Melek Nur Yavuz

Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin's lymphoma.

Cytokines play important roles in the pathogenesis of lymphomas. The aim of this study was to determine the relations between serum levels of interleukin-2 (IL-2), IL-6, and IL-10 and parameters of International Prognostic Index (IPI). Serum levels of IL-2, IL-6, and IL-10 were measured using a sensitive enzyme-linked immunosorbent assay in the pretreatment frozen sera from 43 patients with non-Hodgkin’s lymphoma. The patients we included in the study were divided into two groups, one with high risk and the other with low risk according to the IPI in regard to their ages, stages, performance status, extranodal involvements, and serum levels of lactate dehydrogenase. In the high-risk group, serum levels of IL-2 (0.852 ± 0.268 ng/ml), IL-6 (0.461 ± 0.206 ng/ml), and IL-10 (0.816 ± 0.240 ng/ml) were found to be higher than serum levels of IL-2 (0.667 ± 0.170 ng/ml), IL-6 (0.355 ± 0.075 ng/ml), and IL-10 (0.643+0.177 ng/ml) in the low-risk group (p < 0.05). There was a correlation between the patients with high risk according to the IPI criteria and high levels of serum cytokines (IL-2, IL-6, IL-10). Knowledge of the serum levels of these cytokines in patients with newly diagnosed aggressive non-Hodgkin’s lymphoma may help us to have some information about the possible prognosis, the activation of disease, and to decide on appropriate therapeutic approaches for individual patients.

Primary intraspinal primitive neuroectodermal tumor: case report of a tumor arising from the sacral spinal nerve root and review of the literature.

Primary spinal primitive neuroectodermal tumor (PNET) is a rare condition, 18 cases of which have been reported in the literature. In general, this tumor is treated with surgery followed by radiotherapy and chemotherapy, but prognosis is still poor. An 18-year-old female patient with an intradural, extramedullary mass at L3–L5 levels is presented in this report. This is the first female patient with primary spinal PNET at lumbar region, second patient with spinal nerve root origin, and third one with intradural, extramedullary localization ever reported in the literature. After surgery, she was treated with craniospinal radiotherapy and four cycles of combination chemotherapy regimen consisting of vincristine, cyclophosphamide, doxorubicin alternated with ifosfamide, and VP-16. Currently, she is asymptomatic and alive at 25 months. The histopathologic, radiologic, and clinical findings of the patient are presented and relevant literature is reviewed.

RADIATION THERAPY AND CONCURRENT FIXED DOSE AMIFOSTINE WITH ESCALATING DOSES OF TWICE-WEEKLY GEMCITABINE IN ADVANCED PANCREATIC CANCER

PURPOSE To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of twice-weekly gemcitabine (TW-G) when administered in conjunction with fixed dose amifostine (A) during external radiotherapy (RT) in patients with advanced pancreatic cancer. METHODS AND MATERIALS Ten patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. RT was delivered by using the standard four-field technique (1.8 Gy daily fractions, 45 Gy followed by a boost of 5.4 Gy, in 5-1/2 weeks). The starting dose of TW-G was 60 mg/m(2) (i.v., 30-min infusion), which is equal to the upper limit of previously reported MTD of TW-G when given without A during RT. A was given just before the TW-G, at a fixed dose of 340 mg/m(2) (i.v., rapid infusion). TW-G doses were escalated by 30-mg/m(2) increments in successive cohorts of 3 to 6 additional patients until DLT was observed. Toxicities were graded using the Radiation Therapy Oncology Group and National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS In general, therapy was well tolerated in patients treated at the first two dose levels of 60 mg/m(2) and 90 mg/m(2). The DLT of TW-G given in conjunction with A during RT were neutropenia, thrombocytopenia, and nausea/vomiting at the dose level of 120 mg/m(2). Of the 10 patients eligible for a median follow-up of 10 months, 5 remain alive; 1 complete responder, 3 partial responders, and 1 with stable disease. CONCLUSION A dose of TW-G at a level of 90 mg/m(2) produced tolerable toxicity and it may possess significant activity when delivered in conjunction with 340 mg/m(2) dose of A during RT of the upper abdomen. Due to the higher MTD of TW-G seen in our study, we consider that the A supplementation may optimize the therapeutic index of TW-G-based chemoradiotherapy protocols in patients with pancreatic carcinoma.

Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model

Abstract: The effects of melatonin, a free‐radical scavenger and a general antioxidant, on radiation‐induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4‐wk‐old (75–100 g) male Sprague–Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X‐irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non‐irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 ± 9.5 and a mean percent overall limb discrepancy of 11.2 ± 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 ± 5.8 and 32.2 ± 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 ± 1.6 and 8.9 ± 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01–0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.

Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy.

Abstract Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25–30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43–81 years) and mean baseline citrulline concentration was 38.0 ± 10.1 μmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 ± 5.9 μmol/l; p < 0.0001), treatment end (29.9 ± 8.8 μmol/l; p < 0.0001), and four months post-treatment (34.3 ± 12.1; p = 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity.

Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

PURPOSE The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. METHODS AND MATERIALS Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. RESULTS The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. CONCLUSIONS The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

Comparison of Computed Tomography- and Positron Emission Tomography-Based Radiotherapy Planning in Cholangiocarcinoma

Introduction: The aim of this study was to compare computed tomography (CT)- and positron emission tomography (PET)/CT-based gross tumor volume (GTV) delineation and its subsequent expansion to the planning target volume (PTV), and to analyze the resultant doses of 3-dimensional conformal radiotherapy (3D-CRT) to critical organs. Methods: 15 patients with unresectable extrahepatic cholangiocarcinoma (EHCC) were enrolled into this study. PTVCT-based plans were initially made, and then PTVPET-CT-based plans were created using the same beam angles and isocenter. The dosimetric parameters analyzed included GTVCT, PTVCT, GTVPET-CT and PTVPET-CT. Prescribed and delivered radiation doses to target volumes and delineated organs at risk were also compared. Results: Mean GTV and PTV were significantly reduced in the PET/CT-based plan compared to the CT-based plan; the mean reductions of GTV and PTV were 28.7% and 15.2%, respectively. The mean value for GTVPET/GTVCT mismatch was 49.5 ± 28.9%, and that for GTVCT/GTVPET was 95.9 ± 19.5%. The mean value for PTVPET-CT/PTVCT mismatch was 21.9 ± 7.0% and that for PTVCT/PTVPET-CT was 39.1 ± 9.2%. Liver doses were significantly reduced (17.1%) in the PET/CT-based plan compared to the CT-based plan; the doses received by at least 30% and 50% of the liver were 30.0%, and 27.3%, respectively. Conclusion: The potential benefit of PET/CT is the reduction in geographic misses and regional treatment failures associated with CT-based planning.

Long-term results of a concomitant boost radiotherapy technique for elderly patients with muscle-invasive bladder cancer

OBJECTIVES To evaluate the long-term clinical efficacy and toxicity of concomitant boost radiotherapy (CBRT) in elderly patients with invasive bladder cancer. METHODS AND MATERIALS Elderly patients (n=188; mean 75-year-old, range 70-91 years; 88.3% male/11.7% female) with T1-T4a bladder carcinoma were irradiated with CBRT. A total of 24 (12.8%) patients were diagnosed at stage T1, 117 (62.2%) were at stage T2, 28 (14.9%) at were stage T3a, 14 (7.4%) were stage T3b, and 5 (2.7%) were stage T4a. A dose of 45Gy in 1.8Gy fractions was administered to the whole pelvis 5 days/week over 5 weeks. A concomitant boost limited to the bladder tumor area plus margin or whole bladder of 22.5Gy in 1.5Gy fractions was administered from weeks 3×5. Thus, irradiation totalled 67.5Gy over 5 weeks. The interfraction interval was ≥6h/treatment day. We assessed prognostic factors for overall survival (OS), cause-specific survival (CSS) and relapse-free survival (RFS). RESULTS Median follow-up was 46.2 months (range 4.7-155.7 months). Median overall survival was 27 months (95% CI:21-33 months). In this study, 146 (77.7%) patients had complete response, 39 (20.7%) had residual disease and 4 (1.6%) had progressive disease. The mean 3-, 5- and 10-year OS rates were respectively 41.2% (S.E.±0.036), 29% (S.E.±0.034), and 13.8% (S.E.±0.031). Significant prognostic factors for OS and CSS, by multivariate analysis, were tumor T-stage and urothelial obstruction. CONCLUSION This CBRT protocol provided excellent results with a high complete response rate and good tolerance. This approach may therefore be particularly appropriate for elderly patients with invasive bladder cancer.

Dosimetric comparison of different treatment planning techniques with International Commission on Radiation Units and Measurements Report-83 recommendations in adjuvant pelvic radiotherapy of gynecological malignancies

AIM The study evaluates the different treatment planning techniques according to three recommendation levels of the International Commission on Radiation Units and Measurements Report-83 in gynecologic cancer patients treated with adjuvant pelvic radiotherapy (APR). MATERIALS AND METHODS Computerized tomography images of ten endometrial and cervical cancer patients who were treated with APR were assessed. For each patient, five different treatment plans were created. One homogeneity index and four different conformity indexes (CIs) were calculated for three-dimensional conformal radiotherapy (3D-CRT), field-in-field (FIF), seven-field intensity modulated radiotherapy (7-IMRT) with two different degrees beginning (7A-IMRT, 7B-IMRT) and 9-IMRT treatment plans. Dose volume histogram parameters and normal tissue complication probability (NTCP) were compared for organs at risk (OAR). RESULTS The CI values of the IMRT were closer to 1 with respect to other plans (P < 0.05). The rectum and the bladder volumes which received more than 40 Gy were decreased with IMRT compared to 3D-CRT (P < 0.05). Doses received by the 195 cc volume of the small intestine and NTCP values were significantly decreased with IMRT (P < 0.05). CONCLUSION IMRT provided more protection than FIF plans at high dose volumes of the OAR; however, it did not show any superiority at low-dose volumes. The NTCP results supported IMRT for only small intestine protection. Because IMRT is increasingly used clinically, the comparison of NTCP will become more common in the near future. Therefore, new prospective studies with sufficient number of patients and appropriate NTCP models are needed for this treatment modality.

Breast and Tumor Bed

Radiotherapy (RT) following breast-conserving surgery is effective in improving local control and long-term survival. An additional boost to the tumor bed is also important to further decrease local recurrence after whole-breast irradiation. Precise delineation of RT target volumes and normal organs is critical for conformal RT. In this chapter, target volumes are defined and delineations of these volumes are also described according to the Radiation Therapy Oncology Group (RTOG) breast cancer atlas. Delineations are also shown in the treatment planning computed tomography (CT) scans from two patients who had undergone prior breast-conserving surgery.