PubMed Health⌕ Search

Biomedical subjects

C Harmer

Publications and source records attributed to C Harmer.

At least 19 recordsLinked to original sources
PubMed2005

Differentiated thyroid carcinoma with distant metastases at presentation: prognostic factors and outcome.

BACKGROUND: Differentiated thyroid cancer (DTC) presenting with distant metastases is uncommon. Prognostic factors that affect survival remain unclear. AIM: To evaluate factors influencing the survival of patients with DTC presenting with distant metastases. METHOD: A retrospective study of 111 patients (62 F, 49 M) with DTC who presented with distant metastases (M1) treated at the Royal Marsden Hospital from 1940 to 2002. RESULTS: The median follow-up of living patients was 3.9 years (0.3-48) with a 10-year cause-specific survival rate of 31%. Histology identified 46 papillary, 60 follicular and five Hürthle cell cancers. Sites of metastases comprised 54 lung (49%), 27 bone (24%), 21 multiple sites (19%) and nine with other single sites affected (8%). Near-total, total or completion thyroidectomy was performed in 56% of patients, radioiodine ablation in 76% and radioiodine therapy in 67%. External beam radiotherapy was given to 12 patients and the same number received chemotherapy. Univariate analysis was performed with cause-specific survival as the main outcome measure. Age over 70, poorly differentiated tumours and Hürthle cell cancers were associated with worse outcomes (P < 0.01). Patients with multiple organ metastases had a worse survival (P = 0.02). Radical surgery did not significantly improve outcome compared to more conservative forms of surgery (subtotal thyroidectomy, hemi-thyroidectomy or lobectomy) but patients receiving radioiodine ablation and therapy had improved survival (P < 0.01). Multivariate analysis identified age over 70, poorly differentiated tumours and Hürthle cell variant to be the only independent factors associated with worse outcome (P < 0.01). Treatment in the 1991-2002 era was associated with an improved survival compared to all previous decades (P = 0.009). CONCLUSIONS: Patients with DTC presenting with distant metastases have a worse outcome if aged over 70, have poorly differentiated tumours or have Hürthle cell variant. Despite their unfavourable prognosis, a dramatic improvement in survival was observed in the most recent era (1991-2002).

Adenocarcinoma↗
PubMed2004

Familial medullary thyroid cancer: clinical aspects and prognosis.

OBJECTIVE: To assess clinical features and long-term results of treatment of familial medullary thyroid carcinoma (FMTC). DESIGN: Retrospective analysis of all patients with familial forms of MTC diagnosed between 1949-2000 and treated in our unit. RESULTS: Fifty five patients (25 males, 30 females) were identified with at least two first-degree relatives affected by medullary thyroid cancer; 26 were classified as MEN 2A, 1 as MEN 2B and 28 as FMTC. Median age at diagnosis was 35 years (MEN 2A), 25 (MEN 2B) and 47.5 (FMTC). Median follow-up was 9 years (range: 4-24). Total or near-total thyroidectomy was performed in all patients and 11 received adjuvant external beam radiotherapy. Cause specific survival was 89% at 10 years and 77% at 20 years for MEN patients, 51% and 32% for those with sporadic MTC, and 46% and 26% for those with FMTC. In multivariate analysis, factors predicting survival were presence of metastases, nodal status and age at diagnosis. CONCLUSIONS: Improved survival rates associated with familial types of MTC can be accounted for by the earlier stage at which disease is detected and the younger age at presentation. These observations emphasize the need for early detection in those at risk.

Adult↗
PubMed2004

Treatment of uterine sarcoma at the Royal Marsden Hospital from 1974 to 1998.

