Tomasz Olczyk

13-cis-retinoic acid re-differentiation therapy and recombinant human thyrotropin-aided radioiodine treatment of non-Functional metastatic thyroid cancer: a single-center, 53-patient phase 2 study.

In 30–50% of patients with metastatic non-medullary thyroid cancer the metastases are not radioiodine-avid and so there is no effective treatment. Retinoids have demonstrated inhibition of thyroid tumor growth and induction of radioiodine uptake. The aim of our study was to assess benefits of the retinoic acid (RA) treatment to re-differentiate non-functional NMTC metastases.Patients and MethodsIn this prospective study, 53 patients with radioiodine non avid metastatic disease (45) or hyperthyroglobulinemia (8) were treated with 13-cis-retinoic acid (13-CRA) [1.0 mg/kg/day over 1st week and then 1.5 mg/kg] for six weeks prior to I-131 treatment performed under rhTSH stimulation. The re-differentiating effect of RA was evaluated by serum thyroglobulin (Tg) monitoring before and after cessation of RA treatment and by qualitative analysis of iodine uptake on the post-therapeutic whole body scan (rxWBS).Results13-CRA induced radioiodine uptake in 9 (17%) of patients. In the univariate analysis neither the patients gender, age, tumor histopathology, uptake in thyroid bed nor time since thyroid cancer diagnosis was associated with results of rxWBS.41 (77%) patients were evaluable for Tg response before and after to 13-CRA treatment. There was a statistically significant increase in median Tg level (60 v. 90 ng/ml, p < 0.05). There was no difference in Tg increase between scintigraphic responders and non-responders.13-CRA and RIT was repeated at least once in 8 of 9 scintigraphic responders. None of them showed tumor regression by radiological imaging within 12 months after the first treatment, 4/9 (44%) of them had disease progression.13-CRA treatment was well-tolerated. All but one patient complained of at least one side effect the most prevalent being lip dryness (98%). All side effects were transient and resolved within 2 weeks after 13-CRA cessation.ConclusionOur results show that in patients with non-functional metastases from NMTC, 13-CRA is able to exert some re-differentiation effect by induction of radioiodine uptake in <20% of patients and increase of Tg serum level in about 30% of them. Nevertheless, this does not transfer into clinical benefit as it neither induces measurable tumor response nor prevents disease progression.

Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer.

Cabozantinib (XL-184) is a potent inhibitor of MET, VEGFR 2/KDR, RET and other receptor tyrosine kinases, such as KIT, AXL and FLT3. Its efficacy against MTC has been demonstrated in a prospective, randomized, placebo-controlled study (EXAM). Cabozantinib comparing to placebo significantly prolonged progression free survival both in hereditary and sporadic MTC, 11.2 vs 4.0 months, respectively. Final analysis showed no global differences in overall survival (OS) between cabozantinib and placebo. However, in a subgroup with RET M918T mutation the difference in OS was significant: 44.3 vs 18.9 months, respectively. Among the most frequent cabozantinib-related adverse events (AEs), observed in >30% of patients were diarrhea, palmar-plantar erythrodysesthesia, decreased weight, decreased appetite, nausea, fatigue, dysgeusia, hair color changes and hypertension. Expert Commentary: Cabozantinib constitutes an effective treatment option with acceptable toxicity in MTC patients showing either germinal or sporadic tumor RET M918T mutation as the drug prolonged OS in these subjects.

Role of nuclear medicine imaging in differential diagnosis of accessory spleens in patients after splenectomy.

Summary Background: More than 10% of healthy population has one or more accessory spleens. The most common location is the hilum of the spleen or area near the tail of the pancreas. The radiological appearance of accessory spleens in oncologic patients who underwent splenectomy can be misinterpreted as a recurrence, especially in the case of compensatory growth of an accessory spleen in successive radiological examinations. Caser Reports: We present the cases of three patients who underwent splenectomy for gastric carcinoid, gastric adenocarcinoma and cancer of the left adrenal gland, respectively. CT examination and/or PET-CT scan revealed suspicious findings in the left upper abdomen. In one patient, the dimensional increase of this finding in successive examinations was initially considered suggestive for cancer recurrence. Scintigraphy with 99mTc-nanocolloid was able to confirm the presence of an accessory spleen in all these patients. Conclusions: Splenic scintigraphy is an economical, accessible and accurate tool in differential diagnosis of accessory spleens in patients after splenectomy.

The assessment of side effects of tyrosine kinase inhibitors (TKI) applied in patients with advanced thyroid cancer (TC) - one centre experience

TKI constitute a new group of drugs evaluated in TC patients. The efficacy of some of them in prolongation of progression free survival has been recently documented. However, possible side effects may affect the quality of life as well as limit their clinical use. Only drugs which were known to inhibit VEGFR were considered. In the study adverse effects were evaluated in patients treated in our centre within the prospective clinical trials phase II and III. The aim of the study was to analyze the frequency and severity of side effects related to TKI in TC patients. Thus, we retrospectively re-evaluated side effects on the basis of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The comparison of the drugs was not aimed. 37 therapies with TKI due to advanced TC were assessed. 19 subjects were given vandetanib, 15 - lenvatinib, 3 - axitinib. Median treatment duration was 26.7 months (range: 4.0 - 62.2). The drug was discontinued due to TC progression in 9 subjects, adverse events in 5 and for other reasons in 4. Adverse events leading to treatment withdrawal were: weight loss (1), lymphopenia (1), QTC prolongation (1), tracheo-esophageal fistula (1) and purulent meningitis (1). The results are given in table ​table11. Table 1 Frequency and severity of the most common treatment-related side effects.