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Biomedical subjects

C Harmer

Publications and source records attributed to C Harmer.

At least 37 records · Page 2Linked to original sources

Evaluation of breast cancer incidence: is the increase due entirely to mammographic screening?

OBJECTIVES: To examine the trends in the incidence rates of breast cancer in a population with mammographic screening and in the unscreened women within that population. METHODS: Data consisted of incident cases of breast cancer notified to the Victorian Cancer Registry in Victoria, Australia, between 1988 and 1996 and cases detected in the population-based BreastScreen Program. These data were grouped by age (25-39, 40-49, 50-59, 60-69 and > or = 70 years of age) and size of tumor (< or =10 mm, > 10-< or =15 mm, and > 15 mm). Poisson regression modeling was used to examine trends by age, tumor size, calendar year and availability of screening. RESULTS: The incidence rate of breast cancer in the total population increased between 1988 and 1996. The greatest increase was seen after 1993 when population-based screening became available. In unscreened women, modeling demonstrated a statistically significant (p < 0.01) 1.5% annual increase in the incidence rate. The annual increase in this rate differed by size of tumor and was approximately 8% (p < 0.01) for small tumors (< or = 10 mm) but not significant for tumors > 10 mm. The greatest increase was in small tumors for women > or = 50 years of age. CONCLUSION: The incidence of breast cancer has increased since population-based mammographic screening was introduced in 1994. The rate in unscreened women also showed a significant increase. This was greatest in small tumors for women > or = 50 years of age. Whether this will translate into an increase in mortality is uncertain and long-term monitoring is required to determine if cohort and period effects impact on the underlying incidence of breast cancer in Victoria.

Adult↗

Thyroglobulin antibodies in differentiated thyroid cancer.

A retrospective review of patients with differentiated thyroid cancer (DTC) who were seen between 1984 and 1996 at the Royal Marsden Hospital identified 40 patients with serum thyroglobulin antibodies (TgAb). These antibodies can interfere with the immunoradiometric assay for serum thyroglobulin (Tg) used at this hospital, with resulting underestimation of the Tg level. A review of the case notes was carried out to ascertain the clinical significance of TgAb. The median follow-up from diagnosis of DTC was 26 months (range 3-401). The median age at diagnosis of DTC was 50 years (range 13-83). Patients were grouped according to the TgAb titre (high titre: TgAb >1/100, n = 28; low titre TgAb <1/100, n = 12). Thirteen patients relapsed, 11 in the high titre group and two in the low titre group. Sites of recurrence were: neck (n = 9), lung (n = 5), bone (n = 4) and brain (n = 2). No patient in the high titre group showed an elevated Tg with recurrence. One patient in the low titre group showed a Tg response to recurrence. Overall, the Tg assay failed to detect 92% of recurrences. Eight patients in the high titre group developed TgAb, apparently in response to tumour progression. In a third patient in the low titre group, the TgAb also acted as a 'tumour marker'. Thus, overall TgAb acted as a tumour marker in nine of the 40 (22.5%) patients in whom it was detected, and in nine of the 470 (1.9%) patients on follow-up during this time period. The overall survival of the whole group was 69% at 10 years. For patients with papillary carcinoma (n = 34) overall survival was 78% at 10 years. Laboratories should report routinely the presence of TgAb, with a caution indicating the direction of possible error (which depends on the assay used). Clinicians should appreciate that Tg measurements are unreliable in the presence of TgAb and that the development of TgAb can indicate active tumour.

Adenocarcinoma, Follicular↗

Failure of TSH rise prior to radio-iodine therapy for thyroid cancer: implications for treatment.