AIMS: Uterine sarcomas are rare tumours with histopathological diversity characterised by rapid clinical progression and poor prognosis. Optimal management consists of complete surgical removal, but is not clear whether adjuvant radiotherapy improves the prognosis. The aim of this retrospective study was to investigate the clinical and histopathological characteristics together with treatment and outcome of patients with uterine sarcomas. MATERIALS AND METHODS: Records of 100 patients treated at the Royal Marsden Hospital between 1974-1998 were reviewed: 47 leiomyosarcoma (LMS), 30 mixed mullerian tumours (MMT), 19 endometrial stromal sarcoma (ESS), one haemangiopericytoma, one rhabdomyosarcoma and two unspecified sarcoma. There were 50, 11, 21 and 18 patients with stage I, II, III and IV carcinoma, respectively. Thirty-four patients had high-grade disease. Fifty-three patients received adjuvant radiotherapy. The median age was 55 years (range: 18-83 years). The median follow-up was 54 months (range: 3 months to 27 years). RESULTS: The overall 3, 5 and 10-year survival rates were 39%, 30% and 20%, respectively. Survival was significantly related to stage (P = 0.002), grade (P = 0.003) and histological type (P = 0.04), but not to use of postoperative irradiation. At 3 years, the survival rate was 42% for LMS, 22% for MMT and 63% for ESS. Local recurrence rate, however, was significantly improved after adjuvant radiotherapy with dose higher than 50 Gy (P = 0.001). CONCLUSIONS: Prognosis is dependent on histopathological sub-type, grade and tumour stage. Adjuvant radiotherapy decreases local recurrence rate, but without significant impact on survival.

Adolescent↗
PubMed2004

A phase II study using retinoids as redifferentiation agents to increase iodine uptake in metastatic thyroid cancer.

AIMS: Radio-iodine is effective in treating metastatic differentiated thyroid cancers. In 20% of cases, however, these tumours fail to take up radio-iodine, and treatment options are then limited. Failure of iodine uptake might be reversible using redifferentiating agents. Retinoids redifferentiate a variety of cell types and increase iodine uptake in thyroid tumour cells in vitro. The aim of this study was to assess whether oral isotretinoin could increase radio-iodine uptake in patients with iodine-uptake-negative metastatic thyroid cancer. METHODS: Patients who had iodine-uptake-negative metastatic papillary or follicular thyroid cancers were selected from the thyroid database at The Royal Marsden Hospital and enrolled to an open-label, non-randomised phase II trial. Sites of metastatic disease were assessed using computed tomography or magnetic resonance imaging, and absence of iodine uptake was confirmed using a diagnostic radio-iodine scan before study entry. In eligible patients, isotretinoin was prescribed at 1.5 mg/kg/day orally for 8 weeks. Response was assessed within 2 weeks of completing treatment with repeat radio-iodine scan. All patients were reviewed every 2 weeks during treatment for assessment of toxicity. RESULTS: Sixteen patients were treated with isotretinoin between January 2001 and July 2002: nine with metastatic papillary thyroid cancer, five with metastatic follicular cancer and two with Hurthle cell carcinoma. Median age was 57 years. All patients tolerated 8 weeks of oral isotretinoin. Mucocutaneous side-effects and minor changes in biochemical or lipid profiles were documented in most patients. In one patient, radio-iodine uptake increased after retinoid administration; however, this was not large enough to permit a significant dose of iodine to be given to sites of metastatic disease. In the other 15 patients, no radio-iodine uptake was documented. CONCLUSION: Treatment with isotretinoin does not reliably increase radio-iodine uptake in patients with metastatic thyroid cancer. This treatment alone does not enable radio-iodine to be used for further treatment.

Adenocarcinoma, Follicular↗
PubMed2004

Metastases to the thyroid gland: the Royal Marsden experience.

AIM: A review of patients seen at the Royal Marsden Hospital with metastases to the thyroid gland. METHOD: Experience reported on 15 patients that were seen at our institution between 1985 and 2002. RESULTS: The most common site of origin was the kidney (4/15). Ages ranged between 26 and 76 years. Twelve presented with a neck mass. Most had metastatic disease elsewhere at the time of presentation (9/15). Diagnosis was made by fine needle aspiration cytology (5), tru-cut biopsy (1), or surgery (9); surgery comprised total thyroidectomy (3), subtotal thyroidectomy (3) or lobectomy (3). Radiotherapy resulted in disease stabilisation in three patients. Chemotherapy was used to treat local recurrence in two patients post-operatively. The interval from diagnosis of the primary tumour to thyroid metastasis varied from 0 months to 15 years. Thyroid gland metastasis was the initial manifestation of metastatic disease in five patients. Five patients are alive, with one disease free 7 years following resection of the thyroid metastasis. CONCLUSIONS: Thyroid metastases are clinically rare, with the kidney the most common primary site of origin. They usually occur when there are metastases elsewhere, sometimes many years after diagnosis of the original primary tumour. Surgical resection of an isolated metastasis may result in prolonged disease-free survival. Radiotherapy and chemotherapy may be of value in specific situations.

Adult↗
PubMed2004

Breast cancer: improving outcome following adjuvant radiotherapy.

In the treatment of early breast cancer adjuvant irradiation improves local control following both mastectomy and breast-conserving surgery. For women at high risk of relapse it also increases survival. Breast radiotherapy is usually given using simple planning techniques and serious morbidity is unusual. The greatest concern following adjuvant breast irradiation is of an increase in cardiovascular mortality after 15-20 years. New techniques of breast irradiation including conformal radiotherapy and intensity-modulated radiotherapy (IMRT) have been shown to reduce cardiac and lung irradiation. In addition, improved dosimetry within the breast may improve both local control and cosmesis. To replace current radiotherapy techniques with those requiring more complex planning would demand an increase in resources including both machinery and staff. In this review we outline the indications and benefits of breast radiotherapy along with the planning process. Technical advances are discussed within the context of improving outcome at a time of limited national resources.

Breast Neoplasms↗
PubMed2004

The role of nuclear medicine in the diagnosis of cancer of unknown origin.

Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.

Biomarkers, Tumor↗
PubMed2003

Uterine sarcoma: twenty-seven years of experience.

PURPOSE: A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. PATIENTS AND METHODS: One hundred forty-one patients (median age: 56 years, range: 19-85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed müllerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. RESULTS: At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p = 0.02), grade (p = 0.003), stage (p = 0.007), and age (p = 0.02). Multivariate analysis demonstrated significant prognostic values for stage (p = 0.02) and histology (p = 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant (p = 0.001) in reducing local recurrence. CONCLUSIONS: Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy.

Adult↗
PubMed2003

Indium-111-labelled octreotide scintigraphy in the diagnosis and management of non-iodine avid metastatic carcinoma of the thyroid.

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, were concordant. In nine patients, conventional radiology showed more extensive disease than revealed on the octreotide scans. In one patient with widespread bone metastases, octreotide gave a more detailed assessment of metastatic disease than conventional radiology. These data indicate that (111)In-DTPA(0)octreotide imaging for patients with non-iodine avid carcinoma of the thyroid may be a useful diagnostic and staging tool. One patient with Hurthle cell carcinoma metastatic to bone and a positive octreotide scan has been treated with (90)yttrium-labelled octreotide.

Antineoplastic Agents, Hormonal↗
PubMed2002

Prognosis for fertility and ovarian function after treatment with radioiodine for thyroid cancer.

The aim of this study was to review the outcome of ablative radioiodine treatment on ovarian function in young women treated for differentiated thyroid carcinoma. Of 1398 patients with differentiated thyroid cancer, 496 were women under the age of 40 at the time of diagnosis who had received radioiodine therapy. Of these, 322 received a single 3 GBq ablation dose of radioiodine while the remainder received subsequent treatment with (131)I with a cumulative activity of 8.5-59 GBq for residual, recurrent, or metastatic disease. Transient amenorrhoea or menstrual irregularities lasting up to 10 months were experienced in 83 patients (17%). No cases of permanent ovarian failure were recorded. There were 427 children born to 276 women; only one patient wishing to achieve a successful pregnancy outcome has been unsuccessful. Four premature births and 14 miscarriages occurred but no congenital abnormalities were reported. The risk of permanent damage to the ovaries after ablative radioiodine treatment appears to be low and patients can be reassured they can have normal pregnancies after this treatment.

Adolescent↗
PubMed2001

Improvements in target coverage and reduced spinal cord irradiation using intensity-modulated radiotherapy (IMRT) in patients with carcinoma of the thyroid gland.

