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1.
J Radiat Res ; 64(1): 133-141, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36208871

ABSTRACT

In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who were not eligible for surgery and treated with SRS. Between January 2013 and December 2018, 53 patients with cavernomas were treated using SRS with the CyberKnife® system. Patients' diseases were deeply located or were in subcortical functional brain regions. In addition to bleeding, 23 (43.4%) patients had epilepsy, 12 (22.6%) had neurologic symptoms and 16 patients (30.2%) had severe headaches. The median volume was 741 (range, 421-1351) mm3, and the median dose was 15 (range, 14-16) Gy in one fraction. After treatment, six (50%) of 12 patients with neurologic deficits still had deficits. Rebleeding after treatment developed in only two (3.8%) patients. The drug was completely stopped in 14 (60.9%) out of 23 patients who received epilepsy treatment, and the dose of levetiracetam decreased from 2000 mg to 1000 mg in four (17.3%) of nine patients. Radiologically, complete response (CR) was observed in 13 (24.5%) patients, and partial responses (PR) were observed in 32 (60.2%) patients. Clinical response of CR was observed in 30 (56.6%) patients, PR was observed in 16 (30.2%), stable disease (SD) was observed in three (5.7%) and four (7.5%) patients progressed. In conclusion, SRS applied in the appropriate dose schedule may be an effective and reliable method in terms of symptom control and prevention of rebleeding, especially in patients with inoperable cavernomas.


Subject(s)
Epilepsy , Hemangioma, Cavernous, Central Nervous System , Radiosurgery , Humans , Radiosurgery/adverse effects , Radiosurgery/methods , Hemangioma, Cavernous, Central Nervous System/radiotherapy , Hemangioma, Cavernous, Central Nervous System/diagnosis , Hemangioma, Cavernous, Central Nervous System/etiology , Epilepsy/radiotherapy , Epilepsy/etiology , Epilepsy/surgery , Levetiracetam , Brain , Treatment Outcome , Retrospective Studies , Follow-Up Studies
2.
Cancers (Basel) ; 14(3)2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35158949

ABSTRACT

Selection of head and neck cancer (HNC) patients for proton therapy (PT) using plan comparison (VMAT vs. IMPT) for each patient is labor-intensive. Our aim was to develop a decision support tool to identify patients with high probability to qualify for PT, at a very early stage (immediately after delineation) to avoid delay in treatment initiation. A total of 151 HNC patients were included, of which 106 (70%) patients qualified for PT. Linear regression models for individual OARs were created to predict the Dmean to the OARs for VMAT and IMPT plans. The predictors were OAR volume percentages overlapping with target volumes. Then, actual and predicted plan comparison decisions were compared. Actual and predicted OAR Dmean (VMAT R2 = 0.953, IMPT R2 = 0.975) and NTCP values (VMAT R2 = 0.986, IMPT R2 = 0.992) were highly correlated. The sensitivity, specificity, PPV and NPV of the decision support tool were 64%, 87%, 92% and 51%, respectively. The expected toxicity reduction with IMPT can be predicted using only the delineation data. The probability of qualifying for PT is >90% when the tool indicates a positive outcome for PT. This tool will contribute significantly to a more effective selection of HNC patients for PT at a much earlier stage, reducing treatment delay.

3.
Radiother Oncol ; 167: 7-13, 2022 02.
Article in English | MEDLINE | ID: mdl-34902370

ABSTRACT

BACKGROUND AND PURPOSE: Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres. MATERIALS AND METHODS: We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT. RESULTS: Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%). CONCLUSION: Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT.


Subject(s)
Central Nervous System Neoplasms , Gastrointestinal Neoplasms , Head and Neck Neoplasms , Proton Therapy , Adult , Europe , Humans , Male , Prospective Studies
4.
Radiother Oncol ; 160: 61-68, 2021 07.
Article in English | MEDLINE | ID: mdl-33892024

ABSTRACT

PURPOSE: In the Netherlands, head and neck cancer (HNC) patients are selected for proton therapy (PT) based on estimated normal tissue complication probability differences (ΔNTCP) between photons and protons, which requires a plan comparison (VMAT vs. IMPT). We aimed to develop tools to improve patient selection for plan comparisons. METHODS: This prospective study consisted of 141 consecutive patients in which a plan comparison was done. IMPT plans of patients not qualifying for PT were classified as 'redundant'. To prevent redundant IMPT planning, 5 methods that were primarily based on regression models were developed to predict IMPT Dmean to OARs, by using data from VMAT plans and volumetric data from delineated targets and OARs. Then, actual and predicted plan comparison outcomes were compared. The endpoint was being selected for proton therapy. RESULTS: Seventy out of 141 patients (49.6%) qualified for PT. Using the developed preselection tools, redundant IMPT planning could have been prevented in 49-68% of the remaining 71 patients not qualifying for PT (=specificity) when the sensitivity of all methods was fixed to 100%, i.e., no false negative cases (positive predictive value range: 57-68%, negative predictive value: 100%). CONCLUSION: The advanced preselection tools, which uses volume and VMAT dose data, prevented labour intensive creation of IMPT plans in up to 68% of non-qualifying patients for PT. No patients qualifying for PT would have been incorrectly denied a plan comparison. This method contributes significantly to a more cost-effective model-based selection of HNC patients for PT.


Subject(s)
Head and Neck Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Head and Neck Neoplasms/radiotherapy , Humans , Netherlands , Organs at Risk , Prospective Studies , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
5.
Pract Radiat Oncol ; 11(4): 272-281, 2021.
Article in English | MEDLINE | ID: mdl-33556579

ABSTRACT

PURPOSE: There are no international guidelines for optimal needle insertion during interstitial intracavitary brachytherapy (IS-ICBT) for cervical cancer. We aimed to investigate the clinical feasibility and added value of computed tomography (CT) guidance to optimize needle insertion in IS-ICBT using the Utrecht applicator and to evaluate needle shifts. METHODS AND MATERIALS: We enrolled 24 patients who were treated with interstitial-brachytherapy. Two CT scans each were performed for every patient: (1) after applicator insertion without needles (CTpreneedle) and (2) after needle insertion (CTpostneedle). In addition to magnetic resonance imaging after external-beam radiation therapy, CTpreneedle was used to determine optimal needle locations and insertion lengths based on applicator and organs at risk positioning on the day of treatment; CTpostneedle was used for IS-ICBT planning. The needle-channel axis was used as a reference to determine needle-shift evolution. RESULTS: A total of 266 interstitial needles were inserted in 76 of 93 BT fractions with high intra- and interpatient variations in the number of inserted needles. Based on CTpreneedle findings, needle insertion was avoided in 9, 4, 2, and 2 patients at the first, second, third, and fourth fractions, respectively. The unloaded needle frequency was 4%. Average needle contribution to total dwell time was 37.2% ± 19.2%. Shifting was observed in 68% of the needles (mean shift 2.0 ± 2.3 mm), mostly in the posterior direction, and in needles with a larger insertion length. Needle reinsertion was not needed in any patient. No complication due to needle insertion was observed, except for minor vaginal bleeding in 1 patient after needle removal. CONCLUSIONS: The adaptive CT-guided IS-ICBT application was feasible and resulted in fewer unloaded needle insertions or complications and more efficient use with higher needle contribution to the treatment. Needle shift was frequent but did not require needle reinsertion with the proposed method.


Subject(s)
Brachytherapy , Uterine Cervical Neoplasms , Female , Humans , Needles , Organs at Risk , Tomography, X-Ray Computed , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/radiotherapy
6.
Radiother Oncol ; 151: 206-213, 2020 10.
Article in English | MEDLINE | ID: mdl-32768508

ABSTRACT

PURPOSE: In the Netherlands, head and neck cancer (HNC) patients qualify for intensity modulated proton therapy (IMPT) based on model-based selection (MBS). The aim of this study was to evaluate the first experience in MBS of HNC patients. METHODS: Patients who were subjected to MBS (Jan 2018-Sep 2019) were evaluated. A VMAT plan was created for all patients with optimal sparing of organ at risks (OARs) in normal tissue complication probability (NTCP) models for a number of toxicities. An IMPT plan was created only for those with NTCP difference (ΔNTCP) between VMAT and best-case scenario for proton (assuming 0 Gy dose for all OARs in IMPT plan) that exceeded any ΔNTCP-thresholds defined in Dutch National Indication Protocol. These patients qualified for a robust IMPT-plan creation with similar target doses and subsequent plan comparison. RESULTS: Of 227 patients, 141 (62%) qualified for plan comparison, of which 80 (35%) were eventually selected for proton therapy. Most patients were selected based on the ΔNTCP for dysphagia-related toxicities. The selection rate was higher among patients with advanced disease, pharyngeal tumors, and/or baseline complaints. A significant reduction in all OAR doses and NTCP values was obtained with IMPT compared with VMAT in both selected and non-selected patients, but more pronounced in patients selected for protons. CONCLUSION: Model-based selection of patients with HNC for proton therapy is clinically feasible. Approximately one third of HNC patients qualify for protons and these patients have the highest probability to benefit from protons in terms of toxicity prevention.


Subject(s)
Head and Neck Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Head and Neck Neoplasms/radiotherapy , Humans , Netherlands , Organs at Risk , Proton Therapy/adverse effects , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated/adverse effects
7.
Mol Biol Rep ; 46(4): 4001-4008, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31069614

