Murat Beyzadeoglu

Total parenteral nutrition delays platelet engraftment in patients who undergo autologous hematopoietic stem cell transplantation

OBJECTIVES One of the major challenges in the post-transplant period is nutrition. In this prospective, non-randomized study, total parenteral nutrition (TPN) was given to 31 patients and partial parenteral nutrition (PPN) was given to 30 patients undergoing autologous hematopoietic stem cell transplantation for solid tumors or hematologic malignancies to compare the effects of these parenteral nutrition modalities on post-transplant hematological engraftment, blood chemistry, and supportive therapy requirements. METHODS All patients in the TPN group and 17 patients in the PPN group received growth factor in the post-transplant period. Both groups did not differ with respect to sex, age, and reinfused CD34(+) cell numbers. RESULTS After transplantation body mass index and body weight decreased significantly in both groups (P < 0.001). Whereas serum albumin concentrations did not decrease significantly in the TPN group, it fell markedly in the PPN group at the end of parenteral nutrition (P = 0.019). After parenteral nutrition, blood chemistry was also remarkable for serum urea and glucose levels, which were elevated significantly in the TPN group (P < 0.001 and P = 0.03, respectively). Patients receiving TPN had a higher incidence of positive microbial cultures and clinical infection than did patients receiving PPN (64.5% versus 40%, P = 0.05). The most striking result was a delay in platelet engraftment for the TPN group compared with the PPN group (15.54 and 12.93 d, respectively; P = 0.014). This difference was also noted in patients using growth factor in the PPN group (P = 0.017). Parallel to these results, platelet transfusion requirement increased in the TPN group compared with the PPN group (1.93 versus 1.16 U, P = 0.004). Both groups were unremarkable for leukocyte recovery and red blood cell transfusion requirement. CONCLUSIONS Consequently, TPN has some pitfalls of hyperglycemia, infection tendency, delayed platelet engraftment, and increased platelet transfusion requirement. Therefore, it should not be used as a standard nutrition support for patients undergoing autotransplantation.

Cerebellar aspergillosis: case report and literature review.

OBJECTIVE AND IMPORTANCE An unusual, but not unique, case of cerebellar aspergillosis associated with autologous peripheral blood stem cell transplantation for breast cancer is presented. CLINICAL PRESENTATION A 45-year-old woman with breast cancer underwent chemotherapy and radiotherapy as well as autologous peripheral blood stem cell transplantation. She developed a cerebellar aspergillosis abscess that was treated successfully with two surgical resections. INTERVENTION After removal of pus and the abscess wall, the patient received local application of amphotericin B (AmB). She received AmB 1 mg/kg/d for 3 months and itraconazole 100 mg/kg/d for 1 year. After 3 months of AmB treatment, magnetic resonance imaging revealed that disease had not recurred. CONCLUSION In cases of central nervous system aspergillosis, to increase the therapeutic efficiency, AmB can also be applied to the abscess cavity. Computed tomographic and contrast-enhanced magnetic resonance imaging scans play an important role in establishing early diagnosis in high-risk, immunocompromised patients.

Linear accelerator-based stereotactic radiosurgery in recurrent glioblastoma: a single center experience.

BACKGROUND/AIM Management of patients with recurrent glioblastoma (GB) comprises a therapeutic challenge in neurooncology owing to the aggressive nature of the disease with poor local control despite a combined modality treatment. The majority of cases recur within the high-dose radiotherapy field limiting the use of conventional techniques for re-irradiation due to potential toxicity. Stereotactic radiosurgery (SRS) offers a viable noninvasive therapeutic option in palliative treatment of recurrent GB as a sophisticated modality with improved setup accuracy allowing the administration of high-dose, precise radiotherapy. The aim of the study was to, we report our experience with single-dose linear accelerator (LINAC) based SRS in the management of patients with recurrent GB. METHODS Between 1998 and 2010 a total of 19 patients with recurrent GB were treated using single-dose LINAC-based SRS. The median age was 47 (23-65) years at primary diagnosis. Karnofsky Performance Score was > or = 70 for all the patients. The median planning target volume (PTV) was 13 (7-19) cc. The median marginal dose was 16 (10-19) Gy prescribed to the 80%-95% isodose line encompassing the planning target volume. The median follow-up time was 13 (2-59) months. RESULTS The median survival was 21 months and 9.3 months from the initial GB diagnosis and from SRS, respectively. The median progression-free survival from SRS was 5.7 months. All the patients tolerated radiosurgical treatment well without any Common Toxicity Criteria (CTC) grade > 2 acute side effects. CONCLUSION Single-dose LINAC-based SRS is a safe and well- tolerated palliative therapeutic option in the management of patients with recurrent GB.

