Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors - a single Brazilian center experience.

OBJECTIVE: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. METHODS: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. RESULTS: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). CONCLUSION: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Successful GaAlAs low-level laser therapy of self-inflicted thermal burns of the palate.

Thermal burns of the oral cavity usually arise from ingestion of hot foods or beverages. A 38-year-old female patient presented with two painful ulcerative erythematous patches of the palate. The patient was consulted on the same day lesions appeared. Medical history was unremarkable. Clinically significant self-inflicted injuries may result in wide ulcers in the mouth and usually do not take less than 2 weeks to heal, whereas our patient, treated with low-level laser therapy, had a complete response in day 4, after 2 days of treatment. The fact that multiple lesions were present signaled against the World Health Organization exclusion diagnosis of erythroplakia for red patches. A traumatic ulcer, regardless of its cause of origin, usually heals within 2 weeks, after the source of injury is resolved. A thermal burn in the oral cavity usually takes longer than that to heal, but whenever this time frame is not respected, the suspicion of a potentially malignant disorder should always arise, and a biopsy should be performed. The present case showed two painful thermal burns with great results in terms of speeding up the relieve of symptoms and healing time with soft laser as opposed to the traditional treatment with oral topical corticosteroid.

Secretory carcinoma of salivary glands at the National Cancer Institute: A 20-year retrospective clinical, pathological, immunohistochemical and molecular study.

OBJECTIVES: This study aim was to review cases of acinic cell carcinoma (the main differential diagnosis of secretory carcinoma) that were diagnosed and treated at the National Cancer Institute of Brazil (INCA) between 1996 and 2016. The primary objective was to identify underdiagnosed cases of secretory carcinoma via a clinical, immunopathological and molecular reassessment. MATERIALS AND METHODS: This is a cross sectional study, with retrospective data collection from medical records and histological specimen review, with staining for periodic acid-Schiff (PAS) and PAS with diastase, immunohistochemistry for S-100, mammaglobin, and DOG-1, and droplet digital RT-PCR for ETV6-NTRK3. The Research Ethics Committee approved this study, and the patients allowed their participation through informed consent. RESULTS: Eighty-three cases of acinic cell carcinoma were diagnosed and treated in the specified period at INCA, of which, seven had their diagnosis changed to secretory carcinoma. CONCLUSION: The present study adds seven cases of secretory carcinoma to the literature, contributing to a better understanding of the epidemiological, histological, immunohistochemical and molecular characteristics of this recently described tumor. Also, the use of a comprehensive diagnostic approach, including immunohistochemical and molecular methods, along with classical morphological studies, allowed the reclassification of acinic cell carcinoma to secretory carcinoma.

A systematic review of secretory carcinoma of the salivary gland: where are we?

OBJECTIVE: The aim of this systematic review was to describe the epidemiology, diagnostic criteria, differential diagnosis, treatment, prognostic factors, and treatment outcomes of secretory carcinoma. STUDY DESIGN: A comprehensive search of Lilacs, PubMed, Science Direct, and Web of Science databases was conducted to identify all case reports, letter to the editor, and histopathologic reclassifications regarding salivary gland secretory carcinoma published in English, Spanish, French, and Portuguese. RESULTS: The final analysis included 119 studies, which totaled 642 secretory carcinoma diagnoses, with 239 case reports and 403 diagnostic reclassifications, mostly in the United States. The age range was 5 to 87 years, and cases were predominantly in males (58.7%) and mostly affecting the parotid glands (73.7%). The disease usually presents as a slow-growing, painless mass. The main differential diagnosis is acinic cell carcinoma, and the tumor is usually treated with surgery. The prognosis is considered favorable, although there have been reports of local recurrences, distant metastases, and deaths. CONCLUSIONS: It is important that clinicians become aware of this salivary gland neoplasm and report clinical data, clinical course, management and long-term follow-up. There is an urgent need to conduct more clinical trials, especially on tropomyosin receptor kinase (TRK) inhibitors and other potential target therapy modalities.

Survival data in elderly patients with locally advanced non-small cell lung cancer.

Combined chemoradiation (CRT) is the standard therapy in locally advanced non-small cell lung cancer (NSCLC). Nevertheless, the best approach in the elderly population is still poorly defined. We retrospectively reviewed the charts of elderly (≥ 65 years) patients with unresectable, locally advanced NSCLC, diagnosed at the Brazilian National Cancer Institute between 2003 and 2007. The primary outcome was overall survival (OS), measured from diagnosis until death. Palliative therapy (PT) included best supportive care radiation therapy (RT; ≤ 40 Gy) and palliative chemotherapy. Among patients treated with radical RT, OS was measured from date of treatment beginning until death (OST). One hundred seventy-one patients were included, with median age of 71 years (range 65-90). Thirty-nine percent received PT, 32 % exclusive RT (>40 Gy), and 29 % CRT (concomitant or sequential). Patients treated with RT and CRT had better OS (median 13.7 months [95 % CI 10.9-16.4] and 15.5 months [95 % CI 13.0-17.9]) than PT (median 4.1 months [95 % CI 3.6-4.6]; p < 0.0001). In the multivariate analysis, RT (HR 0.28 [95 % CI 0.18-0.42]; p < 0.0001) and CRT (HR 0.17 [95 % CI 0.1-0.27]; p < 0.0001) were independently correlated to better survival in comparison with PT. Among patients receiving radical RT, the addition of chemotherapy was correlated to longer OST (median 13.8 [95 % CI 10.6-17.0] vs. 10.8 months [95 % CI 8.6-13.1]; p = 0.018). This benefit was confirmed in the multivariate analysis (HR 0.59 [95 % CI 0.36-0.97]; p = 0.039). Elderly patients with locally advanced NSCLC derived significant survival benefit from radical RT and CRT, suggesting that age should not be a contraindication for these aggressive therapeutic strategies.

Amyloid-like fibrils are not detected in non-small cell lung cancer tissue samples.

Some proteins, canonically not associated with amyloid diseases, can aggregate into amyloid-like fibrils under special conditions. Our group hypothesized that stressful cancer microenvironment might induce the formation of insoluble deposits of p53 mutant protein. A cohort of 28 non-small cell lung cancer (NSCLC) patients was used to test the aforementioned hypothesis. Tumor specimens were assessed for TP53 mutations using DNA sequencing and for amyloid formation by Congo red staining. TP53 mutations were present in 57% of patients, whereas no amyloid deposits were detected in tissue sections under polarized light microscopy. Mutant p53 proteins are not associated with the appearance of amyloid-like fibrils in NSCLC samples, and DNA sequencing remains the standard method to detect such abnormality.

Gemcitabine and cisplatin salvage regimen in heavily pretreated metastatic breast cancer: a Brazilian experience.

Gemcitabine and cisplatin combination (Gem-Cis) is a commonly used regimen in metastatic breast cancer (MBC), with proven activity in phase II trials. It is mostly used as a salvage regimen for progressive disease refractory to anthracyclines and taxanes, and when liver dysfunction secondary to liver metastasis precludes these drugs. Retrospective review of medical charts was conducted for patients treated with Gem-Cis for MBC in a single institution in Brazil between January 2004 and July 2007. The purpose of this study was to evaluate the outcomes and toxicity of Gem-Cis in a broad indication, including patients with deteriorated performance status (PS) and liver dysfunction, which were excluded from clinical trials. Fifty-six patients were included. Median age was 52 years, 46.4% were hormone-receptor negative, 57.2% received 3 or more prior chemotherapy lines, and 34 had liver metastasis. The median overall survival (OS) was 7.6 months, the median progression-free survival was 3.3 months, and the response rate was 21.2%. In variable analysis, PS was significantly associated with OS, even after adjusting to other factors. Toxicities included grades 3 or 4 anemia in 19.3%, neutropenia in 21.1%, and thrombocytopenia in 12.3%. Gem-Cis was a relatively active combination in this population that typically carries a poor prognosis. The subgroup of patients with favorable PS experienced longer survival, even when liver metastasis and hepatic dysfunction were a concern. Toxicity was manageable and it was not correlated with PS or liver dysfunction.