Myelopathy following radiotherapy of bronchial carcinoma with large single fractions: a retrospective study.

A series of 387 patients with bronchial carcinoma treated with a concentrated split course regimen was surveyed for radiation myelitis. The total dose was 38 Gy. Three fractions of 6 Gy were given the first week. After a three-week interval the patients had a second course of radiotherapy with fractions of 4 Gy on 5 consecutive days. A spinal shield was used in 230 patients for the last two fractions of radiotherapy. The median survival for all patients was 9.4 months. Seventeen cases of radiation myelopathy were found. The life table method was used to calculate the risk of myelopathy in surviving patients, showing risk levels of 30 +/- 15% in patients surviving three years or more. The average age of the patients with myelopathy was 57.6 years, compared to 62.9% years in the total population. Statistical analysis showed a borderline significant increased risk for myelopathy in females, and a significant increased risk in younger patients (P = 0.03). No difference in the incidence of myelopathy was found in patients treated with or without a spinal shield.

A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.

PURPOSE: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article. METHODS AND MATERIALS: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended. RESULTS: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study. CONCLUSION: The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor.

Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagus. A prospective randomized multicentre study: the second Scandinavian trial in esophageal cancer.

Survival and swallowing function were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radiotherapy was given to 51 patients, while 46 patients had two courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 years in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy.

Irradiation, chemotherapy and surgery in esophageal cancer: a randomized clinical study. The first Scandinavian trial in esophageal cancer.

In a randomized trial, irradiation alone (35 Gy) or irradiation (30 Gy) and bleomycin was given as preoperative treatment of esophageal cancer. In inoperable patients, a split course of irradiation alone (63 Gy) or irradiation (55 Gy) and bleomycin was given. Bleomycin doses were 5 mg i.m. 1/2-1 h before each irradiation dose. No benefit was obtained by addition of bleomycin to irradiation concerning survival or palliation of dysphagia. No benefit of bleomycin was seen either in any subgroup of patients according to different primary tumour classifications, histopathological gradings or localizations of tumour. In patients with advanced/metastatic disease, bleomycin and adriamycin treatment gave a significantly longer survival than bleomycin alone. It was shown that the presence of T1 tumours was a significant prognostic factor for long-term survival and that performing a radical operation was a significant advantage for a longer survival. Female patients treated with irradiation with or without bleomycin survived significantly longer than males, but in operable patients there was no significant difference between the two sexes with regard to survival.

Oligodendroglioma: incidence and biological behavior in a defined population.

The cases of 208 patients with histologically confirmed oligodendrogliomas were studied. The incidence represents 4.2% of all primary brain tumors diagnosed in the Norwegian population over a 25-year period. All of these tumors were cerebral and the majority affected the frontal lobe. The patients' median age at diagnosis was 47 years, with a range from 3 to 76 years; 6% of the oligodendrogliomas occurred in children. The median duration of symptoms before diagnosis was 20.5 months (mean 43 months). Plain skull x-ray films showed calcified deposits in 28% of the tumors. At operation, most of the tumors were poorly defined, without cyst formation, hematoma necrosis, or calcification. The median duration of disease from onset of symptoms until death was 14 months in nine untreated cases. In surgically treated oligodendroglioma patients the median survival time from onset of symptoms was 74 months. The median postoperative survival time was 35 months (mean 52 months). Tumor calcification, as seen on plain skull x-ray films, was associated with a significantly longer survival period. The surgical findings of gross necrosis, gross hypervascularity, and soft tumor consistency were all related to a shorter total duration of disease. Grossly well demarcated lesions were associated with a significantly longer postoperative survival. The length of postoperative survival correlated with the preoperative clinical status. The cumulative proportion of patients surviving 5 years was 0.342. The patient's age and sex did not have a statistically significant influence on survival time. The extent of surgical excision only seemed to play a role when the neurosurgeon considered that he had removed the whole lesion: these patients had a median postoperative survival period 14 months longer than the other oligodendroglioma patients. The ABO blood group of the oligodendroglioma patient was of prognostic value. In particular, patients with blood group A had a distinctly poorer prognosis than patients with O or B blood. The survival data from this unselected series indicate that cerebral oligodendrogliomas have a less favorable prognosis than has generally been believed.

