Biomedical subjects
D Machin
Publications and source records attributed to D Machin.
Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial.
BACKGROUND: Resection of hepatocellular carcinoma is potentially curative, but local recurrence is common. In this prospective randomised trial, we aimed to find out if one dose of postoperative adjuvant intra-arterial iodine-131-labelled lipiodol could reduce the rate of local recurrence and increase disease-free and overall survival. METHODS: Patients who underwent curative resection for hepatocellular carcinoma and recovered within 6 weeks were randomly assigned one 1850 MBq dose of 131I-lipiodol or no further treatment (controls). We compared rates of recurrence and disease-free and overall survival (the primary endpoints) between the two groups by intention to treat. We planned an interim analysis when 30 patients (both groups together) had been followed up for a median of 2 years, with the intention of stopping early if the between-group difference in disease-free survival was significant (p=0.029). FINDINGS: Between April, 1992, and August, 1997, we recruited 43 patients: 21 received intra-arterial 131I-lipiodol and 22 received no adjuvant treatment. During a median follow-up of 34.6 (range 14.1-69.7) months, there were six (28.5%) recurrences among the 21 patients in the adjuvant treatment, compared with 13 (59%) in the controls (p=0.04). Median disease-free survival in the treatment and control groups was 57.2 (0.4-69.7) and 13.6 (2.1-68.3) months, respectively (p=0.037). 3-year overall survival in the treatment and control groups was 86.4% and 46.3%, respectively (p=0.039). The interim analysis showed a significant increase in disease-free survival in the treatment group compared with the controls (p=0.01), so we closed the trial early. 131I-lipiodol had no significant toxic effects. INTERPRETATION: In patients with hepatocellular carcinoma, one 1850 MBq dose of intra-arterial 131I-lipiodol given after curative resection significantly decreases the rate of recurrence and increases disease-free and overall survival.
A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma. European Osteosarcoma Intergroup (EOI).
BACKGROUND: Despite advances in the treatment of primary limb osteosarcoma, the outcome of patients with primary metastatic and axial skeletal disease remains poor. The European Osteosarcoma Intergroup have assessed a combination chemotherapy regimen consisting of ifosfamide (IFOS) 3 g/m2/dl-2, doxorubicin (DOX) 25 mg/m2/dl-3 i.v. bolus and cisplatin (CDDP) 100 mg/m2/dl. PATIENTS AND METHODS: One hundred nine previously untreated patients with primary osteosarcoma were registered. Eligibility was confirmed in 103. At presentation, 45 eligible patients had metastatic disease, 15 axial skeletal primary tumours and 43 non-metastatic limb tumours. RESULTS: The major toxicities were myelosuppression (90%, grade 3 or 4) and nausea and vomiting (74%, grade 3 or 4). Overall mean relative dose intensity (RDI) was 80% (88% CDDP, 75% IFOS, 81% DOX). Clinical response as measured by reduction in tumour volume occurred in 36% (95% confidence interval (95% CI): 27%-47%) of primary tumours. Response of pulmonary metastases to chemotherapy was seen in 33% (95% CI: 19%-49%). Good histological response (> or = 90% necrosis of the tumour) occurred in 33% (95% CI: 22%-45%) of resected tumours. Five-year survival was 62% in limb-non-metastatic, 41% in axial skeletal and 16% in limb metastatic patients. CONCLUSIONS: This regimen is active in osteosarcoma but does not appear to be more active than the two-drug CDDP-DOX regimen currently recommended by EOI.
Using data from studies of health-related quality of life to describe clinical issues examples from a longitudinal study of patients with advanced stages of cervical cancer.
The focus of the paper is to describe how to present data from studies on health-related quality of life (H-QoL) in a way that is simple and clinically relevant. Data from a longitudinal study of patients with advanced stages of cervix cancer are used. One hundred and eighteen patients filled out questionnaires (including EORTC QLQ-C30) 7 times over a period of 2 years. The following issues are considered: (1) The use of a panel for an initial overview of data. (2) The visual difference between using mean and median values. (3) Box-whisker plots to illustrate the variability of the data. (4) The effect of combining categorical data into fewer categories. (5) Individual patient profiles showing the wide variability among patients. (6) A table showing the change of scores over a one-year period. (7) "Prognostic plots" dividing the initial scores and the following scores. (8) Plotting changes over time. (9) Illustration of the impact of non-random dropout. (10) The effect of drop-out for the patients who fill out two sequential assessments. (11) The use of healthy controls to help answer the question "what is normal?".
Neoadjuvant chemotherapy with doxorubicin and cisplatin in malignant fibrous histiocytoma of bone: A European Osteosarcoma Intergroup study.
