Evaluation of treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy accompanied by the G-8 geriatric score: TROD13-003 multicenter study.

INTRODUCTION: The choice of treatment for rectal cancer often differs in older and younger patients, with the rate of radiotherapy use lower among older adults. In our daily practice, when evaluating a frail older patient with rectal cancer, we usually choose to give less treatment. This may be due to concern that the patient will not be able to tolerate radiotherapy. The Geriatric 8 score (G8GS) is a guide to evaluating treatment tolerability as it relates to frailty in older adults with cancer. The aim of this study was to evaluate treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy (RT) accompanied by G8GS. MATERIALS AND METHODS: Patients aged 65 and older with stage I-III rectal adenocarcinoma who were treated with RT and had a G8 evaluation were included in this multicenter retrospective study. Prognostic factors related to G8GS were calculated using Chi-square and logistic regression tests and survival rates were calculated by the Kaplan-Meier test using the SPSS v24.0 software. All p-values ≤0.05 were considered statistically significant. RESULTS: A total of 699 patients from 16 national institutions were evaluated. The median age was 72 years (range 65-96), and the median follow-up was 43 (range 1-190) months. Four hundred and fifty patients (64%) were categorized as frail with G8GS ≤14 points. Frail patients had higher ages (p = 0.001) and more comorbidities (p = 0.001). Ability to receive concomitant and/or adjuvant chemotherapy rates were significantly higher in fit patients (p = 0.002 and p = 0.001, respectively). No significant difference was observed in terms of grade 3-4 early and late toxicity for both groups. Cancer-related death was higher (p = 0.003), and 5- and 8-year survival rates were significantly lower (p = 0.001), in the frail group. Age and being frail were significantly associated with survival. DISCUSSION: Radiotherapy is a tolerable and effective treatment option for older adults with rectal cancer even with low G8GS. Being in the frail group according to G8GS and having multiple comorbidities was negatively associated with survival. Addressing the medical needs of frail patients through a comprehensive geriatric assessment prior to radiotherapy may improve G8GS, allowing for standard treatment and increased survival rates.

Radiotherapy Increases aMMP-8-Levels and Neutrophil/Lymphocyte Ratio Rapidly in Head and Neck Cancer Patients: A Pilot Study.

Radiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.

Serum fetuin-A and RANKL levels in patients with early stage breast cancer.

Background: Breast cancer (BC) is the primary cause of mortality due to cancer in females around the world. Fetuin-A is known to increase metastases over signals and peroxisomes related with growing. Receptor activator of nuclear factor-kB ligand (RANKL) takes part in cell adhesion, and RANKL inhibition is used in the management of cancer. We aimed to examine the relationship between serum fetuin-A, RANKL levels, other laboratory parameters and clinical findings in women diagnosed with early stage BC, in our population. Methods: Women having early stage BC (n=117) met our study inclusion criteria as they had no any anti-cancer therapy before. Thirty-seven healthy women controls were also confirmed with breast examination and ultrasonography and/or mammography according to their ages. Serum samples were stored at -80°C and analysed via ELISA. Results: Median age of the patients was 53 (range: 57-86) while it was 47 (range: 23-74) in the healthy group. Patients had lower high-density lipoprotein levels (p=0.002) and higher neutrophil counts (p=0.014). Fetuin-A and RANKL levels did not differ between the groups (p=0.116 and p=0.439, respectively) but RANKL leves were found to be lower in the favorable histological subtypes (p=0.04). Conclusions: In this study, we found no correlation between serum fetuin-A levels and clinical findings in patients diagnosed with early stage BC. However, RANKL levels are found to be lower in subgroups with favorable histopathologic subtypes such as tubular, papillary and mucinous BC and there was statistically significant difference.

Calculated and measured radiation dose for the low energy xoft axxent eBT X-ray source.

