[High dose rate vaginal brachytherapy in endometrial cancer after surgery]. / Curiethérapie postopératoire du fond vaginal de haut débit de dose dans le cancer endométrial.

PURPOSE: This study aimed at analyzing the evolution and type of recurrence in patients treated for stage I endometrial carcinomas, in order to define the respective roles of adjuvant radiotherapy and brachytherapy. PATIENTS AND METHODS: This monocentric retrospective study was conducted at Centre Alexis-Vautrin, Nancy, France, between January 1995 and December 2000 on all the patients surgically treated for an endometrial cancer, and then treated with high dose rate vaginal brachytherapy. The brachytherapy was delivered in two or three fractions of 7 Gy at 5 mm from the applicator. RESULTS: In the good prognosis group, the specific and overall survivals at 5 years were respectively 96.5 and 94.2% with no local recurrence demonstrated. In the intermediate prognostic group, the specific and overall survivals at 5 years were respectively 88 and 85%, with six locoregional recurrences observed among those who did not undergo lymphadenectomy; the overall survival at 5 years was significantly decreased in the absence of external radiation. In the group of poor prognosis (stages II and III), the specific survival at 5 years was respectively 72.8 and 67 %, and the overall survival at 5 years 66.7 and 56.4%. CONCLUSION: Results for local control and survival as well as for tolerance were good. So we have decided to deliver high rate brachytherapy for all intermediate or poor prognosis patients and we have abandoned pelvic radiotherapy for good prognosis tumours (stages IA: no myometrium invasion with grade 3 and >50% of myometrium invasion with grades 1 and 2), whatever the lymph nodes surgery they had. We now propose pelvic radiotherapy only for intermediate prognosis tumours (such as IA>50% of myometrium invasion with grade 3 and IB stages), if patients did not have any lymphatic surgery, or for bad prognosis tumours.

Contraception and sexuality.

Contraception has changed female sexuality. The possibility of sex without pregnancy is taken for granted by most women and facilitates sexual availability. Potential consequences to female sexual response are linked to the various contraceptive methods in use today. This is a comprehensive review article of existing literature that explores the impact of current contraceptive methods upon the female sexual response cycle with potential sexual dysfunction. The definitions and classifications of female sexual response and female sexual dysfunction are also reviewed. Combination estrogen and progesterone contraceptive products decrease testosterone and increase sex hormone binding globulin without consistent impact upon libido. Progesterone only methods can in small numbers decrease libido and cause vaginal dryness and dyspareunia. Bleeding irregularities contribute to vaginal dryness and vulvar irritation. In the postpartum period and during lactation, these changes are exacerbated. Overall, IUD users have no significant effect on libido. Female sterilization generally has a positive impact upon sexuality unless the woman has been ambivalent over the procedure. Barrier and natural family planning methods are neutral. The freedom of sexual activity without pregnancy must be balanced with known side effects, risks and benefits to sexual health. The impact of contraceptive methods upon sexual function is not often discussed with women prior to initiation of a selected method or at subsequent visits. It is important that as clinicians we recognize the impact of contraceptive methods to sexual functioning and counsel our patients appropriately.

[Brachytherapy for head and neck cancers (nasopharynx excluded)]. / Curiethérapie des cancers de la tête et du cou (cavum exclu).

Brachytherapy is one of the standard treatments of head and neck cancers. The main indications are: the oral cavity, the oropharynx, the lips, the peri-orificial skin carcinomas on the face, the postoperative treatments for T1-2/N0 cancers of the oral cavity with close or positive margins, the second cancers in previously irradiated areas, the intra-operative brachytherapy for recurrent cervical lymph node metastases from previously irradiated tissues after maximal surgical debulking. The major prognostic factors published allowed to improve the technique: using a leaded protection of the mandible, the intersource spacing (1,2-1,4 cm), the volume treated (30 cm3, i.e. three loops), the safety margin (5 mm), the dose rate (0,5 Gy/h), the total dose (65 Gy in case of exclusive brachytherapy, 25 Gy in case of a combination of external beam irradiation [50 Gy] and brachytherapy in the oropharyngeal carcinomas, 35 Gy in case of a combination of external beam irradiation [40 Gy] and brachytherapy in the oral cavity carcinomas, 60 Gy in case of a second cancer in previous irradiated tissues), the delay between external irradiation and brachytherapy (< 20 days). The pulse dose rate brachytherapy should improve results with the control of the dose rate and the optimization of the dose distribution. For high dose rate brachytherapy, more results are needed to recommend this technique for routine use.

