Long-term outcome of definitive radiotherapy for cervical esophageal squamous cell carcinoma

Abstract Background The aim of this study was to identify the long-term clinical outcome of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT) for cervical esophageal squamous cell carcinoma (CESCC). Methods We retrospectively reviewed the medical records of 30 patients with CESCC [clinical stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty-six patients underwent elective nodal irradiation for the neck node levels III, IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy. Twenty-six patients underwent concurrent chemotherapy. Initial disease progression sites, locoregional control (LRC) rate, overall survival (OS) rate, and toxicities were retrospectively evaluated. A univariate analysis was performed to identify prognostic factors. Results With a median follow-up of 110 months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5- and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant and both area accounted for 83%, 6% and 11% of the initial progression sites. Unresectable status and M1LYM were significantly associated with poor LRC (p < 0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in 13.3% of patients. During the follow-up, patients without any disease progression did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events, including hypothyroidism and cardiovascular disease, were observed; 5- and 10-year cumulative incidence rates of grade 2 hypothyroidism and ≥grade 3 cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively. Conclusions Definitive radiotherapy yields a cure for patients with CESCC while preserving their laryngopharyngeal function. The poor LRC rate in the advanced stage needs to be overcome for a better prognosis. As the incidence of radiation-induced hypothyroidism and cardiovascular disease was not low, long-term survivors should be followed up for these symptoms

Protective effects of Alda-1, an ALDH2 activator, on alcohol-derived DNA damage in the esophagus of human ALDH2*2 (Glu504Lys) knock-in mice

Alcohol consumption is the key risk factor for the development of esophageal squamous cell carcinoma (ESCC), and acetaldehyde, a metabolite of alcohol, is an alcohol-derived major carcinogen that causes DNA damage. Aldehyde dehydrogenase2 (ALDH2) is an enzyme that detoxifies acetaldehyde, and its activity is reduced by ALDH2 gene polymorphism. Reduction in ALDH2 activity increases blood, salivary and breath acetaldehyde levels after alcohol intake, and it is deeply associated with the development of ESCC. Heavy alcohol consumption in individuals with ALDH2 gene polymorphism significantly elevates the risk of ESCC; however, effective prevention has not been established yet. In this study, we investigated the protective effects of Alda-1, a small molecule ALDH2 activator, on alcohol-mediated esophageal DNA damage. Here, we generated novel genetically engineered knock-in mice that express the human ALDH2*1 (wild-type allele) or ALDH2*2 gene (mutant allele). Those mice were crossed, and human ALDH2*1/*1, ALDH2*1/*2 and ALDH2*2/*2 knock-in mice were established. They were given 10% ethanol for 7 days in the presence or absence of Alda-1, and we measured the levels of esophageal DNA damage, represented by DNA adduct (N2-ethylidene-2′-deoxyguanosine). Alda-1 significantly increased hepatic ALDH2 activity both in human ALDH2*1/*2 and/or ALDH2*2/*2 knock-in mice and reduced esophageal DNA damage levels after alcohol drinking. Conversely, cyanamide, an ALDH2-inhibitor, significantly exacerbated esophageal DNA adduct level in C57BL/6N mice induced by alcohol drinking. These results indicate the protective effects of ALDH2 activation by Alda-1 on esophageal DNA damage levels in individuals with ALDH2 gene polymorphism, providing a new insight into acetaldehyde-mediated esophageal carcinogenesis and prevention

ELECTRON CLOUD AND COLLECTIVE EFFECTS IN THE INTERACTION REGION OF FCC-ee

The FCC-ee is an e⁺e⁻ circular collider designed to accommodate four different experiments in a beam energy range from 91 to 350 GeV and is a part of the Future Circular Collider (FCC) project at CERN. One of the most critical aspects of this new very challenging machine regards the collective effects which can produce instabilities, thus limiting the accelerator operation and reducing its performance. The following studies are focused on the Interaction Region of the machine. This talk will present preliminary simulation results of the power loss due to the wake fields generated by the electromagnetic interaction of the beam with the vacuum chamber. A preliminary estimation of the electron cloud build-up is also reported, whose effects have been recognized as one of the main limitations for the Large Hadron Collider at CERN

A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive and malignant tumor that predominantly affects young males. No standard therapy is currently available for patients with DSRCT and the prognosis remains extremely poor. In this study, we report a thought-provoking DSRCT case. A 24-year-old male was admitted to our hospital with a chief complaint of hematemesis. Computed tomography revealed a retrovesical mass with a splenic hilar tumor, multiple lung and liver tumors and marked lymph node swellings. The source of hematemesis was gastric varices caused by the compression of the splenic vein by a splenic hilar tumor. The patient was provided with a histological diagnosis of DSRCT based on needle biopsy from the liver tumors and the pelvic mass was thought to be the primary lesion. This is a long-term survival case of metastatic DSRCT treated with multimodal therapy including 15 courses of multiagent chemotherapy, radiation therapy for the hepatic portal region using 42.5 Gy, and four instances of therapeutic endoscopy. The prolonged progression-free survival period (15 months) obtained following chemotherapy suggests the chemosensitive feature of the disease. We used a modified P6 regimen (cyclophosphamide, pirarubicin, vincristine, ifosfamide and etoposide) and a modified PAVEP regimen (cyclophosphamide, pirarubicin, etoposide and cisplatin) to decrease severe adverse events and to improve the completion rate of chemotherapy. DSRCT is an aggressive but chemo-sensitive disease, and continuous chemotherapy using an appropriate regimen with possible supportive care is essential for long-term survival. This case report may represent a treatment option for this rare disease