A. Gerbaulet

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.

Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group

From November 1977 to July 1981, 441 patients with cervical carcinoma were randomized between pelvic irradiation and pelvic and para-aortic irradiation. Included were patients with stage I and IIB with proximal vaginal and/or parametrial involvement with positive pelvic lymph nodes either on lymphangiogram or at surgery, and stage IIB with distal vaginal and/or parametrial involvement and III regardless of pelvic node status on lymphangiogram. Patients with clinically or surgically involved para-aortic nodes were not included. The external beam dose to the para-aortic area was fixed at 45 Gy. There was no statistically significant difference between the two treatment arms in terms of local control, overall distant metastases and survival with no evidence of disease (NED), although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone (pelvic group). The 4-year NED survival rate was 51%. The incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation (para-aortic group). Routine para-aortic irradiation for all high risk patients with cervical carcinoma is of limited value, but patients with a high probability of local control can benefit from extended field irradiation, despite an increase in severe digestive complications.

Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy results of a retrospective study of 386 patients

A retrospective study was carried out on 386 patients with advanced cervical carcinomas treated with radiation therapy between 1973 and 1983. The influence of hemoglobin concentrations and blood transfusions before and/or during treatment on the occurrence of distant and/or local regional failures were examined in a univariate and multivariate analyses. In the multivariate analysis hemoglobin concentrations were prognostic only during treatment and patients with at least one value below the threshold of 10 gm% had a significantly higher risk of local regional failure than the patients with all their values above the threshold. Moreover 70% of these high risk patients had less than half of their values below the threshold. It is possible that blood transfusions might be beneficial when given before treatment. However, although it was not significant, blood transfusions given during treatment tended to be an adverse prognostic factor suggesting that blood transfusions might not have completely offset acute anemia prior to transfusion. Our study suggests that anemia during treatment, even of short duration might be detrimental to patients.

Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma

PURPOSE The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented. METHODS AND MATERIALS Between 1985 and 1988, 204 patients with Stage I and limited Stage II cervical cancer were randomized to receive one of two preoperative brachytherapy low-dose rates (0.4 and 0.8 Gy/hr). The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic arsenal for this patient population, in terms of survival, local control, and complications. The type and severity of all complications were evaluated according to a common glossary and a strict follow-up schedule was established given that the treatment of cervical cancer is multidisciplinary, involving gynecologists, surgeons, and radiotherapists. RESULTS Overall survival: 85% at 2 years and local control: 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%) and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12). Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs. 45% at 2 years (p = 0.03). CONCLUSION The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. This underlines the importance of the regular follow-up of patients and of coding, not only the occurrence of all complications, but also their evolution over time.

LONG-TERM RESULTS OF BRACHYTHERAPY FOR CARCINOMA OF THE PENIS CONFINED TO THE GLANS (N- OR NX)

PURPOSE To analyze the results of exclusive interstitial low-dose-rate brachytherapy (BT) for squamous cell carcinoma (SCC) of the penis, strictly confined to the glans. METHODS AND MATERIALS A total of 144 patients with SSC of the glans penis were treated with BT. Inguinal nodal dissection was performed in 19% of patients (all N-). After circumcision, BT was performed using the hypodermic needle technique. Median iridium length per patients was 24 cm (range, 4-108) and median dose was 65 Gy (range, 37-75). Median treated volume was 22 cm(3) (range, 5-110) and median reference isodose rate was 0.4 Gy/h (range, 0.2-1.2). RESULTS Median follow-up was 5.7 years (range, 0.5-29). The 10-year penile recurrence, inguinal lymph node recurrence, and inguinal nodal metastasis rates were: 20% (CI 95%, 11-29), 11% (CI 95%, 5-17), and 6% (CI 95%, 2-10), respectively. After salvage treatment, 86% patients with local failure were in a complete remission at last follow-up. The 10-year probability of avoiding penile surgery (for complication or local recurrence) was 72% (CI 95%, 62-82). The 10-year cancer-specific survival rate was 92% (CI 95%, 87-97). Diameter of tumor significantly increased the risk of recurrence (p = 0.02). The 10-year painful ulceration and stenosis risk rates were: 26% (CI 95%, 17-35) and 29% (CI 95%, 18-40), respectively. Seven patients required excision for necrosis. Treated volume and reference isodose rate significantly increased the risk of complications. CONCLUSION BT is an effective conservative treatment for SCC confined to the glans. Salvage local treatment is effective. Dose rate should be limited to decrease toxicity.

Interstitial brachytherapy for penile carcinoma: a multicentric survey (259 patients)

Although cancer of the penis is a rare disease, we have collected 506 cases through a multicentric study. In the present study we analyse the results obtained from 259 patients treated by interstitial brachytherapy from 1959 to 1989. Among the 259 patients, 184 males had exclusive brachytherapy (group A) while 75 received a combination of surgery and brachytherapy and/or external beam irradiation (EBI) (group B). Five- and 10-year survival rates are, respectively: overall survival, 66 and 52%; cause-specific survival, 88 and 88%; disease-free survival, 78 and 67%. One hundred and forty-three patients in group A (78%) and 48 (64%) in group B avoided mutilation of the penis while late side effects occurred in 137/259 patients (53%). Survival depends on the volume of the tumor and the presence of involved nodes; systematic groin dissection does not however seem advisable.

RADIOTHERAPY AFTER OVARIAN TRANSPOSITION: OVARIAN FUNCTION AND FERTILITY PRESERVATION

The outcome of ovarian function preservation and fertility after ovarian transposition was examined in women treated for cancer. Of 134 patients, 126 were treated with radiotherapy and 72 with chemotherapy. In a multivariate analysis, three factors appeared to be prognostic of ovarian castration: the age over 25, MOPP chemotherapy and a total dose to the ovaries higher than 5 Gy. The incidence of birth was lower in the general population but no abnormality was observed.

High-dose-rate brachytherapy as sole modality for early-stage endobronchial carcinoma

PURPOSE To evaluate exclusive high-dose-rate brachytherapy for localized early-stage non-small-cell bronchial carcinoma; to develop new insights in treatment-catheter positioning and tumor-volume assessment by computed tomography (CT) scan. METHODS AND MATERIALS Between 1992 and 1996, 34 patients with non-small-cell bronchial carcinoma were treated by brachytherapy alone. All patients were medically inoperable and had contraindications for external beam irradiation. The treatment protocol was six sessions of 5 Gy over 6 weeks. The treatment catheter was placed under fiberoscopy and was positioned with the help of spacer catheters or with a surrounding plastic tube; CT scan was performed in 50% of the cases to measure the spacing between the applicator and the bronchial wall. Dose prescription was individually based on clinical and radiologic evaluation of tumor volume. RESULTS Local disease failure occurred in 5 patients (15%). With a median follow-up of 2 years, the local control rate was 85% and the survival rate 78%. No acute toxicity was found, except one pneumothorax. CONCLUSION Brachytherapy alone can give an optimal therapeutic ratio in small endobronchial carcinomas without radiation-induced morbidity. Such results are achieved after careful tumor volume evaluation and individualized treatment catheter positioning.

Twenty years experience of interstitial iridium brachytherapy in the management of soft tissue sarcomas

From February 1968 to February 1988, 50 patients above 10 years of age with a soft tissue sarcoma were treated with interstitial brachytherapy, combined with a wide excision. After pathologic review, 48 were included in the final analysis. A pathological grading was made possible in 41, which showed a majority of high grades (2 + 3 = 86%). Patients presented mainly with small (less than 5 cm: 36) or mid-size lesions (greater than 5 cm: 12). The tumor was located in the limbs (32), trunk (9), and head and neck (7). Four patients had metastases at the time of treatment. Brachytherapy was part of the initial treatment in 22 cases, and of a salvage procedure after previous excision(s) combined or not with another form of treatment in 26. A uniform technique of iridium 192 wires after-loaded in plastic tubing was used. Sixty Gy median doses were delivered with brachytherapy alone (44) or combined with external beam (4). Sixteen patients also received an adjuvant chemotherapy. Follow up ranged from 16 months to 20 years (median 82 months). At the time of analysis, two patients (4%) only had failed in the irradiated volume, but the marginal failures rate (14:31%) was unexpectedly high. Seven of the patients who failed (43%) were salvaged by a second similar procedure. The 5-year survival was 62% in non-previously treated patients and 56.5% in previously treated ones (pNS). By multivariate analysis, only the tumor location appeared predictive of LF (p less than 0.01), which in turn was strongly correlated with the metastatic outcome (p less than 0.01). Necroses were observed in 17 cases (35%) and associated with a benign course in most of them. High dose brachytherapy combined with conservative surgery is highly effective in small and mid-size soft tissue sarcomas located in the extremities and head and neck, whereas in trunk and in recurrent tumors, the adjunction of large fields external radiotherapy and/or possibly polychemotherapy appears necessary.

Laparoscopic ovarian transposition for pelvic malignancies: indications and functional outcomes

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.