[High fetal irradiation: about one pregnant woman receiving infradiaphragmatic radiotherapy for Hodgkin lymphoma]. / Irradiation foetale élevée: à propos d'une femme dont la grossesse était méconnue irradiée en sous-diaphragmatique pour un lymphome hodgkinien.

We report the case of a 19-year-old young woman for whom was discovered a pregnancy at the end of the irradiation for a Hodgkin lymphoma (stage IV bone Bb), initially treated by chemotherapy. The radiotherapy delivered 36 Gy in infra-diaphragmatic volumes (lombo-aortic, spleen, L5), beginning in a pregnant patient for less than 4 amenorrhea weeks. The calculated received fetal dose (literature data, measurement with software TPS, measurement on phantom) is high: it's between 2.8 and 5 Gy. With a current follow-up of 4 years since the radiotherapy's end, the patient is in complete remission and her child presents with a normal development for the age, in spite of the infradiaphragmatic irradiation.

[Preoperative brachytherapy for clinical stage I and II endometrial carcinoma: results from a series of 780 patients with a 10-year follow-up]. / Curiethérapie préopératoire des adénocarcinomes de l'endomètre de stades cliniques I-II: résultats à dix ans d'une série de 780 patientes.

AIMS OF THE STUDY: Retrospective analysis of patients treated by preoperative brachytherapy for endometrial carcinoma. PATIENTS AND METHODS: From 1973 to 1994, 780 consecutive patients with a clinical stage I-II endometrial carcinoma were treated with brachytherapy followed by surgery and pelvic irradiation if necessary. Tumour was staged according to 1979 UICC classification. There were 462 T1a, 257 T1b, and 61 T2, 62% were well differentiated. Brachytherapy consisted in one low dose rate endocavitary application. Sixty grays were delivered on the reference isodose. Surgery consisted in a TAH/BSO (Piver II) and was performed 6 weeks later. Nodal pelvic irradiation was indicated in case of unfavourable pathological prognostic factors. RESULTS: Median follow up was 122 months. Five year survival rates were: 84% for overall survival, 86% for survival without recurrence, 92.8% for local control, and 3.8% for late complications. Pronostic factors were age, stage, differentiation, grade and postoperative extension. Multivariate analysis showed only age, differentiation and postoperative extension to be independent prognostic factors. CONCLUSION: If for stage 1, initial surgery has now replaced preoperative brachytherapy in most cases because it allows to identify initial prognostic factors, preoperative brachytherapy remains the most interesting option for stage 2 endometrial carcinomas.

[Total body irradiation in France in the past twenty years]. / Irradiation corporelle totale en France au cours des 20 dernières années.

A review of the activity and techniques of total body irradiation (TBI) in France in the last 20 years is presented. In order to have on overall view of the activity and techniques of total body irradiation in France, the group of cancer centre radiation oncologists sent a questionnaire to all the cancer centres or public hospitals radiotherapy departments dealing with this treatment. Thirty-six questionnaires were sent and thirty-one departments answered. Three departments do not offer this treatment. Five departments did not answer. Results, therefore, concern the activity of the 28 departments that agreed to give detailed and clear answers. A total of 10 630 TBIs have been documented, 850 to 900 TBI have been done each year since 1995. Single fraction TBIs are used in only five centres and are being progressively abandoned. For multiple-fraction TBIs, the techniques described here are the ones used in 1999, at the time the questionnaires were sent. A majority (98%) of the teams used linear accelerators. The collected data are synthesised in tables. Nowadays, single fraction TBIs are only indicated in exceptional cases. Most of the TBIs are fractionated in six twice-daily fractions with pulmonary shielding to limit the dose between 6 and 11 Gy depending on departments' protocols and pathologies.

[Brachytherapy of endometrial cancers]. / Curiethérapie des cancers de l'endomètre.