We describe three patients with well-differentiated thyroid carcinoma in whom no rise in serum thyroid-stimulating hormone (TSH) was observed after the discontinuation of thyroid hormone. In one patient, TSH deficiency was due to panhypopituitarism secondary to the empty sella syndrome. This patient initially failed to respond to (131)I but was subsequently given purified porcine TSH prior to further (131)I therapy. This resulted in a significant fall in the thyroglobulin level. In two further patients, TSH levels were suppressed by functioning follicular thyroid cancer. There was an unexpectedly good (131)I uptake by metastases and they responded clinically. The failure of TSH levels to rise after thyroid hormone withdrawal should prompt investigation of the pituitary-thyroid axis. In patients with hypopituitarism, exogenous TSH is recommended, to increase the (131)I uptake. In contrast, when TSH is suppressed by functioning tumour, radio-iodine treatment may still be effective.

Adenocarcinoma, Follicular↗

Squamous cell carcinoma of the thyroid: outcome of treatment in 16 patients.

AIMS AND METHODS: Squamous cell carcinoma of the thyroid is very rare and has a poor prognosis. Treatment and outcome were retrospectively analysed in a consecutive series of 16 patients treated at the Royal Marsden Hospital, with the aim of establishing guidelines for management. RESULTS: Twelve of the 16 patients had locoregional disease only at presentation and four had distant metastases. Eight of the 16 underwent surgery and four were given post-operative radiotherapy. Radiotherapy alone was used in six patients unsuitable for surgery. Median survival was 16 months. There were three long-term survivors; each had localized disease treated with surgery and post-operative radiotherapy. Patients treated with surgery alone all developed local recurrence. Two of six patients treated with radiotherapy alone had a partial response but all subsequently developed progressive local disease. Chemotherapy was used in two patients with no response. CONCLUSIONS: Long-term survival is possible if disease is diagnosed early and is completely resected. Surgery should be followed by radical dose radiotherapy.

Adult↗

Good prognosis in thyroid cancer found incidentally at surgery for thyrotoxicosis.

An analysis of the outcome of thyroid carcinoma incidentally discovered in patients undergoing surgery for hyperthyroidism is presented. Among 986 patients with differentiated thyroid cancer, 23 had presented with symptoms and signs of hyperthyroidism. Graves' disease was diagnosed in 11, multinodular goitre in eight and toxic adenoma in four. Following thyroidectomy, histology revealed papillary (18), follicular (four) and Hurthle cell (one) carcinoma. Tumour size ranged from 4 mm to 5.5 cm, multifocality was detected in three patients, and lymph node involvement in one. Two patients (one with associated Graves' disease, one with multinodular goitre) relapsed locally and required further surgery; one developed distant metastases and died 7 years after initial presentation. Two patients died of unrelated causes; the remaining 20 patients are alive and well with a median follow-up of 16 (1-34) years. Differentiated thyroid cancer found incidentally at surgery for hyperthyroidism has a good prognosis.

Adult↗

Management of differentiated thyroid cancer diagnosed during pregnancy.

OBJECTIVE: To assess the outcome of thyroid cancer diagnosed during pregnancy. DESIGN: Retrospective analysis of patients diagnosed between 1949 and 1997 with thyroid cancer presenting during pregnancy. RESULTS: Nine women with a median age of 28 years were identified. A thyroid nodule was discovered by the clinician during routine antenatal examination in four cases, the remainder had noted a lump in the neck. In all patients, the nodule was reported to almost double in size during the pregnancy. One patient underwent subtotal thyroidectomy during the second trimester; eight were operated on within 3 to 10 months from delivery. Total thyroidectomy was performed in five and subtotal thyroidectomy in four. All tumours were well differentiated and ranged in size from 1 to 6 cm. OUTCOME: The median follow-up was 14 years (5-31 years). One patient relapsed locally requiring further surgery. One patient developed bone metastases dying 7 years after presentation; her planned treatment had been delayed because of an intervening pregnancy. Eight of the original cohort of patients are currently disease free. CONCLUSIONS: Differentiated thyroid cancer presenting in pregnancy generally has an excellent prognosis. When the disease is discovered early in pregnancy, surgery should be considered in the second trimester but radioiodine scans and treatment can be safely delayed until after delivery. In all cases, treatment should not be delayed for more than a year.