Fascin expresion in glial tumors and its prognostic significance in glioblastomas

Fascin is a ‐55 kDa‐actin binding protein. Actin bundles rearranged by fascin proteins are concentrated in cell membrane protrusions and these protrusions provide motility of the cell. In this study, we evaluated fascin expression in glial tumors and its relation with histologic grade. Its prognostic value in glioblastomas (GBs) was also investigated. Seventy‐six glial tumors including 44 glioblastomas with known survival time, 18 anaplastic astocytomas (AAs), six diffuse astrocytomas (DAs), and eight pilocytic astrocytomas (PAs) were examined immunohistochemically for fascin expression. Fascin was observed in the neurons of normal brain tissue and endothelium of vascular spaces in the glial tumors. Fascin expression was correlated with histologic grade in DAs. PAs expressed low levels of fascin. Half of the GBs showed high levels of fascin expression. In the GB group, overall survival was poor for cases with percentage of stained cells >50% having moderate or strong staining intensity. In GBs, overall survival was also poor for >50‐year‐old cases and cases that refused radiotherapy. Multivariate Cox regression analysis revealed that age (>50 years, P = 0.021) and higher level of fascin expression (immunohistochemical score >8, P = 0.040) were independent poor prognostic factors. In conclusion, fascin expression levels are correlated with histologic grade and fascin overexpression may play an important role in the biologic behavior of glial astrocytic tumors and in the prognosis of GBs.

Primary glioblastoma multiforme in younger patients: a single-institution experience.

Aims and Background To report our experience of patients with primary glioblastoma multiforme of young age by evaluating the characteristics, prognostic factors, and treatment outcomes. Patients and Methods Seventy patients with primary glioblastoma multiforme (GBM) treated at our department between 1996 and 2004 were studied. The male-female ratio was 2.6:1. The median age was 53 (16-74). Sixty-eight patients (97%) were operated on before radiotherapy and 2 patients (3%) underwent only stereotactic biopsy. All patients received radiotherapy. Postoperative chemotherapy as an adjuvant to radiotherapy was given to 9 patients (12%). The patients were divided into 2 groups according to their age (group A ≤35 years, n = 21 vs group B >35 years, n = 49). Survival was determined with the Kaplan-Meier method and differences were compared using the log-rank test. Cox regression analysis was performed to identify the independent prognostic factors. Karnofsky performance status (≥70 vs <70), age (≤35 vs >35 years), gender, tumor size (≤4 vs >4 cm), number of involved brain lobes (1 vs more than 1), type of surgery (total vs subtotal), preoperative seizure history (present vs absent), radiotherapy field (total cranium vs partial), total radiotherapy dose (60 vs 66 Gy), and adjuvant chemotherapy (present vs absent) were evaluated in univariate analysis. Results The median survival was 10.3 months in the whole group, 19.5 months in the younger age group and 5.7 months in the older age group. During follow-up re-craniotomy was performed in 2 patients (3%), and 1 patient (1%) developed spinal seeding metastases and was given spinal radiotherapy. In univariate analysis younger age vs older age: median 19.5 months vs 5.27 months (P = 0.0012); Karnofsky performance status ≥70 vs <70: median 15.3 months vs 2.67 months (P <0.0001), and external radiotherapy dose 60 Gy vs 66 Gy: median 11.6 months vs 3 months (P = 0.02) were found as significant prognostic factors for survival. In regression analysis a worse performance status (KPS <70) was found to be the only independent factor for survival (P = 0.014, 95% CI HR = 0.0043 [0.0001-0.15]). Conclusions Younger patients with primary glioblastoma multiforme had a relatively long survival (median, 19.5 months, with a 2-year survival rate of 30%) compared to older patients. This was due particularly to their better performance status.

Proteasome inhibitor bortezomib increases radiation sensitivity in androgen independent human prostate cancer cells.

