recurrence it is about 3578.23 euro and 12704.74 euro respectively. CONCLUSION: Cordectomy by CO2 laser seems to be an efficient cost-effective alternative to radiotherapy for early glottic carcinoma management from the French national Health insurance perspective.

Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary.

PURPOSE: To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP). METHODS AND MATERIALS: Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80 years (median 59 years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only. RESULTS: After a median follow-up of 3.3 years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy (p=0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy (p=0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p=0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status (p=0.013) and the radiation technique (2D vs.3D-CRT or IMRT; p=0.029). There was no difference in loco-regional control (p=0.639) and no difference in survival (p=0.493) when chemotherapy was associated. CONCLUSIONS: Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient's local regional control and survival are significantly improved after 3D-CRT or IMRT.

[The French preliminary experience of the use of a seed-projector for exclusive iodine 125 prostate brachytherapy: feasibility and acute toxicity]. / L'expérience française de l'utilisation d'un projecteur de source pour la curiethérapie prostatique exclusive par implants permanents d'iode radioactif: faisabilité et données de toxicité aiguë.

PURPOSE: To analyse a new technique for prostate brachytherapy with permanent Iodine implants characterized by the use of a seed projector after a 3D dosimetric peroperative treatment planning (FIRST technique). PATIENTS AND METHOD: 395 patients have been treated in France with this technique in six radiotherapy centres between November 2002 and December 2005 for a localized prostate cancer. RESULTS: Thirteen patients (3.3%) developped a urinary retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity. The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS value. A failure of the loading with the seed-projector, leading to a manual loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly related to the loading procedure with the seed-projector in 5 cases. The median duration of the procedure was reduced by 30 minutes for the patients treated in 2005. CONCLUSIONS: This multicenter study establishes the feasibility of the routine use of a seed projector for permanent iodine 125 prostate implants with an initial tolerance similar to the best results published for other implants techniques.

Effect of radiotherapy on pelvic lymph node metastasis in cervical cancer stages IB2-IVA: a retrospective analysis of two comparative series.

Efficiency of radiotherapy in controlling lymph node metastasis is a controversial issue. A continuous series of 87 patients affected by cervical cancer stages IB2-IVA and treated using pelvic radiotherapy is presented. A retrospective comparison is made between two populations. In the two populations, a staging lymphadenectomy was carried out before the onset of the therapeutic program. In the first population (53 patients), the pelvic nodes only were dissected and in the second one (34 patients), the pelvic lymph nodes were left in place and the paraaortic nodes only were dissected. In both series, a completion surgery was performed after finalization of the radiotherapy. It was carried out at open abdomen in both series. It included a systematic pelvic dissection for the patients whose pelvic nodes had been intentionally left in place at the time of the initial staging lymphadenectomy. Both series were identical as far as classic risk factors were concerned (FIGO stage, maximal tumor diameter, lymphovascular space involvement). The radiotherapy administered to the pelvis was the same in both populations. The number of patients with pelvic lymph node metastasis was 21 (39.6%) in the first population versus 6 (17.6%) in the second one (P = 0.03). The percentage of positive lymph nodes among the retrieved lymph nodes was 18.94 in the first population versus 2.8 in the second one (P = 0.0001). Pelvic radiotherapy is likely to control most of the pelvic lymph node metastasis, but not all of them. Practical deductions and further developments are discussed.

[Postradiation dental extractions]. / Extractions dentaires en territoire irradié

INTRODUCTION: Healing may fail after postradiation dental extractions, with a risk of followed osteoradionecrosis, and its dramatic prognosis. We propose a protocol for postradiation extractions. MATERIAL AND METHODS: From January 2000 to December 2001, 107 patients underwent 287 dental extractions after radiation therapy: 80.5% in mandibular jaw, average radiation dose 61.6 Gy, average time between radiation and extraction 6 years. Extractions were performed under general anesthesia, diazanalgesia or local anesthesia, and extraction wounds were sutured after insertion of a collagenic sealant impregnated with gentamicin. General antibiotic prophylaxy was given. RESULTS: Healing failed in only two cases. The first case involved early-stage osteoradionecrosis and the second a tumoral localization. The rate of post-extraction osteoradionecrosis was thus 0.35%. DISCUSSION: A strict protocol associating non-traumatic surgery and an alveolar sealant can considerably decrease the risk of osteoradionecrosis after dental extraction in radiated bone.

Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.

