Mustafa Esassolak

Effect of geometrical optimization on the treatment volumes and the dose homogeneity of biplane interstitial brachytherapy implants

BACKGROUND AND PURPOSE The isodose distributions of HDR stepping source brachytherapy implants can be modified by changing dwell times and this procedure is called optimization. The purpose of this study is to evaluate the effect of geometrical optimization on the brachytherapy volumes and the dose homogeneity inside the implant and to compare them with non-optimized counterparts. MATERIAL AND METHODS A set of biplane breast implants consisting of 84 different configurations have been digitized by the planning computer and volumetric analysis was performed for both non-optimized and geometrically optimized implants. Treated length (TL), treated volume (V100), irradiated volume (V50), overdose volume (V200) and quality index (QI) have been calculated for every non-optimized implant and compared to its corresponding geometrically optimized implant having a similar configuration and covering the same target length. RESULTS The mean TL was 74.48% of the active length (AL) for non-optimized implants and was 91.87% for optimized implants (P < 0.001). The mean QI was 1.83 for non-optimized implants and 2.17 for optimized implants (P < 0.001). The mean V50/V100 value was 2.71 for non-optimized implants and 2.65 for optimized implants (P < 0.001) and the mean V200/V100 value was 0.09 for non-optimized implants and 0.10 for optimized implants (P < 0.001). CONCLUSIONS By performing geometrical optimization it is possible to implant shorter needles for a given tumour to adequately cover the target volume with the reference isodose and thus surgical damage is reduced. The amount of healthy tissues outside the target receiving considerable radiation is significantly reduced due to the decrease in irradiated volume. Dose homogeneity inside the implant is significantly improved. Although there is a slight increase of overdose volume inside the implant, this increase is considered to be negligible in clinical applications.

Fiber enriched diets and radiation induced injury of the gut

The aim of this study was to evaluate the effect of fiber-enriched defined formula diets (DFDs) on radiation-induced enteropathy. Forty-five male Sprague-Dawley rats were assigned randomly after abdominal irradiation to one of three groups (15 in each group): a fiber-free DFD group, a non-soluble fiber-enriched DFD group, and a soluble fiber-enriched DFD group. They kept their diets respectively for seven days. On day eight, the mesenteric lymph nodes were harvested for bacterial translocation, and segments of jejenum and colon were sampled for microscopic examination. The rats in the fiber-enriched DFD groups lost significantly less body weight than the rats in the fiber-free DFD group. The intestinal structure was the worst in the fiber-free DFD group, intermediate in the soluble fiber-enriched DFD group, and the best in the non-soluble fiber-enriched DFD group with significantly higher measures of villous height and jejunal mucosal thickness. These findings suggest that fiber-enriched DFD may effectively protect intestinal structure against radiation-induced damage by improving mucosal integrity.

The Effects of Compliance with Nutritional Counselling on Body Composition Parameters in Head and Neck Cancer Patients under Radiotherapy

Background. Radiotherapy (RT) has been associated with increased risk of malnutrition in cancer patients, particularly in those with head and neck cancer (HNC). The aim of this prospective study was to evaluate the effects of compliance of patients with individual dietary counselling on body composition parameters in HNC patients under RT. Material and Methods. Sixty-nine consecutive patients (mean age: 61.0 ± 13.8) were prospectively followed. Bioelectrical impedance analysis (BIA) was performed to determine body composition parameters before, in the middle of, and at the end of RT. All patients received nutritional counselling and majority of them (94.6%) received oral nutritional supplement (ONS) during RT or chemoradiotherapy. If a patient consumed ≥75% of the recommended energy and protein intake via ONS and regular food, he/she was considered to be “compliant” (n = 18), while those who failed to meet this criteria were considered to be “noncompliant” (n = 30). Results. Body mass index, weight, fat percentage, fat mass, fat free mass, and muscle mass did not decrease significantly over time in compliant patients, but in noncompliant patients, all of these indices decreased significantly from baseline compared to the end of treatment (p < 0.001). Hand grip strength did not differ significantly between the two groups at baseline and over time in each group. When retrospectively evaluated, heavy mucositis was less commonly observed in compliant than noncompliant patients (11.1% versus 88.9%, resp.) (p < 0.009). Conclusion. We conclude that body composition parameters were better in head and neck cancer patients considered as compliant with nutritional counselling than noncompliant ones during RT period.

Risk factors for central nervous system metastasis in patients with metastatic breast cancer

AimsPatients with metastatic breast cancer (MBC) and central nervous system (CNS) involvement have an impaired survival and quality of life. In this study, we investigated the risk factors for CNS metastasis among patients with MBC.MethodsThe risk factors for development of CNS metastasis were analyzed in 154 patients with MBC. Expression of c-erbB-2, Ki-67, p53, and hormone receptors was examined by immunohistochemistry (IHC) in breast cancer tissue samples from the 154 patients. Kaplan-Meier and log-rank tests were used for the analysis of overall survival (OS). Chi-square test was used for univariate analysis.ResultsMedian OS was significantly poorer for patients with CNS metastasis as compared with patients with no CNS metastasis (OS, 23 mo vs 30 mo, respectively;p = 0.03). Ki-67 and p53 overexpressions by IHC, and lung metastasis as the first site of relapse, were associated with a higher risk of developing CNS metastasis in the univariate analysis (p ≤ 0.05). The presence of lung metastasis (odds ratio [OR]= 2.82, 95% confidence interval [CI]: 1.13-7.00,p = 0.02) and p53 overexpression (OR = 2.44, 95% CI: 0.99-6.00,p = 0.05) were the two predictive factors associated with occurrence of CNS metastasis in the multivariate analysis.ConclusionsIn this study, the presences of lung metastasis as the first site of relapse and p53 overexpression were predictive for the occurrence of CNS metastasis in patients with MBC. Life expectancy of patients with CNS metastasis is significantly shorter than those without CNS metastasis. These results may have clinical significance in counseling MBC patients with regard to their prognosis.

Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy?

PURPOSE To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. MATERIALS AND METHODS Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patients tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. RESULTS Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for MTV and 10.15 for SULmax. Three-year LRFS and DFS rates were significantly lower in patients with MTV ≥ 14.00 mL (p=0.026, p=0.018 respectively), and SULmax≥10.15 (p=0.017, p=0.022 respectively). SULmax did not have a significant predictive value for OS whereas MTV had (p=0.025). CONCLUSION Adaptive threshold-based MTV and SULmax could have a role in predicting local control and survival in head and neck cancer patients.

p53 protein accumulation and presence of visceral metastasis are independent prognostic factors for survival in patients with metastatic inflammatory breast carcinoma.

Objective: The aim of this study was to determine the markers of prognosis in metastatic inflammatory breast cancer (IBC). Subjects and Methods: The prognostic value of patients’ clinical characteristics and expression of c-erbB-2, p53, Ki-67, ER and PgR were assessed in the 45 patients with IBC who had developed distant metastasis. Immunohistochemical methods were used to detect the expression of c-erbB-2, p53, Ki-67, ER and PgR in surgical resection specimens of the patients’ primary tumor. Results: The median overall survival (OS) measured from the diagnosis of metastatic disease was 23 months. In the univariate analysis, p53 protein accumulation and the presence of visceral metastasis were predictive of poor survival (p = 0.01 and 0.003, respectively). In the multivariate analysis, accumulation of p53 protein and the presence of visceral metastasis correlated with OS (p = 0.02 and 0.008, respectively). Conclusion: In metastatic IBC, accumulation of p53 protein and presence of visceral metastasis are independent prognostic factors for OS. Established prognostic factors in non-IBC patients such as patient age, histologic grade, hormone receptor status and c-erbB-2 status did not have independent significance in IBC in this study.

Does the prognosis of nasopharyngeal cancer differ among endemic and non-endemic regions?

Abstract Conclusion: The survival rates and prognostic factors for nasopharyngeal cancer (NPC) were found to be similar to the published series from endemic regions. Objectives: The purpose of this retrospective study was to evaluate treatment outcome and prognostic factors of NPC patients treated with radiotherapy or chemoradiotherapy in a non-endemic region. Methods: We analyzed clinical characteristics, treatment outcome, and prognostic factors of NPC patients in a non-endemic region, and compared our institutions results with the published literature including a similar patient population from endemic and non-endemic regions. Among 248 NPC patients, 71 (28.6%) were female and 177 (71.4%) were male with a median age of 48 years. Results: Within a median 59 months (range 22–178) of follow-up, local recurrence developed in 22 (8.9%), regional recurrence in 2 (0.8%), locoregional recurrence in 5 (2%), distant metastases in 21 (8.5%), and both locoregional recurrence and distant metastases in 8 (3.2%) patients. Five-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) rates were 83.7%, 73%, 78.5%, and 71.1%, respectively. In multivariate analysis for LRC, cranial nerve involvement (CNI) (p = 0.009) and tumor response (p = 0.004); for DFS, age (p = 0.003), CNI (p = 0.02), AJCC T classification (p = 0.05), and tumor response (p = 0.01); for DSS, age (p = 0.003), CNI (p = 0.04), AJCC T classification (p = 0.04), and tumor response (p = 0.01); for OS, age (p < 0.001), AJCC T classification (p = 0.005), and tumor response (p < 0.001) were significant prognostic factors.

