Could Amifostine Prevent Experimental Radiotherapy-Induced Acute Pericarditis?

BACKGROUND: Amifostine is a powerful antioxidant that is one of the documented three chemo-radio prototectants recommended for clinical use. There is no data exploring amifostine in prevention of acute pericardial damage. We aimed to investigate whether amifostine has protective effect against acute pericardial injury due to radiotherapy in an experimental rat model. METHODS: Twenty-four rats were divided into four groups: control group, radiotherapy-only group, amifostine-only group, radiotherapy+amifostine group. In groups receiving radiotherapy, hearts were irradiated with a Co 60 teletherapy device at a distance of 80 cm and 20 Gy at a depth of 2 cm. Thirty minutes before interventions, 200 mg/kg amifostine or same volume 0.9% NaCl were administered intraperitoneally. Subjects were sacrificed 24 hours after the procedure. Pericardial histopathological changes were investigated by light microscopy. RESULTS: There was focal inflammation of >= 50% in all rats exposed-to-radiotherapy. All groups receiving radiotherapy revealed a significant increase in pericardial inflammation compared to the groups that did not receive irradiation (p<0.05). There was no difference between the radiotherapy-only group and amifostine+radiotherapy group for pericardial inflammatory response (p>0.05). CONCLUSION: Acute pericarditis was detected in all rats receiving radiotherapy. There was no positive effect of amifostine administration before radiotherapy on acute pericardial inflammation.

Older cancer patients receiving radiotherapy: a systematic review for the role of sarcopenia in treatment outcomes.

BACKGROUND: Previous studies have evaluated the prognostic effects of sarcopenia in cancer patients receiving various treatments, including chemotherapy and surgery, but few studies have focused on radiotherapy (RT). AIMS: We aimed to investigate the prevalence of sarcopenia and the relationship between sarcopenia and outcomes in older cancer patients who underwent RT without chemotherapy. METHODS: A systematic review of the literature was conducted in Pubmed/Medline and Cochrane databases in September 2021. We used the search terms and medical subject heading terms "sarcopenia," "low muscle mass (LMM)," "low muscle strength," "LMM and low muscle strength," "LMM and low muscle strength and low physical performance," and "RT." Outcomes were overall survival (OS), progression-free survival, non-cancer death, cancer death, disease-specific survival, local failure-free survival, distant failure-free survival, and RT-related toxicities. RESULTS: Among 460 studies, 8 studies were eligible for inclusion. The prevalence of sarcopenia was between 42.8% and 72%. Sarcopenia was not associated with OS or OS at 3 years in seven studies in which it was defined as the presence of LMM, while it was related in one study, in which it was defined as the concomitant presence of LMM and muscle strength/function. DISCUSSION: There was heterogeneity between the studies because there was diversity in their inclusion criteria, definition and assessment methods used for detection of sarcopenia, considered cutoffs for low muscle mass and strength, cross-sectional locations on imaging to assess muscle mass and included covariates. The discrepancy in the results of the studies may also result from the variations in diagnoses, sample sizes, and treatment modalities. The low number of included studies and a small number of patients in each study limited generalizability. CONCLUSIONS: Sarcopenia may be a prognostic factor, especially in OS when low muscle strength/function is integrated into its definition. We suggest that clinicians focus on muscle strength/function while considering sarcopenia and its association with cancer and RT-related outcomes.

Prognostic factors and clinical course of extremity soft-tissue sarcomas.

PURPOSE: Although soft tissue constitutes half of the body weight, soft-tissue sarcomas (STSs) are less common than any other types of tumors. MATERIALS AND METHODS: In this retrospective study, the prognostic factors and clinical courses of 64 patients with extremity STSs treated at our clinic between 1996 and 2012 were investigated. RESULTS: Of the 64 patients included in this study, 35 (55%) were male and 29 (45%) were female. By the end of follow-up, 29 (45%) of the patients remained alive while 35 (55%) deceased. The overall survival (OS) time of the patients was 89.1 months, and their 1-, 3-, 5-, and 10-year survival rates were 82.8%, 69.3%, 51.6%, and 39.4%, respectively. Univariate analysis revealed the following variables as prognostic factors: tumor stage (P < 0.001), surgical method applied (P = 0.009), radiotherapy (RT) application (P = 0.018), RT dose (P < 0.001), and development of metastasis during follow-up (P < 0.001). Multivariate analysis revealed only type of surgery to be a prognostic factor (P = 0.016). CONCLUSION: Besides surgery, RT plays a crucial role in the multimodal treatment of STSs and increases local control rates and OS. In our study, stage, surgery, and adjuvant RT were found to be effective factors indicating OS. However, more prospective work in this area is necessary.