PURPOSE: The effectiveness of nonsteroid topical agents for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma has not been demonstrated. The goal of this study was to compare the effectiveness of calendula (Pommade au Calendula par Digestion; Boiron Ltd, Levallois-Perret, France) with that of trolamine (Biafine; Genmedix Ltd, France), which is considered in many institutions to be the reference topical agent. PATIENTS AND METHODS: Between July 1999 and June 2001, 254 patients who had been operated on for breast cancer and who were to receive postoperative radiation therapy were randomly allocated to application of either trolamine (128 patients) or calendula (126 patients) on the irradiated fields after each session. The primary end point was the occurrence of acute dermatitis of grade 2 or higher. Prognostic factors, including treatment modalities and patient characteristics, were also investigated. Secondary end points were the occurrence of pain, the quantity of topical agent used, and patient satisfaction. RESULTS: The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; P <.001) with the use of calendula than with trolamine. Moreover, patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. Calendula was considered to be more difficult to apply, but self-assessed satisfaction was greater. Body mass index and adjuvant chemotherapy before radiotherapy after lumpectomy were significant prognostic factors for acute dermatitis. CONCLUSION: Calendula is highly effective for the prevention of acute dermatitis of grade 2 or higher and should be proposed for patients undergoing postoperative irradiation for breast cancer.

Post-radiation severe xerostomia relieved by pilocarpine: a prospective French cooperative study.

BACKGROUND AND PURPOSE: The aim of the study was: (1) to confirm the action of pilocarpine hydrochloride (Salagen) against xerostomia: (2) to correlate the response to dose/volume radiotherapy parameters. MATERIALS AND METHODS: From June 1995 to February 1996, 156 patients with severe radiation induced xerostomia received pilocarpine hydrochloride orally. IS mg per day with a 5 mg optional increase at S weeks up to a daily dose of 25 mg beyond 9 weeks. RESULTS: One hundred and forty five patients are fully evaluable. Treatment compliance was 75%. Thirty eight patients (26%) stopped treatment before week 12 for acute intolerance (sweating, nausea, vomiting) or no response. No severe complication occurred. Ninety ses en patients (67%) reported a significant relief of symptoms of xerostomia at 12 weeks. Within 12 weeks, the size of the subgroup ith normal food intake almost doubled (13-24 patients) while the size of the subgroup with (nearly) impossible solid food ingestion decreased by 38% (47 vs. 29 patients). The impact on quality of life was considered important or very important by 77% of the responders. CONCLUSIONS: No difference was found according to dose/volume radiotherapy parameters suggesting that oral pilocarpine hydrochloride: (1) acts primarily by stimulating minor salivary glands: (2) can be of benefit to patients suffering of severe xerostomia regardless of radiotherapy dose/volume parameters: (3) all responders are identified at 12 weeks.

Conformal radiotherapy for paranasal sinus and nasal cavity tumors: three-dimensional treatment planning and preliminary results in 40 patients.

PURPOSE: To assess the possibility to deliver a high and homogeneous irradiation with respect to maximal tolerated dose to the visual pathways for paranasal sinus and nasal cavity tumors. METHODS AND MATERIALS: Forty patients with advanced stage malignant tumors were treated with postoperative (30) or primary (10 patients) conformal radiotherapy (CRT). Five patients were previously irradiated. Six to 15 individually shaped isocentric noncoplanar field arrangements, using a multileaf collimator were designed. Dose-volume histograms (DVH) for the planning target volumes (PTV) and the optic pathways were analyzed in 31 cases. RESULTS: Median and maximal delivered doses to the PTV were 60 (+/-3) and 66 (+/-4) Gy. Dose distributions for critical organs are detailed. Median follow-up was 19 months (3 to 48). Local, nodal, and metastatic recurrences occurred in 8, 2, and 7 cases, respectively. Major prognostic factor for local recurrences was central nervous system (CNS) involvement. One patient died of meningitis. Two patients developed cataract, and 1 patient ipsilateral blindness due to vascular glaucoma. CONCLUSION: CRT for locally advanced paranasal sinus and nasal cavity tumors enables the delivery of high homogeneous doses to the PTV with respect to critical organs, with a low toxicity and a high local control.

[Conformal radiotherapy in cancer of the upper aerodigestive tract]. / Radiothérapie conformationnelle des cancers des voies aérodigestives supérieures.

