Biomedical subjects
Publications and source records attributed to P J Hoskin.
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AIMS: To assess the treatment outcomes and toxicity of conformal high dose rate (HDR) brachytherapy boost as a means of radiation dose escalation in patients with localised prostate cancer. MATERIALS AND METHODS: Between December 1998 and July 2004, 65 consecutive patients with localised prostate cancer (magnetic resonance imaging-staged T1-3 N0 M0) were treated with external beam radiation therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The patients selected this treatment modality in preference to entering an ongoing randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA) and Gleason score were included. The primary end point was biochemical disease-free progression. Late treatment-related morbidity was graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria. RESULTS: The median patient age was 67.3 years (range 47.9-80). Sixty patients (92.3%) had intermediate- to high-risk disease defined by clinical stage, presenting PSA and Gleason score/World Health Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6-5.8), two patients had died of metastatic disease and another four patients had PSA relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%. Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal toxicities were observed. CONCLUSIONS: These results suggest that the combined modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality with acceptable acute and late toxicities, comparable with those of EBRT alone. It offers an attractive conformal treatment modality with the potential of further dose escalation in the treatment of localised prostate cancer.
External beam radiotherapy is effective in the management of bone metastases for both local and more widespread pain. It is effective in spinal canal compression and pathological fracture where it also may have a prophylactic role. Single dose radiotherapy for bone metastases is a highly cost effective palliative treatment.
Each year thousands of women within the UK are treated with radiotherapy for breast cancer. The majority of these women are treated using a medial and lateral tangential field. This study evaluates the plans submitted to the quality assurance (QA) team of the START trial and investigates some of the differences between departments. Throughout the START trial, hardcopies of the radiotherapy dose distribution on the central slice for one in three women were submitted to the QA team for analysis. The QA team measured physical parameters including breast size and lung depth as well as noting parameters used for the radiotherapy delivery including beam energy, field size and wedge angle. Over 1400 plans from 36 centres were analysed. The mean patient separation was 19.7 cm (SD 2.7 cm) with a mean lung depth of 1.5 cm (SD 0.7 cm). The modal beam energy was 6 MV and the mean wedge angle was 23 degrees . Significant differences in the choice of wedge angle between departments were noted; however, in 90% of cases the resultant plan complied with the maximum dose gradient of 10% on the central axis specified by the trial protocol. Less than 3% (37 plans) had dose gradients of greater than 12%. This resulted in a mean dose gradient for all patients on the central axis of 5.7% (SD 2.9%).
Involved field (IF) radiation was compared with extended field (EF) radiation in Hodgkin lymphoma (HL) to ascertain whether reduced radiation fields would reduce the late sequelae of radiation without compromising disease control and survival. A total of 603 patients with stage I or II HL were entered into this trial; laparotomy was carried out in 380 (63%) patients. Stage I or IIA disease patients were randomised to receive IF or EF comprising a mantle or inverted Y fields alone. Stage I and IIB patients were randomised between mantle or inverted Y fields and total nodal irradiation (TNI). The dose was 35 Gy to uninvolved sites and 40 Gy to involved sites. The median followup of surviving patients was 25.2 years with only 3.3% lost to follow-up. The treatment failure rate at 25 years in stage IA and IIA was 44% after EF and 54% after IF (P = 0.01); in stage I and IIB this was 80% (EF) and 82% (TNI) at 25 years. No difference in overall survival between the randomised groups was seen. The incidence of second malignancies was 21% after IF and 20% after EF with a slight excess of lung cancer in the EF group. No significant differences in the causes of death between the randomised arms have emerged. In conclusion, IF radiotherapy for stage I and IIA HL results in a 11% greater risk of relapse compared with EF but has no effect on overall survival, risk of second malignancy or cause of death at 25 years.
