The reproductive system after childhood cancer.
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Biomedical subjects
Publications and source records attributed to C Haie-Meder.
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PURPOSE: To report the results of a conservative multimodal approach in girls with nonmetastatic rhabdomyosarcoma (RMS) of the genital tract, treated in International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors 84 and 89 protocols. PATIENTS AND METHODS: From 1984 to 1994, 38 girls with RMS of the genital tract (vulva, vagina, uterus) were treated in SIOP protocols. With the exception of patients with rare small tumors, which were resected at the start of the studies, all patients received initial chemotherapy (CHT) (ifosfamide, vincristine, and actinomycin D). Local treatment including surgery, brachytherapy (BT), and external-beam radiotherapy (ERT) was given only to girls who did not achieve complete remission (CR) with CHT or who subsequently relapsed. RESULTS: The primary tumor originated in the vulva or vagina in 27 girls and in the uterus in 11. The overall survival rate (+/- SE) was 91% +/- 6% at 5 years, and the event-free survival rate was 78% +/- 7%. At a median follow-up of 5 years, 30 girls were alive and in first CR and five were alive and in second CR. Four patients treated with complete resection of the tumor at diagnosis received less CHT. Thirteen patients were treated with CHT alone. In 17 patients, local treatment was necessary to achieve complete local control, for a residual mass after initial CHT (10 patients), for viable tumor on biopsy (three patients), or for local relapse (four patients). The local treatment used was radiotherapy (RT) (ERT in three patients, BT in seven), radical surgery with uterine ablation (three patients), RT and radical surgery (three patients), and conservative surgery with RT (one patient). CONCLUSION: Girls with nonmetastatic RMS of the genital tract have an excellent prognosis. We found no difference in outcome between uterine and vulvovaginal RMS. Local treatment does not seem necessary in patients who have a complete response to CHT. When a local treatment is needed, BT may be an alternative to radical surgery or ERT.
INTRODUCTION: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) 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 update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy. METHODS: Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRLCC. RESULTS: The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are: 1) the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III et IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement); 2) the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1); 3) these results have been obtained by the combination of chemotherapy based on cisplatin alone, or in combination with 5FU. Although of equal benefit, the toxicity of the cisplatin/5FU/hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed; 4) the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.
OBJECTIVE: To assess the indications and effectiveness of laparoscopic ovarian transposition before pelvic irradiation for a gynecologic cancer. DESIGN: Prospective study. SETTING: A gynecologic oncology department in a French anti-cancer center. PATIENT(S): Twenty-four patients treated for pelvic cancer. INTERVENTION(S): Laparoscopic ovarian transposition to paracolic gutters. Uterine conservation in 18 patients. MAIN OUTCOME MEASURE(S): Clinical and laboratory follow-up tests of ovarian function. RESULT(S): Bilateral laparoscopic ovarian transposition was achieved in 22 patients (94%). Twelve patients were treated for clear cell adenocarcinoma of the cervix and/or upper vagina, 6 patients for invasive squamous cervical carcinoma, 3 patients for pelvic sarcoma, 1 patient for recurrent cervical cancer to the upper vagina, 1 patient for ependymoma of the cauda equina, and 1 patient for ovarian dysgerminoma. Ovarian preservation was achieved in 79%. Three pregnancies were obtained. CONCLUSION(S): Laparoscopic ovarian transposition is a safe and effective procedure for preserving ovarian function. Bilateral ovarian transposition should be performed. The main indications for laparoscopic ovarian transposition are a patient with a small invasive cervical carcinoma (<2 cm) in a patient <40 years of age who is treated by initial laparoscopically assisted vaginal radical hysterectomy and a patient with a clear cell adenocarcinoma of the cervix and upper vagina.
In a randomized trial comprising 204 patients with operable cervical carcinomas stages I and II, two low-dose rates in gynaecological brachytherapy were compared. Treatment consisted of Cs-137 uterovaginal application followed by surgery (either immediate or delayed). The results for the two dose rates have been published previously. The present paper concerns the correlation between outcome and tumour size. Tumour size was carefully estimated in two ways: by clinical examination under general anaesthesia and by measurements on the customized vaginal mould used for the brachytherapy. Ninety-one patients (45%) were classified as stage I, and 113 were classified as stage II proximal. The mean tumour size was 39 mm (range 15-64 mm). Cox's multivariate analysis indicated that the factors with a poor prognostic value were for survival: node involvement (N +) (p < 0.001), large tumour size (T +) (p < 0.001) and involvement of the endocervix (E +) (p <0.01); for event-free survival: N + (p <0.001), T + (p < 0.001); for local control; N + (p = 0.0001); for metastasis and regional relapse: N + (p < 0.001) and T + (p < 0.001). Stage was not a prognostic factor over the present range in either univariate or multivariate analysis. In this series tumour size is a powerful independent prognostic factor. It is therefore suggested that for the classification of cervical cancer and the indications for surgical staging and adjuvant treatment, tumour size should be taken into account.