Brain metastasis from ovarian carcinoma: Analysis of eight cases from a single radiotherapy center.

OBJECTIVE: Brain metastasis from epithelial ovarian carcinoma (EOC) is rarely seen having rate of 1-3% with very poor prognosis. Studies on brain metastatic EOC is limited with low number of participants. An increasing trend in EOC related to brain metastasis has been reported recently confronting managing clinicians with new challenges. Therefore, more information on this issue is needed. We aimed to analyze a single radiotherapy center experience on EOC related brain metastases. MATERIALS AND METHODS: Data of all patients treated between January 1998 and December 2016 at a radiation center of a university hospital were reviewed retrospectively. Clinicopathological characteristics, treatment details and outcome were analyzed. RESULTS: We identified only ten cases with EOC related brain metastasis in our department during 18-year period. Two patients were excluded because of data unavailability and therefore our study was performed among 8 patients. The median time between EOC diagnosis and detection of brain metastasis was 19.8 months. Brain metastasis was multiple in majority (75%). Extracranial metastasis at the time of brain metastasis was 62.5%. All patients died in the follow-up. The median survival time after the diagnosis of brain metastasis was 4.5 months. The median overall survival (OS) after the diagnosis of EOC was 28.9 months. The interval between the initial diagnosis and brain metastasis was negatively correlated with survival after brain metastasis (B-OS) occurred as time interval (p = 0.047). Presence of extracranial metastasis at time of occurrence of brain metastasis and application of multimodal treatment after brain metastasis were positively correlated with B-OS time (p = 0.007, p = 0.046, respectively). CONCLUSION: Prognosis of brain metastasis from EOC remains poor. The factors associated with better B-OS were the longer time between initial diagnosis and brain metastasis, absence of extracranial disease at time of brain metastasis, and application of the multimodal treatment.

Radiotherapy in the management of classic Kaposi's sarcoma: A single institution experience from Northeast Turkey.

Kaposi sarcoma is a rare adult neoplasm and there has been no certain consensus on standard treatment, either local or systemic. Radiotherapy is an effective, suitable treatment modality. Between 1996 and 2016, patients who were diagnosed with Kaposi sarcoma and referred to our clinic for radiotherapy were included in this retrospective study. Ninety-two patients were examined in total and it was diagnosed that all the patients had non-HIV associated Kaposi's sarcoma. There were 36 (39%) females and 56 (61%) males and female to male ratio was 2/3. Median age at presentation was 72 (30-93) years. Sixty-eight patients (77%) were treated with 8 Gy (1 fraction), 15 patients (16%) were treated with 20 Gy (2 Gy/fraction), four patients (4%) were treated 25 Gy (2.5 Gy/fraction), and five patients (6%) were treated 30 Gy (3 Gy/fraction). The median follow-up time was 72 (5-192) months. The complete response at 5 years was 91.6% with >20 Gy and 89.6% with 8 Gy. Radiotherapy is an effective, suitable treatment modality of Classic Kaposi sarcoma and usually, radiotherapy is well tolerated with minimal side effects.

Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation.

STUDY OBJECTIVE: To investigate the effects of dexmedetomidine on oxidative injury caused by ionizing radiation. DESIGN: Randomized controlled experimental study. SETTING: Department of radiation oncology and research laboratory of an academic hospital. INTERVENTIONS: Twenty-eight rats were randomized to 4 groups (n=7 per group). Group S rats were administered physiologic serum; group SR rats were administered physiologic serum and 10 Gy external ionizing radiation. Groups D100 and D200 were administered 100 and 200 µg/kg dexmedetomidine intraperitoneally, respectively, 45 minutes before ionizing radiation. MEASUREMENTS: Liver, kidney, lung, and thyroid tissue and serum levels of antioxidant enzymes (glutathione peroxidase [GPX], superoxide dismutase, and catalase) and oxidative metabolites (advanced oxidation protein products, malondialdehyde, and nitrate/nitrite, and serum ischemia-modified albumin) were measured 6 hours postprocedure. MAIN RESULTS: In group SR, IR decreased antioxidant enzyme levels and increased oxidative metabolite levels (P<.05). In plasma, antioxidant enzyme levels were higher and oxidative metabolite levels were lower in groups D100 and D200 than in group SR (P<.01). In tissues, hepatic and lung GPX levels were higher in groups D100 and D200 than in group SR (P<.001). Renal and thyroid GPX levels were higher in D200 than in group SR (P<.01). Thyroid superoxide dismutase levels were higher in groups D100 and D200 than in group SR (P<.01). Renal, lung, and thyroid catalase levels were higher in group D200 than in group SR (P<.01). Hepatic, renal, and lung advanced oxidation protein products and malondialdehyde levels were lower in groups D100 and D200 than in group SR (P<.01). Hepatic, renal, and lung nitrate/nitrite levels were lower in group D200 than in group SR (P<.05). CONCLUSIONS: Dexmedetomidine preserves the antioxidant enzyme levels and reduces toxic oxidant metabolites. Therefore, it can provide protection from oxidative injury caused by ionizing radiation.

