S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study.

OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. DESIGN: This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy. METHODS: The S-GRAS score was calculated as a sum of the following points: tumour stage (1-2 = 0; 3 = 1; 4 = 2), grade (Ki67 index 0-9% = 0; 10-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3), age (<50 years = 0; ≥50 years = 1), symptoms (no = 0; yes = 1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R2D statistic. RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R2D = 0.30, and C-index = 0.79, R2D = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

The increase in thyroid cancer incidence is not only due to papillary microcarcinomas: a 40-year study in 1 778 patients.

AIM: Thyroid cancer incidence has been increased over the last decades. The aims of the present study were: (a) to identify a changing trend in thyroid cancer in Northern Greece, (b) to examine patients' and tumoral characteristics and (c) to investigate the increase of papillary microcarcinomas and that of invasive or larger cancers. PATIENTS AND METHODS: We retrospectively analyzed the records of 1 778 patients who were diagnosed with thyroid cancer between January 1971 and December 2010. The study period was divided into 4 decades: 1971-1980, 1981-1990, 1991-2000, 2001-2010. Patients were separated into 2 groups: in Group A we have included papillary thyroid microcarcinomas (PTM) and in Group B all cancers with diameter >10 mm as well as invasive cancers ≤10 mm. RESULTS: Patients diagnosed with thyroid cancer increased substantially per decade. The relative frequency of papillary thyroid cancer cases increased (from 60% up to 84.6% in the last decade) and follicular cancers decreased (from 40% down to 11.6%). During the study period, cancer size declined. Frequency of PTM (Group A) increased from 0% up to 19.3% in the last decade, but cancers of this group represent only a minority of total cancers. CONCLUSIONS: The increase of thyroid cancer in this cohort was mainly due to tumors larger than 1 cm and also to smaller in size but invasive thyroid tumors. This increase outnumbers the increase in papillary thyroid microcarcinomas.

Effects of thyroxine withdrawal in biochemical parameters and cardiac function and structure in patients with differentiated thyroid cancer.

AIM: Patients with differentiated thyroid carcinoma (DTC) are closely monitored during the first decade after diagnosis. At intervals of 1-2 years withdrawal of suppressive doses of T(4) is recommended in order to check thyroglobulin (Tg) levels under increased TSH. T(4) therapy is usually withdrawn for 5 weeks (during the first 3 weeks patients receive treatment with T(3) instead of T(4), and the last 2 weeks stop all medication). There are a few reported studies looking into the effects of T(4) withdrawal in athyreotic patients in terms of biochemical parameters and ultrasound indices. We studied patients with DTC at two time points: during suppressive T(4) treatment and at the end of the T(4) withdrawal protocol in order to identify acute changes that become apparent after 5 weeks of treatment modification. METHODS: Hormonal and biochemical parameters were measured as well as ultrasound indices of cardiac function and structure. RESULTS: Statistically significant increases were found in total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol and triglycerides with T(4) withdrawal. Creatine phosphokinase showed a striking increase with treatment withdrawal. In addition, liver enzymes, total protein and albumin concentrations increased. Creatinine levels increased significantly and sodium decreased on stopping T(4) treatment. The ultrasound indices of cardiac function and structure did not show significant changes. CONCLUSIONS: Acute hypothyroidism following T(4) withdrawal in DTC patients leads to important biochemical changes without significant alterations in cardiac function and structure. These changes may adversely affect patients, especially older patients or those with other chronic diseases.

Somatostatin receptor expression in vivo and response to somatostatin analog therapy with or without other antineoplastic treatments in advanced medullary thyroid carcinoma.

The long-term treatment of metastatic medullary thyroid carcinoma (MTC) with somatostatin (SST) analogs was evaluated in 22 patients with persistant or relapsed disease and with in vivo positive SST receptor (SSTR) tumors. After surgical intervention all patients but one, initially or at a later time, had persistenly (15) or after relapse (7) elevated serum calcitonin (CT, 252-69482 pg/ml) and carcinoembryonic antigen (CEA, 8-1130 ng/ml) concentrations; also, all of them showed positive uptake in 111In-pentetreotide scanning. Daily doses of 0.4-1.0 mg octreotide subcutaneously, or monthly doses of 20-30 mg long-acting octreotide (LAR) intramuscularly for 3-21 months were administered. Systemic chemotherapy (Ch) with or without external radiotherapy (eRT) was given to 13 patients simultaneously. A beneficial effect on pre-existing diarrhea was observed in 8 patients (subjective partial remmission, sPR 36.4%); 10 other patients showed stable disease, while in 4 a worsening of pre-existing diarrhea was observed. CT and CEA concentrations decreased more than 25% in 4 out of 22 patients (18%) and 11 patients showed a decrease of less than 25% (biological SD). No objective response in tumour growth was demonstrated. Patients (10 survivors in group B) treated with Ch+eRT plus Octerotide showed higher sR (92.5%), lower mortality (23.1%), longer mean time to death (130 months) and longer mean total survival (mts) time (145 months) in comparison to group A patients who had 66.7% sR, 33.3% mortality, only 88.5 months mean time to death and 101 months mts-time. Long-term octreotide and octreotide-LAR treatment offers a subjective and biological partial remission in one third and in one fourth of the MTC patients respectively, but it does not improve the natural course of the tumor. It remains to be answered if these drugs, combined with other antineoplastic therapies, have a synergistic effect relating to treatment response and to patient survival and mortality.