Endometrial adenocarcinomas rank third as tumoral sites en France. The tumors are confined to the uterus in 80% of the cases. Brachytherapy has a large place in the therapeutic strategy. The gold standard treatment remains extrafascial hysterectomy with bilateral annexiectomy and bilateral internal iliac lymph node dissection. However, after surgery alone, the rate of locoregional relapses reaches 4-20%, which is reduced to 0-5% after postoperative brachytherapy of the vaginal cuff. This postoperative brachytherapy is delivered as outpatients treatment, by 3 or 4 fractions, at high dose rate. The uterovaginal preoperative brachytherapy remains well adapted to the tumors which involve the uterine cervix. Patients presenting a localized tumor but not operable for general reasons (< 10%) can be treated with success by exclusive irradiation, which associates a pelvic irradiation followed by an uterovaginal brachytherapy. A high local control of about 80-90% is obtained, a little lower than surgery, with a higher risk of late complications. Last but not least, local relapses in the vaginal cuff, or in the perimeatic area, can be treated by interstitial salvage brachytherapy, associated if possible with external beam irradiation. The local control is reached in half of the patients, but metastatic dissemination is frequent. We conclude that brachytherapy has a major role in the treatment of endometrial adenocarcinomas, in combination with surgery, or with external beam irradiation for not operable patients or in case of local relapses. It should use new technologies now available including computerized afterloaders and 3D dose calculation.

Cervical lymph node relapses of head-and-neck squamous cell carcinoma: is brachytherapy a therapeutic option?

PURPOSE: To report the results of interstitial brachytherapy (IBT) without salvage surgery for isolated cervical lymph node relapses. PATIENT AND METHODS: From 1970 to 1989, 84 patients were treated; 76 patients had relapsed in sites of previous external beam radiation. In 72 patients, IBT was sole salvage treatment (mean, 56.5 Gy). In 12 patients IBT (mean, 38 Gy) was combined with further external beam radiotherapy (mean, 41 Gy). RESULTS: Local control in the neck was 49% at 1 year, 31% at 2 years, and 0% at 5 years. Overall survival was 33% at 1 year, 13% at 2 years, and 1% at 5 years. Significant toxicity occurred in 35% (7% fatal). Multivariate analysis shows survival after salvage was better for patients who had achieved initial control for > or =18 months before relapse (0% vs. 13% at 3 years, p < 0.0002). Lymph node control was better for patients who received total salvage dose > or =60 Gy (0% vs. 56% at 3 years, p = 0.0004). CONCLUSION: Given its poor efficiency and its toxicity, IBT must be considered only when surgery is contraindicated and if lymph node relapse occurs after a minimal interval of 18 months.

Efficacy of external fractionated radiation therapy in the treatment of meningiomas: a 20-year experience.

BACKGROUND: This is a retrospective analysis of a series of meningiomas treated by radiotherapy. MATERIALS AND METHODS: From 1978 to 1997, 45 patients with intracranial meningiomas were referred for external fractionated radiotherapy at Centre Alexis Vautrin. All patients were given 50-70Gy to the tumor bed (median: 56Gy), 1.8-2Gy per fraction. RESULTS: Evaluation was performed in June 1999 using the Kaplan-Meyer actuarial method with a median follow-up of 30 months (range: 1-166), relapse-free survivals (RFSs) were 75% at 5 years and 67% at 8 years; overall survival (OS) was 74% at 5 and 8 years. For the 26 benign histologically documented lesions, RFSs were 95% at 5 years and 81% at 8 years; OS was 85% at 5 and 8 years. One major radiation-induced complication occurred in this series (decline of cognitive function). According to the indication of radiotherapy, we divided the series into four groups: postoperative irradiation after a first subtotal resection (11 patients), 5-year RFS was 90%; after first recurrence (+/-salvage surgery, 14 patients), 73%; after further recurrence (+/-salvage surgery, 11 patients), 67%; as exclusive treatment (nine patients), 80%. Atypical and malignant lesions (n=7) all relapsed before 24 months of follow-up, all patients but one died before 42 months. Age at the time of irradiation (> or =60 vs. <60 years) and radiotherapy dose (> or =60 vs. <60Gy) did not influence local control or OS. Atypical and malignant lesions (WHO grades II and III) meningiomas had a worse outcome than benign lesions (WHO grade I, P<0.01). CONCLUSIONS: These results compare favorably with previously published data. External fractionated radiotherapy is well tolerated and effective. There is still a debate about the place of radiotherapy in the treatment of meningiomas: after subtotal resection, should radiotherapy be given postoperatively or at the time of progression? Should radiotherapy replace surgery when the risk of postoperative sequellae is high? Prospective randomized trials would be required to address these issues.

