The Role of Conventionally Fractionated Radiotherapy and Stereotactic Radiotherapy in the Treatment of Carcinoid Tumors and Large-Cell Neuroendocrine Cancer of the Lung

The occurrence of neuroendocrine tumors among the diagnosed neoplasms is extremely rare and is associated with difficulties in undertaking effective therapy due to the histopathological differentiation of individual subtypes and the scarce clinical data and recommendations found in the literature. The choice of treatment largely depends not only on its type, but also on the location and production of excess hormones by the tumor itself. Common therapeutic approaches include surgical removal of the tumor, the use of chemotherapy, targeted drug therapy, peptide receptor radionuclide therapy, and the use of radiation therapy. This article reviews the current knowledge on the classification and application of radiotherapy in the treatment of lung NETs. Case reports were presented in which treatment with conventional radiotherapy, radical and palliative radiochemotherapy, as well as stereotactic fractionated radiotherapy in the treatment of typical (TC) and atypical (AT) lung carcinoids and large cell neuroendocrine carcinoma (LCNC) were used. We hope that the solutions presented in the literature will allow many radiation oncologists to make the best, often personalized decisions about the therapeutic qualifications of patients.

EPID-07. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OF PATIENTS WITH DIFFUSE GLIOMA IN BRAZIL: PRELIMINARY RESULTS OF A MULTICENTRIC RETROSPECTIVE STUDY - LACOG 0619

INTRODUCTION In Brazil, most of the 9,196 deaths due to brain cancers in 2017 were gliomas. There is a dearth of epidemiological data on diffuse glioma in Brazil. METHODS LACOG 0619 is a multicentric retrospective cohort study, which included patients from nine tertiary oncology centers. Patients aged ≥18 years with histologically proven astrocytoma, oligodendroglioma, oligoastrocytoma or glioblastoma diagnosed from June 2010 to June 2019 were included. The study protocol was approved by each Institutional Review Board. RESULTS 642 patients were included in the analysis. Median age was 51.0 (19-91) years. Most patients were male (n=364, 56.8%), 175 (27.3%) had ECOG 0-1, and 480 (74.8%) had private healthcare insurance. Neurological symptoms were present in 568 (88.5%) patients at diagnosis, and 263 (41.0%) had a history of seizure before surgery. Regarding histology, 361 (56.2%) had glioblastoma, 162 (25.2%) had astrocytoma, 90 (14.0%) had oligodendroglioma, and 23 (3.6%) had glioma NOS. Gross total resection was performed in 168 (26.2%), subtotal resection in 292 (45.5%), biopsy in 108 (16.8%), conventional radiotherapy in 380 (59.2%), and hypofractionation in 44 (6.9%) patients. Concomitant chemoradiotherapy was administered to 370 (57.6%) patients, mostly with temozolamide (n=362, 97.8%). Furthermore, 434 (67.7%) patients received maintenance chemotherapy, 398 with temozolamide (< 6 cycles in 112 [28.4%], 6 cycles in 75 [18.8%], and >6 cycles in 214 [3.8%]). Median follow-up was 29 months (26-33). Median OS according to histology was: 35 months (95%CI 26-46) for glioblastoma, 91 months (95%CI 35-NR) for glioma NOS, and not reached for astrocytoma and oligodendroglioma. Median OS by number of temozolamide maintenance cycles was 18 months (95%CI 15-24) for < 6 cycles and not reached for 6 cycles or more. CONCLUSIONS This is the first multicentric cohort evaluating Brazilian patients with diffuse glioma, providing important data on epidemiology, treatment patterns, and survival in the country.

RBIO-05. THE IMPACT OF STEREOTATIC RADIOSURGERY (SRS) FOR THE RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS (NGGCTS) FOLLOWING CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY

OBJECTIVE To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. METHODS The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter > 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. RESULTS The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P=0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP >500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P=0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. CONCLUSION SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the therapeutic efficacy of conventional radiotherapy combined with SRS warrants further investigations in a large-scale randomized controlled clinical trials.

Focused Versus Conventional Radiotherapy in Spinal Oncology: Is There any Difference in Fusion Rates and Pseudoarthrosis?

IntroductionRadiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newerfocused radiotherapy strategies with enhanced conformalitycould offer improved fusion rates for these patients, but this has not been confirmed.MethodsWe performed a retrospective analysis of patients at three tertiary care academic institutions withprimary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used theLenke fusion score to grade fusion status at6 and 12-months after surgery. Secondary outcomes includedclinical pseudoarthrosis, wound complications, and the effect of radiation timing, radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location,and use of autograft on fusion outcomes.ResultsAfter reviewof 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy,20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such assmoking status,obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p=0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p=0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohortcompared to patients in the focused radiotherapy cohort (19.1% versus 0%,p=0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use ofintra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p=0.043). ConclusionFocused radiotherapy may be associated withan improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategiesin patients with spinal tumors.Use of autograft at the time of surgery may be associated with improved 12-month fusion rates.Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma

Cholangiocarcinomas (CCAs) are rare but aggressive tumors of the bile ducts. CCAs are often diagnosed at an advanced stage and respond poorly to current conventional radiotherapy and chemotherapy. High mobility group A1 (HMGA1) is an architectural transcription factor that is overexpressed in multiple malignant tumors. In this study, we showed that the expression of HMGA1 is frequently elevated in CCAs and that the high expression of this gene is associated with a poor prognosis. Functionally, HMGA1 promotes CCA cell proliferation/invasion and xenograft tumor growth. Furthermore, HMGA1 transcriptionally activates RAD51 by binding to its promoter through two HMGA1 response elements. Notably, overexpression of HMGA1 promotes radioresistance whereas its knockdown causes radiosensitivity of CCA cells to X-ray irradiation. Moreover, rescue experiments reveal that inhibition of RAD51 reverses the effect of HMGA1 on radioresistance and proliferation/invasion. These findings suggest that HMGA1 functions as a novel regulator of RAD51 and confers radioresistance in cholangiocarcinoma.