Hyperfractionated accelerated radiotherapy (HART) for inoperable, nonmetastatic non-small cell lung carcinoma of the lung (NSCLC): results of a phase II study for patients ineligible for combination radiochemotherapy.

PURPOSE: To evaluate a hyperfractionated and accelerated radiotherapy (HART) protocol in patients with inoperable non-small cell lung carcinoma (NSCLC) who were ineligible for combination radiochemotherapy studies. METHODS AND MATERIALS: From February 1989 through August 1994, 23 patients ineligible for available combined modality protocols in our institution were enrolled and treated with HART, consisting of 63 Gy given in 42 fractions of 1.5 Gy each, twice daily, with a minimum time interval of 6 h between fractions, 5 days a week, over an elapsed time of 4.2 weeks, or 29 days. There was no planned interruption. RESULTS: The 1-, 2-, and 3-year survival rates were 61%, 39%, and 19%, respectively, with a median survival of 16.8 months. At the time of analysis, 4 patients are alive and 19 have died, 16 from NSCLC and 3 from cardiac disease. Overall response rate was 48%, with 22% of patients achieving a complete response and 26% a partial response. Correlation between acute response rate and survival was poor. First site of relapse was local-regional in 8 patients (35%), distant in 6 patients (26%), and local-regional and distant in 4 (17%) patients. One patient had Grade IV and 2 had Grade III esophagitis. One patient presented with chronic Grade III lung toxicity. There were no treatment-related deaths. CONCLUSION: In this group of 23 patients ineligible for radiochemotherapy, this HART regime was quite feasible and was followed by little toxicity. Results in this particularly poor prognosis NSCLC patient category should be compared to series with a similar patient profile; however, median survival is at least similar to that obtained in recent series of combination radiochemotherapy.

Altered apoptotic profiles in irradiated patients with increased toxicity.

PURPOSE: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. METHODS AND MATERIALS: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. RESULTS: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (-1.8 sigma) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (-3.6 sigma). CONCLUSION: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.

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.

[Non-mutilating treatment of breast cancer: survival and recurrence]. / Traitement non mutilant du cancer du sein: survie et récidives.

During the last decades considerable progress was made in medical and biomedical techniques, enabling early diagnosis and a better understanding of how tumors develop. At the same time, treatment by surgery has changed, becoming less and less mutilating. In order to analyze loco-regional relapses and factors of prognosis, we studied 420 patients representing 415 cases of breast cancer, all of whom received breast-preservation therapy. The case histories were followed from 1 to 17 1/2 years, with an average observation period of 4 years. The majority of patients underwent enlarged tumorectomy, generally accompanied by axillary dissection and by radiotherapy. Based on an overall study of our patients, actuarial survival was 87% after 5 years and 65% after 10 years. Not taking into consideration patients with tumors at stages pT3 and pT4 recovery was 90% after 5 and 67% after 10 years. We have attempted to demonstrate that this survival rate, as well as the occurrence of a relapse, vary according to different parameters, such as size and invasion of the axillary glands.

[Pancoast's tumor: multi-disciplinary treatment and combined cervico-thoracic approach]. / Tumeur de Pancoast: traitement pluridisciplinaire et abord chirurgical cervico-thoracique combiné.

Five patients were treated from May 1987 to April 1988 in CHUV, Lausanne, for a superior sulcus tumor (3 epidermoid, 2 undifferentiated carcinomas). Treatment consisted of preoperative radiotherapy (3000 cGy)-surgery-postoperative radiotherapy (1500-2500 cGy). Two patients died from metastases. Only one patient presented with a local recurrence. Surgical resection was carried out by combined cervical and thoracic exposure. The cervical approach allows separation of the tumor from the subclavian artery, brachial plexus and vertebrae. Then, by thoracotomy, the superior lobe with tumor and thoracic wall is removed. Technical aspects of the procedure are described.

[Modification of gastric emptying after a selective proximal vagotomy. Barium and isotope studies]. / Modification de la vidange gastrique après vagotomie sélective proximale. Etude par repas baryté et isotopique.

The study of gastric emptying by isotopic and barium feeding, in 43 patients, before and 6 months after highly selective vagotomy, showed no retention after this type of operation. Whereas during the first 45 minutes following ingestion of the test meal, there was no modification of emptying, a significant acceleration thereafter was demonstrated by both methods. The isotopic meal allows continuous study of gastric emptying which appears to be more regular after the operation. There was no difference in gastric emptying between patients suffering from post-prandial gastric fullness, mild diarrhea or dumping syndrome.