PURPOSE: Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP). PATIENTS AND METHODS: Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be </= 65 years of age. Treatment consisted of doxorubicin 25 mg/m(2)/d days 1 through 3 and cisplatin 100 mg/m(2) by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. RESULTS: Forty-one patients had operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 16 (42%) of 38 assessable specimens showed a good pathologic response (>/= 90% necrosis). Median time to progression was 56 months, and the 5-year progression-free survival rate was 56% (95% confidence interval [CI], 40% to 72%). Median survival time was 63 months, and the 5-year survival rate was 59% (95% CI, 41% to 77%). Patients with a good pathologic response had longer survival times and times to progression than did those with a poor response. Also treated were two patients with locally recurrent and nine with metastatic disease, and these patients had a median survival time of 17.5 months. CONCLUSION: Our study suggests that adjuvant or neoadjuvant chemotherapy with DOX/DDP is beneficial in MFH-B. Good pathologic response rates and survivals are quite comparable with those for osteosarcoma, a related bone tumor for which adjuvant or neoadjuvant chemotherapy is an accepted practice.
Seasonal variations in the presentation and growth of thyroid cancer.
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Tamoxifen in hepatocellular carcinoma.
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The distribution and latency of the auditory P300 in schizophrenia and depression.
In a study of 19 right-handed patients with positive symptoms of schizophrenia, fulfilling DSM-III-R criteria, a deficit in the left central-temporal distribution of the auditory P300 was shown compared to a group of 31 controls, who showed a symmetrical distribution. In contrast, 14 right-handed patients fulfilling DSM-III-R criteria for major depressive illness without any psychotic features showed a deficit in the right auditory P300 distribution. These changes did not appear to depend on either age, gender or amount of medication. There was an increase in the P300 latency of 22 and 10 ms over that of the controls in schizophrenia and depressive patients, respectively. Only for those with schizophrenia was the increased latency statistically significant. This increased latency in the schizophrenic group did not appear to be related to medication.
Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: report of a workshop.
In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed.
Photochemotherapy of oral lichen planus.
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Young age is not a poor prognostic marker in colorectal cancer.
BACKGROUND: There is still considerable controversy and debate regarding the features and prognosis of colorectal cancer in young patients. METHODS: One hundred and ten patients (5.1 per cent) under the age of 40 years with colorectal cancer (group Y; male: female ratio 48:62) were compared with 2064 patients with colorectal cancer aged 40 years or more (group O; 917 women, 1147 men). Mode of presentation, stage at diagnosis, tumour characteristics and survival were analysed. RESULTS: Predisposing malignant conditions and family history of colorectal cancer were present in 20.9 per cent of patients in group Y versus 2.2 per cent in group O (P < 0.001). Common chief complaints included change in bowel habits, bleeding from the rectum and a significantly higher incidence of abdominal pain in group Y. There was no difference in stage at presentation between the two groups (the proportion of Dukes stage A, B, C and 'D' lesions in group Y was 8.2, 24.5, 37.3 and 30.0 per cent respectively versus 10.5, 27.9, 33.4 and 28.1 per cent in group O). Tumour site and characteristics were similar in both groups. The incidence of mucinous/signet ring cell and poor grade tumours was 6.9 and 11.8 per cent respectively in group Y and 4.5 and 10.5 per cent in group O. With a mean follow-up of 31.8 months, the overall 5-year survival rate was 54.8 per cent in group Y and 54.1 per cent in group O. Comparing stage for stage, survival was not significantly different in the two groups. However, the adjusted hazard ratios of the age groups Y, M (40-59 years), S (60-79 years), and E (80 years and above) were 1.3, 1 (baseline for calculations), 1.4 and 2.4 respectively, suggesting an adverse outcome for patients in group Y compared with patients aged 40-59 years. CONCLUSION: This study revealed no difference in tumour characteristics and survival in patients with colorectal cancer aged less than 40 years compared with those aged above 40 years. However, a higher hazard ratio in the youngest group may connote a worse prognosis than that for those aged 40-59 years. A significant family history of colorectal cancer and predisposing conditions in the young warrants aggressive screening, surveillance and treatment of the underlying conditions. The detection of colorectal cancer in young patients should be no different from that in the old but demands a high index of suspicion.
Incidence of corneal ulceration in south India.
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Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup.
