Clive L Harmer | University of London (original) (raw)

Papers by Clive L Harmer

The Annals of Thoracic Surgery, 2001

Relatively little evidence exists to guide the decision pathway regarding thoracic metastasectomy... more Relatively little evidence exists to guide the decision pathway regarding thoracic metastasectomy for thyroid malignancy. Single-institution 10-year review. Sixteen patients had surgical treatment for intrathoracic metastatic thyroid malignancy: 12 men and 4 women, mean age 43.7 years (range 19 to 77). Histopathologic type was papillary in 6 cases, follicular in 4, Hurthle cell in 3, and medullary in 3. Indication was either &amp;quot;bulky&amp;quot; disease (8 patients) or poor response to radiotherapy (8 patients). We performed 11 sternotomies and five thoracotomies. Operative mortality was 6.25%. Operative morbidity was 6.25%. Mean survival was 39.5 months (0 to 144). Nine patients died during follow-up (mean survival of 41.2 months). Six patients survived, 4 free of disease (mean survival 70 months) and 2 with further relapse (mean survival 17 months). Five-year survival was 32.5%. The cohort studied is one of the largest in the literature on the topic. Surgical treatment achieved a reasonable survival in a small subgroup of patients where radiotherapy had failed or was deemed inappropriate because of the size or location of the tumor. Further follow-up and more observations will be required for evaluating these preliminary findings.

Clinical Radiology, 1968

The authors conclude that spontaneous pneumothoraces occur more commonly as a complication of pul... more The authors conclude that spontaneous pneumothoraces occur more commonly as a complication of pulmonary metastases from malignant disease in children than in adults and that the primary tumour is most frequently a bone sarcoma. The causal mechanism is discussed. The occurrence of a spontaneous pneumothorax in a child with a bone sarcoma and no evidence of pulmonary metastases is highly suggestive that subclinical pulmonary metastases are present.

Clinical Radiology, 1987

A new treatment for post-radiotherapy telangiectasia is reported. Five patients were successfully... more A new treatment for post-radiotherapy telangiectasia is reported. Five patients were successfully treated by injection of a dilute solution of sodium tetradecyl sulphate. Several (4-7) half hour sessions of injection sclerotherapy at 5-weekly intervals were necessary.

Clinical and Experimental Dermatology, 1976

Sarcoma, 1997

Purpose. Improvements in the systemic management of Ewing' s sarcoma of bone over the last 20 yea... more Purpose. Improvements in the systemic management of Ewing' s sarcoma of bone over the last 20 years have led to a dramatic improvement in survival. The corollary is that treatment of the primary disease requires re-evaluation, since a signi® cant number of patients still suffer local relapse. Patients. The effect of radiation dose on local control was reviewed in a series of 96 patients treated between 1967 and 1986. Seventy-four had no m etastases at presentation (M 0), 22 had metastases (M 1). The 5-year survival of all patients was 28% , and of M 0 patients alone 37% . Although these ® gures are poor by today' s standards, they are consistent with published studies whose patients were enrolled during the same calendar period. Although most deaths occurred by 5 years, survival continued to fall beyond 10 years, which has implications for follow-up in future studies. Results. The local control (LC) rate at 5 years was 56% for all patients and for M0 patients analyzed separately. There was no difference in either LC or survival between the ® rst and second decades of the study. Prim ary site was a signi® cant determ inant of survival and local control, with better outcome for limb tumours compared to pelvic primaries. C hemotherapy also had a major effect on LC . Radiotherapy improved the probability of LC. Omission of radiotherapy, or a dose , 40 Gy, was ineffective. In the dose range 40± 66 Gy, there was no evidence of a dose± response relationship. K ey w ords: E wing' s sarcom a, loca l control, radiotherapy dose± response.

Sarcoma, 1999

Pur pose. Conservative treatment in the form of limited surger y and post-operative radiotherapy ... more Pur pose. Conservative treatment in the form of limited surger y and post-operative radiotherapy is controversial in hand and foot sarcomas, both due to poor radiation tolerance of the palm and sole, and due to technical difficulties in achieving adequate margins. This paper describes the local control and survival of 41 patients with soft tissue sarcoma of the hand or foot treated with conservative surgery and radiotherapy. The acute and late toxicity of m egavoltage radiotherapy to the hand and foot are described. The technical issues and details of treatment delivery are discussed. The factors in¯uencing local control after radiotherapy are analysed. Subjects. Eighteen patients had sarcomas of the hand and 23 of the foot. All patients received post-operative radiotherapy, the majority receiving a dose of 60 Gy in 2-Gy daily fractions using a two-phase treatment. Results . The acute and late toxicity of treatment were within acceptable limits. The actuarial 5-year overall survival of the whole patient group was 67.6% and the local relapse-free survival was 44% .The local control was similar in tumours of hand and foot, and in patients treated at ® rst presentation or relapse. D iscussion. Post-operative radiotherapy to the hand or foot appears to be a well tolerated treatment resulting in long-term local control in a signi® cant proportion of patients. The increased frequency of recurrence within the high-dose volume suggests the need for the use of higher total doses of radiotherapy.

