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.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+ rectal cancer: Istanbul R-02 phase II randomized study.

Radiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group. Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module (EORTC QLQ-CR29) was administered at baseline and at three and six months after CRT. A total of 60 patients with LARC randomized to receive IC-CRT (n = 30) or LC-CRT (n = 30) were included in this phase II randomized trial. No significant difference was noted between groups in terms of pathological outcomes, including pathological response rates (ypT0N0-complete response: 23.3% vs. 16.7%, respectively, and ypT0-2N0-downstaging: 50% for each; p = 0.809) and Dworak score-based pathological tumor regression grade (Grade 4-complete response: 23.3 vs. 16.7%, p = 0.839). The 5-year overall survival (73.3 vs. 86.7%, p = 0.173) rate was also similar. The acute radiation dermatitis (p < 0.001) and any hematological toxicity (p = 0.004) rates were significantly higher in the LC-CRT group, while no significant difference was noted between treatment groups in terms of baseline, third month, and sixth month EORTC QLQ-CR29 scores.

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.

A Hypofractionated Radiotherapy Schedule with a Simultaneous Integrated Boost for Breast Cancer: Outcomes including Late Toxicity and Health Quality.

Introduction: This study aimed to evaluate the long-term adverse effects on the physical appearance and overall well-being of breast cancer patients who receive hypofractionated radiotherapy as whole breast and simultaneous integrated boost (SIB) treatment, utilizing intensive modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), or a hybrid therapy approach. Material/Methods: This investigation involved administering hypofractionated SIB-VMAT therapy to individuals diagnosed with early-stage breast cancer. Treatment was carried out over a three-week period in which a total dose of 48.06 Gy was given to the entire breast and 54 Gy was given to the tumor bed. Data on skin toxicity and cosmetic outcomes were analyzed both during the acute phase and during the three-month and five-year follow-up periods after treatment. Results: A total of 125 patients treated between December 2014 and December 2016 were included in the study. The data of these patients with at least 5 years of follow-up were analyzed. Conclusions: Considering these long-term results, hypofractionated SIB-VMAT can be considered a viable treatment choice, even for patients with unfavorable conditions.

A dosimetric comparison for SBRT plans of localized prostate cancer between Cyberknife and Varian Truebeam STX device.

As the Stereotactic Body Radiotherapy (SBRT) approach began to increase in treating patients with localized prostate cancer, it became necessary to investigate which methods used in practice were better. The aim of this study is to perform a dosimetric comparison of the advantages and disadvantages of SBRT treatments for localized prostate cancer delivered by CyberKnife (CK) and Varian Truebeam STX (FF and FFF). Seventeen intermediate and high-risk patients with localized prostate cancer were included in the study. SBRT plans for the CK system and Varian Truebeam STX systems with and without Flattening Filters (Tru-FF and Tru-FFF) were prepared for each patient. Plans prepared for each patient were planned at a fraction dose of 6.7 Gy at 6 MV energy and a target dose of 33.5 Gy in 5 fractions. For all plans, cumulative dose-volume histograms (DVHs) were generated for target volumes and organs at risk (OAR). The maximum doses of PTV (41 Gy) in CK plans are higher than the maximum doses (35 Gy) in VMAT plans prepared with Tru-FF or Tru-FFF beams. The mean dose of the rectal wall (10.06 ± 2.40Gy for CK) is still relatively low compared to other plans (13.46 ± 2.16 Gy for Tru-FF and 13.61 ± 2.32 Gy for Tru-FFF). The bladder wall (14 Gy for CK, 26 Gy for Tru-FF and Tru-FFF) and femoral head (6.8 Gy for CK, 9 Gy for Tru-FF and 9.4 Gy Tru-FFF) doses were also lower for CK plans. The CK plans provide better tumour control due to low doses in critical organs and high target doses than the Tru-FF or Tru-FFF plans. It was observed that CK and VMAT plans for SBRT with 6 MV photon beams provided acceptable results in term of treatment planning criteria such as Conformity Index and Homogeneity Index. It is recommended to use a target tracking system to provide an accurate and reliable SBRT treatment with VMAT and CK techniques.

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.

Definitive Chemoradiotherapy Results in Synchronous Oligometastatic Non-small Cell Lung Cancer Patients: Turkish Society for Radiation Oncology Group Study (TROD 10-003).

OBJECTIVE: It is aimed to investigate the survival outcomes and prognostic factors after curative treatment of patients diagnosed with synchronous oligometastatic non-small cell lung carcinoma. MATERIALS AND METHODS: Fifty-two patients from 3 centers diagnosed between 2014 and 2019 were analyzed. The treatment results of thoracic and oligometastatic regions were retrospectively evaluated. The Kaplan-Meier method was used to determine the overall survival (OS) and progression-free survival (PFS) and log-rank tests for the factors affecting survival. Cox regression analysis was employed for multivariate analysis. RESULTS: Of the 52 patients, 46 (88%) had <2 organ involvement at diagnosis. Treatment of oligometastasis was radiotherapy (RT) in 37, surgery in 4, and surgery with RT in 11 patients. Median 60 Gy were administered to the thoracic tumor. Median RT dose for oligometastasis was 30 Gy in median 5 fractions with either stereotactic body radiation therapy or conventional RT. The median follow-up was 18 months. The median OS and PFS were 35 and 20 months, respectively. The 1-, 2-, and 3-year OS rates were 80.5%, 60.2%, and 41.2%, while the corresponding PFS rates were 75%, 42.5%, and 21.5%, respectively. Multivariate Cox regression analysis revealed that the Eastern Cooperative Oncology Group performance status of "0" and thoracic RT dose over 60 Gy were significant prognostic factors for both the OS and PFS. CONCLUSIONS: Definitive chemoradiotherapy to the thoracic tumor and treatment of oligometastasis region indicate promising survival outcomes.

Breaking bad news to cancer patients and their families: Attitudes toward death among Turkish physicians and their communication styles.

To investigate how Turkish oncologists' attitudes toward death influence their emotional states, outlooks, and communication styles when breaking bad news to cancer patients and/or their families.Cross-sectional study using self-completed questionnaires.The study sample consisted of 35 physicians working at an oncology department. Physicians completed a quantitative one-time survey developed by the authors and the Death Attitude Profile-Revised (DAP-R).Thirty-one physicians completed the survey and the DAP-R. A mean of 13.39 ± 8.82 minutes was allocated for breaking bad news; 87.1% of the participants avoided using the word "cancer" and 42% avoided using the word "death". The attitudes characterized by "death avoidance" and "fear of death" were found to be related to the emotional difficulty experienced by the physicians, and were also associated with less eye contact with the patient, and less attention paid to the language used while breaking bad news.It is important for physicians to be aware of how their attitudes toward death affect their communication with patients during bad news. They should be provided in-service professional education, and therapeutic support.

Anti-proliferative effects of paroxetine alone or in combination with sorafenib in HepG2 cells

Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib is the first approved drug for the treatment of advanced HCC. Depression is frequent in cancer patients. Moreover, sorafenib might exert depression as an adverse drug reaction and paroxetine, a selective serotonin reuptake inhibitor, is a recommended pharmacotherapy. This study aimed to investigate the potential synergistic effects of paroxetine and sorafenib on HepG2 cell proliferation and death. Paroxetine and sorafenib were administered to HepG2 cells as single-agents or in combination. Cell viability was determined with XTT cell viability assay. Cellular apoptosis and DNA content were assessed by flow cytometry. The expression of anti-apoptotic Bcl-2 was examined by immunofluorescence confocal microscopy. A lower dose of sorafenib was found to be required to inhibit cell proliferation when in combination with paroxetine. Similarly, the coadministration enhanced cellular apoptosis and resulted in cell cycle arrest. Confocal imaging revealed a remarkably lower cell density and increased expression of Bcl-2 following combined treatment of paroxetine with sorafenib. To our knowledge, this is the first study demonstrating the synergistic effect of paroxetine and sorafenib in HCC and might provide a potentially promising therapeutic strategy.

Outcomes of patients with anal cancer treated with volumetric-modulated arc therapy or intensity-modulated radiotherapy and concurrent chemotherapy.

AIMS: To evaluate the results of chemoradiation with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) for the treatment of anal canal cancer patients at three institutions that had advanced devices. MATERIALS AND METHODS: A retrospective analysis was performed for patients treated with 5-fluorouracil and mitomycin-based chemotherapy and IMRT or VMAT for anal cancer from 2011 to 2013. Complete response (CR) rates, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and toxicities were investigated. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, Version 3.0. RESULTS: Fifteen patients were included in the analysis. The majority of patients had T2 (53.3%) and N0 (40%) disease according to the staging system that was developed by the American Joint Committee on Cancer. CR was observed in 14 patients (93%), and the median follow-up was 26 months (13-42 months). The 3-year CFS, DFS, and OS were 86%, 86%, and 88%, respectively. Acute Grade 3 toxicities were observed as 6% of hematological, 26% of gastrointestinal, and 26% of dermatological. CONCLUSION: Early results confirm that IMRT or VMAT for anal cancer treatment reduces acute toxicities while maintaining high control rates.

Outcomes of thymoma after multimodal therapy and determinants of survival: A 16-year experience of a tertiary cancer center.

