Ethical evaluation of artificial intelligence applications in radiotherapy using the Four Topics Approach.

Artificial Intelligence is the capability of a machine to imitate intelligent human behavior. An important impact can be expected from Artificial Intelligence throughout the workflow of radiotherapy (such as automated organ segmentation, treatment planning, prediction of outcome and quality assurance). However, ethical concerns regarding the binding agreement between the patient and the physician have followed the introduction of artificial intelligence. Through the recording of personal and social moral values in addition to the usual demographics and the implementation of these as distinctive inputs to matching algorithms, ethical concerns such as consistency, applicability and relevance can be solved. In the meantime, physicians' awareness of the ethical dimension in their decision-making should be challenged, so that they prioritize treating their patients and not diseases, remain vigilant to preserve patient safety, avoid unintended harm and establish institutional policies on these issues.

Radiation therapy for biliary tract tumors: the joint experience of three centers.

BACKGROUND/AIM: This study presents the joint experience of three centers in the treatment of patients with biliary tract tumors with radiation therapy (RT). MATERIALS AND METHODS: The records of 27 patients were retrospectively reviewed. All of the patients who had undergone surgical resection received postoperative adjuvant RT, whereas all of the patients who had not undergone a surgical resection received RT with palliative intent. Twenty patients with adequate performance status were treated with RT and chemotherapy, while the remaining seven patients were treated with RT alone. RESULTS: Follow-up ranged from 1 to 44 months. Local control was not achieved in 10 out of 11 patients who had received RT with palliative intent. Systemic failure was observed in eight patients at 5 to 16 months. Fifteen patients died due to disease-related causes at 1 to 22 months. At 2 years, overall survival was 33% and disease-free survival was 19%. A surgical resection with curative intent predicted improved local failure-free survival and improved disease-free survival. CONCLUSION: Since local recurrence is still the leading cause of failure following postoperative RT and the outcome following palliative RT is far from satisfactory, the indications, the target volume, and the doses for RT should be reconsidered.

Neuroprotective effects of erythropoietin against oxidant injury following brain irradiation: an experimental study.

INTRODUCTION: Radiation therapy (RT) is a major treatment modality, and the central nervous system is a dose-limiting organ in clinical RT. This experimental study aims to present the evaluation of the neuroprotective effects of erythropoietin (EPO) against oxidant injury following brain irradiation in rats. MATERIAL AND METHODS: Forty Wistar rats were randomly assigned to four groups (n = 10 each). In group 1 the rats received no EPO and underwent sham RT. The rats in groups 2 and 3 received EPO. In group 2 rats underwent sham RT, while in group 3 rats received RT. The rats in group 4 received no EPO and underwent RT. Rats were irradiated using a Cobalt-60 teletherapy machine using a single fraction of 20 Gy covering the whole brain. Cervical dislocation euthanasia was performed. The nitrite and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) and glutathione peroxidase (GSHPX) activities were evaluated in dissected brain tissues. RESULTS: The nitrite and MDA levels were higher in the RT group (2.10 ±0.62 ppm, 26.02 ±2.16 nmol/ml; p < 0.05) and lower in the EPO + RT group (1.45 ±0.12 ppm, 25.49 ±1.90 nmol/ml; p < 0.05). The SOD and GSHPX activity was higher in the EPO + RT group (2.62 ±0.49 U/mg, 1.75 ±0.25 U/mg, p < 0.05). CONCLUSIONS: This study supports the probable neuroprotective effects of EPO against oxidant injury following brain irradiation in a rat model, presumably through decreasing free radical production and increasing expression of antioxidant enzymes.

Defining the "Hostile Pelvis" for Intensity Modulated Radiation Therapy: The Impact of Anatomic Variations in Pelvic Dimensions on Dose Delivered to Target Volumes and Organs at Risk in Patients With High-Risk Prostate Cancer Treated With Whole Pelvic Radiation Therapy.

