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Biomedical subjects

M N Gaze

Publications and source records attributed to M N Gaze.

At least 19 recordsLinked to original sources
PubMed2005

Symptom control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules.

AIMS: To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS. RESULTS: We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197). CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.

Aged↗
PubMed2003

Treatment of neuroendocrine tumours in adults with 131I-MIBG therapy.

This is a retrospective review of 131I-MIBG therapy for metastatic neuroendocrine tumours in 25 adult patients. The tumours comprised 17 carcinoids, six paragangliomas, one somatostatinoma and one intestinal smooth muscle sarcoma. All patients (age range 28-84 years) had stage IV disease and a positive diagnostic 123I-MIBG scan. Patients received 11.1 GBq (300 mCi) of 131I-MIBG given in three cycles at 3-monthly intervals. The mean cumulative dose was 27.7 GBq (751 mCi). Symptomatic response was observed in 80%, hormonal response in 55% and tumour response in 48% (WHO criteria). Of the 25 patients, 40% are still under follow-up. Death was due to disease progression in all except one. The median survival time was 48 months from diagnosis of metastatic disease, and 17 months from the last 131I-MIBG therapy. The 5-year survival rate was 59% (95% confidence interval, 34%-78%). There was no statistical difference in survival between previously treated (chemo/radiotherapy) and treatment-naive patients. Side-effects were minimal and commonly include nausea (in the first 24 h) and a transient fall in platelet count. 131I-MIBG provides a good therapeutic response in patients with metastatic neuro-endocrine tumours.

3-Iodobenzylguanidine↗
PubMed2001

Functional imaging as an aid to decision-making in metastatic paraganglioma.

Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.

3-Iodobenzylguanidine↗
PubMed2000

Variations in dose and dose intensity of adjuvant CMF chemotherapy for breast cancer throughout the UK.

Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a commonly prescribed regimen for the adjuvant treatment of early breast cancer in the UK and in other countries with a high incidence of breast carcinoma. A number of variations in dose and scheduling of these drugs have been reported in the literature, with all of these being recognized under the generic term 'CMF'. To investigate the extent of differences in CMF regimens used for the adjuvant treatment of early breast cancer we sent a postal questionnaire to all consultant medical and clinical oncologists in the UK seeking details of their practice. CMF drug doses were then converted into dose intensity parameters for comparison. The results showed a wide variation in the number of CMF schedules (n = 36) and CMF dose intensities (n = 33) used. The potential consequences of such variation and the evidence for and against dose intensity as an important parameter in the adjuvant treatment of early breast cancer are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

An audit of antiemetic use with CMF chemotherapy.

A two-stage retrospective audit of the efficacy of antiemetics used with intravenous cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 (CMF) chemotherapy for breast cancer has been performed in a single centre. The first audit stage examined emesis rates for 21 patients using a policy of metoclopramide and dexamethasone initially and reserving 5-HT3 antagonists for failure of this combination. Because of high failure rates, the policy was changed so that granisetron and dexamethasone were used in all patients. The second audit stage examined the effectiveness of this new policy in 28 patients. Nine of 21 patients (43%) in the first audit group changed from metoclopramide and dexamethasone because of nausea or vomiting. Emesis occurred in 15 out of 66 (23%) cycles of CMF when metoclopramide and dexmethasone were used. Only eight of 43 patients had emesis episodes with granisetron and dexamethasone (19%). Emesis occurred with only 16 of 206 CMF cycles with granisetron and dexamethasone (8%). The granisetron and dexamethasone combination is superior to metoclopramide and dexamethasone in the prophylaxis of CMF-induced nausea and vomiting, although it is more expensive. A reduced dose of granisetron, 1 mg rather than 3 mg, may allow similar control of emesis at reduced cost.

Antiemetics↗
PubMed1998

A simple reconstructive procedure for radiation-induced necrosis of the external auditory canal.

Localized necrosis of the bone, cartilage, and soft tissue of the external auditory canal is an uncommon side effect of radiotherapy to the parotid region. Five patients developed late onset skin necrosis of a quadrant of the ear canal secondary to an underlying osteoradionecrosis of the tympanic ring. We report a one-stage procedure to excise the necrotic tissue and replace it with a local rotational flap derived from the post-auricular skin. Otological side effects of radiotherapy are discussed.

Adult↗
PubMed1998

Recurrent follicular carcinoma-oxyphilic cell type (Hürthle cell carcinoma) of the thyroid, imaging with iodine-131 and technetium-99m tetrofosmin before and after radiotherapy.

A 68-year-old male with recurrence of malignant follicular carcinoma-oxyphilic cell type of the thyroid after surgery underwent whole body scintigraphy with 131I-sodium iodide and 99Tcm-tetrofosmin (Myoview). 131I scanning demonstrated local uptake most likely to be in the normal remnant, but 99Tcm-Myoview images delineated recurrence of the carcinoma in the neck, with more extensive involvement. We believe that a combination of 131I and 99Tcm-tetrofosmin imaging may be useful to assess the extent of disease in patients with recurrent Hürthle cell type carcinoma of the thyroid.

Adenocarcinoma↗
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

Superior vena cava obstruction: a modern management strategy.

Superior vena cava obstruction (SVCO) is a distressing syndrome. The condition may present to specialists in many branches of medicine, but patients have traditionally been referred on to clinical oncologists for management, as malignancy is the main aetiological factor. Treatment without a histological diagnosis is no longer justified, because management needs to be tailored to the underlying disease. This article reviews the causes, symptoms, methods of diagnosis and therapy options. The role of stenting in SVCO is discussed and a management algorithm is proposed.

Algorithms↗
PubMed1997

The response of adenoid cystic carcinoma to tamoxifen.

Adenoid cystic carcinoma of the parotid gland often recurs locally, or metastases develop, after initial treatment with surgery and radiotherapy. We report a patient with an inoperable local recurrence of previously irradiated adenoid cystic carcinoma, who was treated with tamoxifen, an oestrogen receptor antagonist. After 18 months of treatment with tamoxifen, MRI showed a partial response, and further clinical progression of the disease was halted.

Anticarcinogenic Agents↗
PubMed1997

The effect of cisplatin pretreatment on the accumulation of MIBG by neuroblastoma cells in vitro.

[131I]meta-iodobenzylguanidine ([131I]MIBG) provides a means of selectively delivering radiation to neuroblastoma cells and is a promising addition to the range of agents used to treat neuroblastoma. As MIBG is now being incorporated into multimodal approaches to therapy, important questions arise about the appropriate scheduling and sequencing of the various agents employed. As the ability of neuroblastoma cells to actively accumulate MIBG is crucial to the success of this therapy, the effect of chemotherapeutic agents on this uptake capacity needs to be investigated. We report here our initial findings on the effect of cisplatin pretreatment on the neuroblastoma cell line SK-N-BE (2c). After treating these cells with therapeutically relevant concentrations of cisplatin (2 microM and 20 microM), a stimulation in uptake of [131I]MIBG was observed. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that this effect was due to increased expression of the noradrenaline transporter. These results suggest that appropriate scheduling of cisplatin and [131I]MIBG may lead to an increase in tumour uptake of this radiopharmaceutical with consequent increases in radiation dose to the tumour.

3-Iodobenzylguanidine↗
PubMed1996

The current status of targeted radiotherapy in clinical practice.

Biologically targeted radiotherapy in clinical practice requires a molecule which has a relative specificity for tumour tissue--the missile--coupled to a radionuclide with appropriate physical characteristics--the warhead. When administered to a patient this combination should result in selective irradiation of the target tumour cells with relative sparing of normal tissues. Simple ions and small molecules which follow physiological pathways as either the natural substrates or analogues form the best examples of biological targeting. Clinically valuable results are seen with, for instance, iodine uptake by normal and malignant thyroid cells, incorporation of the calci-mimetic element strontium in areas of increased bone metabolism and accumulation of the catecholamine analogue meta-iodobenzylguanidine in neuroblastoma. The use of monoclonal antibodies as targeting vehicles has not proved to be a panacea, yet some patients with lymphoma, hepatoma and ovarian carcinoma have obtained benefit. Current clinical studies in targeted radiotherapy focus on the integration of radionuclide treatment with conventional treatments, and the optimization of such combined approaches. The development of modifications to offset the limitations inherent in the use of crude antibodies also offers an opportunity for improved clinical outcomes.

3-Iodobenzylguanidine↗
PubMed1995

Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer.

PURPOSE: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. METHODS AND MATERIALS: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. RESULTS: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. CONCLUSIONS: Radiobiological analysis, which incorporates simple models of metastatic spread, emphasizes the importance of the total body irradiation component in a targeting/total body irradiation combination strategy. However, the analysis favors a larger targeting component than is used in clinical practice at present. A cautious escalation of the 131I mIBG component in the combination treatment of advanced neuroblastoma appears justified.