BACKGROUND: A previous trial by the European Osteosarcoma Intergroup (EOI) suggested that a short intensive chemotherapy regimen with doxorubicin and cisplatin might produce survival of operable, non-metastatic osteosarcoma similar to that obtained with complex and longer-duration drug regimens based on the widely used T10 multi-drug protocol. We undertook a randomised multicentre trial to compare these two approaches. METHODS: 407 patients with operable, non-metastatic osteosarcoma were randomly assigned the two-drug regimen (six cycles [18 weeks] of doxorubicin 25 mg/m2 on days 1-3 and cisplatin 100 mg/m2 on day 1) or a multi-drug regimen (preoperatively vincristine, high-dose methotrexate, and doxorubicin; postoperatively bleomycin, cyclophosphamide, dactinomycin, vincristine, methotrexate, doxorubicin, and cisplatin; this protocol took 44 weeks). Surgery was scheduled for week 9 for the two-drug group and week 7 for the multi-drug group. Analyses of survival and progression-free survival were by intention to treat. FINDINGS: Of 407 randomised patients, 391 were eligible and have been followed up for at least 4 years (median 5-6 years). Toxic effects were qualitatively similar with the two regimens. However, 188 (94%) of 199 patients completed the six cycles of two-drug treatment, whereas only 97 (51%) of 192 completed 18 or more of the 20 cycles of the multi-drug regimen. The proportion showing a good histopathological response (> 90% tumour necrosis) to preoperative chemotherapy was about 29% with both regimens and was strongly predictive of survival. Overall survival was 65% at 3 years and 55% at 5 years in both groups (hazard ratio 0.94 [95% CI 0.69-1.27]). Progression-free survival at 5 years was 44% in both groups (hazard ratio 1.01 [0.77-1.33]). INTERPRETATION: We found no difference in survival between the two-drug and multi-drug regimens in operable, non-metastatic osteosarcoma. The two-drug regimen is shorter in duration and better tolerated, and is therefore the preferred treatment. However, 5-year survival is still unsatisfactory and new approaches to treatment, such as dose intensification, are needed to improve results.
Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial.
PURPOSE: The objective of this study was to determine whether the thermal dose delivered during hyperthermia treatments and other thermal factors correlate with outcome after combined radiation and hyperthermia of breast carcinoma recurrences. Data were from the combined hyperthermia and radiation treatment arms of four Phase III trials, which when pooled together, demonstrated a positive effect of hyperthermia. METHODS AND MATERIALS: Four Phase III trials addressing the question of whether hyperthermia could improve the local response of superficial recurrent breast cancer to radiation therapy were combined into a single analysis. Thermal dosimetry data were collected from 120 of the 148 breast cancer recurrence patients who received hyperthermia. The data were analyzed for correlations between thermal parameters as well as important clinical parameters and outcome (complete response rate, local disease free survival, time to local failure, and overall survival). RESULTS: Five thermal parameters were tested, all associated with the low regions of the measured temperature distributions. Max(TDmin) and Sum(TDmin) were associated with complete response where TDmin is the minimum thermal dose measured by any of the tumor temperature sensors during a treatment: Max(TDmin) is the maximum of TDmin over a series of treatments. Using a categorical relationship with a cutoff of 10 min for Sum(TDmin), the complete response rate was 77% for Sum(TDmin) > 10 min and 43% for Sum(TDmin) < or = 10 min (p = 0.022, adjusted for study center and significant clinical factors). The overall complete response rate for hyperthermia and radiation was 61% compared to 41% for radiation alone. Either Max(TDmin) or Sum(TDmin) were also associated with local disease free survival, time to local failure and overall survival. CONCLUSIONS: An earlier report of this trial demonstrated a significant benefit when hyperthermia was added to radiation in the treatment of breast cancer recurrences. The analysis of thermal factors demonstrates that parameters representative of the low end of the measured temperature distributions are associated with initial complete response rate, local disease-free survival, time to local failure and overall survival.
Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer.
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Commentary: educational initiatives deserve randomised controlled trials.
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Assessing quality of life in comparative cancer clinical trials: does it make a difference?
Many randomized Phase III trials of cancer therapy involve quality of life assessments. This paper argues for graphical presentation of quality of life measures in order to visualize changes over time.
The experience of labour: using ethnography to explore the irresistible nature of the bio-medical metaphor during labour.
OBJECTIVE: taking evidence provided by an ethnographic study based on women's experiences of pregnancy and childbirth, and using ritual theory in the analysis of the relationship between the medical metaphor, inherent in contemporary birth settings, and the views and expectations of childbirth which the women bring with them to that setting. DESIGN: small scale qualitative study using ethnographic research techniques. SETTING: GP surgeries, two consultant-led, hospital-based antenatal units, labour suites and postnatal wards, plus the homes of the women involved from the north east of England. PARTICIPANTS: 40 primigravid women providing two sample groups. Half of the women were actively involved in antenatal class programmes run by the National Childbirth Trust and the NHS and the other half did not attend any antenatal classes. MAIN FINDINGS: within the sample there was a clear cultural diversity which carried significant implications on how the women assembled their understanding of pregnancy and birth antenatally. However, this division lost clarity at the onset of labour, rendering delivery experiences more similar than might have been expected. Ritual theory offers significant insight into this phenomenon, analysing birth as a rite of passage provided a necessary tool to explain why this pattern emerged in the data. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: cultural diversity suggests an element of caution should be used when advocating the notion of 'informed choice' across the board, sensitivity to existing cultural values is imperative. Despite an emphasis on informed choice, midwifery practice continues to offer the medical metaphor as the dominant cultural prop in the labour ward.