Evaluation of the radioprotective effect of Turkish propolis on foreskin fibroblast cells.

AIM OF STUDY: Propolis is a resinous bee product, rich of polyphenolic compounds and flavonoids. It is known that in different geographic zones its chemical composition varies due to the different plant sources. Many biological properties including antimicrobial, antioxidative, anti-inflammatory, antitumoral, antigenotoxic, antimutagenic, cytostatic activities have been ascribed to propolis. These biological effects are predominantly attributed to its content of polyphenols. In this study, we aimed to evaluate the radioprotective effect of ethanolic extract of Turkish propolis. (EETP) against γ-ray-induced DNA damage on fibroblast cells using comet assay for the first time. MATERIALS AND METHODS: Fibroblast cells were pretreated 15 and 30 min with concentrations of 100, 200 and 300 µg/mL EETP then they were exposed to 3 Gy γ-rays. Amifostine (synthetic aminothiol compound) was used as a positive control. RESULTS: The results showed a significant decrease in γ-ray-induced DNA damage on cells treated with EETP and amifostine when compared to only irradiated cells. (P < 001). CONCLUSION: It was concluded that EETP prevent γ-ray-induced DNA damage in fibroblast cells and might have radioprotective activity.

The choice of multi-beam IMRT for whole breast radiotherapy in early-stage right breast cancer.

The aim of this study was to identify a rational strategy for the selection of multi-beam IMRT in patients with right breast cancer through the comparison of dosimetric parameters of the planning target volume (PTV) and organs at risk (OARs) using five different radiotherapy modalities. This was a retrospective study using computed tomography scans from ten patients with early-stage right breast cancer who had been treated previously. Three dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), inverse-planned IMRT (inv-IMRT), helical tomotherapy (HT), and volumetric-modulated arc therapy (VMAT) were planned for each patient. The plans were compared according to dose-volume histogram analysis. The most significant impact of inverse-planned multi-beam modalities for right breast cancer was the reduction of Dmax, Dmean, V53.5 and prescribed dose volume (cc) outside of the PTV (breast) (OB-V50) of the PTV. HT decreased the ipsilateral OAR volumes receiving higher doses. In exchange, HT also increased the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies. The heart, LAD, and contralateral doses for 3DCRT and for-IMRT were significantly lower than those for inv-IMRT, HT, and VMAT. In addition, inv-IMRT demonstrated an increase in exposed volume of heart, LAD, ipsilateral lung, and contralateral lung compared with those parameters for HT or VMAT. Although it is known to reduce cardiac toxicity with breath hold technique in left sided breast cancer, similarly it is possible for 3DCRT and for-IMRT techniques in right sided breast cancer even in free breathing.

Prognostic Factors and Clinical Outcome in Parotid Gland Tumors: a Single Institution Experience from the Eastern Black Sea Region of Turkey.

PURPOSE: To review clinical characteristics, treatment outcomes and prognostic factors in patients with parotid gland tumors treated with surgery and postoperative radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed 69 patients with parotid gland tumors, with a median follow-up of 52 months (range, 2-228 months). and a median radiotherapy dose of 60Gy (range, 30-69 Gy). RESULTS: There were 24 (35%) females and 45 (65%) males, at a ratio of 1/1.9. Median age at presentation was 58.9±17.2 (range 13-88) years. The most common histology was adenoid cystic carcinoma (33%) and mucoepidermoid carcinoma (28%). The mean overall survival (OS) was 65.3±8 (95% confidence interval [CI], 49.6-81.1) months and the median overall survival was 40.0 ± 7 (95% CI, 26.2-53.7) months. The -1, -3, -5 and -10 year OS rates were 78%, 52.4%, 35.3% and 19.6% respectively. The mean disease free survival (DFS) was 79.2±10 (95% CI, 59.3-97.1) months and the median disease free survival was 38±13 (95% CI, 7.05-88.7) months. The -1,-3,-5 and -10 year DFS rates were 71.9%, 50.1%, 43.7% and 30.1% respectively. On univariate analysis, the OS was significantly better with female sex (p<0.005), < 50 age (p<0.021), T stage (p<0.0001), absence of lymph node involvement (p<0.0001), lower tumor grade (p<0.0001), absence of lymphovascular invasion (p<0.002), absence of perineural invasion (p<0.0001), absence of extracapsuler extension (p<0.0001), surgical margin negativity (p<0.006), ≤60 Gy radiotherapy dose (p<0.0001) and absence of distant metastasis (p<0.027). CONCLUSIONS: Employing existing standards of postoperative radiotherapy is a possible treatment that was found to be mainly effective in patients with parotid gland carcinomas.

