Stereotactic ablative radiation therapy for spinal metastases: experience at a single Brazilian institution.

BACKGROUND: This study aims to assess the clinical outcomes of patients with spine metastases who underwent stereotactic ablative radiation therapy (SABR) as part of their treatment. SABR has arisen as a contemporary treatment option for spinal metastasis patients with good prognoses. MATERIALS AND METHODS: Between November 2010 and September 2018, Spinal SABR was performed in patients with metastatic disease in different settings: radical (SABR only), postoperative (after decompression and/or fixation surgery), and reirradiation. Local control (LC), pain control, overall survival (OS) and toxicities were reported. RESULTS: Eighty-five patients (corresponding to 96 treatments) with spine metastases were included. The median age was 59 years (range, 23-91). In most SA BR (82.3%, n = 79) was performed as the first local spine treatment, while in 12 settings (12.5%), fixation and/or decompression surgery was performed prior to SABR. Two-year overall survival rate was 74.1%, and median survival was 19 months. The LC rate at 2 years was 72.3%. With regard to pain control, among 67 patients presenting with pain before SA BR, 83.3% had a complete response, 12.1% had a partial response, and 4.6% had progression. Vertebral compression fractures occurred in 10 patients (11.7%), of which 5 cases occurred in the reirradiation setting. Radiculopathy and myelopathy were not observed. No grade III or IV toxicities were seen. CONCLUSION: This is the first study presenting a Brazilian experience with spinal SA BR, and the results confirm its feasibility and safety. SABR was shown to produce good local and pain control rates with low rates of adverse events.

Accelerated partial breast irradiation: Current status with a focus on clinical practice.

Accelerated partial breast irradiation (APBI), a radiation technique in which only the tumor bed is treated, has now become an acceptable radiation modality for selected early-stage breast cancer patients. Compared to conventional whole breast irradiation (WBI), APBI has some benefits with regard to the reduced total irradiated breast volume and the shorter treatment time. The role of APBI, which can be delivered using diverse techniques, has been evaluated in several prospective randomized phase III trials. These clinical trials demonstrate diverging outcomes relating to local recurrence, while establishing comparable effect in terms of survival between APBI with WBI. The aim of this study was to review the current status of APBI with a focus on clinical practice.

Stereotactic Body Radiation Therapy for Biopsy-Proven Primary Non-Small-Cell Lung Cancer: Experience of Patients With Inoperable Cancer at a Single Brazilian Institution.

Purpose Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for patients with non-small-cell lung cancer (NSCLC). We report the clinical outcomes and toxicity for patients with inoperable primary NSCLC treated with SBRT. Methods Between 2007 and 2015, 102 consecutive lung lesions were treated with SBRT at our center, of which 59 primary NSCLC lesions (from 54 patients with inoperable disease) were retrospectively reviewed (43 lesions were excluded because of metastases or because there was no biopsy specimen). We report infield local control (LC) per SBRT target, regional or distant failure-free survival, and overall survival (OS) per patient, using Kaplan-Meier estimates. Serious toxicity was retrospectively scored using Common Terminology Criteria for Adverse Events, version 4. Results Most of the 54 patients were men (n = 41; 76%), median age was 75 years; stage IA (n = 36; 66%) and adenocarcinoma (n = 43; 80%) were the most common stage and histologic diagnosis, respectively. Five patients had two lung lesions. A median of three fractions (range, 3 to 5 fractions) and a total median dose of 54 Gy (range, 45 to 60 Gy) per lesion were prescribed. The median follow-up was 17.8 months (range, 4 to 56.4 months). The 2-year rates of LC, regional or distant failure-free survival, and OS were 89.1% (95% CI, 72.2% to 96%), 79% (95% CI, 59.8% to 89.8%), and 80% (95% CI, 64% to 89.8%), respectively. Grade 3 to 4 toxicities were observed in two patients (3%): grade 3 pneumonitis (n = 1) and grade 4 skin toxicity (n = 1). Conclusion SBRT results in high rates of 2-year LC, regional or distant failure-free survival, and OS with low rates of severe toxicity in patients with inoperable primary NSCLC disease.

Expression of the nonclassical HLA-G and HLA-E molecules in laryngeal lesions as biomarkers of tumor invasiveness.

INTRODUCTION: HLA-G and HLA-E are two nonclassical class I molecules, which have been well recognized as modulators of innate and adaptive immune responses, and the expression of these molecules in virus infected cells has been associated with subversion of the immune response. OBJECTIVE: In this study we performed a cross-sectional study, systematically comparing the expression of HLA-G and HLA-E in benign, pre-malignant and malignant laryngeal lesions, correlating with demographic and clinical variables and with the presence of high-risk and low-risk HPV types. MATERIALS AND METHODS: Laryngeal lesions were collected from 109 patients and stratified into 27 laryngeal papillomas, 17 dysplasias, 10 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastases, 28 laryngeal carcinomas with metastasis along with their respective draining cervical lymph nodes, and 10 normal larynx specimens. The expression of HLA-G and HLA-E molecules was determined by immunohistochemistry. HPV DNA detection and typing was performed using generic and specific primers. RESULTS: HLA nonclassical molecules showed a distinct distribution pattern, according to the larynx lesion grade. HLA-G expression increased in benign and premalignant lesions, and gradually decreased in invasive carcinomas and in respective draining cervical lymph nodes. Conversely, HLA-E expression increased as far as lesion grade increased, including increased molecule expression in the draining lymph nodes of malignant lesions. Only 17 (15.6%) patients were HPV DNA positive. CONCLUSIONS: Overexpression of HLA-E and underexpression of HLA-G appear to be good markers for malignant larynx lesion.

BUBR1 expression in benign oral lesions and squamous cell carcinomas: correlation with human papillomavirus.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, an important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also a significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence on BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC, but not in benign oral lesions.

Low expression of human histocompatibility soluble leukocyte antigen-G (HLA-G5) in invasive cervical cancer with and without metastasis, associated with papilloma virus (HPV).

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICC(W))] and absence [ICC without metastasis (ICC(WT))] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICC(WT) (n=52 patients) and ICC(W) (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.