The aim of this study was to assess the fertility outcome after ovarian transposition with uterine conservation and pelvic irradiation therapy for pelvic cancer. A total of 37 consecutive cases were reviewed. Of these, 27 patients were treated for a clear cell adenocarcinoma of the vagina and/or the cervix (group 1), nine for an ovarian pure dysgerminoma and one for a para-uterine soft tissue sarcoma (group 2). The pregnancy rate was 15% (4/27) in group 1 and 80% (8/10) in group 2 (P=0.01). A total of 18 pregnancies was observed in 12 patients. Of these, 16 pregnancies were obtained spontaneously and two after in-vitro fertilization. Of the spontaneous pregnancies, 12 (75%) were observed with ovaries still in the abdominal cavity (not repositioned). These results show that the prognosis for fertility is excellent after ovarian transposition and irradiation in patients with morphologically normal genital tracts (group 2). The prognosis is not as good for patients treated for a clear cell adenocarcinoma of the vagina and/or the cervix who may have morphological and/ or functional anomalies of the genital tract, following exposure to diethylstilboestrol and brachytherapy (group 1). Furthermore, these results show that repositioning of the ovary is not essential to achieve pregnancy.
In endometrial adenocarcinoma, many risk factors have been demonstrated. Among them, tamoxifene is a factor of low risk. Any endometrial bleeding requires a gynecological exam in order to make an early diagnosis. The positive histologic diagnosis is more often after surgery which is necessary for histo-prognostic stage. Non conservative hysterectomy with pelvic lymphadenectomy (obturator chain) is recommended for the most frequent stages I and II. Radiation therapy alone is recommended for stage III. Palliative therapy (hormonotherapy or chemotherapy) could be proposed for the few stage IV.
BACKGROUND: Penile carcinoma is uncommon in Western countries. Here we report on a large series of patients with squamous cell carcinoma (SCC) of the penis, describing prognostic factors, survival and therapeutic results. PATIENTS AND METHODS: From 1973 to 1993, 102 patients with invasive SCC of the penis were treated at the Institut Gustave-Roussy. Precancerous lesions and conditions associated with penis cancer were analyzed retrospectively. Survival curves were estimated by the Kaplan-Meier method, and groups were compared for outcome by the log rank test for univariate comparisons and by Cox's proportional hazards model for multivariate analysis. RESULTS: The median age at onset was 58 years. Sixty-nine patients presented with Jackson's stage I disease, 17 with stage II and 15 with stage III. The interval between the manifestation of symptoms and the diagnosis was more than a year in 13.7% of cases. Precancerous lesions were found in 17 (16.6%) patients, and a history of phimosis was noted in 25 (24.5%). In situ and invasive carcinoma were observed together in 17 (16.6%) cases and dysplasia was associated with invasive carcinoma in eight (7.8%) further cases. Conservative treatment was administered whenever feasible. Interstitial brachytherapy was performed alone or associated with limited surgery (local excision or circumcision) in 72 (70.6%) patients. Of the 28 patients with a local relapse, nine have died of their neoplasms (32%) compared to 21 of 28 patients with lymph node relapse (75%). The median follow-up was 111 months. Disease-free survival, disease-specific survival and overall survival were, respectively, 56%, 72% and 63% at five years and 42%, 66% and 50% at 10 years. Age (P = 0.01), the N status (P < 0.00001) or palpable nodes (P < 0.0038), corpus involvement (P = 0.006) and a verrucous histology (P = 0.038) had significant prognostic relevance for survival in the univariate analysis whereas the performance status, T status and Broders' grade did not. In the multivariate analysis only two parameters, involvement of the corpus (P < 0.0001) and palpable nodes (P = 0.009), were singled out as being independent variables influencing survival. A subgroup of nine patients with verrucous histologies were distinguished by their freedom from node involvement. These patients had an excellent prognosis: all are alive and disease-free. Penile integrity was preserved during follow-up in 54 patients (52.9%), 31 of whom are still alive. Of 72 patients treated by a conservative approach including brachytherapy, long-term penile integrity was maintained in 49 (68%). CONCLUSION: Corpus involvement and clinically palpable nodes are highly statistically significant independent factors influencing overall survival. Node relapses remain a major cause of death. Thus, better management of lymph nodes is essential for improving survival even when conservative therapy is used to treat the primary.