The outcome of head and neck malignancies is closely related to the achievement of local tumor control. The occurrence of severe late complications is the consequence of the anatomic vicinity between dose-limiting normal tissues and the tumor, thus reducing the curative potential of radiotherapy. Conformal radiotherapy is presently actively investigated as a way to improve the dose distribution in head and neck malignancies (especially when originating from the nasopharynx or the sinuses) while protecting healthy organs. Such an approach requires a chain of sophisticated procedures, including efficient quality assurance programs, in order to achieve the proper degree of safety. The relatively limited clinical studies published to-date have already confirmed the advantage of conformal radiotherapy in terms of dose delivery. The development of beam intensity modulation is likely to further contribute to the improvement of the therapeutic ratio.

Curative irradiation of limited endobronchial carcinomas with high-dose rate brachytherapy. Results of a pilot study.

OBJECTIVES OF THE STUDY: Pilot study to assess high-dose rate (HDR) brachytherapy as sole treatment for limited endobronchial non-small cell lung carcinomas. INCLUSION CRITERIA: Proximal non-small cell lung cancer in a not previously irradiated area, with a maximal diameter of 1 cm, no visible tumor on CT scan, lack of other treatment options in patients with severe, chronic respiratory failure, surgery, or external radiotherapy for a previous lung cancer. TREATMENT PROTOCOL: Treatment was based on an escalating dose protocol. Patients received three to five fractions of 7 Gy prescribed at 10 mm from the center of the applicator, once a week. RESULTS: Nineteen patients were included in this trial. The first two patients received three fractions of 7 Gy, the four next patients received four fractions, and the 13 remaining patients were treated with five fractions of 7 Gy. Two months after the end of the procedure, tumors in 15 of 18 evaluable patients (83%) were locally controlled with negative results of biopsies. At 1 year, local control was still obtained in 12 of 16 evaluable patients (75%). With a mean follow-up of 28-months, 1-year and 2-year actuarial survival rates were 78% and 58%, respectively, with a 28-month median survival. One patient with local control died from hemoptysis 12 months after treatment. Two patients suffered from severe necrosis of the bronchial wall; one of them died from hemoptysis. CONCLUSIONS: HDR brachytherapy is an effective treatment for small endobronchial tumors. Late toxicity on the bronchial wall is still too high and was attributed mainly to contact between the catheter and the bronchial mucosa. Exclusive HDR brachytherapy should be restricted to carefully selected patients for whom there is no alternative curative treatment. New bronchial applicators and a lower dose per fraction may reduce the incidence and attenuate the severity of late complications.

Salvage brachytherapy of posterior pharyngeal wall squamous cell carcinoma in a previously irradiated area.

PURPOSE: Brachytherapy performed in patients with posterior pharyngeal wall carcinoma in a previously irradiated area is evaluated in terms of local control, survival, and complications. METHODS AND MATERIALS: Between January 1982 and July 1993, 14 patients were treated with interstitial low dose rate brachytherapy alone for posterior pharyngeal wall squamous cell carcinoma in a previously irradiated area (local recurrences in five cases and second tumors in nine cases). Tumor size ranged from 1 to 4 cm. No patient had a macroscopic nodal involvement or metastase at the time of diagnosis. Median dose delivered was 55 Gy (39 to 60 Gy). RESULTS: Thirteen patients were assessed for local control. Twelve of them achieved complete macroscopic response within 2 months after brachytherapy. Local relapse occurred in five patients, from 5 to 29 months after brachytherapy. One patient developed distant metastatis without loco-regional relapse. Disease free survival was 69, 59, and 37% at 1, 2, and 5 years, respectively; overall survival was 78, 50, and 21% at 1, 2, and 5 years, respectively. Three patients were still alive without recurrence (8, 8, and 10 years after treatment). We did not observe any severe acute or delayed toxicity. CONCLUSION: Based on these results, interstitial brachytherapy should be considered as a potentially curative treatment for selected patients with posterior pharyngeal wall squamous cell carcinoma in a previously irradiated area. There are no reports in the literature on this subject.

Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France.