PURPOSE: In this study, it was aimed to evaluate the functionality to deliver different prescription dose except 20 Gy for the Xoft Axxent Ebt (electronic Brachytherapy) system and analyzing the system in terms of radiation dosimetry in water and 0.9% isotonic Sodium Chloride (NaCl) solution. MATERIALS AND METHODS: In the Xoft Axxent eBT, different prescription dose in single fraction were calculated for different balloon applicator volumes based on source position and irradiation times. EBT-XD Gafchromic film was calibrated at 6MV photon energy. A balloon applicator filled with 0.9% isotonic NaCl solution was used to deliver a radiation dose of 20 Gy, 16 Gy, 10 Gy on the applicator surface. Then the balloon applicator was filled with water and the same measurements were repeated. Finally, the balloon applicator was irradiated by positioning it at different distances in the water phantom to simulate the isodose contour. RESULTS: At the time the balloon applicator was filled with water and 0,9% NaCl solution, the difference between the planned dose and the absorbed dose was ~ 2% vs. 15% for 30 cc, ~ 5% vs. 14% for 35 cc and ~ 3,5% vs. 10% for 40 cc respectively. Finally, the absorbed dose at a distance of 1 cm from the applicator surface was measured as 9.63 Gy. CONCLUSION: In this study, it was showed that different prescription dose could be possible to deliver in the Xoft Axxent eBT system based on the standard plan. In addition, the absorbed dose was higher than the planned dose depending on the effective atomic number of NaCl solution comparing to water due to photoelectric effect in low energy photons. By measuring the dose distributions at different distances from the balloon applicator surface, the absorbed dose in tissue equivalent medium was determined and the isodose contours characteristics was simulated.

Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study.

The effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (n = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe®/ORALyzer® (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment.

Oral Cavity Calprotectin and Lactoferrin Levels in Relation to Radiotherapy.

BACKGROUND: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. METHODS: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. RESULTS: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. CONCLUSIONS: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.

Various cost functions evaluation of commercial biologically based treatment planning system for nasopharyngeal cancer.

The aim of this study was to evaluate various combinations of Equivalent Uniform Dose (EUD) based and Dose Volume based (DV) cost functions in terms of target coverage and organ sparing for Nasopharyngeal CA. Ten patients diagnosed with Nasopharyngeal CA were selected for this retrospective study. Different hybrid VMAT plans, including EUD- and DV-based cost functions, were generated for each patient to determine the optimum combination in terms of organ sparing and target coverage. The generated VMAT plans were evaluated based on physical and biological dose parameters. No statistical difference was observed among all plans in terms of target coverage. The p values were ≥ 0.005 for V95, Dmean, and tumor control probability (TCP). The MU efficiency was maximum (67%), and the number of segments (285 segments) was minimum in Hybrid plan. Hybrid plan showed a significant difference compared to others (p = 0.001) in terms of serial organs. Moreover, the combination of serial and parallel complication models provided better reduction of radiation dose in the parotid glands in Plan-3 (p = 0.001). In this study, better protection was obtained when DVH-based cost functions were defined for targets and a combination of EUD- and DVH-based cost functions were used for OARs.

Beam modeling and commissioning for Monte Carlo photon beam on an Elekta Versa HD LINAC.

PURPOSE: This study aims at analyzing beam data commissioning along with verifying Monte Carlo-based treatment planning system on the basis of the manufacturer guidelines for Elekta Versa HD Linear Accelerator. Moreover, evaluating the beam match process in terms of quality index, photon profile and multi leaf collimator (MLC) offset is aimed as well. MATERIALS AND METHODS: The process of collecting beam data for Monaco 5.51 Treatment Planning System commissioning was done based on the instructions provided by the manufacturer as well as AAPM TG-106. Monte Carlo analysis was done for output factors in water, percent depth dose and beam profiles. A set of eight static and intensity modulated radiation therapy fields were used to verify the MLC parameters. RESULTS: The difference between the measured and modeled penetrative quality (D10) was achieved to be 0.54%. The output factors for 6 MV photon energy were measured and the difference between the measured and Monte Carlo output results was smaller than 1% for all the fields. The average percentage of passing the gamma criteria for commissioning test fields was (95+-4)%, however, the minimum agreement was 87.5% belonging to "7SEGA". Additionally, the agreement between both LINAC is 96%, however, the second LINAC reveals a positive offset in the point of approximately -4 cm on the x-axis at the crossplane. CONCLUSION: Test commissioning was successfully verified using a homogeneous phantom for point dose measurements, post modelling MLC parameters and patient QA plans. All plan parameters pass the gamma criteria. 6 MV photon beam was successfully commissioned for Elekta VersaHD LINAC and is ready for clinical implementation.

Hippocampal sparing for brain tumor radiotherapy: A retrospective study comparing intensity-modulated radiotherapy and volumetric-modulated arc therapy.

CONTEXT: Radiotherapy may have side effects on the brain, such as radiation necrosis, cognitive impairment, and a high chance of tumor recurrence, which has been considered the most common cause of treatment failure. AIMS: Using intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques, we aimed to test the potential outcome of sparing the contralateral hippocampus (CLH) in radiotherapy for brain tumors by comparing dosimetric parameters. SETTINGS AND DESIGN: A prospective clinical comparative study. SUBJECTS AND METHODS: Using IMRT and VMAT, sparing CLH in radiotherapy of brain tumors was tested in ten patients, and various dosimetric parameters were compared. The treatment plans were accepted only if they met the set of planning objectives defined in the protocol. RESULTS: The dose delivered to 95% of the CLH volume (CLH D95), and the mean (CLH Dmean) and max (CLH Dmax) doses were found to be significantly highest in the standard IMRT (P = 0.002, <0.001, and < 0.001, respectively). The lowest CLH D95, CLH Dmean and CLH Dmax for the hippocampus were detected in sparing VMAT planning than in the other plans (P < 0.05). None of the post hoc comparisons for CLH D95 was different among any of the plans, whereas the mean dose to CLH was statistically different among all paired comparisons (P < 0.008). The maximum dose to CLH was also statistically different among all paired plans (P < 0.008), except the dose difference between standard VMAT and IMRT plans. CONCLUSIONS: Although VMAT planning is troublesome and time-consuming, the advantage of sparing the hippocampus is beneficial, preserving the hippocampus and cognitive functions during radiotherapy.

Impact of histone methyltransferase SUV420H2 in breast cancer.

Breast cancer is the most common type of cancer in women worldwide. Triple methylation of H4 lysine 20 (H4K20me3), a key component of epigenetic regulation of genomic integrity, is catalyzed by the methyltransferase, SUV420H2. Data on the expression status of SUV420H2 in breast cancer are limited. In the present study, the influence of SUV420H2 suppression on the proliferation of breast cancer cells was experimentally investigated. Subsequently, SUV420H2 expression was assessed in resectable breast cancer along with H4K20me3 status. SUV420H2 expression was knocked down in breast cells using small interfering RNA oligonucleotides. SUV420H2 expression was determined semi-quantitatively at the mRNA level. H4K20me3 was measured on extracted histone proteins using an approach similar to ELISA. Suppression of the SUV420H2 gene resulted in increased cell proliferation. Although the median SUV420H2 expression values were similar in tumor tissues and non-cancerous regions in the entire cohort (0.0022 and 0.0015, respectively; P=0.46), there was a notable difference in expression between tumor tissues and the adjacent non-cancerous region in the majority of patients. Increased SUV420H2 expression in tumors compared with healthy tissue was predominantly observed in patients with early-stage breast cancer, whereas reduced SUV420H2 expression was observed in tumors more frequently in patients with advanced stage diseases. There was no association between SUV420H2 expression and the tissue levels of H4K20me3. The results showed that SUV420H2 exhibited anti-proliferative activity in vitro, and exhibits a heterogeneous expression pattern in breast cancer tissues.

Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study.

Background: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy. Research design and methods: Eleven patients, aged 28-74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) for aMMP-8 and ELISA for IL-6. Results: HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachment-loss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1-3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels. Conclusions: Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.

Preventive role of superoxide dismutase on radiation-induced periprosthetic capsule development.

BACKGROUND: Capsule fibrosis is the most important and annoying complication of breast implant surgery. Radiotherapy (RT) used in the local treatment of breast cancer has an increasing effect on the existing fibrous capsule; this is called radiation-induced fibrosis (RIF). In this randomized controlled experimental study, we aim to investigate the reduction effect of superoxide dismutase (SOD) on RIF. METHODS: Sprague-Dawley rats were randomized into four groups, all of which were subjected to implant surgery. No additional procedures were done for the control group. The other groups were the SOD group, the RT + SOD group, and the RT group. The capsules were evaluated histopathologically. RESULTS: Although SOD reduced surgery-induced capsule formation, it neither prevented nor reduced significantly RIF. CONCLUSIONS: In an experimental model that resembled breast cancer treatment, we concluded that SOD cannot reduce RIF but is effective in reducing capsular fibrosis around the silicone after implant surgery.

The value of whole-body contrast-enhanced 18F-FDG PET/CT imaging in the diagnosis and staging of patients with laryngeal carcinoma.

PURPOSE: This study aimed to determine whether intravenous contrast-enhanced dual-phase fluorine-18--fluorodeoxyglucose (F-FDG) PET/CT scans provide additional diagnostic information compared with the MRI/CT in patients with laryngeal carcinoma during the initial staging. PATIENTS AND METHODS: Forty-five consecutive patients (44 men, one woman; mean age±SD, 67.0±9.0 years, range: 45-80 years) with carcinoma of the larynx who had MRI/CT and intravenous contrast-enhanced PET/CT were enrolled. Each patient was scanned on the PET/CT system 1 h (early) and 2 h (delayed) after injection. The maximum standardized uptake values of the primary tumor, nodal, and distant metastatic lesions were measured using the dual-time-point method. Double-blinded F-FDG PET/CT and MRI/CT staging data were compared. The diagnostic accuracy of each modality was compared for primary tumors, nodal metastasis, and the tumor staging. RESULTS: For primary tumor detection, the sensitivity of PET/CT was higher (100%) than MRI/CT (93.3%). The accuracy for N status was 88.8% for PET/CT, being superior to MRI, which had an accuracy of 66.6%. The sensitivity and specificity for the detection of nodal metastasis were 100 and 84.6% for PET/CT compared with 100 and 50% for MRI/CT, respectively. As an initial TNM-staging method, the PET/CT had a diagnostic accuracy of 86.6% compared with 44.4% for MRI/CT. CONCLUSION: The results suggest that contrast-enhanced dual-phase PET/CT imaging contributes additional diagnostic information compared with the conventional methods for the initial evaluation of primary laryngeal tumors. F-FDG PET/CT has a good diagnostic performance for the detection of regional nodal and distant metastasis, and also synchronous tumors in patients with laryngeal carcinoma.

Primary Testicular Diffuse Large B-Cell Lymphoma: A Case Report.

