Geert H. Blijham

Clinical Screening as Compared with DNA Analysis in Families with Multiple Endocrine Neoplasia Type 2A

BACKGROUNDnMultiple endocrine neoplasia type 2A (MEN-2A) is characterized by medullary thyroid carcinoma in combination with pheochromocytoma and sometimes parathyroid adenoma. Missense mutations in the RET proto-oncogene are associated with MEN-2A. Their detection by DNA analysis allows the identification of carriers of the gene, in whom the risk of medullary thyroid carcinoma is 100 percent. We compared the reliability of biochemical tests with that of DNA analysis in identifying carriers of the MEN2A gene.nnnMETHODSnStarting in 1975, we screened 300 subjects in four large families with MEN-2A for expression of the disease, using measurements of plasma calcitonin after stimulation with pentagastrin or calcium and urinary excretion of catecholamines and catecholamine metabolites. We tested for carrier status by DNA analysis, including linkage analysis, and more recently by analysis of mutations in the RET gene.nnnRESULTSnOf 80 MEN2A gene carriers (in 61 of whom carrier status was proved by DNA analysis), 66 had abnormal plasma calcitonin values and medullary thyroid carcinoma. Fourteen young carriers had normal results of plasma calcitonin tests. In 8 of these 14, thyroidectomy revealed small foci of medullary thyroid carcinoma; the remaining 6 have not yet been operated on. Of the other 220 family members, 68 were found by DNA analysis not to carry the MEN2A gene. None of these 68 subjects had medullary thyroid carcinoma or pheochromocytoma; 6 had elevated plasma calcitonin concentrations and underwent thyroidectomy but had only C-cell hyperplasia.nnnCONCLUSIONSnUnlike biochemical tests, DNA analysis permits the unambiguous identification of MEN2A gene carriers.

Long‐Term Quality of Life of Patients With Head and Neck Cancer

Objectives: To describe prospectively the long‐term changes of quality of life and mood in patients with squamous cell carcinoma of the head and neck treated with surgery and/or radiotherapy.

Sociodemographic factors and quality of life as prognostic indicators in head and neck cancer

Pre-treatment quality of life (QOL) has been found to be an independent prognostic factor for survival in cancer patients, in particular in patients with advanced cancer. Sociodemographic factors such as marital and socioeconomic status have also been recognised as prognostic factors. We studied the influence of QOL and mood (measured with the European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) and the Head and Neck Cancer Questionnaire (EORTC QLQ-H&N35), and with the Center for Epidemiologic Studies-Depression Scale (CES-D)) as measured before treatment, the use of cigarettes and alcohol and sociodemographic factors (age, gender, marital status, income and occupation) on recurrence and survival in 208 patients with head and neck cancer prior to treatment with surgery and/or radiotherapy, using Kaplan-Meier and Cox regression analyses. Cognitive functioning and, to a lesser degree, marital status were independent predictors of recurrence and survival, along with medical factors (stage and radicality). Patients with less than optimal cognitive functioning and unmarried patients had a relative risk (RR) of recurrence of 1.72 (95% confidence interval (95% CI) 1.01-2.93) and 1.85 (95% CI 1.06-3.33), respectively, and a RR of dying of 1.90 (95% CI 1.10-3.26) and 1.82 (95% CI 1.03-3.23), respectively. Performance status, physical functioning, mood and global QOL and smoking and drinking did not predict for recurrence and survival. The influence of cognitive functioning might be related to the use of alcohol. Marital status may influence prognosis through mechanisms of health behaviour and/or social support mechanisms.

Pretreatment factors predicting quality of life after treatment for head and neck cancer

Quality of life (QOL) has become an important issue in head and neck cancer. Explanation of factors predicting QOL after treatment has important implications for patient management.

A prospective study on quality of life of patients with cancer of the oral cavity or oropharynx treated with surgery with or without radiotherapy

The aim of this study was to describe prospectively quality of life and mood in patients with oral or oropharyngeal cancer treated with surgery +/- radiotherapy. Seventy-five patients completed the EORTC Core Questionnaire, the EORTC Head and Neck Cancer module and the Center for Epidemiologic Studies Depression Scale before treatment and 6 and 12 months later. There was a significant deterioration of physical functioning, fatigue and almost all head and neck symptoms except pain, which improved. Patients with stage III/IV and patients receiving combined treatment had significantly worse physical symptoms compared to patients with stage I/II and patients treated with surgery only, respectively. Before and after treatment there was a high level of depressive symptomatology. However, after treatment a gradual improvement in emotional functioning occurred. Surgical treatment for oral or oropharyngeal cancer results in significant deterioration of physical functioning and symptoms during the first year, especially when combined with radiotherapy. Despite this, there is an improvement of emotional functioning after treatment, probably as a result of adaptation and coping processes.

A prospective study on quality of life of laryngeal cancer patients treated with radiotherapy

The aim of this study was to describe prospectively quality of life and mood before and after radiotherapy for laryngeal cancer.

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).

The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.

Negative and positive influences of social support on depression in patients with head and neck cancer: a prospective study

Patients with head and neck cancer have to cope not only with a life threatening diagnosis, but also with an altered facial appearance and the loss or impairment of important functions as a result of treatment. As a consequence they are prone to psychosocial problems. Social support might influence their ability to adapt to the illness and its treatment.

Prediction of depressive symptomatology after treatment of head and neck cancer: The influence of pre-treatment physical and depressive symptoms, coping, and social support

Head and neck cancer and its treatment can have important psychosocial implications, and many patients become depressed. The aim of this prospective study is to examine whether pretreatment variables can be used to predict depression 6 and 12 months later.

Familial medullary thyroid carcinoma: Not a distinct entity? Genotype-phenotype correlation in a large family

BACKGROUNDnMultiple endocrine neoplasia type 2A (MEN 2A) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Familial MTC (FMTC) is characterized by MTC only. Both MEN 2A and FMTC are caused by germline mutations of the RET proto-oncogene.nnnPURPOSEnTo assess genotype/phenotype correlations, large families have to be examined periodically over a long period using an extensive screening program.nnnPATIENTS AND METHODSnSince 1973, we screened a large family with hereditary C cell carcinoma for MTC, pheochromocytoma, and parathyroid disease by clinical tests and imaging methods. A germline codon Cys618 to Ser mutation in the RET proto-oncogene was recently identified in this family. The disease phenotype associated with this mutation was compared with that of Cys634 mutations in some other large MEN 2A families.nnnRESULTSnThe distinct course of disease in the family described here is similar to that in other FMTC families and MEN 2A families with a Cys618 mutation of the RET gene, but clearly different from that in families with a Cys634 mutation. The frequency of pheochromocytomas and parathyroid disease is clearly lower, whereas cure rates and life expectancy are higher. However, in families with a Cys618 mutation, pheochromocytoma and parathyroid disease do occur.nnnCONCLUSIONnIn FMTC families with cysteine codon mutations of the RET proto-oncogene, screening for other endocrinopathies is mandatory, since these may not be MTC-only families. Therefore, we suggest that MEN 2A families should not be subclassified into MEN 2A and FMTC, but rather according to their specific mutation in the RET protein (i.e., for this family MEN 2A RET C618S).