[Standards, options, and recommendations for the radiotherapy of patients with endometrial cancer. FNCLCC (National Federation of Cancer Campaign Centers) and CRLCC (Regional Cancer Campaign Centers)]. / Standards, Options et Recommandations pour la radiothérapie des patientes atteintes de cancer de l'endomètre.

OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

Postoperative brachytherapy alone for T1-2 N0 squamous cell carcinomas of the oral tongue and floor of mouth with close or positive margins.

PURPOSE: To evaluate the efficacy of postoperative brachytherapy alone (brachy) for Stage T1-2 squamous cell carcinomas (SCC) of the floor of mouth (FM) and the oral tongue (OT) with close or positive margins. METHODS AND MATERIALS: Between 1979 and 1993, 36 patients with T1-2 N0 (24 T1, 12 T2) OT (19), and FOM (17) SCC with close or positive margins following surgery underwent postoperative brachy. Mean patient age was 56 years (range 37-81) and sex ratio was 3.5:1 male:female. Mean surgery to brachy interval was 36 days (range 16-68). The technique used was interstitial Iridium-192 ((192)Ir) brachytherapy with plastic tubes and manual afterloading. Mean total dose was 60 Gy (range 50-67.4) at a mean dose rate of 0.64 Gy/h (range 0.32-0.94). Mean patient follow-up was 80 months. RESULTS: The 5-year actuarial overall and cause-specific survivals of the entire group were 75% and 85%, respectively. The local control was 88.5% at 2 years, with a plateau apparent after 23 months. Of the 4 local relapses, 2 were salvaged with surgery and external beam radiotherapy (EBR). No tumor or treatment factors, including tumor size, margin status, disease site, or radiation dose, were correlated with local control. The 2 head and neck second primaries underwent curative treatment on nonirradiated tissue. One patient developed a grade 3 sequelae (bone and soft tissue necrosis). Grade 2-3 chronic sequelae were seen in 7 of 17 and 3 of 19 FOM and OT tumors, respectively (p = 0.09). CONCLUSION: Postoperative brachy is a promising approach in T1-2 N0 OT and FOM SCC with close or positive margins. This approach is associated with high rate of locoregional control and low risk of chronic sequelae, obviates major surgery, avoids potential sequelae of EBR (xerostomia, dysgueusia, fibrosis), and avoids treatment of second head and neck primary on nonirradiated tissues.

In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice.

The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the results leading to the definition of parameters needed to demonstrate a possible radiopotentiation by topotecan (TPT) on two representative human rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of radiopotentiation with different doses of topotecan showed that concomitant association of topotecan and RT for 5 consecutive days provided a synergistic therapeutic effect. Response rates were statistically higher with the radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of this combination compared with the sum of the antitumoral activity of these treatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy at the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different from that of radiotherapy at the dose of 40 Gy. According to microscopy results, the analyses performed at different periods after topotecan treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of radiotherapy and/or topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were similar to those obtained with the association of topotecan at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and pathological results are consistent with a radiopotentiation effect of topotecan on the two xenografted human rhabdomyosarcomas and are currently leading to the design of clinical studies.

Curved angiocatheter metal guide for the implantation in velo-tonsillar carcinomas.

Brachytherapy in velo-tonsillar region is not applied in all the institutions because of difficulties to learn it. For the implantation of wires in the soft palate, the Reverdin needle is replaced by a curved guide of angiocatheter 14 Gauge. This technique is easy and reduces the risk of tear mucosa.

Nonmetastatic pelvic Ewing sarcoma: report of the French society of pediatric oncology.

