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Biomedical subjects

C L Harmer

Publications and source records attributed to C L Harmer.

At least 37 records · Page 2Linked to original sources
PubMed1994

Results of external beam radiotherapy in differentiated thyroid carcinoma: a retrospective study from the Royal Marsden Hospital.

Between 1969 and 1991, 113 patients with differentiated thyroid carcinoma (follicular and papillary) received radical dose megavoltage external beam radiotherapy. There were 70 females and 43 males, mean age 53 years (range 11-84). Radiotherapy was delivered to both sides of the neck and superior mediastinum, using either megavoltage photons via anterior and posterior portals, delivering a 60 Gy mid-plane dose in 30 fractions and treating daily over 6 weeks (with spinal cord shielding from the posterior field after 40 Gy), or matched 20 MeV and 35 MeV electron beams (to the neck and superior mediastinum, respectively) delivering a 75 Gy applied dose in 30 daily fractions. All patients received suppressive thyroid hormone and 74 radioiodine. Local recurrence, mostly within field, occurred in 19% of 53 patients with probable and definite residual microscopic disease (both follicular and papillary histologies). For gross residual disease (both follicular and papillary) in 49 patients, complete regression was obtained in 37.5%, partial regression in 25% and no regression in 37.5%. Median follow-up from diagnosis was 49 months (range 3-335). Overall 5-year survival rates were 85% for residual microscopic disease but only 27% for gross disease. 61 patients have died. Nineteen deaths were due to unrelated causes, 15 to distant metastases, 15 to uncontrolled local disease and 12 died with both local and distant tumours.

Adenocarcinoma, Follicular↗
PubMed1994

Surveillance after treatment for well differentiated thyroid cancer: audit for chest radiography.

Well differentiated thyroid carcinoma has an excellent prognosis, with many patients achieving cure. The incidence of pulmonary metastases is about 11%. When thyroid ablation has been used in the initial treatment, serial thyroglobulin (Tg) levels are a sensitive marker of recurrent disease. Data regarding the usefulness of chest radiography (CXR) in monitoring relapse in these patients does not exist and regular CXRs continue to be performed as routine surveillance. To assess their efficacy we have reviewed all serial CXRs and corresponding Tg levels on every patient with well differentiated thyroid cancer who was treated and followed up at the Royal Marsden Hospital between 1984 and 1987. A total of 369 CXRs were performed on 49 patients, with a median follow-up of 81 months. Of these, only 15% were undertaken for a clinical reason, with 85% being requested as routine. Seven patients developed lung deposits, six of whom had CXR performed because of elevated Tg, abnormal 131I uptake imaging or thoracic symptoms. In no case were lung metastases diagnosed by routine CXR in an asymptomatic patient. The cost of routine chest films for the duration of this study was approximately 13,500 pounds. It is concluded that routine chest radiography is neither cost effective nor a sensitive method of screening for relapse in asymptomatic well differentiated thyroid cancer. It should be reserved for patients with chest symptoms, or those in whom Tg has been shown not to be a useful marker of disease.

Adolescent↗
PubMed1993

Radiation dose assessment in radioiodine therapy. Dose-response relationships in differentiated thyroid carcinoma using quantitative scanning and PET.

Dose-response charts have been constructed to determine the tumouricidal dose for differentiated thyroid carcinoma metastases and thus enable precise activities of radioiodine to be prescribed in order to maximise tumour kill and minimise morbidity. Tumour and normal residual thyroid absorbed doses from radioiodine-131 have been determined with increased precision using a dual-headed whole-body rectilinear scanner with special high-resolution low-sensitivity collimators. Improved accuracy in the estimation of functioning tumour mass has been achieved using positron emission tomography (PET) with a low-cost large area PET camera. Dose-response data have been obtained for 33 patients. Following near-total thyroidectomy and 3.0 GBq 131I, a mean absorbed dose of 410 Gy achieved complete ablation of thyroid remnants in 75% of patients. Patients who had persistent uptake in the thyroid region on subsequent radioiodine scanning had received a mean dose of only 83 Gy. Cumulative absorbed doses in excess of 100 Gy were found to eradicate cervical node metastases. Patients with bone metastases, who generally have a poor prognosis, were found to have received doses of the order of only 20 Gy to the tumour deposits. The dose-response data explain the spectrum of clinical responses to fixed activities of radioiodine. In future, they will enable precise prescription of radioiodine to achieve tumouricidal doses whilst avoiding the morbidity and expense of ineffective therapy.