BACKGROUND AND PURPOSE: External beam radiotherapy for thyroid carcinoma poses a significant technical challenge as the target volume lies close to or surrounds the spinal cord. The potential of intensity-modulated radiotherapy (IMRT) to improve the dose distributions was investigated. MATERIALS AND METHODS: A planning study was performed on patients with thyroid carcinoma. Plans were generated to irradiate the thyroid bed alone or to treat the thyroid bed and the loco-regional lymph nodes in two phases. Conventional plans with minimal beam shaping were compared to three-dimensional conformal radiotherapy (3DCRT) and inverse-planned IMRT plans to assess target coverage and normal tissue sparing. IMRT techniques were optimized to find the minimum number of equispaced beams required to achieve the clinical benefit and a concomitant boost technique was explored. RESULTS: For the thyroid bed alone and the thyroid bed plus loco-regional lymph nodes, conventional and conformal techniques produced low minimum doses to the planning target volume (PTV) if spinal cord tolerance was respected. 3DCRT reduced the irradiated volume of normal tissue (P=0.01). IMRT plans achieved the goal dose to the PTV (P<0.01) and also reduced the spinal cord maximum dose (P<0.01). IMRT, using a concomitant boost technique, produced better target coverage than a two-phase technique. For both the two-phase and concomitant boost techniques, IMRT plans with seven and five equispaced fields produced similar dose distributions to nine fields, but three fields were significantly worse. CONCLUSIONS: 3DCRT reduced normal tissue irradiation compared to conventional techniques, but did not improve PTV or spinal cord doses. IMRT improved the PTV coverage and reduced the spinal cord dose. A simultaneous integrated boost technique with five equispaced fields produced the best dose distribution. IMRT should reduce the risk of myelopathy or may allow dose escalation in patients with thyroid cancer.

Humans↗
PubMed2001

The role of radiotherapy in the management of elevated calcitonin after surgery for medullary thyroid cancer.

Among 139 patients with medullary thyroid cancer (MTC) treated at the Royal Marsden Hospital between 1957-1998, 51 had persistently elevated calcitonin levels after initial surgery in the absence of clinically or radiologically demonstrable residual disease. Of these, 24 were treated with radiotherapy because of advanced local disease at presentation; this resulted in normalization of calcitonin in only 1 patient, although 10 remained free of clinical recurrence. Surveillance alone was used in the remaining 27 patients, of whom 8 (30%) remained free of overt disease. Local relapse rate was significantly lower after radiotherapy (29% vs. 59%) but there was no significant difference in 10-year survival between the two groups (72% vs. 60%). In view of this favorable long-term survival of patients with elevated calcitonin on observation, we cannot recommend the routine use of radiotherapy. However, it does appear to have a role in those presenting with more advanced disease to reduce the incidence of loco-regional relapse.

Adult↗
PubMed2000

Thyroid cancer in children: the Royal Marsden Hospital experience.

The first child with well-differentiated thyroid cancer treated at the Royal Marsden Hospital presented in 1917. Since that time 30 children under the age of 16 years have been treated over a period during which many new treatments have been introduced. We have reviewed their management and outcome. The median follow-up is 22.5 years (range: 1-66). The median time to recurrence was 7 years (range: 2-44). There were events up to 44 years after presentation. The risk of recurrence was higher in children aged 10 years or younger [HR 3.45, 95% CI (1.04-11.11) P = 0.03]. Thyroid stimulating hormone (TSH) suppression was the only intervention to be shown to reduce the recurrence rate [HR 11, 95% CI (2.27-50) P = 0.0003]. The median overall survival is 53 years. The only presenting feature predictive of poorer survival was the presence of metastases (HR 28.96, 95% CI 2.51-334, P < 0.001). Patients who developed recurrence had a higher risk of death (HR 9.90, 95% CI 0.98-100, P = 0.02) and a shorter median survival of 30 years. No therapeutic intervention could be shown statistically to impact on survival. Our recommendation for treatment is total or near-total thyroidectomy for all patients and radioiodine ablation for all except those with early T stage node-negative disease aged over 10 years. Modified neck dissection is recommended for children with clinically positive neck nodes and TSH suppression for all. Follow-up with serial thyroglobulin measurement should be lifelong.

Adolescent↗
PubMed2000

Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival.