BACKGROUND: In this study, we aimed to evaluate the factors that contribute to survival outcomes in patients with thymoma treated with multimodal approaches. METHODS: A total of 203 patients (105 males, 98 females; median age: 49 years; range, 17 to 77 years) with Masaoka-Koga Stage II-IV thymoma between January 2002 and December 2018 were retrospectively analyzed. Data including diagnosis of myasthenia gravis, diagnosis of diabetes mellitus, disease stage, histological type of tumor, capsule invasion and surgical margin status, lymphadenectomy, adjuvant radiotherapy or chemotherapy, time from surgery to the first day of adjuvant treatment, length of hospital stay, and overall and disease-free survival rates were recorded. RESULTS: Of the patients, 91 had Stage II, 67 had Stage III, and 45 had Stage IV disease. A total of 123 patients (61%) had myasthenia gravis. Seventy-six patients received adjuvant radiotherapy and 48 patients received either neoadjuvant (n=35) or adjuvant (n=25) chemotherapy. Higher disease stage, presence of R1 resection, and treatment with chemotherapy were significant factors for decreased disease-free survival time. Older age, higher disease stage, longer postoperative hospital stay, chemotherapy, and disease recurrence were effective contributors to decreased overall survival time. Adjuvant radiotherapy had a statistically significant positive effect on overall survival only in patients with completely resected Stage IV disease (five-year overall survival: 94.7% vs. 79.1%, respectively; p=0.015). In the multivariate analysis, older age (hazard ratio: 4.26), higher disease stage (hazard ratio: 2.95), and longer hospitalization time (hazard ratio: 3.81) were significant prognostic factors for overall survival. Patients with local recurrence who underwent complete resection had a survival time comparable to non-recurrent patients (p=0.753). CONCLUSION: For patients with thymoma, higher disease stage, age ≥50 years, longer hospitalization, and need for chemotherapy are associated with worse survival rates. Adjuvant chemotherapy has a positive impact on Stage IV disease. Resection of recurrent lesions has a valuable impact on survival.

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

OBJECTIVE: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey. MATERIALS AND METHODS: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/ß ratio of 10 (BED10 ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity. RESULTS: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED10 was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED10 > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED10 > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]). CONCLUSION: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED10 > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.

Prognostic significance of early complete response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy: Multicentric study of Turkish Society for Radiation Oncology Group (TROD).

BACKGROUND/AIMS: To assess the effect of various parameters on the oncologic outcomes, including the time interval between therapy and surgery (S) in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: The data of 914 LARC patients who received preoperative CRT between 1994 and 2015 were collected retrospectively. Patients received 45-50.4 Gy RT with 5FU based chemotherapy (CT). They all underwent radical resection followed by maintenance CT. Clinical and pathologic variables were compared between the pCR and no-pCR groups. Survival was estimated by the Kaplan-Meier method and Cox proportional hazard model was used in multivariate analysis. RESULTS: After median follow-up of 60.5 (range=12-297.6) months, median overall survival (OS) was 58.75 months and disease-free survival (DFS) 53.32 months. pCR was observed in 18.9% of all cases. pCR, lymphovascular invasion and metastatic lymph node ratio (mLNR) were significantly associated with OS and DFS on multivariate analysis. The 5-year OS and DFS rates were better in pCR group (95.3% vs 80.7% for OS, p<0.0001 and 87.4% vs 71% for DFS, p<0.0001). pCR patients with 4-8 weeks interval had lower rates of distant metastasis (9% vs 20%, p=0.01) and any recurrences (13.6% vs 29.6%, p=0.001) than the remaining. Both OS and DFS were better in favor of pCR achieved at 4-8 week interval time (p<0.0001 for each). CONCLUSION: pCR after preoperative CRT in LARC correlated with better oncologic outcome. The best OS and DFS durations were achieved in patients who experienced pCR after 4-8-weeks interval before surgery.

The Impact of Primary Tumor and Locoregional Metastatic Lymph Node SUVmax on Predicting Survival in Patients with Rectal Cancer.

OBJECTIVES: The aim of this study was to evaluate the impact of maximum standard uptake value (SUVmax) of the primary tumor and locoregional metastatic lymph node in predicting survival in patients with the preoperative rectal adenocarcinoma. METHODS: One hundred and fifteen patients [mean age ± standard deviation (SD): 58.7±11.4 years] with biopsy-proven rectal adenocarcinoma underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging for the staging were included in this study. All patients were followed-up for a minimum of 12 months (mean ± SD: 29.7±13.5 months). Tumor-node-metastasis 2017 clinical staging, SUVmax of the primary rectal tumor and locoregional lymph nodes on the PET/CT studies were evaluated. RESULTS: All patients had increased FDG activity of the primary tumor. The mean ± SD SUVmax of the primary tumor and locoregional metastatic lymph node were 21.0±9.1 and 4.6±2.8, respectively. Primary tumor SUVmax did not have an effect on predicting survival (p=0.525) however locoregional metastatic lymph node SUVmax had an effect (p<0.05) on predicting survival. Clinical stage of the disease was a factor predicting survival (p<0.001). CONCLUSION: 18F-FDG PET/CT is an effective imaging modality for detecting primary tumors and metastases in rectal adenocarcinoma and clinical stage assessment with PET/CT had an effect on predicting survival. Furthermore, in our study locoregional lymph node SUVmax was defined as a factor in predicting survival.

Sertraline in combination with sorafenib: A promising pharmacotherapy to target both depressive disorders and hepatocellular cancer.

INTRODUCTION: Hepatocellular carcinoma (HCC) is found within the first five most common tumors worldwide. Sorafenib is an approved agent in HCC treatment. Sertraline is a selective serotonin reuptake inhibitor. The aim of the study is to investigate the combination of sertraline and sorafenib at hepatocellular cancer cell proliferation and death. METHODS: HepG2 cells were treated with drugs and viability test XTT was performed. Cells were stained with hematoxylin and eosin for histological examination or with anti-Bcl-2 antibody and Hoechst 33258 for immunofluorescence. RESULTS: Viability results supported dose-dependent antiproliferative effect for both sertraline and sorafenib. Microscopic evaluation of stained cells exerts morphological changes. DISCUSSION: This is the first study to show that sorafenib and sertraline have synergistic effect in hepatocellular cancer.

Prognostic significance of carbonic anhydrase IX overexpression in stage III non-small cell lung cancer patients after neoadjuvant treatment.

BACKGROUND: To assess the prognostic importance of carbonic anhydrase IX (CA IX), a hypoxic biomarker, after neoadjuvant treatment in Stage III non-small cell lung cancer (NSCLC) patients. METHODS: Tissue CA IX expression was examined after surgical resection in 77 patients who had undergone neoadjuvant treatment. The effects of CA IX overexpression and other clinical factors on disease-free survival and overall survival were investigated. RESULTS: In multivariate analysis, number of neoadjuvant chemotherapy (CT) courses and gender emerged as significant independent predictors for disease-free survival, where administration of 2-3 courses of neoadjuvant chemotherapy (CT) (HR, 3.2 [95% CI 1.3-7.6], p = 0.009) and female gender were associated with poor survival (HR, 3.2 [95% CI 1.3-7.7], p = 0.009). The only significant independent predictor for overall survival was recurrence (HR, 5.6 [95% CI 2.4-12.8], p < 0.001). On the other hand, CA IX overexpression was not associated with disease free survival (p = 0.560) or overall survival (p = 0.799). DISCUSSION: Our results do not suggest a prognostic role for CA IX overexpression in stage III NSCLC patients who received neoadjuvant treatment.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study.

AIM: To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS: A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS: In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively. CONCLUSION: Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers.

PURPOSE: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. METHODS: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. RESULTS: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). CONCLUSIONS: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

Mutagenic and genotoxic effects of Anilofos with micronucleus, chromosome aberrations, sister chromatid exchanges and Ames test.

We aimed to evaluate the mutagenic effect of Anilofos, organophosphate pesticide, by using Ames/Salmonella/microsome test. Its cytotoxic and genotoxic effects were also determined by chromosome aberration (CA), sister chromatid exchange (SCE) and micronucleus (MN) test in human peripheral blood lymphocytes. In the Ames test, five different concentrations of Anilofos were examined on TA97, TA98, TA100 and TA102 strains in the absence and presence of S9 fraction. According to the results all concentrations of this pesticide have not shown any mutagenic activity on TA97, TA100 and TA102 strains in the absence and presence of S9 fraction. But, 10, 100 and 1000 µg/plate concentrations of Anilofos were determined to be mutagenic on TA98 strain without S9 fraction. Lymphocytes were treated with various concentrations (25, 50, 100 and 200 µg/ml) of Anilofos for 24 and 48 h. The results of the assays showed that Anilofos did not induce SCE frequency, replication index and MN formation at all concentrations for both treatment periods. Anilofos significantly increased CA frequency at 100 and 200 µg/ml concentrations at 24 h treatment periods and at 50, 100 and 200 µg/ml concentrations in 48 h treatment periods. Additionally, it was determined that this pesticide decreased mitotic index and nuclear division index significantly. It was concluded that Anilofos has genotoxic and cytotoxic effects in human peripheral lymphocytes.