PURPOSE: The aim of this study was to evaluate the impact of variations in pelvic dimensions on the dose delivered to the target volumes and the organs at risk (OARs) in patients with high-risk prostate cancer (PCa) to be treated with whole pelvic radiation therapy (WPRT) in an attempt to define the hostile pelvis in terms of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: In 45 men with high-risk PCa to be treated with WPRT, the target volumes and the OARs were delineated, the dose constraints for the OARs were defined, and treatment plans were generated according to the Radiation Therapy Oncology Group 0924 protocol. Six dimensions to reflect the depth, width, and height of the bony pelvis were measured, and 2 indexes were calculated from the planning computed tomographic scans. The minimum dose (Dmin), maximum dose (Dmax), and mean dose (Dmean) for the target volumes and OARs and the partial volumes of each of these structures receiving a specified dose (VD) were calculated from the dose-volume histograms (DVHs). The data from the DVHs were correlated with the pelvic dimensions and indexes. RESULTS: According to an overall hostility score (OHS) calculation, 25 patients were grouped as having a hospitable pelvis and 20 as having a hostile pelvis. Regarding the OHS grouping, the DVHs for the bladder, bowel bag, left femoral head, and right femoral head differed in favor of the hospitable pelvis group, and the DVHs for the rectum differed for a range of lower doses in favor of the hospitable pelvis group. CONCLUSIONS: Pelvimetry might be used as a guide to define the challenging anatomy or the hostile pelvis in terms of treatment planning for IMRT in patients with high-risk PCa to be treated with WPRT.

Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model.

INTRODUCTION: Melatonin is a hormone which is known to be a powerful cardioprotective agent due to its free radical-scavenging properties. This study was carried out to evaluate whether melatonin administration prior to irradiation would have a protective effect on cardiac histopathological changes in an experimental rat model. METHODS: Rats were divided into four groups. Single dose of 18 Gy radiation and sham radiation exposure were used in related groups. 50mg/kg dose of melatonin were injected intraperitonally 15 min prior to radiation exposure. Analyses and assessments were performed 6 months after radiation exposure. RESULTS: Severe myocardial fibrosis was observed prominently in three regions: the apex, tips of papillary muscles and adjacent to the atrioventricular valves. Inflammation was found to be more in irradiated groups. Increased inflammation and fibrosis were in concordance. The number of mast cells was found to be decreased in irradiated groups. Myocyte necrosis and fibrosis were diminished with melatonin while vasculitis was prevented. CONCLUSIONS: Elementary pathological lesions of radiation-induced heart disease (RIHD) are fibrosis, vascular damage, vasculitis and myocyte necrosis. Development of vasculitis was prevented by the use of melatonin. Fibrosis and necrosis were prominently decreased. Prevention of RIHD with the use of melatonin at the long term is encouraging according to the histopathological results.

Assessment of early and late dysphagia using videofluoroscopy and quality of life questionnaires in patients with head and neck cancer treated with radiation therapy.

BACKGORUND: The aim of this study was to evaluate dysphagia in patients with head and neck cancer (HNC) undergoing three-dimensional conformal radiation therapy using objective and subjective tools simultaneously and to associate the clinical correlates of dysphagia with dosimetric parameters. METHODS: Twenty patients were included in the study. The primary tumor and the involved lymph nodes (LN) were treated with 66-70 Gy, the uninvolved LN were treated with 46-50 Gy. Six swallowing structures were identified: the superior pharyngeal constrictor muscle (SPCM), the middle pharyngeal constrictor muscle (MPCM), the inferior pharyngeal constrictor muscle (IPCM), the base of tongue (BOT), the larynx and the proximal esophageal sphincter (PES). Dysphagia was evaluated using videofluoroscopy and European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ-C30) and supplemental EORTC QoL module for HNC (QLQ-H&N35). The evaluations were performed before treatment, at 3 months and at 6 months following treatment. RESULTS: On objective evaluation, the Dmax for the larynx and the sub-structures of the PCM were correlated with impaired lingual movement, BOT weakness and proximal esophageal stricture at 3 months, whereas the V65, the V70and the Dmax for the larynx was correlated with BOT weakness and the V65, the V70, the Dmax or the Dmean for the sub-structures of the PCM were correlated with impaired lingual movement, BOT weakness, reduced laryngeal elevation, reduced epiglottic inversion and aspiration at 6 months following treatment. On subjective evaluation, the V60, the Dmax and the Dmean for SPCM were correlated with QoL scores for HNSO at 3 months, whereas the V70 for SPCM were correlated with QoL scores for HNPA and the V60, the V65, the V70, the Dmax and the Dmean for SPCM were correlated with QoL scores for HNSO at 6 months following treatment. CONCLUSIONS: The use of multiple dysphagia-related endpoints to complement eachother rather than to overlap with one another, as well as the use of multiple evaluations over time to represent a scale of early to late findings might provide a better insight in terms of the association of the clinical correlates of dysphagia with the dose-volume data for the dysphagia-related anatomical structures.

