EFFICACY AND SAFETY OF MULTI-TARGETED KINASE INHIBITORS IN PROGRESSIVE, RADIOIODINE-REFRACTORY DIFFERENTIATED THYROID CANCERS: A META-ANALYSIS

Purpose: A meta-analysis was conducted to evaluate the impact of oral multitargeted kinase inhibitors (MTKIs) in radioactive-iodine refractory locally advanced, recurrent/metastatic differentiated thyroid cancer (DTC) on disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) rates. Materials and Methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database and other search engines were searched to identify randomised controlled trials (RCTs) comparing MTKIs with placebo in locally advanced, recurrent/metastatic DTC. Pooled data were expressed as odds ratio (OR), with 95% con dence intervals (CIs, Mantel–Haenszel xed-effect model). Results: Three RCTs with a total patient population of 954 patients were identi ed. The use of MTKIs was associated with improved PFS (OR: 0.262, 95% CI: 0.19–0.35; heterogeneity (I2) = 22.4%; P < 0.0001), improved DCR (complete and partial responses + stable disease, P < 0.0001) and improved OS 0.66, 95% CI: 0.46–0.96 (I2 = 43%, P = 0.034). Lenvatinib (compliance = 87%) was associated with more grade ≥3 hypertension. However, its other adverse effects were much lower than sorafenib (compliance = 56%) and vandetanib. Conclusion: In radioactive iodine-refractory recurrent, metastatic DTC patients, lenvatinib and sorafenib were associated with improved PFS, DRC and OS rates, while the compliance was better with lenvatinib. Key words: Meta-analysis, multitargeted kinase inhibitors, progressive differentiated thyroid cancer, radioactive iodine- refractory

Bleeding in Locally Invasive Pelvic Malignancies: Is Hypofractionated Radiation Therapy a Safe and Effective Non-Invasive Option for Securing Hemostasis? A Single Institution Perspective

Introduction: Control of bleeding due to locally invasive disease is of paramount importance in the management of cancer patients. This study was undertaken to explore the outcomes of palliative intent hypofractionated radiation therapy (HRT) in advanced stage pelvic malignancies that presented with bleeding. Methods: This study enrolled patients treated with palliative intent hypofractionated radiation therapy from July 2015 to November 2017. In the inclusion criteria, all these patients had the common presenting complaint of bleeding from the tumor. These patients were not treated with radiation therapy before for the same indication. Patients with known bleeding disorders and those undergoing parallel interventions for bleeding control were excluded from the study. Bleeding was categorized based on the World Health Organization (WHO) scale for the classification of bleeding. Response assessment was classified into a complete response, partial response and no response. A comparison was made for the bleeding scale before and after HRT using the Wilcoxon signed rank test. The comparison of mean hemoglobin levels before and after the HRT was calculated by paired t-test. Results: Forty-two patients with advanced pelvic malignancies qualified for inclusion in the study after applying the inclusion/exclusion criteria. Among those analyzed, the median age was 67 years (range 37 – 95 years). The male and female proportion was 38% and 62% respectively. Different cancers included uterine cancer 31%, cervical cancer 24%, bladder cancer 21%, rectal cancer 17% and vulvar cancer in 7%. The baseline bleeding scale in these cases was found to be grade 1 in 12%, grade 2 in 55% and grade 3 in 33% cases. The median dose in our cohort was 20 Gy in five fractions over one week (range was 8 Gy to 40 Gy). Following HRT, the WHO bleeding score at one month was recorded as grade 0 in 57%, grade 1 in 31%, grade 2 in 7%, grade 3 in 5% and grade 4 in none. Toxicity profile did not show any grade 3 or 1 2 3 4 5 6 7 8 6 Open Access Original Article DOI: 10.7759/cureus.2137 How to cite this article Shuja M, Nazli S, Mansha M, et al. (February 02, 2018) Bleeding in Locally Invasive Pelvic Malignancies: Is Hypofractionated Radiation Therapy a Safe and Effective Non-Invasive Option for Securing Hemostasis? A Single Institution Perspective. Cureus 10(2): e2137. DOI 10.7759/cureus.2137 above acute toxicity in the study. Response rates were 57% complete response, 36% partial response and 7% no response. The mean hemoglobin level post-treatment versus pre-treatment was found to be 9.6 g/dL versus 7.3 g/dL. Conclusions: Hypofractionated radiotherapy was found to be a safe and effective non-invasive palliative treatment modality for securing hemostasis in advanced pelvic malignancies that presented with bleeding

Pancreas as Delayed Site of Metastasis from Papillary Thyroid Carcinoma

Introduction. Follicular variant (FV) papillary thyroid carcinoma (PTC) has aggressive biologic behavior as compared to classic variant (CV) of PTC and frequently metastasizes to the lungs and bones. However, metastasis to the pancreas is extremely rare manifestation of FV-PTC. To date, only 9 cases of PTC have been reported in the literature. Pancreatic metastases from PTC usually remain asymptomatic or manifest as repeated abdominal aches. Associated obstructive jaundice is rare. Prognosis is variable with reported median survival from 16 to 46 months. Case Presentation. Herein we present a 67-year-old Saudi woman, who developed pancreatic metastases seven years after total thyroidectomy and neck dissection followed by radioactive iodine ablation (RAI) for FV-PTC. Metastasectomy was performed by pancreaticoduodenectomy followed by sorafenib as genetic testing revealed a BRAF V600E mutation. She survived 32 months after the pancreatic metastasis diagnosis. Conclusion. Pancreatic metastases are rare manifestation of FV-PTC and are usually sign of extensive disease and conventional diagnostic tools may remain to reach the diagnosis

Supraclavicular Lymphadenopathy: Initial Manifestation of Metastasis in Carcinoma of Cervix

Introduction. Carcinoma of cervix rarely metastasizes to cervical lymph nodes and is associated with poor prognosis. To date, only few case reports have been reported in the medical literature. Here, we report a case of this unusual manifestation of carcinoma of cervix. Case Presentation. A 39-year-old Saudi woman who was treated three years ago for bulky IB stage carcinoma of cervix with total abdominal hysterectomy and bilateral salpingo-oophorectomy and adjuvant chemoradiation presented to us during her routine follow-up visit with left supraclavicular lymphadenopathy. Staging workup revealed additional para-aortic nodal and osseous metastases. The biopsy of left supraclavicular mass confirmed the diagnosis of carcinoma of the cervix. Patient was started on chemotherapy and bisphosphonates. Conclusion. Supraclavicular lymph nodes are a rare site of metastasis in carcinoma of cervix, and this can be explained by outlining the drainage of the lymphatic system from the cervix. Supraclavicular lymphadenopathy is associated with variable prognosis

Cerebellum as Initial Site of Distant Metastasis from Papillary Carcinoma of Thyroid: Review of Three Cases

Background. The cerebellum as initial site of distant metastasis from differentiated thyroid carcinoma (DTC) including papillary (PTC) and follicular thyroid carcinoma (FTC) is rare manifestation. Case Presentations. Herein, we present three cases of cerebellar metastasis (CBM) of PTC. Mean age of patients was 67 years (range: 64–72), and mean duration between initial diagnosis and CBM was 49.6 months (range: 37–61). Frequent location was left cerebellar hemisphere and was associated with hydrocephalus. All patients underwent suboccipital craniectomy, and in two patients postoperative intensity modulated radiation therapy (IMRT) was given to deliver 5000 cGy in 25 fractions to residual lesions. Patient without postoperative IMRT had cerebellar recurrence along with lung and bone metastasis after 38 months. However, two patients were found alive and free of disease at the time of last follow-up. Conclusion. CBM from PTC is a rare clinical entity and is often associated with hydrocephalus. Histopathological diagnosis is important to initiate effective treatment, which relies on multidisciplinary approach to prolong the disease-free and overall survival rates

Duodenal metastasis from lung adenocarcinoma: A rare cause of melena

Introduction: We report a rare case of duodenal metastasis from primary lung adenocarcinoma presented with history of melena and weight loss. Presentation of case: A 52-year-old smoker man presented with six months history of epigastric pain, melena and weight loss. Esophago-gastroduodenoscopy revealed a 10 mm ulcerative lesion in the fourth part of duodenum. Histopathology of resected lesion showed poorly differentiated adenocarcinoma. Tumor cells showed immunopositivity for cytokeratin-7 (CK7), thyroid transcription factor 1 (TTF-1), and immunonegativity for CK20, Villin, CDX2 and thyroglobulin, supporting the diagnosis of metastatic adenocarcinoma of the lung origin. Computed tomography (CT) of chest revealed left hilar mass encasing the main pulmonary artery associated with ipsilateral hilar and contralateral mediastinal lymphadenopathy. Bronchoscopy assisted biopsy of lung mass confirmed the diagnosis of primary adenocarcinoma. Patient was staged as T4N3M1. After the resection of duodenal metastasis followed by three cycles of cisplatinum based chemotherapy with Bevacizumab, melena resolved completely. Discussion: Duodenal metastases from lung adenocarcinoma are extremely uncommon, and rarely produce symptoms. Most of cases require duodenectomy or pancreatico-duodenectomy for symptomatic relief. For smaller duodenal metastatic lesions (≤1 cm) endoscopic resection is a feasible therapeutic option. Conclusion: Although rare, duodenal metastasis from lung adenocarcinoma should also be included in the differential diagnosis of melena. Smaller lesions (≤1 cm) can safely be managed with endoscopic resection