Child↗
PubMed1995

Multi-modality megatherapy with [131I]meta-iodobenzylguanidine, high dose melphalan and total body irradiation with bone marrow rescue: feasibility study of a new strategy for advanced neuroblastoma.

New therapeutic approaches are needed for advanced neuroblastoma as few patients are currently curable. We describe an innovative strategy combining [131I]meta-iodobenzylguanidine ([131I]mIBG) therapy with high dose chemotherapy and total body irradiation. The aim of combining these treatments is to overcome the specific limitations of each when used alone to maximise killing of neuroblastoma cells. Five children received combined therapy with [131I]mIBG followed by high dose melphalan and fractionated total body irradiation. Autologous bone marrow transplantation was undertaken in 3 patients and allogeneic in 2 patients. One patient received additional localised radiotherapy to residual bulk disease. One patient is alive without relapse 32 months after treatment. 4 patients relapsed after remissions of 9, 10, 14 and 21 months. These results indicate that this combined modality approach is feasible and safe, but further evaluation is necessary to establish whether it has advantages over conventional megatherapy using melphalan alone.

3-Iodobenzylguanidine↗
PubMed1995

Enhanced tumour uptake and in vitro radiotoxicity of no-carrier-added [131I]meta-iodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma.

In vitro and in vivo neuroblastoma models were used to determine whether improvements in tumour targeting in vivo and therapeutic efficacy in vitro could result from the use of no-carrier-added (n.c.a.) [131I]MIBG. Results were compared with use of the conventional therapy MIBG preparation (ex. [131I]MIBG) of lower specific activity which is produced by iodide exchange reaction. The efficacy of n.c.a. [131I]MIBG was compared with that of [131I]MIBG over a range of specific activities by the assessment of neuroblastoma spheroid growth delay. Whereas n.c.a. [131I]MIBG at a radioactivity concentration of 2 MBq/ml prevented the regrowth of 84% of spheroids, toxicity was significantly reduced by the addition of non-radiolabelled MIBG to the incubation medium. The time-dependent biodistribution of n.c.a. [131I]MIBG in nude mice bearing human neuroblastoma xenografts was compared with that of the conventional therapy radiopharmaceutical. The n.c.a. agent gave improved tumour uptake but also significantly greater accumulation in normal tissues known to accumulate MIBG such as heart, adrenal and skin. However, uptake and retention in the blood was unaltered. For all tissues examined, the 3-day calculations were undertaken to predict organ to tumour dose ratios which would result in human neuroblastoma patients with each of the [131I]MIBG preparations. These results suggest that significant therapeutic gain may be achieved by the use of n.c.a. [131I]MIBG as a treatment agent in neuroblastoma. neuroblastoma.

3-Iodobenzylguanidine↗
PubMed1995

Dosimetric considerations in 131I-MIBG therapy for neuroblastoma in children.

Dosimetric calculations have been made for organ doses in patients receiving 131I-MIBG therapy as treatment for neuroblastoma. As well as whole body and liver dose, consideration has been given to dosimetry of organs (lung, urinary bladder) whose tolerance may become treatment limiting when 131I-MIBG is given as part of combined modality therapy. Data from both adults and children receiving radiolabelled MIBG for diagnostic or therapeutic purposes have been compared in constructing dosimetry models for children. A recently published urodynamic model has been used in the estimation of radiation dose to the bladder. The results show that liver and lung may receive doses greater than the average total body dose (0.58 mGy MBq-1 and 0.35 mGy MBq-1, respectively, as compared with 0.25 mGy MBq-1 to the whole body). The organ dose estimates do not differ greatly from previous analyses except in the case of the bladder for which the new modelling studies have resulted in lower dose estimates (0.76 mGy MBq-1 administered, for dose to bladder surface from bladder contents) than in some published series. This may result from differing assumptions regarding parameters such as bladder content and urine flow rate, an enhanced fluid intake being assumed in the present bladder dose estimates. Average doses to the bladder wall from the contents were estimated to be 7.4-11.3% of the surface doses. The urodynamic modelling analysis shows that the bladder could receive a much greater dose (by an order of magnitude) in patients who were inadequately hydrated or had impaired renal function.

3-Iodobenzylguanidine↗