Clinical Oncology, 1994

Well differentiated thyroid carcinoma has an excellent prognosis, with many patients achieving cu... more 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. 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.

Practical Management of Thyroid Cancer, 2006

World Journal of Surgical Oncology, 2007

Neuroendocrine tumours (NET) are tumours arising from neuroendocrine cells of neural crest origin... more Neuroendocrine tumours (NET) are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare. We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on 123I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy. These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.

Measurement of the protein-bound radioactive iodine level (PBI131) in the plasma of patients foll... more Measurement of the protein-bound radioactive iodine level (PBI131) in the plasma of patients following 131I-iodide administration for thyroid cancer has been re-examined in a retrospective study of 171 patient episodes. It is shown that whereas the previously used threshold value for the measurement at 6 days does not correlate well with the 3-day whole body scan, there is good agreement

Sarcoma, 1998

Purpose. Aggressive fibromatosis (AF) is an uncommon locally infiltrating benign disease of soft ... more Purpose. Aggressive fibromatosis (AF) is an uncommon locally infiltrating benign disease of soft tissue for which treatment comprises complete surgical resection. Radiotherapy can be given postoperatively if the margin is incompletely resected. If the tumour is inoperable radiotherapy provides an alternative treatment. Hormone therapy and cytotoxic chemotherapy have also been used for unresectable or recurrent disease. All treatment modalities carry an associated morbidity. We believe that the natural history of aggressive fibromatosis may include a period of stable disease without progression, during which time, treatment is not always necessary.Patients and methods. We present a retrospective review of 42 patients referred to the Royal Marsden Hospital between 1988 and 1995 with aggressive fibromatosis. Evidence of periods of stable disease and the relationship to delivered treatment was obtained from the case notes, including the natural history prior to referral to our instituti...

British journal of cancer, Jan 21, 2003

Treatment of differentiated thyroid cancer is a success of modern medicine with the use of radioi... more Treatment of differentiated thyroid cancer is a success of modern medicine with the use of radioiodine ((131)I). However, a significant proportion of thyroid cancers may be non-iodine avid. Thyroid tumours are known to express somatostatin receptors. Octreotide, an analogue of somatostatin, can be combined with a radioactive isotope, such as (111)In-DTPA(0) to visualise tumours with high concentrations of somatostatin receptors. We assessed 18 patients with histologically proven metastatic or locally recurrent non-iodine avid thyroid carcinoma to determine the usefulness of (111)In-DTPA(0) octreotide scintigraphy compared to conventional radiology in diagnosing sites of metastasis. The diagnosis of metastatic disease was made using conventional radiology and all had prospective scintigraphy using (111)In-DTPA(0)octreotide. Of the 18 patients, 14 had octreotide-positive scans. In eight, the octreotide scans identified the same sites of metastases as conventional radiology, that is, w...

European Journal of Cancer and Clinical Oncology, 1991

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more yea... more 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.

Nuclear Medicine Communications, 2004

This was a retrospective study to assess the efficacy and morbidity of high activity I therapy in... more This was a retrospective study to assess the efficacy and morbidity of high activity I therapy in patients with advanced differentiated thyroid carcinoma. From 1975 to 2003, 38 patients with locally advanced or metastatic differentiated thyroid cancer (16 follicular, 20 papillary, one Hurthle cell, one insular) were treated with high activity radioiodine therapy (9 GBq) as the cancers had previously not responded to standard activities (5.5 GBq). Cumulative total activities received ranged from 11.8 to 84.5 GBq (mean 29.4 GBq per patient). Staging at presentation showed pT4 and/or M1 disease in 27/38 of patients (71.1%). Moderate (grade 2) and poorly differentiated (grade 3) tumours were present in a total of 9/38 patients (23.7%). Outcomes were evaluated according to the results of I whole-body scans, serum thyroglobulin, radiological assessments and physical examination. Neither [18F]flurodeoxyglucose positron emission tomography (F-FDG PET) nor 99mTc sestamibi were available during this study. The mean duration of follow-up was 83 months. A complete response was observed in 7/38 patients (18.4%), progressive disease in 27/38 (71.1%) and stable disease in 4/38 (10.5%). The mean survival from initiation of high activity treatment was 36.6 months. For patients with lung disease the mean survival was 45 months, neck disease 38.9 months, bone disease 35 months and multiple sites was 30.9 months. Twelve patients died during follow-up (10 due to thyroid carcinoma). After high activity treatment, 9.7% of patients suffered grade 3 and 3.2% suffered grade 4 WHO haematological toxicity. Significant salivary gland morbidity was observed (30% dry mouth, 27% salivary swelling). Repeated treatment with high activity (9 GBq) I in patients with advanced differentiated thyroid carcinoma appears to be of no apparent benefit and may lead to late morbidity.

$Research paper thumbnail of Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation$

International Journal of Radiation Oncology*Biology*Physics, 2007

PURPOSE: To retrospectively determine rates of toxicity, freedom from local progression, and surv... more PURPOSE: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. METHODS AND MATERIALS: Between February 2001 and February 2005, 50 patients with a history of ...

European Journal of Surgical Oncology (EJSO), 1996

Fifty-one patients were treated with radiotherapy for loco-regional medullary thyroid cancer betw... more Fifty-one patients were treated with radiotherapy for loco-regional medullary thyroid cancer between 1960-1992. The actuarial overall survival at 5, 10 and 20 years was 69%, 52% and 30%, respectively. Patients were classified according to clinical stage (node-positive or -negative), post-operative histological residual disease status (none, microscopic or macroscopic) and dose of radiotherapy received. By univariate analysis, loco-regional recurrence-free survival was significantly longer for node-negative patients (P = 0.03). Patients who received at least 60 Gy over 6 weeks showed a trend towards improved local control (P = 0.23). The only significant variable by multivariate analysis for local recurrence-free survival was post-operative residual disease status (P=0.0005). The local control rate at 5 years was 100% for patients with no residual disease, 65% for those with microscopic tumour, and 24% for those with macroscopic residual disease. We conclude that there is a valuable role for radiotherapy in the management of patients with residual microscopic or macroscopic disease following surgery, as well as in those with inoperable disease.

European Journal of Nuclear Medicine, 1994

With the acknowledged problems associated with assessment of functioning thyroid mass and hence r... more With the acknowledged problems associated with assessment of functioning thyroid mass and hence radiation dose, our policy had been to give 75 MBq iodine-131 at 6-monthly intervals to patients with Graves' disease until they became euthyroid. Since positron emission tomography (PET) has been available at this hospital, the radiation dose to the thyroid has been calculated with an accuracy of-20%, the thyroid mass being determined from an iodine-124 PET scan. A dose-response study has been carried out on 65 patients who have received single or cumulative radiation doses of <80 Gy. The results show that patients who receive a low radiation dose (<20 Gy) at their first treatment have a high probability of remaining toxic at 12 months. In contrast, patients who receive higher radiation doses (>40 Gy) at their first treatment have a high probability of control. The probability of becoming euthyroid increases more rapidly with increasing radiation dose than the probability of becoming hypothyroid. Following this dose-response study, a new treatment protocol has been introduced. A 124I PET tracer study prior to 13II therapy will be performed to enable a prescribed thyroid dose of 50 Gy to be delivered to patients with Graves' disease. Further 131I therapy will only be considered if patients are still toxic at 12 months.

Clinical Nuclear Medicine, 2005

An 80-year-old woman was referred for a painless mass arising in right side of her neck of 4 mont... more An 80-year-old woman was referred for a painless mass arising in right side of her neck of 4 months&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; duration. Ultrasound revealed a multinodular goiter, but cytology confirmed a follicular carcinoma. Thyroid function was normal. Total thyroidectomy was performed with evidence of tumor infiltration into the strap muscles extending up to the right submandibular gland and right internal jugular vein, which was completely occluded. Radioiodine was considered as the treatment of choice postoperatively. This is an unusual case of SVC obstruction caused by tumor embolus diagnosed on I-131 scan.

Cancer Chemotherapy and Pharmacology, 1986

Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate o... more Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate of 38% in 42 patients. All these patients treated at The Royal Marsden Hospital plus 30 more (total 67) have now been analysed. Single doses of 5 or 8 g/m2 ifosfamide were given over 24 h by infusion in dextrose saline together with 400 mg/m2 or 600 mg/m2, respectively, of mesnum every 4 h to give a total of 9 doses. A diuresis of 200 ml/hour was maintained during therapy. Treatment was repeated 3-weekly. CR was seen in 6 and PR in 10 patients. More recently doxorubicin was added to ifosfamide therapy in an attempt to improve on these results. At first only 20 mg/m2 doxorubicin was given but this was escalated to 40 mg/m2 and 60 mg/m2. Mesna has been given in higher dosage (5 g/m2 over 24 h), but otherwise the schedule is as above. In all 60 patients have been treated and most are now evaluable for response. Encephalopathy has been seen with both regimens. The incidence and patient characteristics are reported.