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AIMS: Verification of patient position in radiotherapy by the use of portal images is a current practice in most radiotherapy departments. All patients within the Standardisation of Breast Radiotherapy Trial (START) were required to have on-treatment verification images. Measurements of maximum lung and breast depth from these were used to provide details for the case-report forms. This study was undertaken to validate these measurements, assess the reproducibility of patients' set-up within the START trial and to compare reproducibility on a day-to-day basis with reproducibility over a longer period. Analysis also included a subjective assessment of image quality. MATERIALS AND METHODS: Fifty-three patients from 29 departments were studied. Some centres used electronic portal imaging and others used film. Where film verification was the method of choice, information was collected about the type of film and cassette used. RESULTS: The correlation coefficients for inter- and intra-observer variability of breast and lung depth were 0.99. Comparing maximum breast depth on weekly and daily images, the median per cent standard deviation of breast depth was 4% and 3%, respectively. The mean standard deviation of breast depth for all patients, which gives an indication of the individual patient variability, was 5.5 +/- 2.2 mm for weekly and 3.9 +/- 1.5 mm for daily measurements. For lung depth, mean standard deviation was 6.8 +/- 2.5 mm for weekly and 6.8 +/- 2.8 mm for daily measurements. Images taken using Kodak X-omat V film were inferior to those taken with films in corresponding cassettes. CONCLUSION: Differences between lung depth measured in simulator and on the treatment unit were evident for many patients. There was little difference in the standard deviations of breast and lung depth for daily and weekly verification films on the treatment machine.
Central nervous system (CNS) involvement in non-Hodgkin lymphoma (NHL) is a well-recognised complication. There is no consensus regarding indications for prophylaxis or a standard CNS chemoprophylaxis regimen. Current UK practice was evaluated using a questionnaire. A total of 223 questionnaires were sent to clinicians who administered chemotherapy to patients with NHL; 158 (71%) evaluable questionnaires were returned. The overwhelming majority of respondents used prophylaxis in all cases of lymphoblastic lymphoma (97%) and Burkitt lymphoma (96%). Ninety-six per cent of respondents required risk factors to be present before prophylaxis was initiated in cases of diffuse large B-cell lymphoma. The commonest risk factor was site of involvement (paranasal sinus 88%, testicular 85%, orbital cavity 78%, bone marrow 65% and bone 28%). Other risk factors included stage IV, high International Prognostic Index score, >1 extranodal site and raised lactate dehydrogenase levels (34%, 21%, 16% and 10%). A total of 82% did not give prophylaxis in follicular lymphoma and 90% used intrathecal chemotherapy as their preferred method of prophylaxis. The most popular regimen was 12.5 mg methotrexate with each cycle of chemotherapy for six courses. Thirty-nine per cent used systemic chemotherapy for CNS prophylaxis either alone (4%) or as an adjunct to intrathecal prophylaxis (35%). These variations in the indications and methods of prophylaxis indicate that this subject deserves further review.
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Serum haemoglobin has been shown to be an independent prognostic factor for a number of cancers including head and neck, bladder, cervix and anal cancers. This study has investigated the prognostic significance of pre-treatment haemoglobin in 164 consecutive patients receiving radical radiotherapy for non-small cell lung cancer. Forty-six received conventional fractionation to 60 Gy in 30 fractions and the remainder received accelerated fractionation, either CHART, 54 Gy in 36 fractions over 12 days (27 patients) or CHARTWEL, 60 Gy in 40 fractions over 18 days (76 patients). Patients were divided into three equal groups by haemoglobin concentration. The median overall survival in each of the three groups from lowest to highest haemoglobin was 17.5 months (95% CI 7.9 25), 18.4 months (95% CI 15.0 25.9) and 16.3 months (95% CI 13.0-19.6). No significant effect of pre-treatment haemoglobin concentration was seen in predicting overall, local disease free or metastases free survival.
Radiotherapy to the breast is often given as a component of the treatment for women with breast cancer. It has been shown to increase overall survival although an increase in cardiac mortality has also been noted. This study was undertaken as part of the START trial quality assurance programme to record and evaluate the cardiac dose using modern radiotherapy techniques. Departments randomizing patients into the START trial and who had CT facilities for planning breast patients were invited to take part. 62 patients were included. CT slices were taken at the level of the maximum heart depth and on the treatment field central axis. Each patient was planned in the normal way and the distributions were analysed by the quality assurance team at Mount Vernon Hospital. The maximum heart position was found to be inferior to the central axis used for breast planning for the majority of patients; mean position 2.3 cm inferior with a mean maximum heart depth of 0.55 cm. For 45% of patients the maximum heart dose was less than 50% of the prescribed dose. The study showed that the volume of irradiated cardiac tissue has decreased compared with earlier studies, and also highlighted the need to scan away from the central axis if the dose to cardiac tissue is to be assessed.
Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m(-2) pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P=0.0001) for GLUT1 and 0.74 (P<0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.
BACKGROUND: Neither chemotherapy with a single-alkylating agent nor aggressive combination chemotherapy cures advanced stage low-grade non-Hodgkin lymphomas, even when combined with radiotherapy. Our aim was to compare administration of immediate chlorambucil treatment with a policy of delaying chlorambucil until clinical progression necessitated its use, in asymptomatic patients with advanced-stage, low-grade non-Hodgkin lymphoma. METHODS: 309 patients with asymptomatic, advanced-stage, low-grade non-Hodgkin lymphomas were recruited from 44 UK centres between Feb 1, 1981, and July 31, 1990. 158 patients were randomised to receive immediate systemic therapy with oral chlorambucil 10 mg per day continuously. The remaining 151 were randomised to an initial policy of observation, with systemic therapy delayed until disease progression. In both groups, local radiotherapy to symptomatic nodes was allowed. FINDINGS: Median length of follow-up was 16 years. Overall survival or cause-specific survival did not differ between the two groups (median overall survival for oral chlorambucil 5.9 [range 0-17.8] years and for observation 6.7 [0.5-18.9] years, p=0.84; median cause-specific survival 9 [0-17.8] years and 9.1 [0.67-18.9] years, respectively p=0.44). In a multivariate analysis, age younger than 60 years, erythrocyte sedimentation rate (ESR) 20 mm/h or less, and stage III disease, conferred significant advantages in both overall survival (p<0.0001, 0.03, and 0.03, respectively) and cause-specific survival (p=0.002, 0.008, and 0.001, respectively). In the observation group, at 10 years' follow-up, 19 patients were alive and had not received chemotherapy. The actuarial chance of not needing chemotherapy (non-lymphoma deaths censored) at 10 years was 19% (40% if older than 70 years). INTERPRETATION: An initial policy of watchful waiting in patients with asymptomatic, advanced stage low-grade non-Hodgkin lymphoma is appropriate, especially in patients older than age 70 years.
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Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) has a number of potential advantages for the oncologist in refining and improving the management of lymphomas. Currently the most promising appear to be in the early prediction of response to chemotherapy, evaluation of the residual mass and improved radiotherapy planning. Other important areas which require assessment are its value in refining prognostic indices at staging and its role in follow-up. The added value of the new combined PET-CT scanners requires careful evaluation in each of these settings, where combined morphological and functional information may provide optimal disease assessment. The ultimate aim is to improve the management of patients with lymphoma by identifying those patients who can be cured with minimal treatment and equally those for whom conventional treatment is doomed to failure and in whom more intensive strategies should be employed from the outset.
Radiotherapy is an established treatment for metastatic bone pain. It may be delivered as a localised low dose treatment for localised bone pain or systemically for more widespread symptoms using hemibody external beam radiotherapy or intravenous bone-seeking radioisotopes. Bisphosphonates have been shown to reduce morbidity from bone metastases when given to patients with asymptomatic disease from myeloma and primary breast and prostate cancers. They also reduce metastatic bone pain in these sites. In the absence of randomised data comparing radiotherapy with bisphosphonates in the same clinical setting, comparison of the response rates from individual trials of the two modalities suggests that the overall pain response in all tumour types from radiotherapy is around 80% compared to a similar rate in myeloma with bisphosphonates but only 40% in solid tumours. Optimal use of the two modalities requires further investigation but since they have different dose limiting toxicities their incorporation in a combined modality approach to metastatic bone pain is rational using the concepts of additive effect and spatial co-operation in which bisphosphonates provide background control alongside acute pain relief using radiotherapy. They are also an important alternative for bone pain where radiation tolerance has been reached or radiotherapy is not readily available.
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