Comparison of the effects of melatonin and genistein on radiation-induced nephrotoxicity: Results of an experimental study.

The aim of the present study was to compare the effects of melatonin and genistein on radiation-induced nephrotoxicity (RIN). A total of 70 Swiss Albino mice were divided into 7 groups. Five control groups were defined, which were sham irradiation (C, G1), radiation therapy only (RT, G2), melatonin (M, G3), genistein (G, G4) and polyethylene glycol-400 (G5), respectively. The co-treatment groups were the RT plus melatonin (RT+M, G6) and RT plus genistein (RT+G, G7) groups. Irradiation was applied using a cobalt-60 teletherapy machine (80-cm fixed source-to-surface distance, 2.5-cm depth). Melatonin was administered (100 mg/kg, intraperitoneal injection) 30 min before the single dose of irradiation, whereas genistein was administered (200 mg/kg, subcutaneous injection) 1 day before the single dose of irradiation. All the mice were sacrificed 6 months after irradiation. As an end point, the extent of renal tubular atrophy for each mouse was quantified with image analysis of histological sections of the kidney. Tissue malondialdehyde (MDA) levels were also measured in each animal. In the histopathological examination of the mouse kidneys, there was a statistically significant reduction (P<0.05) in the presence of tubular atrophy between the RT+M and RT+G groups and the RT group. There was a statistically significant increase in MDA levels in the irradiated versus sham groups (RT vs. C; P<0.05); however, MDA levels were significantly decreased by co-treatment with melatonin or genistein vs. RT alone (RT+M and RT+G vs. RT; P<0.05). In conclusion, the present experimental study showed that melatonin and genistein supplementation prior to irradiation-protected mice against RIN, which may have therapeutic implications for radiation-induced injuries.

Radiotherapy Induces Development of Fragmented QRS in Patients with Breast Cancer.

BACKGROUND: Myocardial fibrosis is a well-known side effect of radiotherapy. Fragmented QRS (fQRS) has been shown to be a marker of myocardial fibrosis. We postulated that radiotherapy induces development of fQRS in breast cancer patients. PATIENTS AND METHODS: Breast cancer patients receiving locoregional radiotherapy were enrolled. Patients who had fQRS on electrocardiography (ECG) before radiotherapy were excluded. All patients were revaluated for the development of fQRS at 1-year follow-up. An age-matched healthy group served as controls. RESULTS: A total of 52 breast cancer patients receiving locoregional radiotherapy were included (median age 49 years, interquartile range (IQR) 13). Of these, 19 (37%) had developed fQRS at 1-year follow-up. Compared with the control group, prevalence of fQRS was significantly higher in the irradiated group (37 vs. 12%; p < 0.002). Median total cardiac radiation dose was significantly higher in patients who had developed fQRS (5 Gy, IQR 5.2 vs. 1.7 Gy, IQR 4.4; p = 0.003). Cardiac radiation dose, entered either as a continuous variable (odds ratio (OR) 1.35, 95% confidence interval (CI) 104-1.74) or as a dichotomized variable (≥ 2.2 Gy, OR 6.48, 95% CI 1.47-28.61), was independently associated with the development of fQRS at 1-year follow-up. CONCLUSION: Radiotherapy for breast cancer induces development of fQRS on ECG. Cardiac radiation dose is independently associated with the development of fQRS.

Adjuvant radiotherapy in stage 1 seminoma: Evaluation of prognostic factors and results of survival.

