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Biomedical subjects

M Bolla

Publications and source records attributed to M Bolla.

At least 109 records · Page 6Linked to original sources

Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for stage IIIA and stage IIIB non-small cell lung cancer: results of a phase I-II study by the GOTHA group. Group d'Oncologie Thoracique des Régions Alpines.

The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and weeks 6-7 (33 Gy). The dose actually delivered was > 98% for RT, and 85-100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy.

Adult↗

[Feasibility of retroperitoneal pelvic lymph node exploration in cancers of the cervix treated by radiosurgery association or radiotherapy alone. Apropos of a series of 52 cases].

From June 1980 to May 1993, 52 patients with a mean age of 49, underwent a retroperitoneal pelvic lymph node laparoscopic procedure for cervix carcinoma classified as stage IA (14), IB (12), IIA (6), IIB (14), IIIB (3), IVA (3). Two techniques were used: a retroperitoneoscopy in 16 cases and a panoramic retroperitoneal pelviscopy (PRPP) in 36 cases. The aim was to define, with a better accuracy, the pelvic lymph node status, to adapt the target volume, and to estimate the morbidity. More nodes were biopsied with PRPP than with retroperitoneoscopy (p < 0.05). There was a disagreement between the conventional radiologic assessment and the histological results in 28.6%. Specificity is 100%. Intra-operative and post-surgical morbidity was equivalent in the two procedures. One grade 3 urinary late morbidity (3%) was observed among the 33 patients who underwent a pelvic external irradiation. There was no morbidity of the gastro-intestinal tract. Discussion deals with the support offered by the two laparoscopic procedures to define the pelvic lymph node status, to choose the planning target volume, and to precise the lymph node boost.

Adenocarcinoma↗

Lack of prognostic value of epidermal growth factor receptor in a series of 229 T1/T2, N0/N1 breast cancers, with well defined prognostic parameters.

The prognostic value of epidermal growth factor receptor (EGF-R) was prospectively assessed in a series of 229 clinical T1-T2, N0-N1 breast carcinomas diagnosed between May 1987 and October 1989. EGF-R expression was determined by measuring the specific Bmax of 125I EGF to tumor plasma membrane preparations. Tumor with a Bmax > or = 3 fmol/mg of protein were considered positive with regard to EGF-R expression. With a median follow-up of 34 months, the 3-year overall and disease-free survivals are respectively 92% and 88% for EGF-R < or = 3, and 91% and 86% EGF-R > 3 fmol, showing no significant difference, even when comparing axillary lymph node status. We did not succeed in finding an EGF-R cut-off value which might be significant in univariate analysis. Multivariate analysis of our data indicates that pT (p = 0.001), pN (p = 0.04), and Scarff-Bloom grade (p = 0.04) are the only significant predictors of disease-free survival among the parameters investigated in this study.

Analysis of Variance↗

Prevention of second primary tumours with etretinate in squamous cell carcinoma of the oral cavity and oropharynx. Results of a multicentric double-blind randomised study.

Patients who are cured from head and neck carcinomas remain at high risk for developing a second primary in the head and neck area. It is now clear that retinoids exert a prophylactic action on the development of epithelial cancers when tested on laboratory animals and on human premalignant lesions. They are now used in the chemoprevention of epithelial cancers in randomised trials evaluating their efficacy. We prospectively studied 316 patients who developed squamous cell carcinoma of the head and neck, classified as T1/T2, N0/N1 < or 3 cm, M0 according to the UICC TNM classification. Patients were randomly assigned to receive orally, either etretinate (a loading dose of 50 mg/day for the first month, followed by a dose of 25 mg/day in the following months) or a placebo for 24 months. Adjuvant treatment began no later than 15 days after surgery and/or the initiation of radiotherapy. The 5-year survival rate and disease-free survival rate are similar in the two groups. There are no significant differences regarding either local, regional and distant relapses. After a median follow-up of 41 months (range 0-81), 28 patients in the etretinate group and 29 in the placebo group developed a second cancer with, respectively, 12 and 13 in the head and neck region. Adjuvant treatment was definitively discontinued mainly due to toxicity in 33% of patients in the etretinate group versus 23% in the placebo group (P < 0.05). Etretinate, a second-generation retinoid, does not prevent second primary tumours in patients who have been treated for squamous cell carcinoma of the oral cavity and oropharynx.

Adult↗

[Modulation of indications of adjuvant hormone therapy with tamoxifen in T1T2/N0N1 breast cancers. Preliminary results of a multicenter study with 695 cases].

From 1982 to 1990, patients less than 75 years, without any previous or synchonous carcinoma, suffering from an invasive breast cancer classified as T1T2/N0N1/MO according to clinical TNM staging, were enrolled in this study; 82.4% underwent a breast conservative procedure and 17.2% a modified radical mastectomy followed by a postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade, estradiol receptor content, were used to define three groups of patients. The breakdown of patients is not well balanced: 416 women were included in group I (N-, grade I II, ER+) when there was no adjuvant medical treatment, 110 in group II (N-, grade III, ER+), 169 in group III (N+ < or = 3, grade I II, ER+). Patients from the latter two groups were receiving tamoxifene, 20 mg per day for 2 years; Those women not menopaused received first a pelvic irradiation. With a median follow-up of 35 months (1-138) the overall survival is respectively for the three groups 95%, 96%, 96% (P = 0.5) and the disease free survival 86%, 93%, 90% (P = 0.1). The actuarial local regional remission rate is 94%, 97%, 99% (P = 0.07). Such results need to be updated with a longer follow-up, but they show the ability of adjuvant hormonotherapy to tailor the short term survival thanks to prognostic factors.

Adult↗

Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy.

PURPOSE: To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonadotropin values treated with radiotherapy were analyzed. METHODS AND MATERIALS: The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadotropin were found: 96 Stage I, 20 IIA, 7 IIB, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1-12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 IIA, 5 IIB and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also initial chemotherapy (3 Stage IIB 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts). RESULTS: The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group (p < 0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 IIB, 3 III and 1 IV). Of these, there were one in-field recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotrophin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage IIA and 65% for Stage IIB and III [p < 0.001 between I and IIB + III, p < 0.05 between IIA and IIB + III]). Four of the 7 recurrences were salvaged by chimiotherapy +/- radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group (p = 0.10). CONCLUSION: Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and IIA seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low.

Adolescent↗

Protein tyrosine kinase activity as a prognostic parameter in breast cancer, a pilot study.

Protein tyrosine kinase (PTK) activity was assayed in cytosolic extracts from normal breast tissue, benign tumors, and 84 T1-T2, N0-N1 M0, breast carcinomas. Normal breast tissue extracts yielded an average value of 1.9 +/- 1.1 pmol 32P incorporated/min/mg protein, whereas a mean of 12.5 +/- 6.1 was obtained for cancer samples. With a median follow-up of 34 months, in the series of 40 patients classified N-, PTK positive patients presented a significantly smaller 3-year disease free survival than the PTK negative ones. Multivariate analysis shows that PTK activity emerges as a potential prognostic factor in breast cancer (p = 0.02). These preliminary results will be updated on a bigger cohort of patients.

Adult↗

Conformal external radiotherapy of prostatic carcinoma: requirements and experimental results.

The aim of conformal radiotherapy is to deliver, with high precision, a specific dose (which may be a high dose) to a planning target volume, concurrently with irradiating as little as possible healthy tissue and organs at risk. Radiation therapy may suffer from a number of problems that result in both over- or under-sizing the irradiation fields, making over-rough simplifications of the irradiation ballistics and delivering an insufficient tumoral dose (to spare critical organs and reduce toxicity). One of these problems lies in the accurate positioning of the planning target volume with respect to the irradiation system, thence in the correct execution of the ballistics. In this paper, we describe a system aiming at achieving a higher overall accuracy in the delivery of prostatic boost for carcinoma of the prostate. The system is based on the use of ultrasonic images for measuring the actual position of the prostate just before irradiation. Since these images are registered with pre-operative (CT or MR) images, the position and orientation of the planning target volume is computed with respect to the irradiation system, and can be corrected accordingly. First experiments have been performed on dummies, and the results are discussed.

Humans↗

Pre- and intra-irradiation multimodal image registration: principles and first experiments.

Accurately repositioning the patient with respect to CT or MR images is essential for high precision radiotherapy. We show that portal images may be automatically registered with 3D pre-session data (typically morphological images like CT or MR images), thus enabling an automatic adjustment of the planned strategy to the actual position of the patient. Based on computer vision techniques, the principles of this new method of multimodal image registration are presented, and the first experiments with a phantom are analysed.

Humans↗

Prostate cancer treated by radiotherapy: a multivariate study.

According to respective proportions of evolutive status groups, results of multivariate studies are difficult to interpret. Among the 1099 cases of local form of prostate cancer, treated by radiotherapy from 1975 to 1982 in 16 French Anticancer Institutes, we can observe two homogeneous status groups of patients: disease-free survivors (285 cases) and patients who died of prostate cancer (278 cases). These correspond to 51% of the whole population. Among other things, they are comparable in size, for age at the beginning of radiotherapy and for delay between histologic diagnostic and radiotherapy. We chose to analyse them using multivariate analysis. To take survival into account, we used a Cox model and Kaplan-Meier curves; the group deceased of prostate cancer was further analyzed by a tree-structured regression method. The Cox model and the Kaplan-Meier curves confirmed two main explicative factors: Stage (p < 0.0001) and tumor grade (p < 0.001). Poorer evolution occurs in extracapsular forms and grade I has better survival than others. The tree-structured regression method indicates two other pejorative factors: hormonotherapy prior to radiotherapy and the presence of cardiovascular pathology. Though the pelvic dose does not appear to be a main explicative factor, it seems to improve survival and delay between radiotherapy and recurrence or metastasis in some categories of cases. Other factors such as tumor dose, age and delay between diagnosis and radiotherapy were not found to be significant. These results cannot be extended to the whole population for which they do not constitute a predictive study. We consider them as "baseline data".(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