Adult↗

Thyroglossal duct carcinoma: presentation and management, including eight cases reports.

Although thyroglossal duct cysts represent a common developmental abnormality of the thyroid gland, malignant transformation is rare and occurs in only 1%. This article describes eight patients who were referred to the Royal Marsden Hospital between 1956 and 1991. There were five males and three females, aged from 14 to 71 years (mean 44.6). There were seven papillary carcinomas and one follicular carcinoma. Patients were followed for between 6 and 41 years (mean 16.5). Management comprised: surgical excision only in four patients; surgical excision plus thyroidectomy followed by radioiodine in three; and radioiodine following only biopsy in one patient with lingual thyroid carcinoma. Multifocal carcinoma of the thyroid was found in one patient and a single focus of carcinoma in the thyroid gland in another; lymph node metastases were found in only one patient. There was no history of previous exposure to ionizing radiation.

Adenocarcinoma, Follicular↗

Radiotherapy planning techniques for thyroid cancer.

External beam radiotherapy has a role in each histological type of thyroid cancer. For treatment confined to the thyroid bed, an antero--oblique wedged pair of beams is simple to apply. More frequently, however, the volume needs to include both sides of the neck and adequate dose must be given down to the level of the suprasternal notch, precluding use of lateral fields. Thus, anterior and posterior fields are usually necessary, extending from the tips of the mastoid processes or hyoid down to the carina and laterally to include both sides of the neck and supraclavicular fossae. The mandible and infraclavicular portions of both lungs are shielded, but there is no midline lead in the phase one volume. A mid-plane dose of 46 Gy given in 23 daily fractions results in an acceptable early radiation reaction and will avoid late damage to the spinal cord. Because of considerable variation of interplanar distance along the length of the volume, a lateral simulator film should be taken to determine the maximum cord dose. For most patients, a three-dimensional CT planned phase two volume will be required and should be determined prior to completing phase one. The optimum beam arrangement, usually incorporating conformal beam shaping assisted by use of a multileaf collimator, should avoid further dose to the cord. If there is additional dose to the spinal cord, this phase can be introduced before 46 Gy is reached.

Adenocarcinoma, Follicular↗

Thyroid cancer: a review of treatment and follow-up.

The importance of thyroid cancers far exceeds their frequency, since they are uncommon tumours accounting for only 1% of all malignancies and for even smaller proportion of cancer deaths (0.2%). A variety of distinct tumour types arise in the thyroid gland, with variable natural histories resulting from different rates of growth and biological aggressiveness. The long natural history of the majority of thyroid neoplasms imposes a commitment for long-term follow-up and stresses the importance of planning treatment so as to avoid delayed complications that impair the quality of life of patients. The management of thyroid cancer is multidisciplinary, requiring consultation and active intervention by surgeons, endocrinologists and radiotherapists. Surgery is of paramount importance in the successful eradication of the tumours while radioiodine offers a unique therapeutic approach. Treatment must be strongly influenced by consideration of prognostic variables.

Adenocarcinoma, Follicular↗

The significance of MALT histology in thyroid lymphoma: a review of patients from the BNLI and Royal Marsden Hospital.

Data from a series of 45 patients with Stage I and II non-Hodgkin's lymphoma (NHL) of the thyroid gland were analysed retrospectively to determine the incidence and prognostic significance of histopathological features of tumour origin from mucosa associated lymphoid tissue (MALT). The overall 5- and 10-year cause specific survival from NHL for the series was 79%. Evidence of tumour origin from MALT was the only significant prognostic factor for overall survival identified by multivariate analysis of the series (P < 0.01). A total of 31 (69%) tumours showed such evidence, the cause specific patient survival from NHL at 5 and 10 years being 90% compared with only 55% at 5 years for the 14 patients without such evidence. For patients given initial treatment with radiotherapy alone, those with evidence of tumour origin from MALT had a relatively low relapse rate and a relatively high success rate from salvage therapy, compared with a relatively high relapse rate and negligible success from salvage therapy in those without evidence of such tumour origin.

Adolescent↗

Chemodectoma of the head and neck: results of treatment in 84 patients.

Eighty-four patients with chemodectoma of the head and neck presented to the Royal Marsden Hospital between 1949 and 1985. For tumors arising at the skull base (glomus jugulare and glomus tympanicum) 46 were treated with radiotherapy alone resulting in an actuarial local control rate of 73% at 25 years; 13 were treated with surgery plus radiotherapy with no recurrences during a median follow-up of 9 years; 4 had surgery alone but all recurred by 7 years. For tumors of the soft tissues of the neck (carotid body and glomus vagale) 13 were treated with surgery alone with an actuarial control rate of 54% at 15 years; 4 were treated with radiotherapy which resulted in local control at 1, 2, 8 and 11 years; and one patient who received both surgery and radiotherapy remained controlled at 1 year. Although comparison between radiotherapy and surgery in terms of tumor control is not simple, the case is argued for more frequent use of radiotherapy at all sites. This case is strengthened by minimal morbidity from radiotherapy in doses which appear effective: in the range of 45-50 Gy in 25 daily fractions over 5 weeks.

Adult↗

Intra-arterial adriamycin, conventionally fractionated radiotherapy and conservative surgery for soft tissue sarcomas.

Thirteen patients with soft tissue sarcomas were treated with a combination of intra-arterial Adriamycin, conventionally fractionated radiotherapy (2 Gy per day), and conservative surgery (trimodal therapy). Severe acute complications occurred in 10 patients: 3 brachial artery thromboses, 6 delayed wound healing, 4 wound infections, and 3 cases of necrosis of the skin plus subcutaneous tissues. Three patients have developed local recurrence. Five patients are alive, 4 of whom are disease-free, and the median follow up time of surviving patients is 56 months. One has significant impairment of limb function due to joint ankylosis. An additional 2 patients were treated with intra-arterial Adriamycin and conservative surgery for local recurrence after previous surgery and radiotherapy; both died of subsequent metastatic disease, one having a further local recurrence. One patient with multifocal angiosarcoma was treated with intra-arterial Adriamycin and radiotherapy but no surgery, and is alive free of disease 49 months later. The combination of radiotherapy and intra-arterial Adriamycin with surgery resulted in significant acute toxicity. This small study has not demonstrated any improvement in local control compared with that expected with conservative surgery and radiotherapy alone.

Adult↗

High dose hyperfractionated radiotherapy in the treatment of extremity soft tissue sarcomas.

A hyperfractionated radiotherapy schedule has been evaluated in the treatment of 29 adults with limb or limb girdle soft tissue sarcomas. The objective was to increase the total administered dose and possibly improve local control, without increasing late normal tissue damage. Twice daily 1.25 Gy fractions (with a minimum interval of 6 h) have been given over 5 to 6 weeks to 12 patients pre-operatively, 10 post-operatively and 7 palliatively. Five patients received 62.5 Gy in 5 weeks pre-operatively and 3 palliatively. Nineteen of the remaining 21 patients received 75 Gy in 6 weeks with a field size reduction after 5 weeks. Sixteen of 29 tumours were situated in the thigh and only 2 were in the upper limb. Twenty were of high grade. The mean tumour size of those treated radically was 13.1 cm (range 5 to 40 cm). Sixteen patients (76%) given 75 Gy developed moderate or severe skin erythema maximal at 5 weeks. Despite the large field sizes used (mean phase one of 34.5 cm, and phase two of 22.8 cm) only 2 patients failed to complete the planned treatment because of the severity of these reactions. Two other patients developed partial wound breakdowns after the end of treatment--both healing spontaneously. Fourteen patients developed an area of moist desquamation--11 mild, 2 moderate and one severe. There have been four late wound breakdowns requiring surgical intervention; all have since healed well. The median follow up is short at 556 days. Ten of 19 evaluable patients have developed moderate/severe induration, 5/19 mild and 4/19 none.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of extremity soft tissue sarcomas with surgery and radiotherapy.

The results of treatment with a combination of surgery and radiotherapy of 102 patients with nonmetastatic extremity soft tissue sarcoma are reported. Seventy-nine patients were previously untreated and 23 had locally recurrent disease. Sixty-six tumours were situated in the lower limb and 16 in the limb girdles. Fifty-nine were high grade lesions, and 64 were over 5 cm in length. Surgical clearance was "good" (wide or radical) in only 34 cases. Sixty-eight patients received post-operative irradiation, 23 pre-operative irradiation and 11 both pre- and post-operative radiotherapy. Seventeen patients subsequently developed local recurrence and 9 of these remain disease-free after further surgery. Actuarial 5 year local control and disease-free survival rates for new cases were 87 and 65.4%; and for previously recurrent cases these figures fell to 75 and 54.8%. Following a univariate analysis of patient, tumour, surgical and radiotherapeutic factors only previous local recurrence (p less than 0.1 greater than 0.05) was found to significantly increase the risk of further local relapse. Multivariate analysis found high tumour grade [relative risk (RR) 8.4], tumour size greater than 15 cm (RR 3.66), previous local recurrence (RR 6.47) and proximal site (RR 12.7) to be independent poor risk factors for survival.

Actuarial Analysis↗

Thyroid cancer causing death after 40 years: rationale for initial intensive treatment.

Three cases of death after 40 years of differentiated thyroid cancer are presented. Prolonged follow-up identified relapses in patients assumed to have been cured. Thus the case is argued for intensive initial therapy comprising near-total thyroidectomy (including excision of any macroscopic nodal disease) and ablative iodine-131 therapy in addition to thyroid hormone suppression.

Adenocarcinoma↗

Soft-tissue sarcoma: neutrons versus photons for post-operative irradiation.

Between November 1980 and June 1981, 14 patients with soft-tissue sarcoma were entered into a prospective randomized trial comparing the efficacy of megavoltage photon irradiation with cyclotron-generated fast neutrons as post-operative adjuvant therapy. It became apparent that patients whose primary tumours had been treated with very wide excision, in particular by compartmental resection, suffered severe late tissue damage when subsequently irradiated with fast neutrons. It was therefore decided to terminate the trial after only 14 patients had been entered. Unacceptable late tissue damage may result from the therapeutic use of fast neutron irradiation when applied in these circumstances.

Clinical Trials as Topic↗

Chemotherapy for thyroid cancer.

Twenty-nine patients with advanced thyroid cancer have been treated with sequential chemotherapy regimes using the single agents etoposide, carboplatin, cis-platinum or methotrexate, and the combination of adriamycin, bleomycin and vincristine (ABC). Indications for chemotherapy were progressive, symptomatic recurrent or metastatic disease unresponsive to conventional treatment, or advanced anaplastic carcinomas. In these 29 patients there were a total of 60 evaluable drug exposures: 4 out of 22 responded to etoposide, 2 out of 9 responded to carboplatin, 5 out of 13 responded to cis-platinum, 1 out of 3 responded to methotrexate and 5 out of 13 responded to ABC. There was only one complete response in this series, seen with etoposide. Patients under 65 years and those with medullary carcinoma had the highest response rates. Mean survival in these 29 patients was 11.9 months. Mean survival in responders was 19 months compared to 5.4 months in non-responders. Etoposide, carboplatin and cis-platinum used as single agents are active in thyroid carcinoma and useful symptom control and improved survival may be achieved in those patients responding to sequential exposure to these agents.

Adolescent↗