Prolidase could be considered a sign of inflammation associated with cigarette smoking.

Objectives: Smoking causes inflammation, thickening, and narrowing of the airways. This inflammatory process is a reaction to free radicals and oxidants. Smoking affects collagen metabolism and tissue remodeling. Prolidase enzyme hydrolyzes iminodipeptides with hydroxyproline and C terminal proline. It plays a crucial role in the metabolism of collagen and the remodeling of the matrix. The present study aims to reveal the association of prolidase with inflammation caused by smoking and to compare serum prolidase levels with oxidative-antioxidative status in healthy individuals. Methods: A total of 76 participants (38 smokers and 38 nonsmokers) were involved in the present study. Serum cotinine levels were measured to show the exposure to nicotine in tobacco smoke by using the competitive inhibition enzyme immunoassay method. Serum prolidase, total oxidant status (TOS), and total antioxidant status (TAS) were determined by the enzyme-linked immunosorbent (ELISA) method, respectively. The correlation between smoking, serum prolidase levels, TOS, and TAS was investigated. Results: TAS and serum prolidase levels of smokers were considerably lower than those in non-smokers (p < 0.001, p = 0.012 respectively). However, no differences were observed in TOS between the two groups. There was no statistically significant correlation between serum prolidase levels, TAS, and TOS. Moreover, no relationship was observed between respiratory function parameters and serum prolidase levels. Conclusion: To the best of our knowledge, the present study is the first study to demonstrate the role of prolidase in smoking-related inflammation. The results achieved in the present study suggest that smoking creates an imbalance in the oxidant-antioxidant activity. Smoking decreases prolidase levels, leading to decreased collagen turnover. Chronic pulmonary disease might be related to this decrease in collagen turnover.

Who would be the winner? A prognostic nomogram for predicting the benefit of postoperative radiotherapy ± chemotherapy in patients with locally advanced gastric cancer: TROD-02-01 study.

OBJECTIVES: We aimed to develop a basic, easily applicable nomogram to improve the survival prediction of the patients with stage II/III gastric cancer (GC) and to select the best candidate for postoperative radiotherapy (RT). METHODS: In this multicentric trial, we retrospectively evaluated the data of 1597 patients with stage II/III GC after curative gastrectomy followed by postoperative RT ± chemotherapy (CT). Patients were divided into a training set (n = 1307) and an external validation set (n = 290). Nomograms were created based on independent predictors identified by Cox regression analysis in the training set. The consistency index (C-index) and the calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. A nomogram was created based on the predictive model and the identified prognostic factors to predict 5-year cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: The multivariate Cox model recognized lymph node (LN) involvement status, lymphatic dissection (LD) width, and metastatic LN ratio as covariates associated with CSS. Depth of invasion, LN involvement status, LD width, metastatic LN ratio, and lymphovascular invasion were the factors associated with PFS. Calibration of the nomogram predicted both CSS and PFS corresponding closely with the actual results. In our validation set, discrimination was good (C-index, 0.76), and the predicted survival was within a 10% margin of ideal nomogram. CONCLUSIONS: In our relatively large cohort, we created and validated both CSS and PFS nomograms that could be useful for underdeveloped or developing countries rather than Korea and Japan, where the D2 gastrectomy is routinely performed. This could serve as a true map for oncologists who must make decisions without an experienced surgeon and a multidisciplinary tumor board.

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study.

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26-87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients' performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78-7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79-6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12-2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.

Thoracic Radiotherapy Effect on the Outcome in Extensive Stage Small Cell Lung Cancer.

OBJECTIVE: To evaluate the efficacy of thoracic radiotherapy to primary site in patients with extensive stage small cell lung cancer (SCLC) who had responded completely to systemic chemotherapy. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Departments of Radiation and Medical Oncology, Baskent University and Dr. Ersin Arslan Research and Training Hospital in Turkey, between the years of 2011 and 2020. METHODOLOGY: The study included 125 patients with extensive stage SCLC. Demographic data and outcomes of chemotherapy and radiotherapy were collected. The efficacy of thoracic radiotherapy to primary site was evaluated in patients who had responded completely to systemic chemotherapy, in terms of progression-free survival and overall survival (OS). RESULTS: The median follow-up time was 12 months and 98 (78.4%) patients died during follow-up. Seventy-three (58.4%) patients had complete response. Progression-free survival (PFS) for complete responder patients was 8 months, and OS for the whole group was found 13 months. Twenty (16%) patients received thoracic radiotherapy to primary site after complete response to platinum etoposide combination treatment. Patients receiving thoracic radiotherapy had better OS than those who did not (19 versus 12 months respectively and p=0.002). Patients receiving thoracic radiotherapy had better PFS than those who did not (11 versus 8 months, respectively, and p=0.01). CONCLUSION: Thoracic radiotherapy to primary site may improve the survival outcomes in extensive stage SCLC patients who had complete response to initial systemic chemotherapy. KEY WORDS: Small cell lung cancer, Thoracic radiotherapy, Complete response, Outcomes, Lung cancer.

