PubMed HealthSearch

Biomedical subjects

P Bey

Publications and source records attributed to P Bey.

At least 19 recordsLinked to original sources

Thymidylate synthase expression and activity: relation to S-phase parameters and 5-fluorouracil sensitivity.

Six human cancer cell lines exhibiting a large range of sensitivity to 5-fluorouracil (5-FU) were evaluated for thymidylate synthase (TS) and p53 gene expression, TS and dihydropyrimidine dehydrogenase (DPD) activity, as well as cell cycle parameters, S-phase fraction (SPF), bromodeoxyuridine labelling index (LI) and S-phase duration (SPD). All these parameters were investigated for 7 days in asynchronously growing cell populations and compared with the cell sensitivity to 5-FU. No significant correlation was found between S-phase parameters and TS gene expression and/or activity. TS activity was higher in proliferating cells; however, it was not significantly higher in rapidly growing cell lines with short SPD. Neither TS gene expression nor activity was found to correlate with 5-FU sensitivity. On the another hand, a statistically significant correlation (P < 0.0001) was observed between LI and SPD and 5-FU sensitivity. The present results suggest that cell cycle parameters such as SPD and/or LI could be better parameters for 5-FU sensitivity prediction than TS gene expression and/or activity. This could be especially informative in cases of concomitant radio-chemotherapy as S-phase parameters are already proposed for hyperfractionated radiotherapy planning.

Antimetabolites, Antineoplastic

Combined flow cytometry and immunohistochemistry analyses for the assessment of nasopharyngeal carcinoma cell kinetics by in vivo bromodeoxyuridine infusion.

Thirty-eight previously untreated patients with a histologically proved diagnosis of nasopharyngeal carcinoma were evaluated for in vivo cell kinetics before treatment by conventional radiation therapy. Thirty-seven tumors were analyzed by flow cytometry. Values of median potential doubling time (Tpot), labelling index (LI), and duration of S phase (Ts) were, respectively, 10.9 days, 3.8%, and 10.8 hours. In 35 cases, the results obtained from two biopsies of the same tumor were compared. A good reproducibility was obtained for LI and Tpot (P < 0.01). Thirty-one tumors were analysed by immunohistochemistry and labelling index (HLI) was determined in 24 tumors with a percentage of labelled cells varying from 6.1% to 39.2% (median value = 18.5%). No correlation was found between LI and HLI, but when observations were focused on the restricted group of DNA aneuploid samples, mean values of LI and HLI were closer (respectively, 12.8 +/- 4.5% and 18.3 +/- 7.7%) and a good correlation was obtained (P = 0.01). Moreover, no difference in proliferation was found between diploid and aneuploid tumors. Considering these results, a combined Tpot was calculated that allowed classification of tumors as highly or slowly proliferative.

Adult

Cervical lymph node metastasis from an unknown primary: is a tonsillectomy necessary?

PURPOSE: The detection of an infraclinical primary by tonsillectomy in case of cervical lymph node of an epidermoid carcinoma with unknown primary after a radical neck dissection, allows avoiding irradiation of the normal larynx. The aim of this study is to quantify the rate of tonsil primary to justify this procedure. METHODS AND MATERIALS: From 1969 to 1992, 87 patients had a tonsillectomy as part of the workup for cervical nodal metastasis of an epidermoid carcinoma with unknown primary. The mean age was 57 years (range: 39-75 years) and the sex ratio was 8.6. Sixty-seven patients had a single cervical adenopathy (17 N1, 30 N2a, 5 N3, 15 Nx), and 20 patients multiple cervical adenopathies (17 N2b, 3 N2c). The treatments included always an irradiation to the node areas (50 Gy), and to the pharyngolarynx in case of normal tonsil (50 Gy), or to the tonsil if it was the primary (50 Gy with a brachytherapy boost of 20-25 Gy). In this last case, the larynx could be protected. RESULTS: Tonsillectomy never induced specific complication. Out of 87 patients, 26% had a tonsil primary. There was not specific histological differentiation in this group. In the 67 patients with a single cervical adenopathy, 31% had a tonsil primary (6 N1, 7 N2, 1 N3, 7 Nx). It was a subdigastric adenopathy in 38%, a submandibular in 28% and a midjugulocarotidian in 23%. Among the 17 patients N2b, none had a tonsil primary. In the three patients N2c, two presented a tonsil carcinoma (two subdigastric nodes). CONCLUSION: Tonsillectomy allows avoiding irradiation of normal larynx in 26% of patients who have a cervical lymph node with unknown primary. It should be performed in case of a single node of the subdigastric, midjugulocarotidian or submandibular area or bilateral subdigastric adenopathies.