Adenocarcinoma, Follicular↗
PubMed1993

Head and neck sarcomas: prognostic factors and implications for treatment.

One hundred and thirty patients with soft tissue sarcoma of the head and neck were treated at the Royal Marsden Hospital between 1944 and 1988. Pathological review was possible in 103 of these cases; only pathologically reviewed cases have been analysed. The median age at presentation was 36 years, and 53% were male. Four had neurofibromatosis type I, and one previous bilateral retinoblastoma. Six had undergone previous radiotherapy, 12 to 45 years prior to developing sarcoma. The tumours were < or = 5 cm in 78% of cases and high grade in 48%. Only one patient presented with lymph node metastases and only one with distant metastases (to lung). Malignant fibrous histiocytoma was the commonest histological type, occurring in 30 cases. The overall 5 year survival was 50% (95% CI 39-60). Local tumour was the cause of death in 63% of cases and 5 year local control was only 47% (95% CI 36-58) with local recurrence occurring as late as 15 years after treatment. The only favourable independent prognostic factor for survival was the ability to perform surgery (other than biopsy), with or without radiotherapy, as opposed to radiotherapy alone (hazard ratio 0.39; P = 0.003). Only one patient had a biopsy with no further treatment. Favourable independent prognostic factors for local control at 5 years were site (tumours of the head as opposed to the neck, hazard ratio 0.42; P = 0.02) and modality of treatment (combined surgery and radiotherapy compared to either alone, hazard ratio 0.31; P = 0.002). Patients in the combined modality and single treatment modality groups were well balanced for T stage, grade and tumour site. The patients in the combined treatment group had less extensive surgery, yet their local recurrence-free survival was longer. Unlike soft tissue sarcomas at other sites, those in the head and neck region more often cause death by local recurrence. The addition of radiotherapy to surgery may result in longer local recurrence-free survival.

Adult↗
PubMed1992

Preoperative radiotherapy for initially inoperable extremity soft tissue sarcomas.

The results and complications of a combination of preoperative radiotherapy and surgery in the treatment of 70 patients with large or fixed extremity soft tissue sarcomas are reported. Sixty-one patients were referred with a primary tumour and 9 had recurrences. Thirty-three patients had tumours in the thigh and 38 tumours were fixed to neighbouring structures. The mean preoperative dose was 53 Gy (range 21-75). Eleven patients received a postoperative boost to tumour site. Four patients received preoperative intra-arterial Adriamycin. Overall, 42 patients (60%) responded to the radiotherapy, 4 with complete tumour resolution. Eighty per cent of those receiving greater than or equal to 60 Gy responded and a significant correlation between 2 Gy equivalent dose and response was demonstrated (P less than 0.005). The degree of tumour necrosis was increased in 23 of 52 evaluable patients following radiotherapy, although there was no correlation with dose or clinical response. There have been eight local recurrences and 17 deaths after a median follow-up of 2 years. Tumour size less than 10 cm was the only significant factor in the development of local recurrence (P = 0.04). Thirty-six patients developed immediate postoperative complications: 9 major (13%), 13 moderate (19%) and 14 minor (20%). Increasing patient age was the only significant independent factor for the development of complications (P = 0.015). Preoperative radiotherapy will usually permit limb conservation of extremity sarcomas which otherwise would be inoperable or require amputation. However, the increased incidence of wound complications in older patients demands meticulous technique.

Adolescent↗
PubMed1992

The role of diagnostic CT scanning of the brachial plexus and axilla in the follow-up of patients with breast cancer.