Radiation-Associated Chronic Dysphagia Assessment by Flexible Endoscopic Evaluation of Swallowing (FEES) in Head and Neck Cancer Patients: Swallowing-Related Structures and Radiation Dose-Volume Effect

Purpose We aimed to restore dose-volume parameters of swallowing-related structures (SRSs) by evaluating long-term swallowing dysfunctions after radiotherapy (RT) in head and neck cancer patients (HNCPs). Materials and Methods Head and neck cancer patients whose pharyngeal region was involved in RT portal and treated with definitive RT/chemoradiotherapy (CRT) were included in the analyses. Patients underwent objective swallowing assessment by flexible endoscopic evaluation of swallowing (FEES). Volumes of SRSs that received 55 Gy (V55) (mean dose [Dmean]) were evaluated according to the dose-volume histograms of each patient. For every SRS, optimal dose-volume cut-off values were determined by receiver operating characteristic curve analysis. Results Fifty-five patients at a median 20 months (range, 12-26 months) after their treatments were evaluated. There was a strong negative correlation between FEES scores and dose-volume parameters of SRS (r ⩽ –0.5, P < .0001). According to our results, middle pharyngeal constrictor (MPC) and inferior pharyngeal constrictor (IPC) had a Dmean > 57 Gy, base of tongue (BOT) Dmean > 50 Gy, supraglottic larynx (SGL) and glottic larynx (GL) Dmean > 55 Gy, and cervical esophagus (CE) Dmean > 45 Gy. MPC V55 > 70%, IPC V55 > 50%, BOT V55 > 65%, CE V55 > 40%, and SGL and GL V55 > 50% were significant predictors for dysphagia. Conclusion It was found that dysphagia correlates strongly with dose-volume parameters of SRSs. IPC, SGL, and CE were found to be structures significantly associated with dysphagia.

Evaluation of the Radiation Dose–Volume Effects of Optic Nerves and Chiasm by Psychophysical, Electrophysiologic Tests, and Optical Coherence Tomography in Nasopharyngeal Carcinoma

Purpose: To evaluate the radiation dose–volume effects of optic nerves and chiasm by visual psychophysical, electrophysiologic tests, and optical coherence tomography in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods: A series of visual tests including visual acuity, visual field, contrast sensitivity, visual evoked potential, and optical coherence tomography were administered to 20 patients with locally advanced (T3-T4) nasopharyngeal carcinoma who were treated with definitive chemoradiotherapy. Volume that received 55 Gy (V55), mean dose (D mean), highest dose to 5% of the volume (D5), and maximum dose (Dmax) for optic nerves and chiasm were evaluated for each patient. Cutoff values were identified as V55: 50%, Dmean: 50 Gy, D5: 55 Gy, and Dmax: 60 Gy. The effects of radiation dose–volume on ophthalmologic tests were evaluated. Results: Ophthalmological evaluation revealed optic neuropathy with simultaneous retinopathy in 6 eyes of 4 patients and radiation retinopathy alone in both eyes of 1 patient. Regarding radiation dose–volume effects of the optic nerve, significant detrimental effect of all parameters was observed on visual acuity. Visual field and contrast sensitivity were affected significantly with V55 ≥ 50% and Dmean ≥ 50 Gy. Visual evoked potential latency was affected significantly with Dmean ≥ 50 Gy, D5 ≥ 55 Gy, and Dmax ≥ 60 Gy. For the chiasm, significant detrimental effect of all parameters was observed on visual acuity as well. Retinal nerve fiber layer thickness and visual evoked potential amplitude were not affected by any of the dose–volume parameters neither optic nerves nor chiasm. Conclusion: The volume receiving the threshold dose, mean dose, and 5% of the volume receiving the maximum dose are important parameters besides maximum dose to optic nerves and chiasm. A comprehensive ophthalmological evaluation including visual field, contrast sensitivity, visual evoked potential latency, and amplitude should be performed for these patients. Visual evoked potential latency is an objective predictor of vision loss before the onset of clinical signs.

Practice patterns for oropharyngeal cancer in radiation oncology centers of Turkey.

Aims and Background The aim of the study was to review the current clinical practices of radiation oncologists involved in the treatment of oropharyngeal cancer. Methods and Study Design The daily practices of radiation oncology centers for patients diagnosed with oropharyngeal cancer in 2010 were evaluated by a two-part questionnaire that separately assessed the information of the participating center and the charts of the treated patients. Results A total of 22 centers participated in the study, and 105 oropharyngeal cancer patients reported for our review. The use of positron emission tomography was a common practice in staging and radiotherapy planning. Multidisciplinary head and neck cancer clinics were available in 14 (64%) centers and were absent in 8 centers. Thirty-six of the 105 patients were not evaluated by a multidisciplinary clinic before the initiation of therapy, and adjuvant radiotherapy administration was found to be higher in this group. Percutaneous endoscopic gastrostomy tube placement was not a routine practice in any of the centers. Seventy-five patients received chemotherapy – 46 concurrently with radiotherapy and 29 as induction chemotherapy. Two centers administered conventional radiotherapy alone, 20 centers conformal radiotherapy, and 7 centers were able to provide intensity-modulated radiotherapy. Conclusions Across all the centers there were small differences in the pretreatment evaluation of patients with oropharyngeal cancer. The greatest difference was in the technical delivery of radiation, with most of the centers using conformal radiotherapy despite the increasing availability of intensity-modulated radiotherapy. The use of chemotherapy has more readily adopted the current international standards in the treatment of oropharyngeal cancer.