Annie Rey

Overall treatment time in advanced cervical carcinomas : a critical parameter in treatment outcome

PURPOSE To search for possible influence of overall treatment time on the clinical outcome of advanced cervical carcinomas treated with radiation alone. METHODS AND MATERIALS Three hundred and eighty-six patients with Stage IIB and III cervical carcinomas treated with external radiation and intracavitary curietherapy between 1973 and 1983 were entered in the study. A multivariate analysis was carried out on data concerning these patients to determine whether overall treatment time was a prognostic factor. RESULTS Overall treatment time and blood transfusions during treatment were the two most highly significant factors in the multivariate analysis. Loss of local control and overall survival, when treatment exceeded 52 days, was approximately 1% per day in both cases. CONCLUSION These results suggest that overall treatment time might be a highly significant prognostic factor in the treatment outcome of advanced cervical carcinomas. Prospective randomized studies are strongly warranted to confirm this hypothesis.

Treatment of Nonmetastatic Rhabdomyosarcoma in Childhood and Adolescence: Third Study of the International Society of Paediatric Oncology—SIOP Malignant Mesenchymal Tumor 89

PURPOSE To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy. PATIENTS AND METHODS Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage. RESULTS Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy. CONCLUSION Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).

Lymphatic spread in stage Ib and II cervical carcinoma: Anatomy and surgical implications

Objective To determine the frequency and topography of pelvic and para-aortic node involvement in cervical carcinoma and to identify the appropriate level for resection of the lymphatic chains. Methods Between 1985 and 1994, 421 women with stage Ib or II cervical carcinoma were treated by surgery in combination with irradiation. Each underwent a radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy. Results A median of 34 lymph nodes were removed per patient. The overall frequency of lymph node involvement was 26%, and the frequency of para-aortic metastases was 8%. The frequency of lymph node metastasis was associated significantly with stage (x2 = 7.8; P < .02), tumor size (x2 = 14.8; P < .001), and patient age (x2 = 5.9; P < .05). The frequency of para-aortic involvement was below 3% in patients with small tumors (under 2 cm). When pelvic nodes were involved, the obturator group was concerned in 76 cases (18%) and the external iliac group in 48 patients (11%). When para-aortic nodes were involved, the left para-aortic chain was the most frequently concerned (23 patients [5%]). In eight of these patients, nodal involvement was found only above the level of the inferior mesenteric artery. Among 106 patients with pelvic positive nodes, 28 (26%) also had para-aortic metastatic nodes. Conclusion Para-aortic lymphadenectomy should remove all of the left para-aortic chain (inframesenteric and supramesenteric) and so should be performed up to the level of the left renal vein. According to the low frequency of para-aortic involvement when tumor size is below 2 cm, such a procedure could be avoided in patients with small tumors.

Treatment of intracranial ependymomas of children: review of a 15-year experience

PURPOSE There are still major controversies in the optimal management of children with intracranial ependymomas. To assess the impact of tumor site, histology, and treatment, the outcome of children treated at the Institut Gustave Roussy was reviewed retrospectively. METHODS AND MATERIALS Between 1975 and 1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave Roussy for postoperative management of an intracranial ependymoma. Location of tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment consisted of complete resection in 38, incomplete resection in 38 and biopsy only in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33. Surviving patients have been followed from 12-197 months with a median of 54 months. RESULTS The 5-year actuarial survival and event-free survival are 56% and 38%, respectively. Thirty-four patients relapsed from 3-72 months after diagnosis (median 25 months). In 20 patients, the only site of failure was the original tumor site. Three patients failed locally and at distance, while 10 others failed only at distance. Survival at 5 years was significantly better for patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free survival at 5 years was superior in patients with complete resection of the tumor (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs. 0%, p < 0.001). Sex and tumor site had no impact on survival or event-free survival. There was no difference in survival, event-free survival, or pattern of failure between patients treated with local field, whole brain or craniospinal irradiation, while severe longterm sequelae were noted predominantly in the latter two groups. CONCLUSION Considering that failures were predominantly local and that there was no apparent benefit from prophylactic irradiation, we recommend local field irradiation with doses above 50.0 Gy for all children with intracranial ependymomas, without meningeal dissemination at diagnosis. Special considerations are necessary for children < 3 years of age.

Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination

OBJECTIVE To assess the indications, effectiveness, and complications of ovarian transposition before pelvic irradiation for cervical cancer. DESIGN Prospective study. SETTING Gynecologic oncology department at a French cancer center. PATIENT(S) One hundred seven patients treated for cervical cancer. INTERVENTION(S) Ovarian transposition to the paracolic gutters with radical hysterectomy and lymphadenectomy. MAIN OUTCOME MEASURE(S) Clinical and laboratory follow-up tests for ovarian function. RESULT(S) Bilateral ovarian transposition was achieved in 104 patients (98%). Twelve patients were lost to follow-up or excluded because of evolution of the disease. Preservation of ovarian function was achieved in 83% of the patients having follow-up. The rates of ovarian preservation were 100% for patients treated exclusively by surgery, 90% for patients treated by postoperative vaginal brachytherapy, and 60% for patients treated by postoperative external radiation therapy and vaginal brachytherapy. The main risk for ovarian failure was found in patients treated by external radiation therapy. CONCLUSION(S) Ovarian transposition is a safe and effective procedure for preserving ovarian function in patients treated by a radiosurgical combination. This procedure should be performed in patients <40 years of age with a small invasive cervical carcinoma (<3 cm) treated by initial surgery. In such selected cases, the risk of ovarian metastasis is low.

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.

Treatment of Orbital Rhabdomyosarcoma: Survival and Late Effects of Treatment—Results of an International Workshop

PURPOSE Orbital rhabdomyosarcoma (RMS) historically has been associated with an excellent survival rate. The majority of patients are cured with the use of both chemotherapy and radiation therapy, but a significant number experience important late sequelae of treatment. In an attempt to determine optimal therapy in relation both to cure and to sequelae, the experience of the four international collaborative groups (Intergroup Rhabdomyosarcoma Study Group [IRSG], International Society of Paediatric Oncology [SIOP] Sarcoma Committee, German Collaborative Soft Tissue Sarcoma Group [CWS], and Italian Cooperative Soft Tissue Sarcoma Group [ICG] studies) was shared at an international workshop. PATIENTS AND METHODS A total of 306 eligible patients were identified from group records (186 from IRS, 43 from SIOP MMT, 40 from CWS, and 37 from ICG). Median age was 6.8 years, and median follow-up was 6.5 years. Eighty percent of patients received radiation therapy (RT) as part of primary therapy, but there were significant differences in the use of RT between the individual groups (93% in IRSG, 76% in ICG, and 70% in CWS, but only 37% in the SIOP MMT group). RESULTS At 10 years, event-free and overall survival for the whole cohort were 77% (range, 71% to 81%) and 87% (range, 82% to 92%), respectively. There was no difference in overall survival between the collaborative groups regardless of differences in the use of initial RT. In total, 34 (12%) of 273 survivors had not received RT, although this varied between the different groups (41% in the SIOP MMT group, 20% in CWS, 7% in ICG, and 6% in IRSG). There was no difference in overall survival for the whole cohort regardless of whether radiotherapy was used as part of initial therapy (86% at 10 years for both). CONCLUSION These data suggest that a subset of patients with orbital RMS can be cured without systematic local therapy, although the total burden of treatment (primary therapy and treatment for relapse) must be taken into account when assessing the implications for late sequelae.

Infantile Fibrosarcoma: Management Based on the European Experience

PURPOSE To retrospectively analyze the clinical features and results of treatment in 56 infants with fibrosarcoma enrolled onto cooperative European protocols between 1979 and 2005 and treated with a combination of surgery and chemotherapy. PATIENTS AND METHODS We performed a retrospective case review of infants under the age of 2 years with fibrosarcoma treated between 1979 and 2005 in six European studies. Patients were staged according to the Intergroup Rhabdomyosarcoma Staging System international classification as a function of the type of initial surgery and the extent of disease and were treated with surgery and chemotherapy. Survival was calculated using the Kaplan-Meier method. RESULTS Primary tumor site was the limbs in 66% of patients; median tumor diameter was more than 5 cm in 63% of patients; and postoperative staging was as follows: group I, 22%; group II, 27%; group III, 47%; and group IV, 4%. Response rate to chemotherapy was 75%, and the specific response rate to vincristine-dactinomycin was 71%. Local control was obtained in 84% of patients. At the end of follow-up, 45% of survivors had been treated by surgery alone, 6% by chemotherapy alone, 46% by surgery and chemotherapy, and 2% by surgery, chemotherapy, and radiotherapy. The 5-year overall survival (OS) rate was 89%. The 5-year OS and event-free survival rates for localized patients were 89% and 81%, respectively. CONCLUSION Although complete resection is rarely feasible at diagnosis, conservative surgery remains the mainstay treatment for infantile fibrosarcoma. An alkylating agent-free and anthracycline-free regimen is usually effective and should be chosen as first-line chemotherapy for inoperable tumors. Overall prognosis is good, but progression or relapse, mainly local, remains possible.

Conservative Treatment for Girls With Nonmetastatic Rhabdomyosarcoma of the Genital Tract: A Report From the Study Committee of the International Society of Pediatric Oncology

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.

Prognostic factors for survival in patients with brain metastases from renal cell carcinoma

Patients presenting with brain metastases from renal cell carcinoma portend a poor prognosis, with a reported median survival of 4‐6 months. Given their short life expectancy, these patients generally have been excluded from clinical trials that assess the efficacy of medical treatments. However, clinical impression suggests that some patients may achieve long term palliation.