Testicular lymphoma was first reported by Malassez and Curling in 1866. Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non Hodgkin lymphoma. We report the case of a 47-year-old man without a particular past medical history, who presented with a painful left testicular swelling that he has noticed for several weeks. Radiological findings consisted in multiple hypoechoic masses that corresponded in histological examination to a diffuse intratubular lymphomatous infiltration situated away from the spermatic cord, the epididymis, ductuli efferentes and rete testis. Immunohistochemical study showed positivity of MUM-1, Bcl-2 and B-cell marker (CD20) and TdT, CD 3, CD5, Bcl-1, CD10, Bcl-6 and Myeloperoksidaz were negative. Ki-67 proliferation index was 90% of neoplastic lenfoid infiltration. The patient underwent full staging for lymphoma by positron emission tomography, showing right superior paratrakeal, precarinal, subcarinal, left paraaortic and retrocrural and left iliac involvement lymph nodes also the right testis and of extra-testicular involvement by the skeleton sistem. The diagnosis of stage III primary testicular large B-cell lymphoma of germinal center B-cell-like group was made. The patient is now treated by chemotherapy. Primary testicular lymphoma is a rare tumor whose diagnosis is based on histological findings. There are non consensual etiological or predisposing factors. Treatment modalities consist in surgical excision, chemotherapy and radiation therapy but the accurate procedures are not standardized. Factors that have been linked to more favorable outcomes include younger patient age, localized disease, presence of sclerosis at pathologic analysis, smaller tumor size, lower histological tumor grade and lack of epididymal or spermatic cord involvement.

Field-in-field IMRT versus 3D-CRT of the breast. Cardiac vessels, ipsilateral lung, and contralateral breast absorbed doses in patients with left-sided lumpectomy: a dosimetric comparison.

PURPOSE: This study evaluated dose distribution and homogeneity of field-in-field intensity-modulated radiation treatment (FIF-IMRT) compared with standard wedged tangential-beam 3D conformal radiotherapy (CRT) of the left breast in patients who have undergone lumpectomy. Our aim was to improve dose-distribution homogeneity in the breast and decrease the dose to organs at risk (OAR), i.e, heart and vessels, ipsilateral lung, and contralateral breast. MATERIALS AND METHODS: FIF-IMRT and wedge plans of 3D-CRT were carried out for 18 patients with cancer of the left breast. Plans were compared according to cumulative dose-volume histogram (c-DVH) analysis in terms of planned treatment volume (PTV), homogeneity index (HI), and conformity index (CI), as well as dose and volume parameters of OARs. RESULTS: When the targeted volumes receiving 105 % and 110 % of the prescribed dose in the PTV were compared, significant decreases were found with the FIF-IMRT technique. With the 105 % dose to the OARs, monitor unit (MU) counts were significantly lower with the FIF-IMRT technique. V2 of pulmonary artery, left atrium, and aorta and V1 for the contralateral breast were statistically significantly lower with FIF-IMRT plans (p = 0.001). PTV showed a better HI and CI with FIF-IMRT. CONCLUSIONS: FIF-IMRT enables better dose distribution in the PTV and reduces dose to OARs in breast cancer radiotherapy.

Immunohistochemical study of E-cadherin and ß-catenin expression in colorectal carcinomas.

Parameters of histological type, differentiation, lymph node metastasis and stage have been observed to indicate the prognosis of colorectal carcinomas. Immunohistochemically E-cadherin and ß -catenin expression of tumour cells have been evaluated to define life expectancy, response to the treatment, metastatic disease and recurrence of tumour in correlation with these prognostic parameters. 60 cases diagnosed as colorectal adenocarcinoma were selected to be studied retrospectively. Immunohistochemistry was performed using E-cadherin and ß -catenin primary antibodies and avidin-biotin-peroxidase. 53 of 60 adenocarcinoma tissues were evaluated as classical type adenocarcinoma and 7 of them as mucinous carcinoma. 48 classical type adenocarcinoma tissues showed membranous staining for E-cadherin, 13 tissues showed cytoplasmic staining. All 53 adenocarcinoma tissues expressed nuclear or membranous type ß -catenin in different intensities. Reduced E-cadherin expression significantly correlated with lymph nodes metastasis (p = 0.01). E-cadherin expression significantly correlated with increasing histological differentiation (p = 0.04). When E-cadherin and ß -catenin expressions were compared, there was a significant difference between the tumour stage, histological differentiation and the existence of lymph node metastasis. When both E-cadherin and ß -catenin expressions were reduced, there was a significant unfavourable prognosis.