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.

Diagnostic performance of magnetic resonance imaging in preoperative local staging of rectal cancer after neoadjuvant chemoradiotherapy

PURPOSE: This paper aims to investigate the diagnostic performance of magnetic resonance imaging (MRI) in predicting the pathologic stage of locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) and the role of MRI in selecting patients with a pathologic complete response (ypCR). METHODS: Restaging MRI (yMRI) examinations of 136 patients with LARC treated with neoadjuvant CRT followed by surgery were retrospectively analyzed by two radiologists. All examinations were performed on a 1.5 Tesla MRI machine with a pelvic phased-array coil. T2-weighted turbo spin-echo images and diffusion-weighted imaging were obtained. Histopathologic reports of the surgical specimens were the reference standard. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) of yMRI in predicting the pathologic T-stage (ypT), N-stage, and ypCR were calculated. The inter-observer agreement was evaluated using kappa statistics. RESULTS: The yMRI results showed 67% accuracy, 59% sensitivity, 80% specificity, 81% PPV, and 56% NPV in identifying ypT (ypT0-2 versus ypT3-4). In predicting the nodal status, the yMRI results revealed 63% accuracy, 60% sensitivity, 65% specificity, 47% PPV, and 75% NPV. In predicting ypCR, the yMRI results showed 84% accuracy, 20% sensitivity, 92% specificity, 23% PPV, and 90% NPV. The kappa statistics revealed substantial agreement between the two radiologists. CONCLUSION: Utilization of yMRI showed high specificity and PPV in predicting the tumor stage and high NPV in predicting the nodal stage; in addition, yMRI revealed moderate accuracy in the T and N classifications, mainly due to underestimating the tumor stage and overestimating the nodal status. Finally, yMRI revealed high specificity and NPV but low sensitivity in predicting the complete response.

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.

A Promising, Novel Radiosensitizer Nanodrug Complex for Oral Cavity Cancer: Cetuximab and Cisplatin-Conjugated Gold Nanoparticles.

BACKGROUND: Nanomedicine has provided promising tools for the imaging, diagnosis, and treatment of cancer. Gold nanoparticles (GNPs) may be useful in enhancing the efficacy of radiotherapy, such as radiosensitization, in cancer therapy. AIMS: To develop a nanodrug complex containing cetuximab (C225,CTX) and cisplatin (CDDP) conjugated with GNPs and to investigate its cytotoxic effects on oral cavity cancer cells when combined with radiotherapy. STUDY DESIGN: In vitro cell culture study. METHODS: The GNPs were synthesized and successfully conjugated with cetuximab and cisplatin. Cell viability was monitored by the xCELLigence real-time cell analysis (RTCA) single-plate (SP) system in GNP-treated UPCI-SCC-131 cells for 48 hours. Cells with/without GNPs were irradiated with 6 MV X-rays, and colony formation was assayed to investigate the long-term effects of GNPs and the nanodrug complex after irradiation on radiotherapy-resistant oral cavity cancer cells. RESULTS: The GNPs entered the tumor cells, and GNP-CDDP (P <.0001) and GNP-CDDP-CTX (P < .0001) were shown to cause a decrease in cell viability. GNP and GNP-CTX combined with radiotherapy led to greater reduction on UPCI-SCC-131 colony numbers, than radiation alone (P = .0369) and radiation with free CTX, with sensitizing enhancement ratios of 1 : 2 and 1 : 9, respectively. CONCLUSION: The cetuximab and cisplatin-conjugated gold nanodrug complex has a great potential to increase cytotoxicity and overcome resistance to radiotherapy, in the treatment of oral cavity cancer.

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.

Modulation of radiation-induced oral mucositis (mouse) by dermatan sulfate: effects on differentiation processes.

PURPOSE: During head and neck cancer radiotherapy, oral mucositis is the most frequent early side effect. Systemic dermatan sulfate (DS) administration has been shown to significantly decrease oral mucosal radiation reactions during daily fractionated irradiation (IR) in an established mouse model. The aim of this study was to investigate the mechanism of the oral epithelial differentiation process, during IR alone and in combination with DS treatment in the same mouse model. METHODS: Fractionated IR 5â€¯× 3 Gy/week was given to the snouts of mice over two weeks, either alone (IR) or in combination with daily DS treatment of 4 mg/kg (IR + DS). Groups of mice (n = 3) were sacrificed every second day over the course of 14 days in both experimental arms. Their tongue was excised and subjected to immunohistochemical processing. RESULTS: In the p16 analysis as a proliferation marker, the difference between IR alone and IR + DS in the germinal (proliferation) layer was not significant, not stimulating the proliferation process. For the p21 analysis as a differentiation marker on the functional (differentiation) layer, the difference between IR alone and IR + DS arms was significant, indicating that DS inhibited the differentiation process. In the cytokeratin (CK) analysis as the indicator of cellular skeletal integrity, the percentage of antibody-positive cells was above the normal level in both experimental arms and significantly superior in the IR + DS arm. CONCLUSION: The mucosal protective activity of DS, instead of stimulating proliferation, is based on prevention of cell loss by a combination of effects leading to the inhibition of cellular differentiation and an increase in the expression of epithelial mechanical strength between intercellular mechanical junctions.

Treatment results in patients with ductal carcinoma in situ treated with adjuvant radiotherapy

Background/aim: The aim of this study was to evaluate the treatment results of patients undergoing adjuvant radiotherapy (ART) after breast surgery with the diagnosis of ductal carcinoma in situ (DCIS). Materials and methods: A total of 61 women who had undergone radiotherapy following extensive surgical excision were enrolled. All patients underwent 50 Gy ART. Survival analysis was performed using Kaplan­Meier analysis and SPSS 20.0. Results: The median age was 52 years (range: 28­86). The median follow-up period after RT was 92 months (range: 23­237). The median overall survival and distant and regional recurrence-free and disease-specific survival was 96 months (range: 26­240), while disease-free and local recurrence-free survival was 96 months (range: 22­240). While the 15-year and 20-year overall survival rates were 87% and 87%, respectively, the recurrence-free survival rates were 98% and 98%, respectively; the rates of disease-specific survival were 100% and 100%, respectively. Conclusion: The results of this study with a long follow-up period have shown that ART in DCIS is an effective treatment method to provide local disease control. However, further large studies are needed to identify the prognostic factors.