Vuslat Yurut-Caloglu

An ambiguous phenomenon of radiation and drugs: recall reactions.

The term ‘radiation recall’ describes an acute inflammatory reaction in previously irradiated areas after the administration of certain inciting systemic agents. It was first described in 1959 by D’Angio that dermatitis is related to the application of actinomycin D on the skin. Though this reaction occurs frequently on the skin, it may also be seen in the oral mucosa, the larynx, esophagus, small intestine, lungs, muscle tissue, and brain. Most drugs associated with recall reactions are cytotoxics, however, several other drugs may also elicit the phenomenon. Although this phenomenon is well known, its etiology is not understood. Radiation recall reactions are generally associated with megavoltage radiotherapy. The time interval between the completion of radiotherapy and the recall reaction ranges from days to years. The recall reaction occurs on average 8 days (3 days to 2 months) after the application of the promoting agent. Although no standard treatment exists, some authors suggest discontinuation of the inciting drug and the use of corticosteroids or nonsteroidal anti-inflammatory agents.

Postmastectomy irradiation in breast in breast cancer patients with T1-2 and 1-3 positive axillary lymph nodes: Is there a role for radiation therapy?

BackgroundWe aimed to evaluate retrospectively the correlation of loco-regional relapse (LRR) rate, distant metastasis (DM) rate, disease free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients who are at intermediate risk for LRR (T1-2 tumor and 1-3 positive axillary nodes) treated with or without postmastectomy radiotherapy (PMRT) following modified radical mastectomy (MRM).MethodsNinety patients, with T1-T2 tumor, and 1-3 positive nodes who had undergone MRM received adjuvant systemic therapy with (n = 66) or without (n = 24) PMRT. Patient-related characteristics (age, menopausal status, pathological stage/tumor size, tumor location, histology, estrogen/progesterone receptor status, histological grade, nuclear grade, extracapsular extension, lymphatic, vascular and perineural invasion and ratio of involved nodes/dissected nodes) and treatment-related factors (PMRT, chemotherapy and hormonal therapy) were evaluated in terms of LRR and DM rate. The 5-year Kaplan-Meier DFS and OS rates were analysed.ResultsDifferences between RT and no-RT groups were statistically significant for all comparisons in favor of RT group except OS: LRR rate (3%vs 17%, p = 0.038), DM rate (12% vs 42%, p = 0.004), 5 year DFS (82.4% vs 52.4%, p = 0.034), 5 year OS (90,2% vs 61,9%, p = 0.087). In multivariate analysis DM and lymphatic invasion were independent poor prognostic factors for OS.ConclusionPMRT for T1-2, N1-3 positive BC patients has to be reconsidered according to the prognostic factors and the decision has to be made individually with the consideration of long-term morbidity and with the patient approval.

Recurrent solitary fibrous tumor of the pleura: significant response to radiotherapy

Solitary fibrous tumor (SFT) of the pleura is an uncommon neoplasm with non-specific symptoms and non-pathognomonical radiological findings. Surgery allows establishment of a definitive diagnosis as well as a cure of the disease. The role of radiotherapy or chemotherapy in the management of the disease is unclear because of the rarity of the disease and the successful results of the surgical treatment. Long-term clinical follow-up may be useful for the patients with SFT because of the potential adverse biological behavior of this tumor, which may lead to repeated recurrences and/or malignant transformation. We reported a 66-year-old woman with recurrence of SFT in the right lung, which had significant response to external thoracic radiotherapy.

Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

1 The aim of the present study was to compare the protective effects of l‐carnitine and amifostine against radiation‐induced late nephrotoxicity using technetium‐99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2 Seventy‐one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., l‐carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., l‐carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3 The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post‐treatment time to peak count (Tmax) and time from peak count to half count (T½) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T½ of the right kidney was 8 ± 2 and 21 ± 2 min, respectively. The Tmax values for the AMI + RAD and LC + RAD groups (2.8 ± 0.2 and 3.2 ± 0.2 min, respectively) were similar to those in the control group (2.5 ± 0.3 min). 4 Based on the results of the present study, l‐carnitine and amifostine have comparable and significant protective effects against radiation‐induced late nephrotoxicity.

Oncocytic Carcinoma of the Parotid Gland

Background: Oncocytic carcinoma is a rare tumor of major salivary glands. Despite being described 5 decades ago, not much is known about these rare tumors. Histochemical or electron microscopic confirmation of the oncocytic nature of the tumor cell is needed for differential diagnosis. The main treatment modality is surgery with or without adjuvant radiotherapy. Malignant oncocytomas have the potential risk of developing distant metastases and demand long term follow-up after therapy. Case Report: A 58-year old man presented with a recurrent mass in the left parotid gland with a prior diagnosis of monomorphic adenoma in the same localization which had been treated by tumor excision in July 2002. Left superficial parotidectomy followed by radiotherapy into tumor bed and upper neck were carried out in September 2004. To date, he has had no evidence of recurrence for 14 months. Conclusion: For an accurate approach in the management of patients, oncocytic adenocarcinoma should be considered in the differential diagnosis of lesions of the parotid gland, most of which are benign.

Amifostine Use in Radiation-Induced Kidney Damage

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.

Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods.