This study describes 64 cases of ovarian adenocarcinoma seen in the Gustave-Roussy Institut between 1978 and 1988 and who had a negative second-look laparotomy. The median age was 51 years (30-74). FIGO stages were: I: 7 (11%); II: 3 (5%); III: 39 (61%); IV: 3 (5%); and undetermined: 12 (19%). There were 53% of serous type, 14% of endometrioid type, 13% of undifferencied type, 8% of clear cells type, 3% of mucinous type, and 9% of mixed type tumors. There were 50% of grade 3 tumors. Initial debulking surgery was as complete as possible in 59 patients, with a residual tumor after surgery superior or equal to 2 cm in 25 patients. Post second-look surgery treatment (n = 57) consisted of chemotherapy (CT) alone in 22 patients (34%), radiotherapy (RT) alone in 31 patients (49%), and CT associated with RT in 4 patients (6%). Median follow-up is 100 months. The overall survival rates at 3 and 5 years were respectively 86 and 81%, and disease free survival rates 70 and 61%. Among the 64 patients, 26 relapsed (39%). Median time to relapse was 96 months. There is a statistical difference in the survival between patients who had no or inferior to 2 cm residual tumor and others. Residual tumor was the only factor to be significant in univariate and multivariate analysis of survival.
Proton therapy offers considerable potential advantages in the management of poorly resectable, radio-resistent tumors close to critical anatomical structures. So far over 15,000 patients have been treated worldwide with two major indications: conservative management of ocular melanomas in which local control exceeds 95% at 5 years and curative irradiation of sarcomas at the base of the skull and cervical canal, with a survival rate between 84 and 94% at 5 years. The different protocols tested currently worldwide are discussed.
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Non-parametric methods have recently been proposed to take into account the recurrent nature of complications in clinical trials, by estimating the prevalence Q(t), defined as the probability of relapse-free patients being in a complication state at time t. Recoveries are also considered. These methods have been adapted in this paper to take into consideration not only the recurrent nature of complications but also their severity through the interpretation of average weight functions. Results of a randomized trial comparing late complications following two alternative doses of pre-operative internal brachytherapy in patients with localized stage cervix carcinoma are used to illustrate the methods.
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The authors present the summary of a workshop of a group of radiation oncologists and radiation physicists on three dimensional treatment planning and conformal radiation therapy with multileaf collimator. It appears that this technic must be considered as experimental and that it cannot be promoted in all radiotherapy departments without scientific and clinical evaluation.
Between 1962 and 1986, 32 patients with intracranial meningiomas were referred to the Institut Gustave-Roussy for external radiotherapy either after incomplete surgery, or unfavorable histology (meningiosarcoma/anaplastic meningioma), or after recurrences. In the latter case, the mean time interval between the first surgery and the recurrence was 2 years (range: 1-6 years). Radiotherapy was performed using photons, electrons or mixed photons-electrons. The mean total dose was 48 Gy (range: 9-65 Gy) delivered in a mean time of 35 days with a 19 mean number of fractions. Radiotherapy was interrupted in three cases at 9 Gy-17 Gy-20 Gy because of neurological worsening. The actuarial 5-year survival was 64%. Among the 32 patients, 11 died, eight of tumoral progression or recurrence and three of other causes (one ovarian carcinoma, two unknown). Among the 21 alive patients, eight presented a recurrence; five of them could be reoperated on with two complete resections. None of the following factors were found to be of prognostic value on the survival nor on the recurrence occurrence: age, tumor location, first surgical resection type, and, in the group of patients treated at the time of recurrence, the quality of the surgery at the time of recurrence and the time interval between the first surgery and the recurrence. Only one factor was evidenced as of significant value on the recurrence as well as the 10-year survival: the total dose of irradiation with a 10-year survival rate of 74% for total doses higher than or equal to 47 Gy versus 14% when the total dose was lower than 47 Gy.
From 1974 to 1992, 1245 patients with cervix carcinoma were treated at the Institut Gustave-Roussy using several treatment protocols all of which included LDR brachytherapy. We present and discuss the results of our experience.