Alaattin Özen

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.

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.

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.

Capecitabine-related intracranial hypotension syndrome mimicking dural metastasis in a breast cancer patient: case report and review of the literature.

Spontaneous intracranial hypotension (SICH) is an entity, which is secondary to iatrogenic manipulation and breaching of dura. Postural headache in patients should be suspected, cranial magnetic resonance imaging (MRI) is essential for precise diagnosis. Hallmark of MRI is regular shape of pachymeningeal gadolinium enhancement and subdural effusion. It may mimic central nervous system (CNS) metastasis. Prevention of such cases from receiving cranial radiotherapy by misinterpretation of the gadolinium enhancement as CNS metastasis is an important issue. Capecitabine is an antineoplastic agent, of which metabolites can cross blood-brain barrier in CNS via epithelial tissue. It may cause decrease in CSF production. SICH might be the clinical reflection of this decrease in CSF production. Review of the English literature revealed limited data because of the very little experience with oncologic patients suffering from intracranial hypotension. We report a case of spontaneous intracranial hypotension during capecitabine treatment. Patient was completely well following drug discontinuation and supportive treatment.

Unknown primary adenocarcinomas: a single-center experience.

This study aimed to elucidate the clinical and prognostic characteristics of a homogeneous group of patients with cancer of unknown primary (CUP). Between 1999 and 2014, CUP was diagnosed in 159 (1.3%) of 11,742 cancer patients at Trakya University Hospital (Edirne, Turkey). Ninety-seven (61%) of the 159 patients were retrospectively reviewed. Among these, 61 (62.8%) patients with adenocarcinoma were included in this study. The most frequently predicted primary tumor site was the lung (37.7%), and 59% of the patients were smokers. There was a significant relationship between smoking and the lung as a potential primary cancer site (p = 0.042). The most frequent site of metastasis was the liver (60.7%). The median number of metastases per patient was two, but patients with liver metastases had a median of five metastases. The overall median survival time was 7 months. Median survival was significantly longer in patients with a predicted primary site than in patients without the predicted site (7 vs. 6 months, respectively; p = 0.038). When the patients with predicted ovarian and peritoneal tumors were excluded from the comparison, the statistical p value was still close to significant (p = 0.07). Multivariate analysis revealed that smoking, liver metastasis, serum alkaline phosphatase ≥92 U/L, and progression in response to chemotherapy were independent predictors of a poor prognosis. The present study identified several independent prognostic factors in patients with unknown primary adenocarcinomas who received chemotherapy. Smoking, the presence of liver metastasis, and response to chemotherapy were independent risk factors for both progression-free and overall survival.

Carnitine or dimethyl sulfoxide, or both, for the treatment of anthracycline extravasation in rats

Abstract This study aimed to compare the efficacy of topical dimethyl sulfoxide (DMSO), intralesional and systemic carnitine as monotherapy and in combination against ulceration in rats induced by intradermal doxorubicin extravasation. Sixty-nine 3-month-old male Wistar albino rats, weighing between 200–225 g, were used in this study. Rats were applied monotherapy or a combination of topical DMSO, intraperitoneal or intralesional carnitine. Control groups received saline or no drug. The necrotic area was measured and extravasated neutrophil leukocytes were counted in healthy tissue adjacent to necrotic areas. Monotherapy with topical and systemic carnitine did not significantly reduce the size of necrotic areas. However, topical DMSO had reduced necrotic areas and inflammatory cells significantly and the addition of systemic carnitine to topical DMSO had increased the efficacy. DMSO is an effective, safe, and easy-to-apply treatment for doxorubicin-induced extravasation. Further clinical studies are needed to evaluate the use of carnitine in combination with DMSO.

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.

Is there a relation between the changes in circulating lymphocyte counts due to neoadjuvant chemoradiotherapy and intratumoral lymphocytic response and tumor regression grade in locally advanced rectal cancers

There are controversies about the relation between the peripheral lymphocyte levels and response to neoadjuvant therapy. While some authors have reported that a positive correlation between peripheral lymphocyte levels and tumor response, others have suggested the opposite. In the present study, we aimed to investigate the possible relations between the changes in circulating lymphocyte counts due to neoadjuvant chemoradiotherapy (CRT) and intratumoral lymphocytic response (ILR) and tumor regression grade (TRG) in locally advanced rectal cancers. Lymphocyte levels before, during and after CRT as well as before surgery and pathologic findings including ILRs and TRGs were recorded. Lymphocyte levels before CRT were accepted as absolute values. After the changes in the lymphocyte levels during and after CRT and before the surgery were recorded as ratios to the absolute values, the relation between the changes in lymphocyte levels, ILR and TRG were studied by using Pearson and Spearman correlation tests. There was a positive correlation between changes in peripheral lymphocytic levels after neoadjuvant CRT and ILRs. However, there were no other correlations between changes in lymphocytic levels and TRGs and ILRs. The changes in the peripheral lymphocyte counts after CRT may be predictive for ILR. Further studies may provide more information about the relation between peripheral lymphocytes and TILs and tumor response to neoadjuvant CRT.

Trimodality treatment in patients with superior sulcus tumors: hopes and realities

AIMS AND BACKGROUND In late 2001 at our institution, we started offering induction radiochemotherapy as a treatment option for superior sulcus tumors. Our aim was to evaluate treatment choices and outcome in this patient group treated over the past 7 years at our institution. METHODS The records of 34 patients were retrospectively reviewed and 33 were assessable for the analysis. RESULTS Twenty of 28 patients with M0 disease had operable disease. The induction radiochemotherapy for superior sulcus tumors was possible in about two-thirds (14/20) of the cases with operable disease, with only one-third (5/14) of these having undergone surgery. The most common reason for not proceeding to surgery following induction radiochemotherapy was patient refusal (n = 5). The median follow-up of all 33 patients was 17 months. In curatively treated patients with (n = 11) or without surgery (n = 15), the median overall survival time was 26 months (range, 10-26) and 26 months (range, 7-71), respectively ( P = 0.534). Local-regional and/or distant failure developed in 20 of 26 patients treated curatively. In patients treated with the trimodality regimen (n = 5), no local-regional failure was observed, and distant failure occurred in one case. CONCLUSIONS The trimodality treatment was possible in 25% of cases with operable disease due to the high rate of patient refusal to proceed to surgery following induction radiochemotherapy. No difference in survival was observed between patients treated with surgery and those treated with radiochemotherapy only because of a limited follow-up. So, the benefit of additional surgery is not clear, and a longer follow-up is needed before final conclusions can be drawn.