The effects of irradiation on the blood dynamics.

AIM: The present study evaluates the effects of irradiation on the blood dynamics. MATERIALS AND METHODS: Thirty-six volunteers providing written consent participated. A blood sample was transferred into three tubes containing CPDA-1 solution while another blood sample was transferred into three tubes containing heparin. Each tube containing CPDA-1 solution was paired with another tube containing heparin. The first pair was not irradiated, not stored and analyzed immediately (Group 1). The second pair was not irradiated, stored and analyzed at seven days (Group 2). The third pair was irradiated, stored and analyzed at seven days (Group 3). The blood count was performed and the blood viscosity was determined. RESULTS: The mean hemoglobin contents were 126 g/l for Group 1, 128 g/l for Group 2 and 129 g/l for Group 3. For the mean hemoglobin contents, the difference between Group 1 and Group 3 (P<0.001) and Group 2 and Group 3 (P=0.01) were significant. The mean red blood cell volumes were 81.8 fl for Group 1, 82.1 fl for Group 2 and 82.3 fl for Group 3. For the mean red blood cell volumes, the difference between Group 1 and Group 2 (P=0.003) and Group 1 and Group 3 (P=0.006) were significant. The mean blood viscosities were 2.2 mPa s for Group 1, 2.8 mPa s for Group 2 and 3.2 mPa s for Group 3. For the mean blood viscosities, the difference between Group 1 and Group 2 (P<0.001), Group 1 and Group 3 (P<0.001) and Group 2 and Group 3 (P=0.004) were significant. CONCLUSION: The present study indicates that the recommended doses of irradiation for the blood products to be used in attempt to prevent the transfusion associated graft versus host disease leads to marked alterations in the blood dynamics and might decrease the viability of the red blood cells following transfusion.

Endobronchial metastases from a leiomyosarcoma of the uterus.

A 63-year-old woman presented with dyspnea, non-productive cough and chest pain. On computed tomography of the thorax, near total atelectasis of the left lung was reported. On bronchoscopic examination, a mass lesion was observed in the mucosa of the left main bronchus leading to near total obstruction. Her medical history revealed that she had been treated with total abdominal hysterectomy and adjuvant radiation therapy for a leiomyosarcoma of the uterus one year ago. She was diagnosed as having a metastatic leiomyosarcoma and was treated with palliative radiation therapy. Six months later, she presented with disseminated disease involving the thorax and the pelvis. She refused further treatment and died one month later. Patients with leiomyosarcomas of the uterus might follow an aggressive clinical course, with relatively early metastases at unusual sites.

The histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy in a rat model.

