Mert Saynak

Extrapulmonary Small-Cell Carcinoma Compared With Small-Cell Lung Carcinoma A Retrospective Single-Center Study

The study was conducted with the aim of reviewing the clinical features, therapy, and natural course of patients with extrapulmonary small‐cell carcinoma (EPSCC) and small‐cell lung carcinoma (SCLC) to better define current concepts regarding EPSCCs.

Factors associated with the development of brain metastases: analysis of 975 patients with early stage nonsmall cell lung cancer.

The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%‐50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors.

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.

Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters.

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.

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.

Dural sinus vein thrombosis in a patient with colon cancer treated with FOLFIRI/bevacizumab

The adverse effects of regimes in cancer treatment have forced us to change to new targeted therapy options. Understanding these side effects, which can lead to discontinuation of the new therapy strategies, will allow the clinical management of these side effects and result in continuing therapies with effective medications. Bevacizumab, which is an IgG1 antibody against vascular endothelial growth factor, has side effects such as proteinuria, hypertension, venous and arterial thromboembolic events, and hemorrhage. This is the first reported case of dural sinus vein thrombosis, during the treatment with bevacizumab.

Non–Small Cell Lung Cancer: Prognostic Importance of Positive FDG PET Findings in the Mediastinum for Patients with N0–N1 Disease at Pathologic Analysis

PURPOSE To assess the prognostic implications of mediastinal positron emission tomographic (PET) findings in patients undergoing curative resection of non-small cell lung cancer (NSCLC) who have histologically negative mediastinal lymph nodes (LNs), with the hypothesis that positive findings at PET are prognostic even in patients with negative histologic findings in the LNs. MATERIALS AND METHODS Records of patients with a preoperative PET undergoing curative surgery, without adjuvant radiation, for pathologic T1-3N0-1 NSCLC at the University of North Carolina between 2000 and 2006 were reviewed as an institutional review board-approved HIPAA-compliant retrospective study. Ninety patients were evaluable (all histologically negative in mediastinum; 44 with both mediastinoscopy and surgery); 13 patients had positive mediastinal PET findings, and 77 had negative mediastinal PET findings. Local-regional and distant failure rates in patients with and those without mediastinal abnormalities at preoperative PET were compared by using logistic regression and log-rank tests. RESULTS Median follow-up was 54.3 months (range, 1-99 months). There were higher rates of local-regional (P = .001) and distant (P < .001) failure as well as death (P = .001) in patients with postive PET findings than in patients with negative findings. In multivariable analysis (adjusting for other prognostic factors), positive PET findings in the mediastinum remained prognostic for distant failure (P < .001, hazard ratio = 6.9) and were marginally prognostic for local-regional failure (P = .093, hazard ratio = 1.9). CONCLUSION Positive findings at preoperative PET in the mediastinum appear to have prognostic implications despite the mediastinal LNs being histologically negative. The high rate of local-regional and distant failure suggests that postoperative radiation therapy and/or chemotherapy may be particularly helpful in patients with positive mediastinal findings at preoperative PET.