Adult

Results of a European randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas.

PURPOSE: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma. METHODS AND MATERIALS: A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m2, three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization. RESULTS: Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99). CONCLUSION: Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).

Adult

Conservative treatment by irradiation of epidermoid carcinomas of the anal margin.

PURPOSE: Few series have described treatment results of anal margin tumors as defined in the UICC 87 classification. The purpose of this article is to describe experience with an uncommon condition in a single cancer center. METHODS AND MATERIALS: From 1971 to 1995, 32 patients with carcinoma of the anal margin were irradiated with a curative intent, and 31 were followed-up for more than 6 months (mean = 4.5 years). There were 9 T1, 15 T2, 7 T3, and 1 T4 (vulvar), with 26 N0 and 6 N1. There was a minor invasion of the lower canal in 17 patients. The histological types were 24 squamous cell and 7 basocellular carcinomas, and 1 Paget's disease. The treatment was a combined External Beam Irradiation (EBI) and Brachytherapy (BT) in 16 patients, an exclusive BT in 12 patients, and an exclusive EBI in 4 patients. No prophylactic inguinal irradiation was delivered. RESULTS: The 5-year actuarial results are as follows: overall survival = 67%, specific survival = 89%. The only prognostic factor was nodal involvement (p < 0.001). T-stage, T-size, age, sex, and treatment schedule were not significant. The overall local control was 77%, and 93.5% after salvage. Two N0 patients relapsed in inguinal areas (one was salvaged). Twenty-six percent presented a Grade 3 or 4 late complication, necessitating a temporary colostomy in only one patient. The sphincter conservation reached 84% for the whole series, 80% for patients followed-up 5 years or more, and 89% for cured patients. CONCLUSION: Results are similar to other series, and seem better than for anal canal cancer. We recommend exclusive irradiation. There is no data recommending concomitant chemotherapy. Depending on the tumor size and localization, the tumor boost can be applied by EBI or BT. Surgery is reserved for small tumors far from the canal or for salvage. An inguinal prophylactic bilateral irradiation should be recommended for N0, with tumors over 4 cm.

Adult

Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients).

PURPOSE: To study the rate and severity of complications in a series of 1134 patients treated by definitive irradiation for tumors of the oral cavity (772 cases) or the oropharynx (361 cases). METHODS AND MATERIALS: Patients were staged as 29.5% T1, 42% T2, 26% T3, 2.5% T4-Tx, and 74.5% N0 tumors. We treated 364 patients with brachytherapy only (192Ir) for the primary lesion. External irradiation and brachytherapy were combined for 770 patients. RESULTS: The results included local control and survival. Out of 1134 patients, 330 had 376 complications. Grade 1 complications occurred in 20% of the patients, Grade 2 in 9%; Grade 3 in 4%; and Grade 4 in 0.2%. Of the Grade 1 complications, 78% were soft tissue and only 24% were bone complications. For the more severe grades (2, 3, and 4), there were 56 soft tissue complications and 90 bone complications out of 1340 patients. The statistical analysis included tumor-related factors and treatment-related factors. For the first two factors, only tumor location was significant. The treatment-related factors significant for complications were studied in univariate and multivariate study. This multivariate study confirmed that for soft tissue complications dose rate and volume treated were important (p < 0.001). It also confirmed that for bone complications, total dose > 80 Gy, dose rate > 0.7 Gy/h, and the absence of leaded protection of the mandible were all important factors. CONCLUSION: This statistical study should allow future reduction of severe complications (Grades 2, 3, 4), if treatment factors inducing them can be taken into account. This is not always possible for very large tumors.

Analysis of Variance

Conservative treatment by irradiation of epidermoid cancers of the anal canal: prognostic factors of tumoral control and complications.

UNLABELLED: We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermoid cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC). METHODS AND MATERIALS: From 1976 until 1994, 118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1-3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal resection (APR). The mean follow-up was 6 years. RESULTS: At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for T1, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (> or = 4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3, 16 patients; and Grade 4, 1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for T1, 82% for T2, 58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control. CONCLUSION: The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC.

Adult

Treatment duration as a prognostic factor for local control and survival in epidermoid carcinomas of the tonsillar region treated by combined external beam irradiation and brachytherapy.

PURPOSE: We wanted to study the influence of the time factor in a combination of external irradiation and brachytherapy from a retrospective study of 370 squamous cell carcinomas of soft palate and tonsil. PATIENTS AND METHODS: From 1977 to 1993, 370 soft palate and tonsillar carcinomas were treated at the Centre Alexis Vautrin. All patients received external irradiation (ERT) with a minimum dose to the tumour of 45 Gy, followed by low dose rate brachytherapy by Iridium 192 using the technique of plastic tubes; 22 patients received neo-adjuvant chemotherapy. We treated 85 T1, 159 T2, 117 T3 and nine T4 or TX carcinomas; 128 of these had palpable nodes. There were 267 men and 24 women. The median age was 55 years (range 33-81 years). RESULTS: The median duration of the total treatment was 57 days. The rate of local control was 88% at 5 years when the treatment time was 7 weeks and 74% when it was 9 weeks (P = 0.001). The rates of overall survival at 5 years were 63 and 44%, respectively (P < 0.0001). For the interval between external irradiation and brachytherapy the series was divided into three groups, i.e. patients treated with a delay inferior or equal to 16 days (2 weeks), patients for which the interval was between 16 and 20 days and patients treated with a delay greater than 20 days (3 weeks). The rates of local control and overall survival at 5 years were not significantly different in the two first groups so we amalgamated these two groups and compared them with the third group. In this way the time cut-off for the delay between external irradiation and brachytherapy was 20 days. At 5 years, the rate of local control was 85% for the group for which the interval was inferior to 3 weeks and 73% when the delay was greater (P = 0.01). The rates of overall survival at 5 years were 59 and 38%, respectively (P < 0.001). Multivariate analysis confirmed that protraction of treatment was a factor for poorer local control. This factor was independent of the other prognostic factors. CONCLUSION: The total duration of irradiation and the delay between external irradiation and brachytherapy were significant prognostic factors for local control and overall survival of soft palate and tonsil carcinomas. The overall duration should not be greater than 7 weeks (external irradiation, 5 weeks plus a delay of 12-15 days between ERT and brachytherapy). The delay should never be greater than 20 days, but a boost should be considered to make up for the loss of local control.

Adult

Carcinoma of the cervical stump: retrospective analysis of 77 cases.

BACKGROUND AND PURPOSE: Although supracervical hysterectomy is becoming a rare procedure, there are still many women with retained cervical stump. The purpose of this retrospective study was to assess the results of treatment in patients with carcinoma of the cervical stump. MATERIALS AND METHODS: From 1974 to 1990, 77 patients were treated for an infiltrating carcinoma of the cervical stump. This group accounted for 6.6% of the cervical carcinoma diagnosed during the same period. The pathological examination showed, 91% of squamous cell carcinomas and 9% of adenocarcinomas. FIGO stage distribution was: I (35%), II (45%), III (18%), IV (2%). According to the stages, the treatment used a combination of external beam radiation therapy (EBRT) with plesiobrachytherapy (PBT), and in a few cases, patients underwent surgery or interstitial brachytherapy (IBT). In patients with bulky tumour or advanced stage and/or lymphatic node involvement, EBRT was first delivered. Most of Stage I and Stage II patients, began their treatment with PBT. All stages included, 95% of the patients were treated by exclusive radiation therapy. Complications were classified according to the recommendations of late effects normal tissues (LENT) scoring system described by the EORTC/RTOG. RESULTS: Three-year pelvic control was achieved in 59 of 77 patients (76.6%) in the whole series. Three-year pelvic control probabilities were 77% (95% CI: 66-85%), and 89% (95% CI: 72-96%), 73.7% (95% CI: 65-88%) and 56% (95% CI: 28-80%) in the whole series and in Stage I-III tumour patients, respectively. The 5-year and 10-year overall survival probabilities in the whole series, were 66.4% (95% CI: 55-76%) and 61.2% (95% CI: 50-72%), respectively. Ten patients (12.8%) developed 17 late complications distributed as follows: G1, nine patients (11.7%); G2, five patients (6.5%); G3, one patient (1.3%); and G4, two patients (2.6%). CONCLUSIONS: Treatment results are similar both in patients with carcinoma of the cervical stump and in patients with carcinoma of the intact uterus. Indeed, it is sometimes difficult to perform a correct PBT application because of the pelvic anatomic modifications induced by the subtotal hysterectomy and its consequences on the new organisation of critical organs into the treated volume.

Adenocarcinoma

Post-operative brachytherapy: a prognostic factor for local control in epidermoid carcinomas of the mouth floor.

The aim of this study was to analyse the role of post-operative brachytherapy (BT) in a group of patients with a high risk of local relapse (positive or narrow surgical margins) for squamous cell carcinoma of the mouth floor (SCCFM). A comparison with post-operative external beam irradiation (EBI) in a group of patients with standard risk of local relapse for SCCFM with free margins is performed to estimate the benefit of BT. From 1979 to 1992, an initial group of 32 patients with SCCFM (12, T1-2; 20, T3-4x) received an Ir 192 low dose rate BT using plastic tubes (+EBI for 20 patients) after surgery with positive or close margins. BT was applied in one or two planes to the surgical scar. The mean dose of BT was 57 Gy (range: 50-60) for exclusive BT and 22 Gy (range: 15-30) when a boost was applied (mean EBI dose = 50 Gy). During the same period, 36 patients had post-operative external irradiation alone after satisfactory surgical resection. Excluding the post-operative margin, these two groups were comparable for other prognostic factors. The mean follow-up was 46 months (range: 5-145) with a minimum follow-up of 2 years. For BT and EBI groups, the 5-year results (Kaplan-Meier) were, respectively, overall survival 62% and 43%, local control 81% and 60% (P = 0.09) (log-rank) and severe complications 4/32 and 1/36. Post-operative BT achieves good local control for patients with narrow or positive margins by increasing the dose to the surgical scar, with good tolerance. Given these encouraging results, we confirm this treatment for these patients.

Brachytherapy

Breast cancer in patients treated for Hodgkin's disease: clinical and pathological analysis of 76 cases in 63 patients.

In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN > 3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.

Adult

[Bilateral breast cancer after Hodgkin disease. Clinical and pathological characteristics and therapeutic possibilities: an analysis of 13 cases].

PURPOSE: Though Hodgkin's disease (HD) is one of the malignancies in which considerable progress has been made, long-term side effects have been observed, second primary cancer being the most significant. Several recent reports have indicated an increased risk of breast cancer (BC) in girls and young women among HD patients. MATERIALS AND METHODS: In a retrospective multicenter analysis, 63 women treated for HD subsequently developed BC. Results that were obtained in 13 women (21%) who developed either synchronous (five cases) or metachronous (eight cases) BC were analyzed. The median age at diagnosis of HD was 19 years. Seven patients underwent exclusive radiotherapy (RT) (including "mantle" supradiaphragmatic irradiation) and six received concomittant radiation therapy and chemotherapy. RESULTS: The first breast tumor occurred after a median delay of 16 years. According to the TNM classification, we showed nine stage T0 (non palpable lesions), four stage T1, five stage T2, one stage T3, two stage T4 and five stage Tx BC. Seventeen infiltrating carcinomas, two fibrosarcomas and seven ductal carcinomas in situ were observed. Among 15 axillary dissections performed for invasive carcinomas, histological involvement was found in 10 cases. Seventeen tumors were treated by mastectomy and nine patients underwent conservative surgical treatment. With a 70-month median follow-up (range: 15-125), three patients developed locoregional recurrence and four other metastases. At present, eight are alive with no evidence of disease and one died of intercurrent disease. CONCLUSION: According to previous works, BC represents 6.3 to 9% of all second cancers occurring after HD treatment. The risk is higher in young women treated before 20 years of age, especially before 15 years of age. Factors that favour the development of secondary BC are: supradiaphragmatic irradiation, very young age at treatment, chemotherapy with alkylating agents, and probably genetic factors. We conclude that young women and girls treated for HD should be carefully monitored at least 10 years after the end of the treatment for HD, using clinical examination, mammography and ultrasonography. The optimal rythm of this follow-up is not yet clearly defined. Moreover, after multidisciplinary concertation, we suggest that secondary BC be sometimes treated by conservative radiosurgical approach.

Adolescent

[Optimization of dose distribution of radiation in cancers of the cavum: association of an expert-system and a mathematical algorithm].

Optimization of radiation therapy in nasopharyngeal carcinoma is particularly complex due to both the proximity of at risk organs and the high dose that has to be delivered. To obtain an optimal dose distribution, a knowledge-based optimization technique has been designed that associates an expert-system, named CAVCAV, with numeric optimization (gradient projection method). Based on clinical and physical criteria, CAVCAV determines the geometric characteristics of the radiation fields (beam direction, location and shape of the shielding blocks) for the three stages of radiation therapy of nasopharyngeal carcinomas. Stage 2-treatment fields proposed by CAVCAV, though not perfectly adapted to the patient, are mathematically (beam weights, beam directions, isocenter position) and geometrically (adaptation of fields and shape of blocks by virtual simulation) optimized.

Algorithms

[Indications and results of exclusive radiotherapy in early prostatic adenocarcinoma].

Prostate adenocarcinoma incidence are rising rapidly, especially in early stages. Even if some of these carcinomas may be latent or slow growing either spontaneously or under hormonal therapy, most patients 75 years old or less presenting a localized tumor, T1b-c, T2, T3, N0, M0, whatever the grading, will require treatment with curative intent: radical prostatectomy, external beam radiation therapy (ERT) and/or brachytherapy. After ERT limited to the prostate or including seminal vesicles and/or pelvic lymph nodes, the overall survival and the survival without clinical evolution at 5, 10 and 15 years are good. However survival rates without biochemical evolution are about 30% lower and 70% or less at 5 years for the more favorable group (T < or = T2a and Gleason < 7 and PSA < 10 ng/mL). Brachytherapy alone yields good results for the same favorable group. In the unfavorable group (T > or = 2c and Gleason > or = 7 and PSA > or = 20 ng/mL), adjuvant hormonal therapy improves survival. Conformal radiation therapy allows an increase in dose to the tumor by about 15% without increasing complications. It can increase the biological remission rate in the intermediate group (T < or = 2a or Gleason > or = 7 or PSA > or = 20 ng/mL).

Adenocarcinoma

[An exceptional variety of medulloblastoma: melanotic medulloblastoma].

We report a new case of melanotic medulloblastoma of the vermis in a 3 1/2 year old boy. This tumor showed a typical histological appearance with pseudoepithelial pigmented structures immunoreactive for S100 protein and vimentin. The tumor did not recur after total surgical removal and post operative radiation. However, after a 10 year follow-up, imaging demonstrated that a second tumor occurred in the left cerebellar hemisphere, which, on histological examination, was a typical glioblastoma. Hypothesis concerning the histogenesis of the second tumor, as well as a causal association with radiation therapy and possible contribution of growth hormone therapy are discussed.

Cerebellar Neoplasms

A double-blind, placebo-controlled trial of i.v. dolasetron mesilate in the prevention of radiotherapy-induced nausea and vomiting in cancer patients.

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P = 0.024) and administration of rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P = 0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.

Adult

[Recent progress in radiotherapy].

UNLABELLED: Radiation therapy has considerably evolved in 1 century. After the revolution due to cobalt in the beginning of the sixties, we are now entering the 2nd revolution in three fields in external radiotherapy. METHODOLOGY: the development of quality assurance programmes gives the guarantee that the treatment is done as it is prescribed. Technology: recent developments allow conformal radiation therapy which permits to increase the dose without increasing side effects. Biology: the implementation of predictive assays will permit to choose the best modality of treatment for each patient. In brachytherapy, the use of high dose rate radioactive sources increases indications in locations not yet accessible. Pulse dose rate brachytherapy increases radio-protection and will make optimization possible in complex volumes. In the future, indications of curative radiotherapy will probably increase in regard to earlier diagnosis of many cancers and to increase of efficacy of general treatments on metastatic disease.

Brachytherapy