PURPOSE: This study presents the histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy. MATERIALS AND METHODS: Thirty-two Wistar rats were divided into four groups. The rats in Group 1 received melatonin and underwent radiation therapy. The rats in Group 2 received no melatonin and underwent radiation therapy. The rats in Group 3 received melatonin and underwent sham radiation therapy. The rats in Group 4 received no melatonin and underwent sham radiation therapy. Melatonin was administered at a dose of 100 mg/kg using an intraperitoneal injection. Radiation therapy was delivered on a Cobalt-60 unit using a single fraction of 18 Gy through an anterior portal covering the right lung in entirety. The rats underwent euthanasia at 6 weeks following radiation therapy. The lungs were dissected and blinded histopathological evaluation was performed. RESULTS: Concerning the right lung, a decrease in intra-alveolar edema and intra-alveolar erythrocytes was observed despite an increase in activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis and alveolar wall thickness for the rats in Group 1 as compared to the rats in Group 2. Concerning the left lung, a decrease in alveolar neutrophils and intra-alveolar erythrocytes was evident despite an increase in activated macrophages, hyaline arteriosclerosis and alveolar wall thickness for the rats in Group 1 as compared to the rats in Group 2. CONCLUSIONS: This study puts forward the histopathological evidence regarding the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy through restrained inflammation, regrettably at the expense of promoted fibrosis. The effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy needs to be evaluated further for the unresolved concerns regarding the safety.

[Chondroradionecrosis in two patients with laryngeal carcinoma]. / Larenks karsinomlu iki hastada kondroradyonekroz.

Postradiotherapy necrosis in the larynx is a rare but serious complication. It must be differentiated from tumor recurrence with radiological and histopathological studies. Herein, we presented two patients with stage II and stage IV larynx carcinoma who developed chondroradionecrosis following radiotherapy. The first patient did not accept surgical treatment and was treated with curative radiotherapy at a dose of 70 Gy. The other one received adjuvant radiotherapy at a dose of 46 Gy following total laryngectomy and bilateral functional neck dissection. The two patients were evaluated with computed tomography and magnetic resonance imaging, respectively. Pathologic examination of multiple biopsies taken from both cases showed coagulation necrosis without malignancy. The first patient had grade IV radionecrosis according to the Chandler classification and underwent total laryngectomy because of non-functional larynx. Histopathologically, there were no malignant cells, but widespread fibrosis and coagulation necrosis. The other patient was treated with conservative treatment and local debridement.

The effects of granulocyte colony-stimulating factor on the healing of tracheal anastomosis following radiation therapy in rats.

OBJECTIVE: This study evaluates the effects of granulocyte colony-stimulating factor on the healing of tracheal anastomosis following radiation therapy in rats. METHODS: Fifty-six male Wistar rats were divided into four groups. Group 1 underwent tracheal anastomosis. Group 2 underwent radiation therapy followed by tracheal anastomosis. Group 3 underwent radiation therapy followed by tracheal anastomosis and received granulocyte colony-stimulating factor. Group 4 underwent sham radiation therapy followed by sham tracheal anastomosis. At 10 days following radiation therapy, the trachea was dissected for histopathological, mechanical and biochemical evaluation. RESULTS: Median scores for inflammation were three points for Group 1, two points for Group 2, two points for Group 3 and one point for Group 4. Median scores for angiogenesis were four points for Group 1, two points for Group 2, three points for Group 3 and one point for Group 4. Median scores for connective tissue regeneration were four points for Group 1, two points for Group 2, three points for Group 3 and one point for Group 4. Median scores for epithelial regeneration were two points for Group 1, one point for Group 2, one point for Group 3 and one point for Group 4. Mean anastomotic bursting pressures were 853 mmHg for Group 1, 293 mmHg for Group 2, 417 mmHg for Group 3 and 966 mmHg for Group 4. Mean hydroxyproline concentrations were 159 microg/mg for Group 1, 177 microg/mg for Group 2, 120 microg/mg for Group 3 and 117 microg/mg for Group 4. CONCLUSIONS: This study suggests that granulocyte colony-stimulating factor contributes to the healing of tracheal anastomosis following radiation therapy through improved connective tissue regeneration.

The evaluation of the oxidant injury as a function of time following brain irradiation in a rat model.

This study presents the evaluation of the oxidant injury as a function of time following brain irradiation in a rat model. Thirty-five Wistar rats were divided into seven groups. The rats in Group 1 through Group 6 underwent irradiation, whereas the rats in Group 7 underwent sham irradiation. The rats in Group 1 through Group 6 underwent euthanasia at 1 through 48 h following irradiation, whereas the rats in Group 7 underwent euthanasia immediately following sham irradiation. At the time of euthanasia, the brain tissue was dissected for evaluation of the malondialdehyde (MDA) level and the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPX) activities. The mean MDA levels were increased and the mean SOD, CAT and GSHPX activities were decreased at all of the time points for evaluation for the rats that underwent irradiation as compared to the rats that underwent sham irradiation, substantial for Group 1 and gradually leveling out through Group 6. This study confirms that the oxidant injury is evaluated at its best through the first several hours following brain irradiation.

The use of recursive partitioning analysis grouping in patients with brain metastases from non-small-cell lung cancer.

BACKGROUND: This study evaluates the use of recursive partitioning analysis (RPA) grouping in an attempt to predict the survival probabilities in patients with brain metastases from non-small-cell lung cancer (NSCLC). METHODS: Seventy-two patients with brain metastases from NSCLC treated with radiation therapy were included in the study. Sixty-three patients were male and nine patients were female. Their median age was 57 years and their median Karnofsky performance status was 70. At the time of brain metastases, there was no evidence of the intrathoracic disease in 27 patients and the extrathoracic disease was limited to the intracranial disease in 42 patients. In accordance with RPA grouping, 12 patients were in Group 1, 24 patients were in Group 2, and 36 patients were in Group 3. Radiation therapy was delivered to the whole brain at a dose of 30 Gy in 10 fractions in most of the patients. RESULTS: The median survival time was 7 months for Group 1, 5 months for Group 2 and 3 months for Group 3. The survival probability at 1 year was 50% for Group 1, 26% for Group 2 and 14% for Group 3. CONCLUSIONS: This study presents evidence supporting the use of RPA grouping in an attempt to predict the survival probabilities in patients with brain metastases from NSCLC.

Extraskeletal Ewing's sarcoma presenting with multifocal intrathoracic mass lesions associated with mediastinal shift.

Extraskeletal Ewing's sarcoma is an uncommon disease that predominantly involves the soft tissues of the trunk or the extremities. This article presents a patient with multifocal intrathoracic mass lesions involving the mediastinum and the lingula associated with mediastinal shift, eventually diagnosed as extraskeletal Ewing's sarcoma.

Compressive optic neuropathy due to orbital metastasis of a sacral chordoma: case report.

A 44-year-old man presented with unilateral proptosis and progressively deteriorating vision of his left eye over a 2-week period. He had a history of recurrent sacral chordoma for 1 year that had previously been treated with combined surgical excision, chemotherapy, and radiation therapy. MRI showed compression of the optic nerve by an orbital mass that proved to be an orbital metastasis of his sacral chordoma. The tumor mass was excised subtotally, and adjuvant orbital radiation therapy was administered.

Metastatic fibrosarcoma of the brain: transformation from conventional to epithelioid form--case report.

A 45-year-old woman presented with an extremely rare metastatic fibrosarcoma of the brain manifesting as persistent headache. She had undergone surgery for a fibrosarcoma of the soft tissue of the thigh 2 months earlier. She had a history of previous surgery and radiotherapy for this tumor. She was somnolent with papilledema and left hemiparesis. Magnetic resonance imaging of the brain revealed a right frontal lesion with mass effect and heterogeneous enhancement. Computed tomography and scintigraphy showed multiple metastatic lesions of the lung. Right frontal craniotomy was performed for gross total removal of the yellowish-white tumor. Histological examination showed signs of epithelioid transformation based on positive staining for epithelial membrane antigen compared to the primary tumor. Postoperatively the patient was alert and the left hemiparesis improved. She refused radiotherapy or chemotherapy. Follow-up computed tomography showed multiple intracranial metastases. She died 5 months after the surgery.