Primary Tumor Multifocality Research Articles

Dynamic Risk Stratification for Predicting Treatment Response in Differentiated Thyroid Cancer.

Prognosis in Differentiated Thyroid Cancer (DTC) patients is excellent, but a significant degree of overtreatment still exists because of the inability to accurately identify small patient cohorts who experience a more aggressive form of the disease, often associated with certain poor prognostic factors. Identifying these cohorts at an early stage would allow patients at high risk to receive more aggressive treatment while avoiding unnecessary and invasive treatments in those at low risk. Most risk stratification systems include age, tumor size, grade, presence of local invasion, and regional or distant metastases. Here we discuss these common factors as well as their association with treatment response, but also other upcoming markers including histology and multifocality of primary tumor, dose administered and preparation method for Radioiodine Therapy (RAI), Thyroglobulin (Tg), Anti-thyroglobulin Antibodies (Tg-Ab) levels both at initial management and during follow-up, and the presence of previously existing benign thyroid disease. In addition, we examine the role of remnant size and avidity as well as surgeons’ experience in performing thyroidectomies with recurrence rate, discussing its impact on disease prognosis. Our results reveal that treatment response has a statistically significant association with histology, T and M stages, surgeons’ experience, Tg levels and remnant score both during RAI and follow up and Tg-Ab levels during follow-up whole body scan (WBS).

Routine Prophylactic Central Neck Dissection May Not Obviously Reduce Lateral Neck Recurrence for Papillary Thyroid Microcarcinoma

Background: The role of routine prophylactic central compartment neck dissection (pCCND) for papillary thyroid microcarcinoma (PTMC) remains controversial. The lateral neck recurrence-free survival (LRFS) advantages achieved by pCCND are still under investigation. Methods: The records of 2,074 consecutive patients with papillary thyroid carcinoma (PTC) at the time of surgery from 1996 to 2009 were retrospectively reviewed. A total of 611 consecutive patients were included in the final analyses. We used R version 3.5.1 to match patients with total thyroidectomy (TT)/lobectomy + pCCND with patients with TT/lobectomy alone and analyzed the following factors with a potential influence: age at diagnosis, sex, extrathyroid extension, and primary tumor multifocality and bilaterality. LRFS was analyzed. Moreover, the data were reanalyzed after separating the pairs of patients with pN1a from those with pN0. Results: We were able to select 159 pairs sharing the major prognostic risk factors as listed. Overall, there was no difference in the LRFS, although patients with pCCND more often had recurrence. Moreover, the central lymph node metastasis status had no significant influence on the risk of recurrence. Conclusion: Routine pCCND was not a protective factor for LRFS in PTMC patients with cN0. The difference in LRFS between pN0 and pN1a was not statistically significant (p > 0.05).

The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model

IntroductionContemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies. For very rare tumors, like hepatoblastoma, the development of biologic markers, and the identification of reliable prognostic risk factors for tailoring treatment, remains very challenging. The Children's Hepatic tumors International Collaboration (CHIC) is a novel international response to this challenge. MethodsFour multicenter trial groups in the world, who have performed prospective controlled studies of hepatoblastoma over the past two decades (COG; SIOPEL; GPOH; and JPLT), joined forces to form the CHIC consortium. With the support of the data management group CINECA, CHIC developed a centralized online platform where data from eight completed hepatoblastoma trials were merged to form a database of 1605 hepatoblastoma cases treated between 1988 and 2008. The resulting dataset is described and the relationships between selected patient and tumor characteristics, and risk for adverse disease outcome (event-free survival; EFS) are examined. ResultsSignificantly increased risk for EFS-event was noted for advanced PRETEXT group, macrovascular venous or portal involvement, contiguous extrahepatic disease, primary tumor multifocality and tumor rupture at enrollment. Higher age (≥8 years), low AFP (<100 ng/ml) and metastatic disease were associated with the worst outcome. ConclusionWe have identified novel prognostic factors for hepatoblastoma, as well as confirmed established factors, that will be used to develop a future common global risk stratification system. The mechanics of developing the globally accessible web-based portal, building and refining the database, and performing this first statistical analysis has laid the foundation for future collaborative efforts. This is an important step for refining of the risk based grouping and approach to future treatment stratification, thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases.

Abstract P1-02-02: Locoregional assessment by FDG PET/CT in stage II/III breast cancer patients: A multivariate analysis

Abstract Aim : Previously we demonstrated the additional value of PET/CT in prone position for breast cancer detection. The purpose of the present study was to evaluate, with a multivariate analysis, the factors influencing detection and quantification of FDG–avid primary tumors (PT) and regional lymph node metastases (LN) detected with PET/CT in patients with stage II/III breast cancer. Materials and methods : From August 2010 to April 2012 we included 198 patients (mean 51 yr, range 26–82), with stage II/III breast cancer. A dose of 18F–FDG between 180–240 MBq, was administered intravenously. After 60±10 minutes a PET/CT of the thorax in prone position was acquired, scanning 3.00 min per bed position and reconstructed in high–resolution using 2x2x2 mm voxels and 2 mm CT slice thickness. Subsequently, a standard PET/CT was performed in supine position from skull base to thighs, scanning 1.30 min per bed position and using a standard reconstruction with 4x4x4 mm voxels, a standard 5mm CT slice reconstruction and an extra 2 mm CT slice reconstruction. On all PET/CT images we quantitatively assessed the SUVmax of FDG–avid PTs and LNs. We qualitatively assessed tumor multifocality, PT visibility, LN detection in defined regions and the occurrence of anatomical mismatch between PET and CT. The obtained results were then evaluated with a multivariate analysis for scanning position, patient age, breast size, tumor volume, number of FDG–avid lesions, lymph node location and anatomical mismatch between PET and CT. Results: Prone position imaging positively influenced the visualization of tumor multifocality (p&amp;lt;0.001), the total number of lymph nodes (p&amp;lt;0.001) and of axillary LNs (p&amp;lt;0.001). PT visibility was not significantly influenced by any of the parameters. A higher SUVmax of the primary tumor was found solely with increased tumor volume (p=0.001) or breast size (p&amp;lt;0.001). The standard 5mm CT slice reconstruction of the supine PET/CT was the only factor causing an increase in anatomical mismatch between PET and CT for axillary lymph nodes (p=0.004). Conclusion: Prone position for PET/CT influences the visualization of primary tumor multifocality and the number of FDG avid loco-regional lymph nodes. Tumor FDG-uptake appears to be most influenced by tumor volume and breast size. Both results can be important for adequate staging and subsequent breast cancer treatment. Citation Format: Suzana C Teixeira, Bas B Koolen, Wouter V Vogel, Marcel P Stokkel, Marie-Jeanne Vrancken-Peeters, Vincent van der Noort, Emiel J Th Rutgers, Renato A Valdés-Olmos. Locoregional assessment by FDG PET/CT in stage II/III breast cancer patients: A multivariate analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-02.

