First Line Sorafenib Treatment for Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare disease, the prognosis of advanced and metastatic disease is poor and few therapeutic options are available in this setting. Based on the results of phase II and III studies with sorafenib in differentiated thyroid cancer and the lack of availability of registered tyrosine kinase inhibitors, vandetabin and cabozantinib in Hungary, we designed a uncontrolled, prospective efficacy and safety study of patients with metastatic MTC treated with first-line sorafenib in five Hungarian oncology centers. METHODS: Ten consecutive patients with progressive or symptomatic metastatic MTC were included and started sorafenib 400  mg twice a day between June 2012 and March 2016. The primary end point was median progression-free survival (mPFS). Secondary endpoints included disease control rate, biochemical response, symptomatic response and toxicity. RESULTS: Four patients achieved partial remission (40%) according to RECIST 1.1 evaluation. Five patients had stable disease beyond 12 months (50%) and one patient had progressive disease (10%). Median PFS was 19.1 months. The disease control rate was 90%. Association between radiologic response and biochemical or symptomatic response was inconsistent. Most common side effects were Grade 1-2 fatigue (60%), palmar-plantar erythrodysesthesia, rash/dermatitis 50-50%, alopecia 40%. CONCLUSIONS: In our prospective case series in patients with MTC first-line sorafenib showed at least similar efficacy as in other small phase II trials and case reports. Based on comparable efficacy with registered tyrosine kinase inhibitors and it's manageable toxicity profile, we believe that sorafenib has role in the sequential treatment of MTC.

[The feasibility and the role of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer]. / Az ôrszemnyirokcsomó-biopszia alkalmazhatósága és jelentôsége neoadjuváns kemoterápia után emlôrákban.

INTRODUCTION AND AIMS: The feasibility, accuracy and clinical significance of sentinel lymph node biopsy for patients with breast cancer after neoadjuvant chemotherapy has not yet been determined. The aim of this study was to investigate these questions. PATIENTS AND METHOD: Dual agent-guided sentinel lymph node biopsy with preoperative lymphoscintigraphy was performed on 17 breast cancer patients after neoadjuvant chemotherapy at the Department of General and Thoracic Surgery, National Institute of Oncology, Budapest, from April 2004 to August 2005. Patients with clinically lymph node-negative breast cancer less than 3 cm in size after neoadjuvant chemotherapy were enrolled in the study. RESULTS: Lymphoscintigraphy showed no axillary lymphatic drainage in 7 patients (41%), and no sentinel lymph node could be identified during surgery in these patients. Axillary lymph nodes were histologically positive in 6 (86%) out of these 7 patients. Sentinel lymph node biopsy was successful in 10 patients (59%), and in 8 (80%) of them the sentinel lymph node proved to be positive pathologically. False negative sentinel lymph node biopsy did not occur. Axillary lymph node status was histologically positive in 14 (82%) out of the 17 patients. The predictable value of the clinical examination of the axilla after neoadjuvant chemotherapy, for the histological nodal status, was very low. DISCUSSION AND CONCLUSIONS: Our sentinel lymph node identification rate is lower than the published average in the literature. This difference can be explained by the differences in the indication for neoadjuvant chemotherapy. Our false negative rate (0%) is, however, significantly better than that of others. On the basis of international experiences sentinel lymph node biopsy after neoadjuvant chemotherapy is technically feasible, but its accuracy is not satisfactory and its clinical significance has not yet been determined. Our success rate is specifically low, which cannot be explained by the lack of practice. Taking the histologically very high axillary positive rate into consideration, sentinel lymph node biopsy has no clinical role in our practice after neoadjuvant chemotherapy.

Influence of thymidylate synthase gene polymorphisms on the survival of colorectal cancer patients receiving adjuvant 5-fluorouracil.

The present study aimed to prospectively investigate the influence of thymidylate synthase (TS) polymorphisms (5'-TSER, 3'-TSUTR) on the disease-free survival (DFS) and overall survival (OS) of patients with colorectal cancer (CRC) who were treated with adjuvant 5-fluorouracil (5-FU) therapy. Patients were followed up for 19+/-14 months (median+/-SD). TS genotypes were determined from the peripheral blood mononuclear cells of 166 patients by polymerase chain reaction-polyacrylamide gel electrophoresis and restriction fragment length polymorphism methods. 5'-TSER 3R homozygotes showed significantly longer DFS (P = 0.048) and OS (P = 0.009). The 5'-TSER and 3'-TSUTR genotype combination groups showed a significant difference for DFS (P = 0.039) and OS (P = 0.029). Significantly better DFS (P = 0.049) and OS (P = 0.043) were observed for 6 bp/6 bp genotypes in 5'-TSER heterozygotes (n = 80). Based on this, and on hazard ratios obtained by Cox regression analysis of the DFS of genotype-combinations, the patients were classified as belonging to prognostic groups A and B. The DFS and OS of these two groups showed a highly significant difference (P = 0.002 and 0.001). In the multivariate Cox regression model, beside tumour location, the prognostic classification (groups A and B) proved to be an independent prognostic factor. Our data suggest that those TS genotypes and their combinations (group A: 3R/3R with any 3'-TSUTR genotype and 2R/3R with 6 bp/6 bp), which have been reported earlier as having high TS expression, predict significantly longer DFS and OS. We found that a combination of germline TS polymorphisms is an independent prognostic marker in selecting CRC patients with worse prognosis, and it may be worthwhile to examine whether these patients would benefit from an alternative therapy.