BACKGROUND: Since January, 1984, 59 children with histologically confirmed Ewing sarcoma of the pelvic bone have been treated with three successive chemotherapy protocols recommended by the French Society of Pediatric Oncology. The purpose of the current study was to evaluate the role of surgery and/or radiotherapy in local progression-free, disease-free, and overall survivals (LPFS, DFS, and OS, respectively). PROCEDURE: We retrospectively examined 59 children treated for nonmetastatic, pelvic Ewing sarcoma over the last 12 years. All were first treated with chemotherapy according to the current French protocol. Six patients developed progressive disease before local treatment and were excluded for local control and survival analysis. Local treatment was surgery alone in 17 cases, radiation therapy in 27 cases, and surgery plus radiation therapy in 9 cases. RESULTS: With a median of follow-up of 6.5 years, no significant differences in local control or survival were observed with the three chemotherapeutic protocols. Of the 53 patients evaluable for local control, 6 relapsed locally only, 8 had local and distant relapses, and 9 had distant metastases only. The 5-year OS rate was worst for patients with radiotherapy alone compared to those with surgery or combined modality treatment (44 % vs. 72 %, P = 0.043). The 5-year LPFS and DFS rates were worst in the radiotherapy-alone group but not significantly (63% vs. 79%, P = 0. 22 and 42% vs 71%, P =0.07, respectively). The importance of surgery to OS and DFS was confirmed by multivariate analysis (P = 0.026 and P = 0.048, respectively). One surviving patient was diagnosed with in-field fibrosarcoma, which was presumably radiation induced. CONCLUSIONS: Despite intensive, multiagent chemotherapy, survival from pelvic Ewing sarcoma has not improved over the past decade; however, the survival rate does not seem to be worse than that from Ewing sarcoma at other locations, insofar as at least 50% of the patients were cured. Surgery or a combination of surgery and radiation therapy are the best local treatment; exclusive radiation therapy should be reserved for patients with inoperable lesions or partially or nonchemosensitive tumors or when surgery would be an amputation.

Impact of targeting deviations on outcome in medulloblastoma: study of the French Society of Pediatric Oncology (SFOP).

PURPOSE: To correlate targeting deviation in external beam radiation therapy with site of relapse in a prospective study of 174 patients treated for medulloblastoma. METHODS AND MATERIALS: Between February 1992 and February 1998 the radiotherapy treatment records were reviewed by a panel of radiation oncologists for 174 children treated with radiation therapy for medulloblastoma. The review was done without knowledge of patient outcome. Patterns of relapse were correlated with the results of the quality control review. RESULTS: Among the 174 patients five relapsed before the start of radiotherapy. One hundred sixty-nine patients were evaluable for correlation between targeting deviation and site of relapse. Number of major deviations in radiation therapy treatment is strongly correlated with the risk of tumor relapse (67% [95% CI: 28-91] of 3-year relapse rate in patient group with 2 major deviations and 78% [95% CI: 35-96] with 3 major deviations). This is particularly correlated with relapse in the frontal region of the brain: 5 relapses occurred in the frontal region in patients with major deviation in this area. An erroneous choice of electron beam energy is also linked with craniospinal fluid (CSF) relapse (3-year relapse rate of 68% [95% CI: 42-86]). Minor deviations in therapy technique are slightly associated with an increased risk of relapse in the same range as the group with only one major deviation. CONCLUSION: The quality of medulloblastoma radiation therapy technique is strongly correlated with outcome. Pretreatment central quality assurance review or standardized computer-designed blocks would improve survival to an extent equivalent to that attributed to adjuvant chemotherapy.

[Radiotherapy in leukemia excluding total body irradiation]. / Irradiations pour leucémie à l'exclusion de l'irradiation corporelle totale.

Radiation techniques and indications in leukemias have been described in detail, yet prophylactic cranial irradiation in acute leukemia still has few indications. Cerebrospinal and testicular irradiation are reserved for relapsing disease. Radiation usually results in rapid functional improvement when used in neurologic emergencies and symptomatic neurologic or gross tumors relapses. Nevertheless, the improvements recently obtained by systemic chemotherapy have resulted in the reduction in the use of irradiation, especially in children, where it was considered deleterious with neuropsychological sequellae. Splenic irradiation remains useful for symptomatic myeloproliferative syndrome.