The BRAFT1799A mutation is not associated with occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma.

The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the BRAFT1799A mutation is associated with aggressive PTMC, the relationship between BRAFT1799A mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including BRAFT1799A mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. From January 2011 to December 2013,we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. BRAFT1799A mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was 0.33±0.21 cm. The BRAFT1799A mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

Overrepresentation of HLA-DQ2 in small intestinal neuroendocrine tumor patients.

Toinvestigate whether celiac disease risk haplotypes HLA-DQ2 and DQ8 also increase the risk for developing small intestinal neuroendocrine tumor (SI-NET). Thirty-five patients with serotonin-producing jejunal and ileal SI-NET were examined with HLA-DQ genotyping and serology for IgA anti-tissue transglutaminase (tTG) antibodies. Twenty-one patients (60 %) carried HLA-DQ2 or DQ8, twice the frequency of the general population (P < 0.001). In particular DQ2 was overrepresented (P = 0.013). Gender, age, disease stage, histopathological grade, or multifocality of primary tumor did not differ between patients with DQ2 or DQ8 and patients with other HLA-DQ haplotypes. No patient in the study was diagnosed with celiac disease (latent or symptomatic) as anti-tTG antibodies were negative in all 35. HLA-DQ haplotypes associated with celiac disease are overrepresented also in patients with SI-NET, in particular HLA-DQ2.

Preoperative BRAF Mutation is Predictive of Occult Contralateral Carcinoma in Patients with Unilateral Papillary Thyroid Microcarcinoma

The optimal resection extent for clinically unilateral papillary thyroid microcarcinoma (PTMC) remains controversial. The objective was to investigate risk factors associated with occult contralateral carcinoma, and put emphasis on the predictive value of preoperative BRAF mutation. 100 clinically unilateral PTMC patients all newly diagnosed, previously untreated were analyzed in a prospective cohort study. We assessed the T1799A BRAF mutation status in FNAB specimens obtained from all PTMC patients before undergoing total thyroidectomy (TT) and central lymph node dissection (CLND) for PTMC. Univariate and multivariate analyses were used to reveal the incidence of contralateral occult cancer, difference of risk factors and predictive value, with respect to the following variables: preoperative BRAF mutation status, age, gender, tumor size, multifocality of primary tumor, capsular invasion, presence of Hashimoto thyroiditis and central lymph node metastasis. 20 of 100 patients (20%) had occult contralateral lobe carcinoma. On multi-variate analysis, preoperative BRAF mutation (p = 0.030, OR = 3.439) and multifocality of the primary tumor (p = 0.004, OR = 9.570) were independent predictive factors for occult contralateral PTMC presence. However, there were no significant differences between the presence of occult contralateral carcinomas and age, gender, tumor size, capsular invasion, Hashimoto thyroiditis and central lymph node metastasis. Total thyroidectomy, including the contralateral lobe, should be considered for the treatment of unilateral PTMC if preoperative BRAF mutation is positive and/or if the observed lesion presents as a multifocal tumor in the unilateral lobe.

Occult Contralateral Carcinoma in Patients with Unilateral Papillary Thyroid Microcarcinoma

The optimal resection extent for papillary thyroid microcarcinoma (PTMC) confined within a unilateral lobe remains controversial. We reviewed the medical records of 132 consecutive patients who underwent total thyroidectomy for the treatment of clinically unilateral PTMC between March 2005 and March 2009. The frequency, pattern, and predictive factors for occult contralateral carcinoma in these patients were analyzed with respect to the following variables: age, gender, tumor size, multifocality of primary tumor, presence of perithyroidal invasion, lymphovascular invasion or capsular invasion, presence of central lymph node metastasis, and the presence of coexistent benign nodules in the contralateral lobe based on preoperative evaluation and final pathology. A total of 22 patients (16.7%) had occult PTMC in the contralateral lobe. In multivariate analysis, multifocality of the primary tumor (P = 0.026, odds ratio = 7.714) and the presence of coexistent benign nodule in the contralateral lobe by preoperative evaluation (P = 0.036, odds ratio = 3.500) were independent predictive factors for occult contralateral PTMC presence. However, there were no significant differences between the presence of occult contralateral carcinomas and age, gender, tumor size, perithyroidal invasion, lymphovascular invasion, capsular invasion, central lymph node metastasis, and coexistent benign nodules by final pathology. Based on our findings, total thyroidectomy, including the contralateral lobe, should be considered for the treatment of unilateral PTMC if it presents as a multifocal tumor in the unilateral lobe and/or if nodules are found in the contralateral lobe during preoperative evaluation.