Risk Management for Radiation-Induced Cardiovascular Disease (RICVD): The 2022 Consensus Statement of the Taiwan Society for Therapeutic Radiology and Oncology (TASTRO) and Taiwan Society of Cardiology (TSOC).

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of vinorelbine in lung adenocarcinoma cells.

The standard treatment regimen for patients diagnosed with non-small cell lung cancer (NSCLC) with locally advanced stage III disease is concurrent chemoradiotherapy (CCRT). This study investigated the molecular effects of vinca alkaloid vinorelbine (VNR)-based CCRT. We reviewed the records of 68 patients with stage III NSCLC: 42 patients received VNR-based CCRT, and 26 were treated with radiation alone. Human lung adenocarcinoma cells were used in this study to investigate the molecular effects of glucosylceramide synthase inhibition on VNR-based CCRT. There was response rate of 66.7% with CCRT, which was better than the response rate observed with radiation alone (30.8%; P<0.001). CCRT caused an increase in cell cycle arrest at G2/M phase accompanied by apoptosis. Oxidative c-Jun N-terminal kinase (JNK) activation was involved in the increased apoptosis levels but not the cell cycle arrest. CCRT also induced an increase in ceramide accompanied by a decrease in glucosylceramide that was positively correlated with the cytotoxic effects. Pharmacologically inhibiting glucosylceramide synthase facilitated VNR- and CCRT-induced apoptosis by promoting the JNK pathway. Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of VNR by promoting JNK-mediated apoptosis in lung adenocarcinoma cells.

Isolated osteoradionecrosis of the dens mimicking metastasis of nasopharyngeal carcinoma after radiotherapy.

Nasopharyngeal carcinoma (NPC) is common in southern China, and radiotherapy remains the mainstay of treatment. A rare late complication of this treatment is the development of osteoradionecrosis (ORN), which seldom involves the cervical spine. We describe a 47-year-old female with undifferentiated carcinoma of the nasopharynx, stage II (T2N0M0), who had undergone radiotherapy 51 months prior, and complained of a twitching headache on neck flexion/extension. Imaging studies, including MRI and 18-fluoro-2-deoxyglucose positron emission tomography scan, suggested the diagnosis of cervical spinal metastasis. However, plasma Epstein-Barr virus DNA was undetectable, favoring absence of tumor recurrence. The patient underwent atlantoaxial sublaminar wiring for an unstable spine and a subsequent transoral biopsy, the histopathologic diagnosis of ORN. The postoperative clinical course was uneventful and follow-up MRI, 2 years later, revealed gradual resolution of the lesion. To our knowledge this is the first report of an isolated ORN lesion of the dens confirmed surgically in a patient with a history of previously treated NPC, a lesion at the cervical spine, and inconclusive imaging and biological marker results. We recommend that ORN be suspected until proven otherwise in a previously irradiated patient.

Neurophysiological and histopathological evaluation of low-dose radiation on the cauda equina and postlaminotomy fibrosis: an experimental study in the rat.

STUDY DESIGN: We evaluated the electrophysiological changes to the cauda equina after low-dose external irradiation in a postlaminotomy fibrosis model in rats. OBJECTIVE: To clarify the immediate and long-term electrophysiological responses of antifibrotic radiation therapy in a fibrosis model. SUMMARY OF BACKGROUND DATA: Low-dose perioperative radiation therapy inhibits scar formation. However, its efficacy for preventing fibrosis-induced compressive neuropathy and its potential adverse effect on underlying neural structures have not been studied. METHODS: Twenty-four rats were placed in 3 groups of 8: group I, sham operation (laminar exposure alone) with a single fraction of 700 cGy external irradiation given using a 9-MeV electron beam 24 hours postsurgery; group II, left L5 hemilaminectomy (laminotomy) alone; and group III, left L5 hemilaminectomy with the same radiation protocol as group 1. We recorded mixed-nerve-elicited somatosensory-evoked potentials (M-SSEP)- and dermal (D)-SSEP at the thoracolumbar junction, and L1-L2 interspinous ligament after percutaneously stimulating the posterior tibial nerve at the bilateral medial ankle and L5 dermatomal fields. We compared the potentials recorded immediately before, 30 minutes, 2 weeks, and 1, 2, and 3 months after surgery on the operated and nonoperated sides. We used gross dissection and histologic sections to evaluate the degree of perineural fibrosis and walking-track analysis for neurologic evaluation. RESULTS: Pre- and postoperative (30 minutes and 2 weeks) M- and D-SSEP were not statistically different. In group II, the relative amplitude of D-SSEP (elicited from 5 dermatomes) 1, 2, and 3 months postsurgery was lower; however, the M-SSEP in all groups and D-SSEP of groups I and III remained constant. Histologic evaluation of radiation efficacy showed that the frequency and extent of peridural fibrosis was consistently lower in group II than in group III. CONCLUSION: Low-dose irradiation reduced peridural fibrosis and prevented fibrosis-induced radiculopathy. The radiation caused no adverse neuropathic complications.

Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17 cM interval.

PURPOSE: The genetic basis for gastrointestinal and ampullary carcinomas remains uncertain. This study was performed to pinpoint novel chromosomal region involved in the tumorigenesis of gastrointestinal tract. METHODS: We screened the allelic status on 16 chromosomal arms in a patient with synchronous ampullary carcinoma and gastric cancer, but who had no family history of familial cancer syndrome. The significance of the shared 14q deletion was examined on clinical cohorts of sporadic gastric (n=12) and ampullary (n=10) carcinoma, respectively. Then, high-density allelotype mapping was performed on 14q32 by using 23 microsatellite markers for the synchronous tumors. RESULTS: The synchronous gastric and ampullary carcinomas had no frameshift mutations in the APC, MSH2, MSH3, and MSH6 genes. Among the microsatellite markers screened, only D14S267 showed identical loss in the synchronous tumors. The same allelic loss was also detected in one of ampullary carcinomas (10%) and two of gastric cancers (16.7%). Fine mapping of 14q determined a minimally deleted region between D14S65 and D14S1010 (17 centiMorgans) for the synchronous tumors. CONCLUSIONS: This study illustrates a paradigm using molecular genetic approach in identifying chromosome 14q32 that may harbor a tumor suppressor gene involved in the pathogenesis of a subset of gastrointestinal and ampullary malignancies.

Clinical significance of allelotype profiling for urothelial carcinoma.

OBJECTIVES: To perform a global loss of heterozygosity (LOH) analysis on a cohort of urothelial carcinoma to investigate the clinical implication of specific chromosomal loss. Allelic deletions detected as LOH have been used to study the markers for carcinogenesis. METHODS: We examined the allelic loss on 14 chromosomal regions in a total of 71 cases of urothelial carcinoma. The results were analyzed in relation to biologic indicators of urothelial carcinoma and the clinical outcome with a mean follow-up of 101 months. RESULTS: The incidence of LOH in order of frequency was 9p (54.9%), 9q (49.3%), 13q (40.8%), 14q (40.8%), 10q (39.4%), 17p (39.4%), 8p (38.0%), 21q (36.6%), 11p (31.0%), 18q (23.9%), 4q (21.1%), 3p (16.9%), 6q (14.1%), and 1q (8.5%). Positive association with one of the indicators was observed in 3p, 9p, 9q, 10q, 14q, and 18q. The chromosomes that correlated with two biologic indicators were 4q, 6q, 11p, 17p, and 21q. Univariate analysis found that patients having combined 9p and 14q deleted tumors had particularly poor long-term survival compared with those with other patterns of chromosomal alterations (P = 0.01). In the multivariate model, nonpapillary tumors had a greater risk of recurrence, and stage classification was the only important indicator in predicting patient survival (P = 0.04). CONCLUSIONS: LOH assessment does not provide independent prognostic value compared with stage classification. However, chromosomes 4q, 6q, 9p, 11p, 14q, 17p, and 21q may harbor important tumor suppressor genes involved in the progression of urothelial carcinogenesis.