Assessment of ER Stress and autophagy induced by ionizing radiation in both radiotherapy patients and ex vivo irradiated samples.

Acute radiation leads to several toxic clinical states and triggers some molecular pathways. To shed light on molecular mechanisms triggered by ionizing radiation (IR), we examined the expression profiles of endoplasmic reticulum (ER) stress and autophagy-related genes in individuals who were exposed to IR. Blood samples were collected from 50 cancer patients before radiotherapy and on the 5th, 15th, and 25th days of the treatment. Peripheral blood samples from 10 healthy volunteers were also obtained for ex vivo irradiation, divided into five and irradiated at a rate of 373 kGy/h to 0, 0.1, 0.5, 1, and 3Gy γ-rays using a constant gamma source. GRP78, ATG5, LC3, ATF4, XBP1, and GADD153 genes were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR) using beta 2 microglobulin (B2M) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as references. In both groups, expressions of the selected genes have increased. It can be concluded that IR induces ER stress and related authophagy pathway in the peripheral lymphocyte cells proportionally by dose.

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

Dosimetric investigation of radiation-induced trigeminal nerve toxicity in parotid tumor patients.

PURPOSE: We aimed to describe the association between trigeminal nerve (TN) dose and toxicity and determine a threshold value that leads to TN toxicity in patients with parotid tumors treated with adjuvant conventional fractionated radiation therapy. METHODS AND MATERIALS: Eighteen patients who underwent adjuvant radiotherapy (RT) between 2013 and 2018 were included in this retrospective study. TN and its branches were outlined subsequently on the planning CT scans. The doses received by TN were obtained based on the dose-volume histogram. The dose and toxicity relationship was investigated over the total prescribed dose. RT-related toxicity was graded according to Common Terminology Criteria for Adverse Events V4.0 (CTCAEv4.0). RESULTS: The median follow-up was 29.5 months. After RT, 61% of patients had Grade I-II late TN toxicity divided into Grade I in 4 (22%) and Grade II in 7 (39%) patients. TN injury symptoms were as follows: loss of sensation in the chin area in 3, difficulty in jaw movements in 3, and paresthesia in 5 patients. The total RT dose (p = 0.001), Dmax (p = 0.001), PTV-TN Dmax (p = 0.001), D1cc (p = 0.004), D0.5cc (p = 0.001), and D0.1cc (p = 0.01) had a significant effect on TN toxicity. Cut-off values leading to toxicity were determined as 66, 65.5, 65.25, 63.6, and 62.7 Gy for Dmax, PTV-TN Dmax, D0.1cc, D 0.5cc, and D1cc, respectively. CONCLUSIONS: Radiation-induced TN injury in head and neck cancer patients may further be investigated in clinically prospective trials by virtue of high toxicity rates with current RT doses in our retrospectively designed dosimetric study in parotid tumors.

The effect of tianeptine in the prevention of radiation-induced neurocognitive impairment.

Radiation-induced neurocognitive impairment is an undesirable radiation-induced toxicity and a common health problem in patients with primary or metastatic brain tumor. It greatly impairs quality of life for long-term brain tumor survivors. Hippocampus is the most important brain structure for neurocognitive functions. It has been shown that radiation affects the hippocampal neurogenesis due to either induce the apoptosis or reduce the precursor cell proliferation in the hippocampus. Radiation-induced microglial inflammatory response is also negative regulator of neurogenesis. Tianeptine is a clinically effective antidepressant that induces neurogenesis. It has also been shown that tianeptine is able to reduce apoptosis and cytoprotective against the effects of proinflammatory cytokines in the hippocampus. Given the putative role of impaired hippocampal neurogenesis in radiation-induced neurocognitive impairment we think that tianeptine can be effective for preventing radiation-induced neurocognitive impairment by increasing hippocampal neurogenesis.

Evaluation of the radiation pneumonia development risk in lung cancer cases.

BACKGROUND: Concurrent chemo-radiotherapy is the recommended standard treatment modality for patients with locally advanced lung cancer. The purpose of three-dimensional conformal radiotherapy (3DCRT) is to minimize normal tissue damage while a high dose can be delivered to the tumor. The most common dose limiting side effect of thoracic RT is radiation pneumonia (RP). In this study we evaluated the relationship between dose-volume histogram parameters and radiation pneumonitis. This study targeted prediction of the possible development of RP and evaluation of the relationship between dose-volume histogram (DVH) parameters and RP in patients undergoing 3DCRT. MATERIALS AND METHODS: DVHs of 41 lung cancer patients treated with 3DCRT were evaluated with respect to the development of grade ≥ 2 RP by excluding gross tumor volume (GTV) and planned target volume (PTV) from total (TL) and ipsilateral (IPSI) lung volume. RESULTS: Were admitted statistically significant for p<0.05. CONCLUSIONS: The cut-off values for V5, V13, V20, V30, V45 and the mean dose of TL-GTV; and V13, V20,V30 and the mean dose of TL-PTV were statistically significant for the development of Grade ≥ 2 RP. No statistically significant results related to the development of Grade ≥ 2 RP were observed for the ipsilateral lung and the evaluation of PTV volume. A controlled and careful evaluation of the dose-volume histograms is important to assess Grade ≥ 2 RP development of the lung cancer patients treated with concurrent chemo-radiotherapy. In the light of the obtained data it can be said that RP development may be avoided by the proper analysis of the dose volume histograms and the application of optimal treatment plans.

Comparison of 2-dimensional and 3-dimensional conformal treatment plans in gastric cancer radiotherapy.

BACKGROUND: Postoperative chemoradiotherapy is accepted as standard treatment for stage IB-IV, M0 gastric cancer. Radiotherapy (RT) planning of gastric cancer is important because of the low radiation tolerance of surrounding critical organs. The purpose of this study was to compare the dosimetric aspects of 2-dimensional (2D) and 3-dimensional (3D) treatment plans, with the twin aims of evaluating the adequacy of 2D planning fields on coverage of planning target volume (PTV) and 3D conformal plans for both covering PTV and reducing the normal tissue doses. MATERIALS AND METHODS: Thirty-six patients with stage II-IV gastric adenocarcinoma were treated with adjuvant chemoradiotherapy using 3DRT. For each patient, a second 2D treatment plan was generated. The two techniques were compared for target volume coverage and dose to normal tissues using dose volume histogram (DVH) analysis. RESULTS: 3DRT provides more adequate coverage of the target volume. Comparative DVHs for the left kidney and spinal cord demonstrate lower radiation doses with the 3D technique. CONCLUSIONS: 3DRT produced better dose distributions and reduced radiation doses to left kidney and spinal cord compared to the 2D technique. For this reason it can be predicted that 3DRT will result in better tumor control and less normal tissue complications.