Radiosurgery effects and adverse effects in symptomatic eloquent brain-located Cavernomas.

In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who were not eligible for surgery and treated with SRS. Between January 2013 and December 2018, 53 patients with cavernomas were treated using SRS with the CyberKnife® system. Patients' diseases were deeply located or were in subcortical functional brain regions. In addition to bleeding, 23 (43.4%) patients had epilepsy, 12 (22.6%) had neurologic symptoms and 16 patients (30.2%) had severe headaches. The median volume was 741 (range, 421-1351) mm3, and the median dose was 15 (range, 14-16) Gy in one fraction. After treatment, six (50%) of 12 patients with neurologic deficits still had deficits. Rebleeding after treatment developed in only two (3.8%) patients. The drug was completely stopped in 14 (60.9%) out of 23 patients who received epilepsy treatment, and the dose of levetiracetam decreased from 2000 mg to 1000 mg in four (17.3%) of nine patients. Radiologically, complete response (CR) was observed in 13 (24.5%) patients, and partial responses (PR) were observed in 32 (60.2%) patients. Clinical response of CR was observed in 30 (56.6%) patients, PR was observed in 16 (30.2%), stable disease (SD) was observed in three (5.7%) and four (7.5%) patients progressed. In conclusion, SRS applied in the appropriate dose schedule may be an effective and reliable method in terms of symptom control and prevention of rebleeding, especially in patients with inoperable cavernomas.

Oncological outcomes for encapsulated papillary carcinoma of the breast: Multicentric study of Turkish Society for Radiation Oncology breast cancer study group (TROD 06-014 study).

BACKGROUND: Encapsulated papillary carcinoma (EPC) is a rare malignant papillary breast cancer accounting for approximately .5%-2% of all breast tumors. The aim of this multicenter study was to evaluate clinicopathologic features of EPC in addition to oncological outcomes and radiotherapy (RT) details. METHODS: From 10 different academic hospitals in Turkey, we obtained pathology reports of 80 patients with histologically confirmed EPC between 2005 and 2022. Demographic, diagnostic, and treatment data were collected from medical records, retrospectively. Local failure, distant progression, toxicity-adverse effects, overall survival (OS), and disease-free survival were evaluated, and survival analyzes were performed using the Kaplan-Meier method. RESULTS: Eighty patients with the diagnosis of misspelled sorry (ECP) were retrospectively evaluated. The median age of the patients was 63 (range, 35-85). After a median follow-up of 48 (range; 6-206) months, local recurrence was observed in three patients (4%). Local recurrence was less common in the patients who received whole breast RT with a tumour bed boost (p = .025). There were not any distant metastasis or disease-related death. RT was applied to 61% of the cases, and no treatment-related grade 3 or higher toxicity was reported in any of the patients. Five year OS, cancer-specific survival (CSS), and  were observed as 85%, 100%, and 96%, respectively. CONCLUSIONS: ECP is a rare, slow-progressing breast carcinoma associated with good prognosis, it is a disease of elderly patient, and usually occurs in postmenopausal women. It responds extremely well to optimal local treatments and appropriate adjuvant treatments on a patient basis, and has excellent OS and CSS ratios.

Results of salvage treatment with CyberKnife® fractioned radiosurgery in recurrent large chordoma.

AIM: Chordomas and chondrosarcomas are locally destructive tumors with high progression or recurrence rates after initial multimodality treatment. This report examined the role of radiosurgery in patients who were considered inoperable after the recurrence of large chordoma disease having undergone previous surgery and/or radiotherapy. METHODS: All patients who were referred to Okmeydani Education and Research Hospital between 2012 and 2019 for treatment of recurrent or metastatic chordoma and considered not suitable for surgical treatment were included in the study. We included patients presenting with recurrent or metastatic chordoma, those who had undergone surgery and/or radiotherapy and were now considered to be surgically inoperable, patients whose tumors could lead to severe neurologic or organ dysfunction when resected, and those who underwent salvage treatments for definitive or palliative purposes with radiosurgery. After radiosurgical salvage therapy was performed on 13 patients using a CyberKnife® device, the effect of this treatment in terms of local control and survival and the factors that might affect it was investigated. Thirteen lesions were local (in-field) recurrence, and five lesions were closer to the primary tumor mass or seeding metastatic lesions. Tumor response was evaluated using the Response Evaluation Criteria for Solid Tumors (RECIST) system and volumetric analysis. RESULTS: The median age of the 13 patients was 59 years, and the median tumor volume of 18 lesions was 30.506 cc (R: 6884.06-150,418.519 mL). The median dose was 35 Gy (R: 17.5-47.5), the median fraction was 5 (R: 1-5), and the median biological effective dose BED2.45 was 135 Gy (R: 63.82-231.68). The median time for radiosurgery was 30 months after the first radiotherapy and 45 months after the last surgery. The median follow-up time was 57 (R: 15-94) months. The progression-free survival was 24 months. The median survival was 33.9 months. Local control was achieved in 84.6% of patients after 1 year, and 76.9% after 2 years, with the mass shrinking or remaining stable. Survival after recurrence was 69.2% for the 1st year, 61.5% for the 2nd year, and 53.8% for the 5th year. CONCLUSION: In patients with recurrent and surgically inoperable chordomas, stereotactic body radiation therapy (SBRT) is a reliable and effective treatment method. Promising result has been obtained with radiosurgery treatment under local control of patients. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Stereotactic Radiotherapy for Adrenal Metastases: A Multi-Institutional Review of Patient Characteristics and Outcomes - Turkish Society for Radiation Oncology SBRT Group Study (Trod SBRT 10-004).

INTRODUCTION: This study aimed to report the outcomes of stereotactic body radiotherapy (SBRT) for adrenal metastasis in a retrospective multi-institutional cohort. METHODS: The outcomes of 124 patients with 146 adrenal metastases who underwent SBRT within 11 years (2008-2019) were retrospectively evaluated. Survival outcomes were analyzed by the Kaplan-Meier method. Patient, tumor, and treatment characteristics and their effects on survival, local control (LC), and toxicity outcomes were analyzed by log-rank and multivariate Cox regression methods. RESULTS: The median age was 60 years. The most frequent primary tumor site was the lung, followed by the gastrointestinal system and breast. The adrenal gland was the only metastatic site in 49 (40%) patients. Median biologically effective dose (BED)10 was 61 Gy. The overall LC rate was 83%, and it was positively correlated with the BED10 and fraction dose. The 1- and 2-year local recurrence-free survival, overall survival (OS), and progression-free survival (PFS) rate was 79% and 69%, 83% and 60%, and 31% and 12%, respectively. OS significantly improved with non-lung cancer and <4-cm lesion and PFS with a fraction dose ≥8 Gy, BED10 >65 Gy, and an isolated adrenal metastasis. Fourteen patients reported an acute toxicity, and late toxicity was observed in 3 patients, including one grade 5. CONCLUSION: A satisfactory LC rate was achieved for adrenal metastasis via SBRT. A higher BED10 and fraction dose were positive prognostic factors for tumor control. However, the main problem is DM in these patients, and systemic treatment options are needed to be improved.

Evaluation of Nutritional Status and Anxiety Levels in Patients Applying to the Radiation Oncology Outpatient Clinic during the COVID-19 Pandemic: Turkish Society for Radiation Oncology Group Study (TROD 12:02).

Cancer patients often face malnutrition, which negatively affects their response to cancer treatment. This study aims to analyze the effects of the COVID-19 pandemic on nutritional status and anxiety in cancer patients with different types and stages of cancer. This is a cross-sectional cohort study that includes 1,252 patients with varying cancer types from 17 radiation oncology centers. The nutritional risk scores (NRS-2002) and coronavirus anxiety scale (CAS) scores of all patients were measured. NRS-2002 ≥ 3 and CAS ≥ 5 were accepted as values at risk. Of all patients, 15.3% had NRS-2002 ≥ 3. Breast cancer was the most prevalent cancer type (24.5%) with the lowest risk of nutrition (4.9%, p < 0.001). Nutritional risk was significantly higher in patients with gastrointestinal cancer, head and neck cancer, and lung cancer (p < 0.005) and in patients with stage IV disease (p < 0.001). High anxiety levels (CAS ≥ 5) were significantly related to voluntary avoidance and clinical postponement of hospital visits due to the pandemic (p < 0.001), while clinical postponement was particularly frequent among patients with NRS-2002 < 3 (p = 0.0021). Fear and anxiety in cancer patients with COVID-19 cause hesitations in visiting hospitals, leading to disrupted primary and nutritional treatments. Thus, nutritional monitoring and treatment monitoring of cancer patients are crucial during and after radiotherapy.

Influenza viruses and SARS-CoV-2 in adult: 'Similarities and differences'.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing a global pandemic starting from December 2019, showed a course that resulted in serious mortality in the world. In order to understand SARSCoV-2 better, here we aimed to compare the similar and different characteristics of Influenza viruses occurring in the same season with SARS-CoV-2. MATERIALS AND METHODS: A total of 144 patients (31 patients with COVID-19, 62 patients with H1N1 influenza, and 51 patients with influenza B) were included in the study. Demographic findings, chronic diseases, laboratory values, chest x-ray, and chest CT findings of the patients were evaluated retrospectively. RESULT: Median age of the COVID-19 patients and rate of male patients were higher than other patient groups (55 years; p< 0.001) (61% male; p< 0.001). The most common chronic medical conditions were hypertension and diabetes. Platelet numbers and alanine aminotransferase values were significantly higher in COVID-19 patients. Radiologically, bilateral (74.2%) and nonspecific distribution (58.1%), ground-glass opacities with consolidation (51.6%), patchy image (25.8%), ground-glass opacities with interstitial changes (22.6%) and halo sign (22.6%) were quite evident than other groups in COVID-19 patients (p< 0.05). CONCLUSIONS: We suggest that due to the higher PLT values observed in COVID-19 patients, initiation of anticoagulant therapy should be considered in the early stage and routine follow-up with d-dimer and fibrinogen should be applied for suspected patients. Moreover, attention should be paid in terms of possible liver toxicity of the drugs to be used in treatment due the higher ALT values observed in COVID-19 patients. Since we did not detect SARS-CoV-2 and influenza viruses concurrently in the same patient, it may be helpful to focus on only one virus in a patient with symptoms, and radiographic differences can be used to differentiate COVID-19 from influenza.

Role of serological rapid antibody test in the management of possible COVID-19 cases.

BACKGROUND: Although the detection of viral particles by reverse transcription polymerase chain reaction (RT-PCR) is the gold standard diagnostic test for coronavirus disease 2019 (COVID-19), the false-negative results constitute a big challenge. AIM: To examine a group of patients diagnosed and treated as possible COVID-19 pneumonia whose multiple nasopharyngeal swab samples were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR but then serological immunoglobulin M/immunoglobulin G (IgM/IgG) antibody against SARS-CoV-2 were detected by rapid antibody test. METHODS: Eighty possible COVID-19 patients who had at least two negative consecutive COVID-19 RT-PCR test and were subjected to serological rapid antibody test were evaluated in this study. RESULTS: The specific serological total IgM/IgG antibody against SARS-CoV-2 was detected in twenty-two patients. The mean age of this patient group was 63.2± 13.1-years-old with a male/female ratio of 11/11. Cough was the most common symptom (90.9%). The most common presenting chest computed tomography findings were bilateral ground glass opacities (77.2%) and alveolar consolidations (50.1%). The mean duration of time from appearance of first symptoms to hospital admission, to hospital admission, to treatment duration and to serological positivity were 8.6 d, 11.2 d, 7.9 d, and 24 d, respectively. Compared with reference laboratory values, serologically positive patients have shown increased levels of acute phase reactants, such as C-reactive protein, ferritin, and procalcitonin and higher inflammatory markers, such as erythrocyte sedimentation rate, lactate dehydrogenase enzyme, and fibrin end-products, such as D-dimer. A left shift on white blood cell differential was observed with increased neutrophil counts and decreased lymphocytes. CONCLUSION: Our study demonstrated the feasibility of a COVID-19 diagnosis based on rapid antibody test in the cases of patients whose RT-PCR samples were negative. Detection of antibodies against SARS-CoV-2 with rapid antibody test should be included in the diagnostic algorithm in patients with possible COVID-19 pneumonia.

Upfront thoracic radiotherapy to primary lesion improves outcomes in patients with stage IV non-small cell lung cancer harboring EGFR mutations.

PURPOSE: The role of thoracic radiotherapy in the treatment of metastatic EGFR mutant non-small cell lung cancer (NSCLC) patients in literature data are insufficient.The purpose of this study was to examine the effectiveness of upfront thoracic radiotherapy in metastatic EGFR mutant NSCLC patients treated with chemotherapy or tyrosine kinase inhibitors (TKI). METHODS: This study was designed as a hospital-based retrospective observational case-series study. A total of 141 patients with metastatic EGFR mutant NSCLC who were followed in two different oncology centers in Turkey between 2014 and 2019 have been included into this study. RESULTS: The median patient age was 63 years (range 35-91). EGFR mutation results of exon 19 deletion, exon 21 mutation and exon 18 mutation were found in 82 (58.2%), 56 (39.7%) and 3 (2.1%) patients, respectively.The median follow-up time was 22 months and 94 (33.3%) patients died during follow-up. Median overall survival (OS) was 26 months and progression free survival (PFS) (for first line treatment) was 10 months for the whole cohort, respectively. Radiotherapy was given to the primary tumor site in 32 (22.6%) patients. Patients receiving radiotherapy to primary tumor site had better OS than those who had not (31 versus 23 months respectively, p=0.02). Survival advantage was also seen for patients group taking TKI at upfront setting (33 versus 23 months respectively, p=0.05). CONCLUSION: In this study, we have shown that upfront thoracic radiotherapy to primary lesion as combination with EGFR-TKI treatment may improve the outcome in advanced stage IV NSCLC patients harboring EGFR mutations.

The Relationship between COVID-19 Severity and Bacillus Calmette-Guérin (BCG)/ Mycobacterium tuberculosis exposure history in healthcare workers: a multi-center study.

The COVID-19 pandemic has brought countries' health services into sharp focus. It was drawn to our group's attention that healthcare workers (HCWs) had a lower mortality rate against higher COVID-19 incidence compared to the general population in Turkey. Since risk of exposure to tuberculosis bacillus among healthcare workers are higher than the population, we aimed to investigate if there is a relationship between BCG and Mycobacterium tuberculosis exposure history with COVID-19 severity in infected HCWs. This study was conducted with 465 infected HCWs from thirty-three hospitals to assess the relationship between COVID-19 severity (according to their hospitalization status and the presence of radiological pneumonia) and BCG and Mycobacterium tuberculosis exposure history. HCWs who required hospital admission had significantly higher rates of chronic diseases, radiological pneumonia, and longer working hours in the clinics. Higher rates of history of contact and care to tuberculosis patients, history of tuberculosis, and BCG vaccine were observed in hospitalized HCWs. HCWs who had radiological pneumonia had a significantly increased ratio of history of care to tuberculosis patients and a higher family history of tuberculosis. The findings from our study suggest that the lower mortality rate despite the more severe disease course seen in infected HCWs might be due to frequent exposure to tuberculosis bacillus and the mortality-reducing effects of the BCG vaccine.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.

Role of vaginal brachytherapy boost following adjuvant external beam radiotherapy in cervical cancer: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-002).

OBJECTIVE: There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer. METHODS: Patients treated with post-operative external beam radiotherapy ± chemotherapy ± vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy. RESULTS: A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors. CONCLUSION: Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer.

Microbiome and Longevity: High Abundance of Longevity-Linked Muribaculaceae in the Gut of the Long-Living Rodent Spalax leucodon.

With a world population living longer as well as marked disparities in life expectancy, understanding the determinants of longevity is one of the priority research agendas in 21st century life sciences. To this end, the blind mole-rat (Spalax leucodon), a subterranean mammalian, has emerged as an exceptional model organism due to its astonishing features such as remarkable longevity, hypoxia and hypercapnia tolerance, and cancer resistance. The microbiome has been found to be a vital parameter for cellular physiology and it is safe to assume that it has an impact on life expectancy. Although the unique characteristics of Spalax make it an ideal experimental model for longevity research, there is limited knowledge of the bacterial composition of Spalax microbiome, which limits its in-depth utilization. In this study, using 16S rRNA amplicon sequencing, we report the gut and skin bacterial structure of Spalax for the first time. The diversity between fecal and skin samples was manifested in the distant clustering, as revealed by beta diversity analysis. Importantly, the longevity-linked Muribaculaceae bacterial family was found to be the dominating bacterial taxa in Spalax fecal samples. These new findings contribute toward further development of Spalax as a model for longevity research and potential linkages between microbiome composition and longevity.

Stereotactic radiotherapy in patients with oligometastatic or oligoprogressive gynecological malignancies: a multi-institutional analysis.

INTRODUCTION: Data supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer. METHODS: The clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival. RESULTS: A total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9-95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0-16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities. CONCLUSIONS: Patients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival.