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Biomedical subjects

A Gregor

Publications and source records attributed to A Gregor.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prophylactic cranial irradiation in small-cell lung cancer: is it ever indicated?

Prophylactic cranial irradiation (PCI) is being reintroduced into multimodality treatment protocols of patients with small-cell lung cancer (SCLC). The history of its use brings interesting insights into clinical evaluations of treatment strategies and design of relevant and informative trials. The critical issues of effectiveness and overall health gains of prophylactic cranial irradiation have been addressed in a series of recently completed clinical trials. These trials tested prophylactic cranial irradiation in small-cell lung cancer patients achieving good response to induction therapy and confirmed the ability of standard prophylactic cranial irradiation schedules to significantly reduce the lifetime risk of brain metastases. A subset of these trials evaluated neurotoxicity in a formal and prospective manner. No sustained or significant detriment in neuropsychometric function could be linked to the use of prophylactic cranial irradiation. In addition, all the large trials have shown a consistent survival advantage in favor of the prophylactic cranial irradiation arm. None of the individual sample sizes were large enough to statistically confirm this survival benefit, but a meta-analysis is in progress and will report on this aspect of evidence shortly. Issues that remain to be answered are the optimal dose and schedule of prophylactic cranial irradiation as well as the timing of this administration. These questions form the nucleus of the next generation of collaborative trials that are being designed.

Brain Neoplasms↗
PubMed1998

[Localization of NADPH-d positive cells in the thymus of pheasants and mice].

The presented study was designed to clarify the localization and distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity, a marker of NO synthase, in pheasant and mouse thymuses. To provide a morphological basis for understanding the role of nitric oxide (NO) in the thymus. The NADPH-d histochemistry revealed dark blue stained cell structures. In the pheasant thymus, NADPH-d positive cells were present as clusters which were distributed in the medulla and the corticomedullar area. NADPH-d positive cells were observed mostly in the medulla of the mouse thymus. They were round, oval or irregular in shape, with various intensity of staining. There were found NADPH-d positive nerve fibres in the perivascular location in both groups of experimental animals. (Fig. 4, Ref. 14.)

Animals↗
PubMed1998

Gemcitabine and radiation therapy for non-small cell lung cancer.

Patients with stage III non-small cell lung cancer (NSCLC) frequently progress either within the irradiated field or systemically, due to uncontrolled microscopic dissemination present before the time of initial diagnosis. The use of combined modality therapy has led to improved survival rates in recent years. In particular, the use of cisplatin and vinblastine as induction chemotherapy is supported by two large randomized clinical trials. Nevertheless, the large majority of patients still die of progressive disease, thus providing a rationale for the integration of new active agents into the overall treatment plan of these patients. Gemcitabine has demonstrated significant single-agent activity in NSCLC. In addition, preclinical and early clinical data indicate that it is a powerful radiation enhancer. Clinical trials investigating this drug with concurrent radiation therapy in NSCLC are reviewed.

Antimetabolites, Antineoplastic↗
PubMed1998

[Quantification of pericentral NADPH-diaphorase neurons in the spinal cord of rabbits].

BACKGROUND: The freely diffusible radical nitric oxide is generated by nitric oxide synthase, and is bioregulatory molecule that functions as a major neurotransmitter. Constitutive nitric oxide synthase exhibits NADPH-diaphorase activity that can be demonstrated histochemically. OBJECTIVE: The purpose of the present investigation was to characterize and determine number of NADPH-diaphorase positive neurons around the central canal in all segments of the rabbit spinal cord. METHODS: Rabbits Chinchilla were used in this experiment. After intracardiac perfusion the spinal cords were removed, cut into slices and histochemical analysis of NADPH-diaphorase activity was performed. Sections were evaluated by using light microscope. RESULTS: NADPH-diaphorase positive pericentral neurons were present in cervical, thoracic, lumbar; sacral and coccygeal segments. They differed in the shape of their bodies and in length and branching of their processes. The main differentiation was observed in their number depending on the place of localisation. The highest number of these NADPH-diaphorase positive neurons was in sacral part (6 in average), the lowest one was noticeable in thoracic spinal cord (1-2 in average). CONCLUSION: Thus, our study suggests that pericentral neurons of the rabbit spinal cord which are capable of synthesizing nitric oxide, differs in number amount depending on the place of their localization in each spinal cord segments. (Tab. 2, Fig. 9, Ref. 21.)

Animals↗
PubMed1997

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.

Bone Neoplasms↗
PubMed1997

Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC)

Prophylactic cranial irradiation (PCI) reduces the risk of cranial metastasis in small cell lung cancer (SCLC), but the magnitude and value of this reduction, the risks of radiation morbidity and whether PCI influences survival are unclear. We conducted a randomised trial in patients with limited-stage SCLC who had had a complete response to induction therapy. Initially, patients were randomised equally to (1) PCI 36 Gy in 18 daily fractions, (2) PCI 24 Gy in 12 fractions and (3) no PCI; subsequently, to increase the rate of accrual, randomisation was to clinicians' choice of PCI regimen versus no PCI (at a 3:2 ratio). The endpoints were appearance of brain metastases, survival, cognitive function, and quality of life (QoL). Three hundred and fourteen patients (194 PCI, 120 No PCI) were randomised. In the revised design, the most commonly used PCI regimens were 30 Gy in 10 fractions and 8 Gy in a single dose. With PCI, there was a large and highly significant reduction in brain metastases (HR = 0.44, 95% CI 0.29-0.67), a significant advantage in brain-metastasis-free survival (HR = 0.75, 95% CI 0.58-0.96) and a non-significant overall survival advantage (HR = 0.86, 95% CI 0.66-1.12). In both groups, there was impairment of cognitive function and QoL before PCI and additional impairment at 6 months and 1 year, but no consistent difference between the two groups and thus no evidence over 1 year of major impairment attributable to PCI. PCI can safely reduce the risk of brain metastases. Further research is needed to define optimal dose and fractionation and to clarify the effect on survival. Patients with SCLC achieving a complete response to induction therapy should be offered PCI.

Adult↗
PubMed1997

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.

Adult↗
PubMed1997

Gemcitabine plus radiotherapy for non-small cell lung cancer.

Radiosensitization promises to improve local control in patients with locally advanced non-small cell lung cancer (NSCLC). The nucleoside analogue gemcitabine, which is not only a potent radiosensitizer but also has significant antitumor activity in this disease, is an important candidate for such a strategy. This report describes the design of a clinical phase I study for treatment of patients with locally advanced NSCLC using gemcitabine and radiotherapy. It also discusses some of the practical constraints that must be taken into consideration when evaluating this type of combined modality strategy in the clinic.

Antimetabolites, Antineoplastic↗
PubMed1996

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.

Adult↗
PubMed1996

Management of lung cancer in South East Scotland.

BACKGROUND: There are few reports which describe the management of unselected groups of patients with lung cancer. This study was undertaken to audit prospectively the presentation, diagnosis, management, and outcome of patients presenting with lung cancer in South East Scotland. METHODS: Data were recorded on all patients with newly diagnosed lung cancer who presented to a multidisciplinary group of clinicians over a 12 month period. Subsequent follow up data on treatment and survival were collected. RESULTS: Six hundred and twenty two patients were registered, 80% of whom were referred from primary care. There was a considerable variation in the length of history, but the diagnosis was rapidly made after referral (87% within two weeks). In 82% of patients the pathological examination was positive; 70% were treated with palliative intent. Only 36% of patients who underwent surgery had computed tomographic scanning and 55% had sampling of mediastinal nodes. A wide variety of regimens was used for treatment with radiotherapy and chemotherapy, and follow up data were difficult to obtain in these patients. Survival was poor in all patients treated with palliative intent. CONCLUSIONS: This audit confirms the importance of previously noted prognostic factors. Significant variation in referral practice, diagnostic and management evaluation has been shown. The data serve as a useful background for the formation of local management guidelines.

Adult↗
PubMed1996

[Acetylcholinesterase-positive innervation of the thymus in old rats after ovariectomy].

Surgical ovariectomy in aged rats entails regeneration of the involuted thymus. These results correlate with our study of acetylcholinesterase positive innervation of regenerated thymuses. We found out a marked autonomous innervation of the perivascular tissues, as well as that of the functional parenchyma of the thymus. We proved a significant increase in the density of ACHE-positive nerves in the thymus of aged rats after surgical ovariectomy. These results are considered to represent and indirect evidence of the fact that cholinergic nerves stimulate lymphopoiesis in the thymus. (Fig. 5, Ref. 9.)

Acetylcholinesterase↗
PubMed1996

Referral pattern and management of patients with malignant brain tumours in south east Scotland.

We reviewed hospital case notes of all incident cases of intracerebral tumours in SE Scotland to analyse referral pattern and time intervals between presentation, diagnosis and treatment. We identified 439 new patients with intracerebral tumours in a two year period: 64% single (primary brain tumours 43%: metastasis 21%) and 36% multiple (metastases). Ninety-two per cent of patients were referred by GP's and 88% were self referrals to hospital or were initially identified at hospital follow-up clinics. Only 27% of patients were initially referred to the specialist centre (Western General Hospital) but 57% were CT scanned at the specialist centre and 83% were referred to there at some time. Time from GP referral to CT scan was related to availability of local CT scanning. Only 10% of cases with probable single metastases and 39% with HGG were treated with surgery plus radiation. Cranial irradiation was started within four weeks of CT diagnosis in 79% of those with metastases but in less than 5% of patients with HGG. The patterns of care for patients with brain tumours show great variation. Hospital referral guidelines, better inter-hospital and inter-department communications and more available access to CT scanning and radiotherapy should improve the quality of care and possibly treatment outcome in this group of patients.

Adolescent↗