AIMS: The aims of this study were to assess the long-term results of treatment of medullary thyroid carcinoma (MTC) and to define prognostic factors. METHODS: Retrospective analysis of all patients diagnosed with MTC between 1949 and 1998 and treated in our unit was carried out. RESULTS: One hundred and sixty-two patients (87 females, 75 males) were identified; 52 patients (32%) had familial disease. Median follow-up was 9 years (2-20 years). The majority of patients (90%) presented with a thyroid mass or enlarged neck nodes. Total/subtotal thyroidectomy was performed in 129/18 patients respectively; 45 patients also underwent neck dissection while 52 had simple nodal excision. External beam radiotherapy (RT) was given to 76 patients with advanced disease at presentation. Overall survival was 72% at 5 years and 56% at 10 years; case-specific survival was very similar. In multivariate analysis the factors which were significant predictors of survival were age at diagnosis, extent of nodal disease, extent of surgery and metastases at presentation. RT significantly reduced local relapse in patients with ipsilateral nodal disease. CONCLUSIONS: MTC may be associated with prolonged survival; the best prognosis occurs in young patients undergoing total thyroidectomy and neck dissection. External beam RT significantly reduces local relapse in patients with limited nodal disease.

Adolescent↗
PubMed2000

Recurrent differentiated thyroid cancer without elevation of serum thyroglobulin.

Thyroglobulin (Tg) is a reliable tumor marker in patients with well-differentiated thyroid cancer (WDTC). We identified 11 patients who had undetectable serum Tg and no thyroglobulin antibody (TgAb) in the presence of clinical disease. Three had residual disease after ablation of the thyroid by surgery plus radioiodine and 8 relapsed after a disease-free interval. Histologic review confirmed that 7 of the tumors were papillary carcinomas and 4 were follicular carcinomas. Immunohistochemical staining for Tg was positive in 6 of 7 papillary and in 3 of 4 follicular carcinomas. There were no identifiable histologic or clinical features that could be used to predict further patients who may relapse with absence of this serum marker. Negative serum Tg did not appear to be an adverse prognostic feature. During follow-up, measurement of Tg and TgAb should be supplemented by radioiodine scanning and radiological imaging in patients in whom recurrence is likely or suspected.

Adenocarcinoma, Follicular↗
PubMed2000

Effective treatment of a patient with a high-grade endometrial stromal sarcoma with an accelerated regimen of carboplatin and paclitaxel.

The rarity of endometrial stromal sarcoma (ESS) and its poor response to treatment provides fertile ground for investigational therapies. An accelerated regimen of carboplatin and paclitaxel is investigated. A patient with a recent history of treated tuberculosis of the lung represented with infertility and acute abdominal pain from suspected fibroids, and underwent a laparotomy with a diagnosis of a high-grade ESS. A novel therapeutic approach using a regimen of carboplatin and paclitaxel with the reinfusion of filgrastim-mobilized peripheral blood progenitor cells is described. A partial response was observed following six cycles of chemotherapy. Grade IV thrombocytopenia occurred after the last cycle, with recovery prior to pelvic radiotherapy. The patient remained well 1 year post-diagnosis. High-grade ESS is responsive to combination chemotherapy with paclitaxel and carboplatin, and requires further evaluation. The use of an accelerated regimen may also have contributed to the response and this question awaits randomized trials.

Adult↗
PubMed1999

Phase II evaluation of high dose accelerated radiotherapy for anaplastic thyroid carcinoma.

BACKGROUND AND PURPOSE: Anaplastic thyroid cancer responds poorly to conventional radiotherapy and prognosis in the absence of effective chemotherapy is dismal. The median survival following diagnosis is only 4 months and the majority of patients die with uncontrolled local disease. This study describes the use of accelerated radiotherapy aiming to improve local response in patients with anaplastic thyroid carcinoma. Toxicity was assessed prospectively. PATIENTS AND METHODS: Seventeen patients with anaplastic thyroid carcinoma were treated and assessed for both outcome and treatment toxicity. Eight further patients with primary carcinomas arising in the neck were also treated with this protocol but were assessed for treatment toxicity only. Patients were treated twice daily, 5 days a week, to a total dose of 60.8 Gy in 32 fractions over 20-24 days in two or three phases. RESULTS: Three patients with anaplastic carcinoma demonstrated a complete clinical response and seven patients achieved a partial response. Five patients had stable disease and two patients died before radiotherapy was completed. Toxicity from oesophagitis and dysphagia was high with 10 patients requiring intravenous fluids or nasogastric tube feeding. CONCLUSION: This approach improved the response rate to radiotherapy but toxicity was unacceptable. A modified accelerated radiotherapy protocol is being explored.

Adult↗