PURPOSE The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC) and amifostine against radiation-induced acute ovarian damage. MATERIALS AND METHODS Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7); irradiation alone RT: radiation therapy (RT, n = 8); amifostine plus irradiation (AMI + RT, n = 8); LC plus irradiation (LC + RT, n = 8); LC and sham irradiation (LC, n = 7); and amifostine and sham irradiation (AMI, n = 7). The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg) and amifostine (200 mg/kg) was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA) and advanced oxidation protein product (AOPP) were measured. RESULTS Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P < 0.0001). LC increased the median number of antral follicles and corpus luteum (P: 0.009 and P < 0.0001, respectively). Amifostine improved median corpus luteum numbers but not antral follicle (P < 0.000, P > 0.05). The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P < 0.0001, respectively). MDA and AOPP levels were significantly reduced by LC (P: 0.003, P < 0.0001) and amifostine (P < 0.0001, P: 0.018). When comparing CONT group with AMI + RT and LC + RT groups, MDA and AOPP levels were similar (P > 0.005). The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005). CONCLUSIONS L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

Does low-dose X-irradiation promote mineralization of fracture callus in a rat model?

We read the study “Low-dose X-irradiation promotes mineralization of fracture callus in a rat model” by Zhou et al. [1] published early this year in the journal, with great interest. In the “Introduction”, the authors stated that low-dose irradiation (LDI) showed beneWts as “accelerating wound healing” where Schindl et al. [2] were cited. However, in the study mentioned, “low-intensity laser irradiation with a single helium–neon (He–Ne, 632.8 nm)” was used. It should be noted that these two modalities (ionizing irradiation and laser irradiation) are very diVerent from each other radiobiologically. The methods seem to have some controversy that may alter the results, thus the conclusions. The authors stated that the rats were irradiated with a dose of 1 Gy using a 31 £ 23 cm Weld. This size corresponds to an area even more than a whole body irradiation Weld for a SpragueDawley rat. Whole body irradiation should be avoided in experiments investigating local eVects, and when previous studies were considered the authors used local irradiation like 3-cm diameter Welds [3]. In addition, irradiation should be applied under anesthesia to prevent excessive movements of the subjects. We believe that “Materials and methods” section is one of the most important parts of an experimental study and should be standardized to avoid subject, time and resource consuming where “reproducibility” can be provided. As the last but not the least, results should also be interpreted more carefully and our tendency to draw enthusiastic conclusions should be repressed. In the study, Wnal Wndings at week 4 showed no statistically signiWcant diVerences between the groups to reach a conclusion of “low dose irradiation promoting mineralization of fracture callus”. Most of the results that drive the authors to conclude were obtained from week 3 observations (Table 1). We should note that all mechanical properties were found as lower for LDI group than SHAM group at week 2. Even stiVness and energy showed lower results for LDI group, although they were not statistically signiWcant. The Wnal observation at week 4 should help us to draw more conclusions, where no statistically signiWcant diVerences between the groups could be detected in any of the results. In conclusion, “beneWcial” eVects of X-irradiation with 1 Gy should better be regarded cautiously and there is a greater likelihood of “no eVect” than “beneWcial” eVects.

Treatment of anemia by recombinant human erythropoietin in cancer patients undergoing radiotherapy

Anemia is a deficiency in red blood cells or in the hemoglobin (Hb) levels that leads to a decrease in the transport capacity of oxygen in the blood, which can reduce tolerance in radiotherapy (RT) and chemotherapy. The relationship between anemia and hypoxia, however, is complex and influenced by multiple variables. Although the blood Hb values that might develop hypoxia in tumors were not described clearly, optimal oxygen pressure was accepted in patients with an Hb value of 12–14 g/dL. Erythropoietin is a glycoprotein, which acts via EPOR to stimulate the growth, to prevent apoptosis, and to induce differentiation of red blood cell precursors. RhuEPO‐α and ‐β are classically administered subcutaneously three times per week at doses ranging from 150 to 300 IU/kg. Darbepoetin‐α has been shown to exhibit a longer elimination half‐life, thus allowing a once‐weekly administration at the dose of 2.25 µg/kg. Side‐effects related to rhuEPO include hypertension and thromboembolic events. RhuEPO can be used effectively in the treatment of anemia in patients with solid tumor being treated by RT or chemoradiotherapy. Furthermore, the use of rhuEPO has been demonstrated to have a sustained beneficial impact on quality of life in cancer patients. However, the role of combination of rhuEPO with external RT still remains inconclusive and several clinical trials have been pointed increased mortality in patients treated with rhuEPO. In this paper, the probable radiobiological effects of anemia in patients treated with RT, the beneficial and adverse effects of rhuEPO, and related studies are reviewed. Future directions for the use of rhuEPO are proposed.

RADIATION-INDUCED CHRONIC-OXIDATIVE RENAL DAMAGE CAN BE REDUCED BY AMIFOSTINE

In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Thirty Wistar albino 3–4 months old, female rats, were randomly divided into Group I (n = 10): Control, Group II (n = 10): Irradiation-alone, Group III (n = 10): Amifostine before irradiation. In Group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a 60Co treatment unit. Rats in Group III received 200 mg/kg amifostine intraperitoneally, 30 min prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One-way ANOVA, Post hoc Bonferroni, Dunnett T3, and Mann–Whitney U tests. Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (P = 0.004, P = 0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (P = 00.02, P = 0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (P = 0.002, P = 0.016; respectively). Tissue GSH activity was increased following amifostine administration (P = 0.001). There was no statistically significant result on histopathological evaluation. Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy.