Anna Gregor

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules

BACKGROUND The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial. PURPOSE To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases. MATERIALS AND METHODS In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain. RESULTS Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters. CONCLUSIONS It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.

Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

PURPOSE Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087). CONCLUSION Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma

The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL.

Age has no impact on acute and late toxicity of curative thoracic radiotherapy

BACKGROUND AND PURPOSE Radiotherapy is a treatment method frequently employed in the management of thoracic tumours. Although the highest incidence of these tumours is found in elderly people, tolerance to radiotherapy is not well documented in older age groups. Many physicians are tempted to alter the radiotherapy planning in a population with a supposed lower life expectancy in order to prevent acute reactions whereas late reactions are often ignored. The current study aimed to determine the influence of age on the frequency and severity of acute and late side-effects and also whether the prognosis of tumours sufficiently differed between ages to justify different attitudes towards their management. MATERIALS AND METHODS Data from 1208 patients receiving chest irradiation and included in arms designed with RT of six EORTC randomized trials were evaluated. Data were extracted by a computer program elaborated for each study and were merged in a single database for analysis. Patients were split into six age ranges from 50 to 70 years and over. Survival and late toxicity were calculated with the Kaplan-Meier method and comparison between age groups was performed with the logrank test. The gamma-statistic test was used to test the impact of age on acute toxicity occurrence. RESULTS Survival adjusted for the primary location of the tumour was comparable in each age group (P = 0.82). Data regarding age and acute toxicity were available for 1208 patients who experienced 640 grade > or =1 toxicities. The difference in distribution over age was not significant for acute nausea, dyspnea, oesophagitis, weakness and WHO performance status alteration. Weight loss was significantly different with regards to age with a trend toward increased weight loss in older age groups (P = 0.002). To minimize actuarial bias, only patients surviving more than 90 days were analyzed for late effect risks. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first and second line treatments. In such conditions, 1082 grade > or =1 late toxicities were recorded in 935 patients of 1106 available for analysis. The mean time to complication was 13 months and was similar in all age groups. Forty percent of patients were free of complication at 4 years, the logrank test showing no significant difference between age groups (P = 0.57). For grade >2 side-effects, the calculation did not show any difference between each age group (P = 0.1). A detailed analysis of late dyspnea and late weakness studied with the same method did not demonstrate any difference between age groups. Only grade >2 late oesophagitis demonstrated a significant trend to be more frequent in older patients (P = 0.01), but this difference disappeared after adjustment on study (P = 0.32). CONCLUSION The absence of toxicity observed in the current study regardless of age reinforces the conviction that age per se is not a sufficient reason to exclude patients in good general condition with thoracic tumour from curative radiotherapy when medically indicated.

Neuropsychometric evaluation of long-term survivors of adult brain tumours: relationship with tumour and treatment parameters

BACKGROUND Cognitive deficits are the hallmark of dose limiting late radiation morbidity in the CNS. Little is known about the neuropsychometric morbidity of treatment in adults with primary brain tumours. We set out to evaluate systematically the neuropsychometric function of all long-term survivors in order to document the frequency and severity of impairment and study its relationship with tumour and treatment related parameters. MATERIALS AND METHODS 30 patients surviving in clinical and radiological remission for > 4 years following irradiation were recalled for clinical examination, CT/MRI scan and neuropsychometric testing. The 14 males, 16 females, (mean age 42.5 years), represented all but one long term survivors treated with radiotherapy in the Department of Clinical Oncology between 1971 and 1990. Twenty-five patients had a histological diagnosis of glioma. Patients treated before 1987 (n = 16) received whole brain irradiation (WBI); focused irradiation (FI) has been used since (n = 14). RESULTS The two groups were similar were in age, initial tumour type and surgical treatment, but the WBI group showed more evidence of neuropsychometric impairment than the FI group with significantly lower group median scores in tests of visuospatial organisation (WAIS Block Design, P = 0.01), visual memory (Rey Complex figure, P = 0.003) and complex information processing (Trails A, P = 0.003; Trails B, P = 0.002). Pre-morbid IQ estimated from sociodemographic variables, was comparable in the 2 groups which were not significantly different in their emotional state as assessed by the HADS. On univariate analysis radiation volume (P = 0.05) and time from treatment (P = 0.02) were the main factors associated with neuropsychometric deficit. Multivariate analysis by logistic regression confirmed WBI as the only independent predictor of neuropsychometric impairment (WBI vs. FI, odds ratio = 7.1, 95% C.I. 1.2-42.3, P = 0.03). CONCLUSIONS Neuropsychometric deficits are common and can be related to time from treatment and radiation technique. Neuropsychometric testing can be a useful tool in the evaluation of different treatment strategies.

Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study.

PURPOSE To evaluate the effectiveness of alternating or sequential schedules of cyclophosphamide, doxorubicin, and etoposide (CDE) chemotherapy and irradiation in patients with previously untreated small-cell lung cancer (SCLC). MATERIALS AND METHODS A total of 335 eligible patients were randomized between five courses of CDE chemotherapy followed by thoracic irradiation 50 Gy in 20 daily fractions (S) and the same total dose of chemotherapy and irradiation split into four courses of five daily fractions delivered on days 14 to 21 of the second and subsequent chemotherapy courses (A). Patients had a median age of 61 years (range, 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weight loss less than 10%. RESULTS The overall median survival duration was 15 months, with 62% (95% confidence interval [CI], 57% to 67%) 1-year, 25% (95% CI, 20% to 30%) 2-year, and 14% (95% CI, 10% to 18%) 3-year survival rates. There was no significant difference between the arms. The median survival time was 14 months in A and 15 months in S. One-year survival was 60% in A (95% CI, 53% to 67%) and 64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%) and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6% to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 90% of A and 77% of S patients (P < .001) and WHO grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P < .001). Rates of other acute and late toxicities were similar in both arms. Hematologic toxicity compromised treatment dose delivery; less than 50% of A patients received greater than 95% of prescribed chemotherapy and 77% their full radiation course, compared with 60% and 93% for arm S (P < .009). Local relapse was the site of first failure in 60% of all patients and 75% of these suffered an in-field relapse; no difference could be seen between the two arms. CONCLUSION This trial failed to confirm the superiority of an alternating schedule of delivery. For this combination of chemotherapy and irradiation, hematologic toxicity compromised treatment delivery and could have contributed to the overall result. The poor rates of local control are disappointing and require intensification of the radiation therapy strategy.

Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.

Imaging features of leptomeningeal metastases.

AIMS To assess the range of appearances, and accuracy of various methods of diagnosing leptomeningeal metastases. MATERIALS AND METHODS In a retrospective study, the notes and imaging of all patients with a radiological and/or CSF cytological diagnosis of leptomeningeal metastasis (LM) were identified, and assessed for the following: age and sex, primary tumour type, presenting symptoms, initial radiological and cytological diagnosis, radiological appearances and length of survival following diagnosis. Discordance between the CSF cytology and radiological diagnosis of LM was also noted. RESULTS 41 positive cases (36 female) of LM were identified over a 2.7 year period (diagnosis based on: imaging only--19 cases, cytology only--6, both--16 cases). The average age was 48 years, and the most frequent primary tumour was breast carcinoma (27/41). Two thirds of patients presented with at least one cranial or spinal nerve palsy. Where performed, contrast-enhanced CT was normal in 40% (10/25), with LM mistaken for parenchymal disease in a further 24% (6/25). CSF cytology was positive in 85% (22/26). Gadolinium-enhanced MRI was positive in all cases where it was performed (25/25). Pial enhancement and nodularity was the commonest finding (67%), but other manifestations included nodular disease, neural enhancement and white matter changes. Prognosis was uniformly poor. CONCLUSION Leptomeningeal metastatic disease has a poor prognosis, and treatment regimen may differ from those of parenchymal CNS metastases. CT is normal or misleading in two thirds of patients, and CSF cytology may also be negative. Gadolinium-enhanced T1-weighted MRI complements CSF cytology, and is the investigation of choice in patients with a non-haematological primary tumour and suspected LM.

Incidence of second brain tumours after pituitary irradiation in Edinburgh 1962–1990

Two hundred and ninety-six patients irradiated for pituitary adenoma in Edinburgh between 1962 and 1990 were reviewed. The number of subsequent tumours was noted. The expected incidence of tumours was estimated, based on data from the Scottish Cancer Registry, for an age and sex matched population. One malignant brain tumour was found; the expected incidence was 0.3 (95% CI 0-12). One meningioma was reported. Thirty non-CNS tumours were found, compared with an expected incidence of 17.5 (95% CI 12-26). We see no reason at present to alter our practice as a result of radiation induced neoplasia in this group, although close follow-up continues.

Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study

BACKGROUND AND PURPOSE To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. PATIENTS AND METHODS The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10 x 3.0 Gy WBRT. Response and neurological functions were evaluated after 6, 18 and 36 weeks. RESULTS Twenty of 22 eligible patients were evaluable for response. In six patients a complete response was seen and in five patients a partial response was seen giving a response rate of 50% (95% CI 28-72%). Response duration was 5.4 months (range 63-260 days) and median survival was 4.7 months (range 14-743 days). In the majority of patients the first site of progression after WBRT was in the central nervous system. Twelve of the patients had stabilization or improvement of the neurological function. CONCLUSION WBRT for brain metastases of small cell lung cancer gives a 50% response rate with stabilization or improvement of neurological function. Response duration and survival are short.