In order to assess the value of computed tomographic scanning of the axilla and brachial plexus in the management of patients with arm symptoms following treatment for breast cancer, the case notes and diagnostic films of 102 such patients who underwent scanning between 1985 and 1990 at this institution were analysed retrospectively. The clinical indications for requesting computed tomography (CT) of the brachial plexus and axilla included arm oedema (52 patients, 51%), brachial plexus neuropathy (73 patients, 72%), and/or the presence of a palpable axillary mass (18 patients, 18%). Of 102 CT scans, 80 showed either no abnormality (31 patients, 30%), or axillary fibrosis (49 patients, 48%), and 22 (21%) showed radiological evidence of recurrent tumour. Only 4 of 84 patients with no palpable mass had computed tomographic evidence of occult recurrent tumour; all of these had concurrent evidence of distant metastatic disease (lung, liver, bone). Patients have been followed up for from between 1 and 15 years from diagnosis (median 5.5 years). The extremely low yield of tumour recurrence on computed tomographic scanning in the absence of a palpable axillary mass (4/84 patients, 5%; 95% CI 1-12), cannot justify CT as a method of screening for clinically occult axillary relapse in patients with arm symptoms following axillary surgery and radiotherapy for breast cancer. Computed tomographic scanning in these patients should only be employed to confirm the clinical suspicion of tumour as a baseline prior to further treatment.

Axilla↗
PubMed1992

Value of conformal planning in the radiotherapy of soft tissue sarcoma.

The late complications and subsequent limb function seen following treatment of extremity sarcoma are related to the radiation dose used and the volume of tissue irradiated. The potential value of the use of 3D-planning and conformal blocking has been studied in 11 patients with lower limb sarcoma. Tumour, target and normal tissue volumes were reconstructed in 3D following a CT planning scan. Dose calculations were performed for conventional and conformal plans, using customized blocks with a margin of 6 mm around the target volume. No compromise of target dosimetry was permitted. The volumes of tissue receiving 50%, 80% and 90% of the prescribed dose were compared using cumulative volume dose histograms. The treatment volume was reduced in all patients, and by greater than 20% in four of five with thigh tumours. The mean volume of muscle outside the target volume which was irradiated to the 50% isodose was 4.2 litres. The volume irradiated to 90% or greater isodose was reduced by greater than 30% in five of eight patients with thigh and lower leg tumours. Similarly, the volumes of femur, tibia/fibula and ilium were reduced by 38%, 18% and 14% respectively by conformal blocking. Considerable sparing was achieved in the volumes of pelvic contents irradiated, including gonads and rectum. This simple, but time consuming, technique can achieve major reductions in normal tissue irradiation with potential improvements in limb function. To confirm its value and safety, prospective randomized trials must be performed and similar advances in patient immobilization and treatment verification are essential.

Humans↗
PubMed1992

Re-irradiation of soft-tissue sarcoma.

Re-irradiation for local recurrence of malignancy after radical radiotherapy is of proven benefit at head and neck sites but has seldom been used elsewhere. This paper reports a series of 10 patients re-irradiated with external-beam techniques for local recurrence of soft-tissue sarcoma of the limb and limb girdle following initial limb conserving management with surgery and radiotherapy (dose range 33-60 Gy). Median survival was 14 months following re-treatment. Two cases received treatment with high-energy electrons and the rest with megavoltage photons. Five patients re-treated with radical intent (dose range 40-60 Gy) had a median survival of 36 months and median recurrence-free survival of 16 months. All five patients treated palliatively (dose range 12-50 Gy) have died, although two demonstrated local control until death. Acute reactions were not severe. Radionecrosis was seen in one patient who was re-irradiated twice (total dose 145 Gy) and subsequently required amputation. One other case required amputation for persistent local disease, but in the remaining eight, limb conservation was achieved. Re-irradiation of soft-tissue offers good local control and may avoid amputation.

Adult↗
PubMed1991

Hormone replacement therapy and survival after surgery for ovarian cancer.