PURPOSE: The purpose of this study was to evaluate the prognostic factors affecting overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and survival among patients undergoing adjuvant radiotherapy (RT) for stage-1 seminoma. MATERIALS AND METHODS: Between August 1997 and May 2013, 68 patients diagnosed with stage-1 seminoma were retrospectively evaluated. The median age was 39 (24-74) years. All patients received adjuvant RT after inguinal orchiectomy. Fifty-eight (85.3%) patients received paraaortic RT; 10 (14.7%) received dog-leg field RT. The median RT dose was 23.4 (23.4-30.6) Gy. RESULTS: The median follow-up period was 77.5 (6.7-198.5) months. During the follow-up period, two patients developed distant metastasis, and none developed local recurrence. Two patients died from seminoma, and three died for other reasons. The 5, 10, and 15-year OS rates were 94.7%, 89.6%, and 89.6%, respectively. The 5, 10, and 15-year CSS rates were 98.5%, 96%, and 96%, respectively. The 5, 10, and 15-year PFS rate was 96.1%. The univariate analysis showed that only histological subtype was significant for OS. The 10-year survival rate was 100% among patients with seminoma histology, 90.8% among patients with a classic seminoma histology, and 50% among patients with an anaplastic seminoma histology (P < 0.001). A multivariate analysis showed that the anaplastic seminoma was a negative prognostic indicator for OS (P = 0.042). CONCLUSION: Adjuvant RT resulted in excellent long-term survival and local control in patients with stage-1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM) and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains.

Dosimetric comparison of left-sided whole-breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and volumetric arc therapy.

PURPOSE: This study evaluated the dose distribution and homogeneity of four different types of intensity-modulated radiotherapy (IMRT) in comparison with standard wedged tangential-beam three-dimensional conformal radiotherapy (3DCRT) of the left breast in patients who had undergone lumpectomy. MATERIALS AND METHODS: Five radiotherapy treatment plans, including 3DCRT, forward-planned IMRT (for-IMRT), inverse IMRT (inv-IMRT), helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT), were created for 15 consecutive patients. RESULTS: All modalities presented similar target coverage. Target max doses were reduced with for-IMRT compared to 3DCRT, and these doses were further reduced with inv-IMRT and HT. HT resulted in the lowest max doses delivered to the heart, left anterior descending artery (LAD), and ipsilateral lung, but had higher mean, max, and low doses delivered to contralateral breast. HT resulted in increased low doses to a large volume of healthy tissue. Compared to other techniques, all inverse-planned modalities significantly improved conformity number; however, VMAT had worse homogeneity. The for-IMRT plan significantly lowered monitor unit (MU) compared to the inverse-planned techniques. CONCLUSION: All modalities evaluated provide adequate coverage of the whole breast. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned inv-IMRT and HT. HT decreases the ipsilateral OAR volumes receiving higher and mean doses with an increase in the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies.

Observational cohort study on correlates of mortality in older community-dwelling outpatients: The value of functional assessment.

AIM: To analyze correlates of mortality with admission features/factors in older community-dwelling outpatients. METHOD: This is an observational cohort study including 608 patients aged >60 years admitted to the geriatrics outpatient clinics of a university hospital. On admission, demographic characteristics, history of smoking-alcohol consumption, individual comorbidities, individual drugs, number of comorbidities, number of drugs and the components of comprehensive geriatric assessment (functional status, nutritional status, depression and cognition screening) of the patients were recorded. Survival status was assessed through the related official website. The relationship between mortality and recorded parameters were analyzed individually by univariate analyses. Consequently, stepwise forward Cox regression analysis was carried out to detect independent correlates for mortality (for those variables statistically significantly related to mortality.) RESULTS: The mean age was 73.8 ± 6.9 years. 66.6% of participants were female. The mean follow-up time was 40.4 ± 25.3 months. The mortality rate was 17.8%. Correlates of mortality were calculated using univariate analysis. They were age, sex, nutritional status, activities of daily living (ADL), instrumental ADL, diabetes mellitus (P < 0.001 for all), suspected dementia (P = 0.002), hyperlipidemia (P = 0.048) and total number of diseases (P = 0.025). Independent correlates of mortality were advanced age (HR 1.10, 95% CI 1.06-1.13; P < 0.001, low ADL score (HR 1.22, 95% CI 1.12-1.32; P < 0.001), the presence of diabetes (HR 2.64, 95% CI 1.78-3.91, P < 0.001), male sex (HR 1.68, 95% CI 1.13-2.49; P = 0.01) and suspected dementia (HR 1.51, 95% CI 1.02-2.22; P < 0.05). CONCLUSION: In the present study--taking many factors into consideration--the variables associated with mortality were advanced age, low ADL score, presence of diabetes, male sex and suspected dementia. Functional status emerged as the second most significant factor associated with higher mortality--after advanced age. The present study highlights the importance of functional assessment in geriatric outpatient clinics.