Statistical analysis of clinicopathological features, radiotherapy, and survival in 170 cases of oligodendroglioma.

The postoperative survival time of 170 nonrandomized patients treated for cerebral oligodendrogliomas in Norway from 1953 to 1977 was studied. Survival times were significantly prolonged if postoperative irradiation was performed in addition to surgery (median survival time 26.5 vs. 38 months, p = 0.039). In the group without postoperative radiotherapy, the 5-year rate of survival was 27% compared with 36% in the irradiated patients. The respective survival rates after 8 years were 14% versus 17%; thus, there was little effect on long-term survival. Irradiation appears not to be of benefit after "total" removal. Patients with partly resected lesions appeared to benefit from postoperative radiotherapy; the median survival period after subtotal tumor resection was 37 months with and 26 months without radiotherapy (p = 0.0089). The findings also indicate that irradiation doses between 40 and 50 Gy were as effective as doses between 50 and 60 Gy in increasing the patients' probability of surviving 5 years after subtotal tumor resection. Since the risk of radiation necrosis is proportional to the dose applied, the lower dose is recommended. These conclusions were also valid when adjustments were made for prognostically significant histological and clinical features.

Sightsaving therapy in retinoblastoma. Experience with external megavoltage radiotherapy.

In Norway, sightsaving therapy in retinoblastoma has only been given to least affected eyes in bilaterally affected children. The results in 8 eyes given external high energy radiotherapy are reported. Additional focal therapy was given to 3 eyes for residual tumours and to one eye with new tumour at the ora serrata. Cataract was treated in 2 of the 3 eyes in which it developed. Vitrectomy was performed in 2 eyes with vitreous haemorrhage and persisting vitreous haze. Secondary enucleation has been avoided in all eyes 3-9 years after irradiation. One patient developed metastases in the temporal region at the enucleated side. Visual acuity is 6/12-6/6 if the macula has not been destroyed by tumour or focal therapy. Sightsaving therapy is presently also offered to unilateral cases and worst affected eyes in bilateral cases if the eyes belong to Reese-Ellsworth groups I-IV.

Endobronchial radiotherapy for malignant bronchial obstruction or recurrence.

Forty-five lung cancer patients who had recurrence and/or endobronchial obstruction were treated with intrabronchial radiotherapy (IBRT). The majority had been heavily treated previously, mainly by external radiotherapy; six patients were treated surgically. IBRT was given with high-dose-rate equipment, either 18 Gy in three fractions or 15 Gy as a single dose was originally planned. For different reasons several patients received other regimens. Palliation of dyspnoea was obtained in 64% of the patients. Palliation of hemoptysis (12/14) and cough (11/17) was registered, as well as improvement in atelectasis in 11/26 patients. Palliation of dyspnoea was enhanced with an IBRT dose > 15 Gy. The median survival after IBRT was 13 weeks. Fatal hemoptysis (FH) occurred in 12 patients; 10 of these within 6 months after treatment. The risk of FH significantly increased with an IBRT dose > 15 Gy.

Symptomatic treatment versus combination chemotherapy for patients with extensive non-small cell lung cancer.

In a randomized clinical trial, 87 patients with inoperable, extensive non-small cell lung cancer (NSCLC) were randomized to receive either combination chemotherapy (cisplatin at 70 mg/m2 intravenously [i.v.] on day 1 and etoposide at 100 mg/m2 i.v. on day 1 and 200 mg/m2 orally on days 2 and 3) or symptomatic treatment. No statistically significant differences in survival time were found between the two treatment techniques. A major problem in the interpretation of the results was the use of semicurative radiation therapy (3000 to 4200 cGy) to the primary tumor and mediastinum, which was given with symptomatic intent. Three long-term survivors were seen in the latter group.

Pulmonary complications after bleomycin, irradiation and surgery for esophageal cancer.

Eight patients with epidermoid carcinoma of the esophagus were given radiotherapy of 3000 rads and 120 mg of bleomycin. Esophageal resection was performed five to six weeks later. Four of these patients died within six weeks, three from respiratory failure, and one from complications secondary to an anastomotic fistula. Of the remaining four patients, three showed varying degrees of pulmonary infiltration for several weeks. Interstitial pneumonitis was demonstrated in all the fatal cases. Four patients given the same irradiation and bleomycin doses were only subjected to exploratory surgery. They had no postoperative pulmonary complications. Ten patients given the same irradiation and bleomycin treatment without surgery also showed no pulmonary complications. Sixteen patients received higher doses of radiotherapy and bleomycin. Seven of these developed lung infiltrations terminating fatally in four. The likely mechanism of the observed postoperative pulmonary complications is that the preoperative treatment sensitized the lungs, while the subsequent surgical trauma triggered a reaction in the lungs leading to respiratory failure.

[Long-term survival following surgery and radiotherapy of brain tumors in childhood]. / Langtidsoverlevelse etter kirurgi og strålebehandling av hjernesvulster i barnealder.

BACKGROUND: Brain tumours are seen in about one third of children with neoplastic disease. Treatment usually includes surgery and/or radiotherapy. Radiotherapy may have serious late effects, especially in children under the age of three; but is necessary for survival in children with medulloblastomas or high-grade gliomas. MATERIALS AND METHODS: We report ten and 20 years survival rates in 115 children with primary brain tumours (58 medulloblastoma, 14 high-grade gliomas, and 43 low-grade gliomas) operated at the National Hospital and given radiotherapy at the Norwegian Radium Hospital during the years 1970-1995. RESULTS: No patients with medulloblastomas or high-grade gliomas relapsed after ten years. Overall ten and 20 years survival in children treated with radiotherapy to tumour doses > 50 Gy for medulloblastoma was 51.5% and for high-grade gliomas 20%. Median survival for patients with low-grade gliomas was not reached at 20 years, but these patients were still at risk for late deaths. INTERPRETATION: Long-term survival in children with high-grade gliomas or medulloblastoma equals cure, while late relapses may occur in low-grade gliomas.

Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer.

In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.

Combined modality treatment of operated astrocytomas grade 3 and 4. A prospective and randomized study of misonidazole and radiotherapy with two different radiation schedules and subsequent CCNU chemotherapy. Stage II of a prospective multicenter trial of the Scandinavian Glioblastoma Study Group.

A prospective and randomized trial has been performed in order to evaluate combined modality therapy in patients with astrocytomas grade 3 and 4. Follow-up information is available on 244 patients. One half of the series received radiation therapy twice a week (40.00 Gy/5 weeks), the other half five times a week (50.00 Gy/5 weeks). Misonidazole 1.2 g/m2 was given orally to one half of the patients in the first radiation treatment group 3 1/2 to 4 hours before the treatment. The other half received placebo. The second radiation treatment group was also divided in two halves, one receiving 0.48 g/m2 misonidazole and the other placebo 3 1/2 to 4 hours before radiation. The randomization also included a subdivision of the material into eight groups of which four were given CCNU and four no chemotherapy, beginning 3 months after operation. The dose of CCNU was 120 mg/m2 body surface every 6 weeks. All eight treatment groups showed practically identical periods of median survival, and no statistically significant differences were observed with regard to performance status, side effects, or complications. Another dosage and timing of misonidazole administration in relation to the irradiation schedule, and a consideration of effects of concomitant drugs like dexamethasone and phenytoin are discussed.

Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group.

In a controlled, prospective, randomized investigation, started in 1974, 118 patients with supratentorial astrocytoma Grade III--IV were divided into three groups. Groups 1 and 2 received 45 Gy postoperatively to the whole supratentorial brain. Bleomycin in 15-mg doses and a total dose of 180 mg or placebo was given intravenously three times a week, one hour prior to radiotherapy, during weeks 1, 2, 4 and 5. Group 3 received conventional care but no radiotherapy or chemotherapy. Median survival rates of patients were 10.8 months in Groups 1 and 2, and 5.2 months in Groups 3, a statistically significant difference. With regard to performance, the patients in Group 3 deteriorated faster than patients in Groups 1 and 2. Bleomycin had no positive or negative influence on survival.