OBJECTIVES To investigate the effects of a strong proteasome inhibitor, bortezomib alone or in combination with radiotherapy on androgen-independent DU145 human prostate cancer cells. Proteasomes play important roles in cell cycle, proliferation, apoptosis, angiogenesis, and cellular resistance to chemotherapy and radiotherapy. METHODS Increasing concentrations of bortezomib alone or in combination with radiation were applied to DU145 cells and IC(50) values that inhibited cell growth by 50% were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium-bromide assay. Apoptosis was determined using annexin V staining by flow cytometry. mRNA levels of proapoptotic caspase-3 and antiapoptotic Bcl-2 genes were examined by reverse transcriptase polymerase chain reaction. RESULTS The IC(50) value of bortezomib was found to be 28 microm although 400- and 800-cGy radiation decreased the cell proliferation by 14% and 28%, respectively. In 400- and 800-cGy radiation applied DU145 cells, IC(50) value of bortezomib decreased to 23- and 12 microm, respectively. Exposure to 5 microm bortezomib for 48 hours caused apoptosis in 35% of the population whereas 800-cGy radiation resulted apoptosis in 14% of cells. However, 42% of DU145 cells that were exposed to 800 cGy and 5 microm bortezomib underwent apoptosis. Reverse transcriptase polymerase chain reaction results showed a significant decrease in mRNA levels of antiapoptotic Bcl-2 gene and an increase in proapoptotic caspase-3 gene expression in the combination group compared to control group. CONCLUSIONS Bortezomib increases radiation sensitivity in androgen-independent human DU145 prostate cancer cells through inhibition of Bcl-2 and induction of caspase-3 genes.

The value of postoperative radiotherapy in renal cell carcinoma: a single-institution experience.

Aim To evaluate the efficacy of postoperative irradiation in renal cell carcinoma. Patients and methods Forty patients with localized renal cell carcinoma admitted to our hospital between 1986 and 1999 were evaluated. All patients were initially treated with radical nephrectomy. Postoperative radiotherapy was given to 26 of 40 patients (65%). Fourteen patients (35%) received no adjuvant therapy. Median age was 55 years (range, 20–70 years). Twenty-four patients (60%) were men and 16 patients (40%) were women. Histopathological diagnosis was renal cell carcinoma in all of the patients. N+ disease was present in 3 patients (7%). Stage I and II disease was present in 25 patients (63%) and stage III and IV disease in 15 patients (37%). Two patients (5%) had T1a disease, 11 patients (27%) had T1b, 15 patients (38%) had T2, 11 patients (27%) had T3a and 1 (3%) patient had T3b. In the radiotherapy group, renal bed and regional lymphatic fields were irradiated with daily fractions of 180–200 cGy/fraction to a total dose of 46–50 Gy, using parallel opposing fields. Results The 5-year overall survival rates were 70% in the postoperative radiotherapy group and 20% in the no adjuvant treatment group, showing no significant difference (P = 0.1). The 5-year disease-free survival rates were 66% in the radiotherapy group and 16% in the no treatment group, with a significant difference in both univariate and multivariate analyses (P = 0.045 and P = 0.0007, respectively). Stage III and IV disease, tumor size ≥7 cm, presence of distant metastasis and lactate dehydrogenase level >450 U/L were found to be adverse prognostic factors for overall survival in both univariate and multivariate analyses. Analyzing the factors affecting disease-free survival, absence of postoperative radiotherapy and tumor size ≥7 cm were found to be adverse prognostic factors in univariate and multivariate analyses. Conclusion Multi-institutional prospective randomized trials using modern radiotherapy techniques such as conformal radiotherapy and intensity-modulated radiotherapy are necessary to evaluate the real role of radiotherapy and its effect on survival in renal cell carcinoma, especially in selected patients with a high risk of local or regional failure.

Management of patients with recurrent glioblastoma using hypofractionated stereotactic radiotherapy.

Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The chance of cure is very limited due to treatment-refractory disease course with frequent recurrences despite aggressive multimodality management. In this retrospective study, we evaluated treatment outcomes of hypofractionated stereotactic radiotherapy (HFSRT) in the management of recurrent GBM and report our single-center experience. Methods Twenty-eight patients receiving HFSRT for recurrent GBM between September 2008 and February 2014 were retrospectively assessed. Total radiotherapy dose was 25 Gy delivered in 5 fractions over 5 consecutive days for all patients. High-precision, image-guided volumetric modulated arc therapy was delivered with a linear accelerator using 6-MV photons using the frameless technique. Analyzed prognostic factors were age, gender, Karnofsky performance status (KPS), tumor location, planning target volume (PTV) size, overall survival (OS), progression-free survival (PFS), time interval between completion of treatment with Stupp protocol at primary diagnosis and recurrence. Results Median follow-up time was 42 months (range 2–68). Median time interval between primary chemoradiotherapy and HFSRT was 11.2 months (range 4–57.9). Median OS and PFS calculated from reirradiation was 10.3 months and 5.8 months, respectively. Longer interval between initial treatment and recurrence (p = 0.01), smaller PTV size (p = 0.001), KPS ≥70 (p = 0.005) and younger age (p = 0.004) were associated with longer OS on statistical analysis. Conclusion HFSRT offers a feasible and effective salvage treatment option for recurrent GBM management. Prognostic factors associated with longer OS in our study were longer interval between initial treatment and recurrence, smaller PTV size, KPS ≥70 and younger age.

Evaluation of active breathing control-moderate deep inspiration breath-hold in definitive non-small cell lung cancer radiotherapy.

The purpose of this study is to evaluate the effect of Active Breathing Control-moderate deep inspiration breath-hold (ABC-mDIBH) on tumor motion and critical organ doses in non-small cell lung cancer (NSCLC) radiotherapy. 23 patients with locally advanced NSCLC were included in the study. All patients were scanned at free breathing and ABC-mDIBH for radiation treatment planning. 3 separate treatment plans were generated for each patient including one plan with ABC-mDIBH and uniform margins, one plan with free breathing and uniform margins, and one plan with free breathing and 3-dimensional non-uniform margins determined by Cone Beam Computed Tomography (CBCT) and XVI Motion View (X-ray Volume Imaging, Elekta, UK). Critical organ dose-volumes and physical lung parameters were comparatively evaluated on 3 separate dose-volume histograms of each patient acquired from planning software. Individual tumor motion of each patient with and without ABC-mDIBH was documented and compared. Use of ABC-mDIBH resulted in statistically significant improvement in physical lung parameters of V20 (lung volume receiving ≥ 20 Gy) and mean lung dose (MLD) which are predictors of radiation pneumonitis (p<0.001). Reduction in spinal cord dose and tumor motion with ABC-mDIBH was also statistically significant (p<0.001). ABC-mDIBH increases normal lung tissue sparing in definitive NSCLC radiotherapy by improving physical lung parameters along with spinal cord dose reduction through exact tumor immobilization. The incorporation of ABC-mDIBH into NSCLC radiotherapy may have implications for potential margin reduction and dose escalation to improve treatment outcomes.

Evaluation of fractionated total body irradiation and dose rate on cataractogenesis in bone marrow transplantation.

PURPOSE To assess dose rate effect on cataractogenesis in allogeneic or autologous bone marrow transplanted patients conditioned with fractionated total-body irradiation (FTBI). MATERIALS AND METHODS Between 1987 and 2001, a total of 105 patients have received TBI conditioning for Bone Marrow Transplantation (BMT) for hematological malignancies at Gulhane Military Medical School. 12 Gy FTBI was applied in 6 fractions over 3 consecutive days with a Co60 teletherapy machine. 46 patients who have survived and were followed up after more than one year were evaluated for cataractogenesis in relation to dose rate. Conditioning therapy included only cyclophosphamide (60 mg/kg/day for two days) + TBI with no steroid and veno-occlusive disease prophylaxis. RESULTS The median follow-up is 32 months. Posterior subcapsular cataract developed in 5 eyes of three patients out of 46 patients. The 5-year and 10-year estimated cataract incidence in the high-dose rate (> 0.04 Gy/min) group was 29% and 43% respectively while no cataracts occurred in the low-dose rate (< or = 0.04 Gy/min) group. Cataract development in the high-dose rate group versus low-dose rate group was statistically significant (p < 0.039). CONCLUSION Cataract is a late side effect of TBI. Low-dose rate fractionated TBI is a reliable conditioning program in BMT with effective lens sparing to avoid cataractogenesis.