Fatemi et al., Los Angeles, CA, USA, retrospectively studied the prognostic value of a 2 year
post-thyroidectomy (Tx) serum Tg (during TSH-suppressive T4 treatment) using a threshold of
2 µg/l, to indicate risk of recurrence/persistence (R/P) in patients with treated papillary
thyroid carcinoma. A group of 285/1419 patients from a large multi-center health plan met the
study criteria (papillary ca, initial Tx, no Tg antibodies,.4 years of Tg measurements). Of
these patients 245/285 (86.6%) had a 2 year post-Tx serum Tg <2 µg/l . The <2 µg/l group had
a lower percentage R/P at 5 and 10 years (2.8% and 4% respectively), P < 0.001 compared with
the >2 µgTg group (77.5% and 82.5% respectively. When in the <2µgTg patients, no-, low dose-
or high dose 131I treatment was related to R/P, no effect of 131I was detected. The authors
conclude that using a threshold of a Tg 2 µ/l, is an excellent parameter for risk stratification
and therapeutic decision-making when found 2 years after thyroidectomy in patients with papillary
thyroid carcinoma. (Comment: This is an excellent study and helps a lot in risk stratification
and decision-making in patients thyroidectomized for papillary thyroid carcinoma. It should
be noted that the 2 year post-thyroidectomy Tg threshold is obtained during TSH suppressive
T4 treatment. In patients having a Tg =2 µ/l, according to this study, treatment with 131I
is not necessary). Santini et al., Pisa, Italy, studied the effect of endogenous TSH
stimulation (by partially withdrawing T4 treatment) or exogenous TSH stimulation (recombinant
human TSH) in two groups of patients (7 in each group) suffering from advanced poorly
differentiated thyroid carcinoma with demonstrated metastases, when treated with a combination
of carboplatinum and epirubicin administered at 4-6 weeks interval for 6 courses. When a
positive response was defined as stable disease or reduction of metastases, 11/14 patients
had a positive response. Serum Tg dropped significantly after chemotherapy in 9 patients.
No differences were seen in response rate between the two groups. The authors speculate
that the relatively favorable response may be at least in part caused by TSH stimulation
allowing cytotoxic drugs to enter carcinoma cells. At present, mean survival from start of
chemotherapy is 7.5 months in these 11 patients. (Comment: No control group, i.e. without
TSH stimulation, was studied at the same time). Toubert et al., Paris, France, evaluated
the sensitivity of high resolution ultrasound (HRUS) + color flow-Doppler (CFD) in three
groups of patients with persistent or recurrent differentiated thyroid carcinoma (DTC).
Group 1 (n = 85) comprising of patients with high risk DTC, group 2 (n = 13) discordant
Tg/WBS, and group 3 (n = 10) present circulating anti-Tg antibodies. All tissues considered
suspect with HRUS + CFD were biopsied. Out of 47 patients with suspected recurrence or
persistence, 43 had positive cytology. The authors conclude that HRUS + CFD is a reliable
method to detect cervical persistent or recurrence of DTC. Pacini et al., Pisa, Italy,
compared the performance of 5 prognostic scoring systems for patients with differentiated
thyroid carcinoma (DTC) in a series of 1053 patients. They tested the following systems:
Clinical Class, MACIS, EORTC, OHIO, TNM. Their final results show that these five systems
have similar prognostic values. The OHIO system is better in defining risk groups. The
Clinical Class is the easiest to work with and the MACIS has the greatest overlap in low-risk
categories. Gubala et al., Gliwice, Poland, performed reverse transcription polymerase chain
reaction (RT-PCR) to detect Tg mRNA in 75 lymph nodes from 66 patients with suspected DTC
recurrence. Classical cytology confirmed lymph node metastases in 22/75 (29%) of lymph
nodes while Tg mRNA was positive in 20/22 (92%). Additionally 3 positive Tg mRNAs were
found in initially negative lymph nodes on cytology but positive after re-examination of
cytology. The authors conclude that with a sensitivity of 86% to histo-pathology
examination and a specificity of 100%, Tg mRNA determination in suspected lymph nodes
is a useful technique. (Comment: Apparently these authors had a maximal specificity of Tg
mRNA evaluation in tissue of lymph nodes whereas other authors, see next 2 reports, find
much lower specificity when tested in serum of patients with DTC). Fugazzola et al., Milan
and Rozzano, Italy, measured serum Tg and blood Tg mRNA at days 1-6 after administration of
recombinant human TSH (rhTSH) in 37 patients treated by total thyroidectomy and
radio-ablation for differentiated thyroid carcinoma (DTC). They tested 2 Tg kits
(Immulite and Delfia). Immulite having a functional sensitivity of 1.0 ng/ml lacked
sensitivity resulting in a predictive value of 62%. Delfia (functional sensitivity
0.1 ng/ml) performed much better and was highly sensitive, predictive value 86% after
rhTSH stimulation. Blood Tg mRNA determinations in basal and stimulated conditions were
concordant with clinical status in only 68% of patients, mainly due to false positive
cases, i.e low specificity. Vivaldi et al., Pisa, Italy, assessed performance of RT-PCR
measurement of serum Tg mRNA in 63 patients treated by total thyroidectomy for DTC.
Blood was collected while off LT4 suppressive therapy. Four groups were studied:
The results show no differences in Tg mRNA between groups 1, 2, and 3. Unfortunately 62.5% of definitively cured patients still showed positive Tg mRNA. Although sensitivity was high, the low specificity found, invalidated this technique for the follow-up of patients with DTC. Elisei et al., Pisa, Italy, analyzed Na+/I-symporter (NIS) gene expression in human thyroid carcinoma tissues. They found expression in 9/19 primary papillary carcinoma (PTC) and in 21/26 PTC node metastases. Remarkable is that NIS expression was positive in 8/18 PTC thyroid tumors and 6/7 PTC positive lymph nodes that were cold at 131-I scanning before surgery. A dissociation of NIS expression between primary tumors and their corresponding lymph nodes was observed in 28% of cases. From these and other data the authors conclude that
(Comment: The absence of iodine uptake in tissues that still express NIS may be explained on the basis that gene expression in these studies was done at the messenger RNA level so that no information is present about protein expression and furthermore that it is not known if tissues were cold due to absent NIS protein or to other abnormalities such as absent incorporation of radioactive iodine in thyroglobulin or even absence of Tg itself). Orgiazzi et al., Lyon, France, studied the efficacy of somatostatin receptor scintigraphy (SRS) in 22 patients with recurrence of DTC without iodine concentrating characteristics. They found SRS positive in 16/22 patients. SRS differed according to metastatic sites. SRS was positive in 7/13 patients with lung metastases in 1 of 4 patients with bone metastases, all 13 patients with mediastinal localizations. On the basis of these and other results the authors conclude that SRS is valuable when tumor metastases do not concentrate iodine. It is especially valuable in patients with mediastinal lesions but underestimates lung metastases. (Comment: It is hoped that radioactive somatostatin may also be useful for the treatment of this type of SRS-positive lesions). |