PURPOSE: To define the role of a 10-Gy boost to the primary tumor in the conservative treatment of early infiltrating breast carcinoma treated by limited surgery and radiotherapy. PATIENTS AND METHODS: Between 1986 and 1992, 1,024 women with early breast carcinoma (< or = 3 cm in diameter) were treated by local excision, axillary dissection, and conventional 50-Gy irradiation given in 20 fractions over 5 weeks and then randomly assigned to receive either no further treatment or a boost of 10 Gy by electrons to the tumor bed. The median follow-up time was 3.3 years as of September 1994. The occurrence of telangiectasia was reported, and the patients were asked to evaluate the cosmetic result. RESULTS: At 5 years, 10 patients of 521 who had received the boost (Kaplan-Meier estimate of local relapse rate, 3.6%) and 20 of 503 who had received no further treatment (Kaplan-Meier estimate of local relapse rate, 4.5%) had developed a local recurrence (P = .044). After adjustment for the main prognostic variables, the relative risk was still significantly lower for the boost group (0.3; range, 0.12 to 0.95). The boost group had a higher rate of grade 1 and 2 telangiectasia (12.4% v 5.9%), but no difference was seen between the two treatment arms in the self-assessment score for the cosmetic result. CONCLUSION: Delivery of a boost of 10 Gy to the tumor bed after 50 Gy to the whole breast following limited surgery significantly reduces the risk of early local recurrence, with no serious deterioration in the cosmetic result. Additional follow-up evaluation will be required to assess the long-term results.

Medulloblastoma in adults: survival and prognostic factors.

The authors report a series of 30 adults with medulloblastoma treated after surgery between 1975 and 1990. Half the patients presented a classical medulloblastoma and the other half presented desmoplastic medulloblastoma. Brainstem infiltration was noted in 3 patients, cerebellar peduncle infiltration in 6 cases and 4 patients had cerebrospinal fluid (CSF) involvement. Tumor resection was achieved in all patients except 1, and in 5 surgery was incomplete. All patients but 2 received postoperative cerebral radiotherapy. Six patients did not receive chemotherapy before radiotherapy, 7 patients received CCNU-Vincristine concomitantly with and after irradiation, 1 patient was given a CHOP regimen, and the remaining 16 patients received the 8 drugs in a 1-day (8/1) regimen before irradiation. The median follow-up time was 104 months. The 5- and 10-year overall survival rates were 58.5% and 41%, respectively. Two toxic deaths occurred under the 8/1 regimen, and no better survival was observed for this group of patients in comparison with those receiving other regimens. Persistence of malignant cells in the CSF, brainstem involvement, cerebellar peduncle infiltration, non-radical surgery and a postoperative performance status (PS) of more than 2 were significantly correlated with an adverse outcome for overall survival in adult patients with medulloblastoma.

An original technique of brachytherapy for T1 T2 carcinomas of the mobile tongue.

Twenty-four patients with T1 or T2 (17 T1 N0, 7 T2 N0 not exceeding 3 cm) epidermoid carcinomas from the middle third of the mobile tongue benefit from brachytherapy with "cavaliers-legos" consisting of guide-gutters that are inserted in a rigid support (legos) and covered with a lead plate. Several advantages can be advocated with this technique: easy implantation even with local anaesthetic, no risk of bleeding, good parallelism between Iridium wires, protection of the mandible with the lead plate. Local control was achieved in 22/24 patients (92%). Four patients (16%) developed soft tissue necrosis but only one required surgical intervention and no mandibular necrosis was seen.

[Conservative treatment of breast cancer (the Lyon experience during 1963-1983)]. / Traitement conservateur du cancer du sein (expérience lyonnaise 1963-1983).

Over a 20-year period (1969-1983), 570 infiltrating primary breast carcinomas were conservatively treated in Lyons. Two different protocols were used: a first group of 162 patients with T1 T2 less than 3 cm NO lesions was treated, between 1963 and 1973, by lumpectomy and external beam irradiation with 60cobalt. The 5 and 10 year overall survival rates are 86% and 66% respectively. Local and regional failure rates are 10% and 2.5%. Cosmetic result was good or excellent in 70% of patients with only 5% poor results; a second group of 408 patients with T1 T2 less than 3 cm lesions was treated between 1973 and 1983 by tumorectomy and axillary dissection, followed by cobalt irradiation and 192iridium boost. The 5-year overall survival rate was 90% and, at 5 years, the probability of failure is 5% in the breast and 2% in the axilla. Cosmetic results are comparable in the 2 groups. Comparison of these 2 groups indicates an improvement in local control with Iridium boost. No obvious change in axillary recurrence rate and overall survival rate was observed. Boost modalities are discussed, with regard to cosmetic results. A prospective randomized study was initiated in 1986, in order to assess the value of the boost in the conservative treatment of breast cancer.