OBJECTIVE: To evaluate whether hormone replacement therapy affects survival in women who have undergone bilateral salphingo-oophorectomy because of epithelial ovarian cancer. DESIGN: Retrospective analysis by review of patients' notes and questionnaires completed by general practitioners to compare the overall survival and disease free survival in patients with ovarian cancer who did or did not receive hormone replacement therapy after diagnosis. Data were analysed by Cox regression, with hormone replacement therapy as a time dependent covariate because patients who received hormone replacement did so at different times after diagnosis. SETTING: Gynaecological oncology unit of Royal Marsden Hospital. PATIENTS: 373 patients aged 50 years or younger who attended the hospital from 1972 to 1988. All of the women had undergone bilateral salpingoophorectomy for epithelial ovarian cancer. In all, 78 had received hormone replacement therapy, starting at a median of four months after diagnosis. INTERVENTION: A questionnaire was sent to the general practitioners of all patients who were not recorded as having received hormone replacement therapy. MAIN OUTCOME MEASURES: Overall survival and disease free survival. RESULTS: There was no significant difference in survival between women receiving hormone replacement therapy and those not receiving it after accounting for the effects of other known prognostic factors (stage of cancer, differentiation of tumour, histological results, and time to relapse). The relative risk of dying in those who received hormone replacement therapy was 0.73 (95% confidence interval 0.44 to 1.20). In addition, there was no significant difference in disease free survival (relative risk in those receiving hormone replacement therapy was 0.90; 95% confidence interval 0.52 to 1.54). CONCLUSIONS: This study shows that hormone replacement therapy is unlikely to have a detrimental effect on the prognosis of patients with ovarian cancer, but this would be shown conclusively only by a randomised controlled trial.

Adult↗
PubMed1991

Limb function following conservation treatment of adult soft tissue sarcoma.

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more years after limb-conserving treatment for soft tissue sarcoma of the leg or pelvic girdle. Tumours of the thigh predominated (25 patients) and the mean tumour size was 9.9 cm. 41 patients had been treated with a combination of surgery and radiotherapy (29 with conventional and 12 with high dose), 12 with surgery alone and one with irradiation and intra-arterial doxorubicin. Only 15 patients had a normal range of movement in all lower limb joints and only 12 had normal power in all muscle groups; tumours of the lower leg were particularly unfavourable in this respect. Gait was normal in 42 patients but 8 required a walking aid and 4 a joint support. 16 had detectable lymphoedema but only 2 needed to wear compression hosiery. 35 patients still experienced pain at some time but only 6 required analgesia. However, when assessed by questionnaire for locomotion, grooming and home/leisure/vocational activities, 37 patients (68%) reported excellent function, and only 2 had moderate impairment. Function loss was most marked in leisure (25 patients) and vocational (8) activities, but was mild in 66% of cases. Multivariate analysis was carried out to determine the prognostic factors for poor limb function. The results suggested that overall functional score was predominantly determined by gait (P less than 0.001), muscle power or range of movement (P less than 0.001), with increasing age, female sex and the use of radiotherapy poor prognostic factors. Reduced muscle power or range of movement were the major factors determining gait (P less than 0.02) with the use of radiotherapy the significant prognostic factor for both in the conventionally treated group. Doses in excess of 60 Gy resulted in increased fibrosis and a worse functional outcome. Extent of surgery was not an independent prognostic factor for limb function, although univariate analysis suggested an association with range of movement in the conventionally treated group (P less than 0.025). Despite significant objective loss of range of movement and muscle power patients retain excellent limb function and quality of life following limb conserving treatment. For optimal function, radiotherapy should be given with small fractions to a dose not exceeding 60 Gy.

Adult↗
PubMed1991

Treatment of metastatic para-aortic paraganglioma by surgery, radiotherapy and I-131 mIBG.

A patient with a malignant, functioning, aortico-sympathetic paraganglioma and a solitary bone metastasis causing paraplegia was treated by spinal decompression, irradiation of the metastasis, surgical excision of the primary tumour and systemic I-131 meta-iodobenzyl-guanidine (mIBG). Sixteen months after treatment there was no clinical, radiological or biochemical evidence of residual disease and neurological function was restored. The case supports the use of combined treatment incorporating mIBG in patients with metastatic neuroendocrine tumours which demonstrate mIBG uptake.

3-Iodobenzylguanidine↗
PubMed1990

Thyroid imaging using positron emission tomography--a comparison with ultrasound imaging and conventional scintigraphy in thyrotoxicosis.

Forty-six comparative studies were performed on 41 patients with hyperthyroidism. Clinically these comprised two groups: those with Graves' disease, and those with multinodular goitre. All patients underwent an ultrasound examination and positron emission tomography (PET) using 124I, then gamma camera pinhole imaging following their 131I therapy administration. Although the 131I pinhole imaging was not performed for diagnostic purposes, there was good correlation (78% agreement) between it and 124I PET in determining relative lobe size. Hence either imaging modality could be used as an indicator of the relative radiation dose delivered to each thyroid lobe at a macroscopic level. In terms of gland morphology the PET images corresponded well to the high resolution ultrasound images (78% agreement), unlike the pinhole images which correlated poorly (only 28% agreement). The results showed that PET imaging gives better anatomical and physiological detail than 131I pinhole imaging. In 77% of cases where the pinhole image showed a uniform distribution of radioisotope, the improved spatial resolution of the PET images revealed non-homogeneous distribution indicating a non-uniform distribution of radiation dose. Since all dosimetry calculations are based on the assumption of uniform distribution of radioiodine, this non-uniformity could possibly have important consequences in the outcome of radioiodine therapy in thyrotoxicosis.

Adult↗
PubMed1989

Radiation dose assessment in radioiodine therapy. 2. Practical implementation using quantitative scanning and PET, with initial results on thyroid carcinoma.

We have designed special high-resolution, low-sensitivity collimators for a dual-headed whole-body scanner for imaging and quantifying therapy levels of iodine-131. In addition, we have used positron emission tomography (PET) with a low-cost large-area PET camera to achieve improved accuracy in the estimate to tumor mass. The physical performance of these two imaging systems is described. In order to illustrate the practical implementation of these systems for the assessment of radiation dose to normal and tumour tissue during radioiodine therapy, three clinical examples are reported, and a summary of the initial clinical results obtained from 16 patients with carcinoma of the thyroid is presented. The dose to normal thyroid remnants for patients undergoing ablation ranged from 16 to 400 Gy, while the dose to involved neck nodes ranged from 2.5 to 33 Gy for patients undergoing post-ablation radioiodine therapy. In one patient with distant metastasis in the spine, a dose of 100 Gy was achieved. The techniques described in this paper can be used to determine if sufficient activity can be accumulated in tumours to provide a therapeutic effect while minimising irradiation of normal tissues by avoiding administrations which do not provide tumouricidal radiation doses.

Carcinoma↗
PubMed1989

Primary medical therapy for operable breast cancer.

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy. With a median follow-up of 19 months (range 6-42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease. Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.

Adult↗
PubMed1989

Hemibody irradiation (HBI) for metastatic bone pain in two histologically distinct groups of patients.

Fifty patients with hemibody irradiation (HBI) for metastatic bone pain have been reviewed. A total of 60 treatments were given (9 upper HBI, 31 lower HBI and 10 both upper and lower HBI). Seventeen patients had metastatic myeloma and 30 had metastatic prostatic carcinoma. The overall response rate was 83% with a 5% complete response rate. Response was seen within 24 hours in 25% of treatments and lasted until death in 74%. No difference in the response characteristics was seen between those patients with myeloma and those with prostatic carcinoma. Significant toxicity occurred in 60% of patients, predominantly gastrointestinal toxicity and bone marrow suppression. One case of fatal pneumonitis occurred. The possibility of maintaining these response rates but reducing toxicity using lower doses of HBI is discussed.

Adult↗
PubMed1988

Family screening in medullary thyroid carcinoma presenting without a family history.

Systematic screening of the families of a series of 39 patients with apparently sporadic medullary thyroid carcinoma detected seven new cases in four families. A negative family history in a patient presenting with medullary thyroid carcinoma is not reliable in excluding familial disease, and family screening should be considered for new patients with medullary thyroid carcinoma.

Adolescent↗