ABSTRACT

The Fibulins are a recently discovered family of extracellular matrix proteins. In this study, expression levels of the fibulin-2 (FBLN2) gene and its role in the formation of different metastatic foci were investigated in lung cancer patients. We analyzed 106 lung cancer patients and eight paraffin-embedded tissues, and 27 ethnical-, age- and sex-matched healthy controls for expression levels of the FBLN2 gene. cDNAs obtained from the enriched epithelial cells of peripheral blood lymphocytes and tumor tissues of patients were amplified with specific primers for the target FBLN2 gene and HPRT1 housekeeping gene using quantitative real-time polymerase chain reaction. FBLN2 gene expression levels of the enriched epithelial cells of peripheral blood lymphocytes were found to be decreased approximately twofold in all subsets of patients compared to healthy controls. Our results indicate a significant difference between patient subgroups and controls [F(4.124) = 14.846, p0.05] among patient subgroups: bone metastases versus non-metastatic groups (p = 0.997), bone versus brain metastases (p = 0994), bone metastases versus two primary tumors (p = 0.999), brain metastases versus two primary tumors (p = 0.999), brain metastases versus non-metastatic (p = 0.755), non-metastatic versus two primary tumors (p = 0.996), non-metastatic versus all other metastatic patients (p = 0.731). Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues compared with the enriched epithelial cells of peripheral blood lymphocytes of patients. In the study, the enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment, nevertheless, it is needed further research whether the importance of FBLN2 on lung cancer oncogenesis and as a biomarker for metastatic lung cancer.


Subject(s)
Cell-Free Nucleic Acids/genetics , Fibrillin-2/genetics , Lung Neoplasms/genetics , Aged , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Count , Cell Movement/physiology , Cell Proliferation/physiology , Cell-Free Nucleic Acids/metabolism , Female , Fibrillin-2/biosynthesis , Fibrillin-2/blood , Humans , Lung Neoplasms/blood , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Real-Time Polymerase Chain Reaction , Transcriptome , Tumor Microenvironment
8.
Asian Pac J Cancer Prev ; 19(12): 3597-3603, 2018 Dec 25.
Article in English | MEDLINE | ID: mdl-30583688

ABSTRACT

Background: Neuroendocrine tumors are a heterogeneous group of tumors that can originate from all of the neuroendocrine cells in the body, mostly from the gastrointestinal tract. In addition to early diagnosis, streaming patients into appropriate prognostic groups is an important component of treatment. In this study, we examined the factors that affect survival in patients we followed in our center between 2000-2016. Methods: The demographic data, clinical and pathological features of patients were obtained from their medical files. TNM staging and tumor grading were performed according to AJCC and WHO 2010 classification. SPSS 15.0 for Windows programme was used for statistical analysis. Results: 85 patients (32 male, 53 female) were included into the study. The median age of the patients was 55,7 (27-83) years. Eighty percent of the tumors were of gastroenteropancreatic system, most commonly stomach (27.1%) origin. Nineteen patients (22.4%) died during follow-up. In univariate analysis; age (p<0,001), stage (p=0.002), primary tumor localization (p=0.005), grade (p<0.001), Ki-67 value (p<0.001), number of metastases (p=0.001) and type of surgery (p<0.001) were found to be factors affecting survival. Age (p=0.024) and Ki67 (p <0.001) were the independent prognostic factors for survival in multivariate analysis. For the cut-off value of 6%, Ki-67 had a sensitivity of 83.3% and specifity of 71.4% for survival determination. Conclusion: Ki-67 ratio and age were the most important factors affecting survival in neuroendocrine tumors in our study. Ki-67 ratio has a high sensitivity and specificity for predicting survival, a cut-off value of 6% may be used to predict survival.


Subject(s)
Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Ki-67 Antigen/metabolism , Male , Middle Aged , Neoplasm Grading/methods , Neoplasm Staging/methods , Neuroendocrine Tumors/metabolism , Prognosis
9.
J Med Phys ; 42(3): 128-132, 2017.
Article in English | MEDLINE | ID: mdl-28974857

ABSTRACT

PURPOSE: This study aims to investigate the factors that reduce fetal dose in pregnant patients with breast cancer throughout their radiation treatment. Two main factors in a standard radiation oncology center are considered as the treatment planning systems (TPSs) and simple shielding for intensity modulated radiation therapy technique. MATERIALS AND METHODS: TPS factor was evaluated with two different planning algorithms: Anisotropic analytical algorithm and Acuros XB (external beam). To evaluate the shielding factor, a standard radiological purpose lead apron was chosen. For both studies, thermoluminescence dosimeters were used to measure the point dose, and an Alderson RANDO-phantom was used to simulate a female pregnant patient in this study. Thirteen measurement points were chosen in the 32nd slice of the phantom to cover all possible locations of a fetus up to 8th week of gestation. RESULTS: The results show that both of the TPS algorithms are incapable of calculating the fetal doses, therefore, unable to reduce them at the planning stage. Shielding with a standard lead apron, however, showed a slight radiation protection (about 4.7%) to the fetus decreasing the mean fetal dose from 84.8 mGy to 80.8 mGy, which cannot be disregarded in case of fetal irradiation. CONCLUSIONS: Using a lead apron for shielding the abdominal region of a pregnant patient during breast irradiation showed a minor advantage; however, its possible side effects (i.e., increased scattered radiation and skin dose) should also be investigated further to solidify its benefits.

10.
Breast Cancer ; 24(4): 544-551, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27812996

ABSTRACT

BACKGROUND: Early identification of patients coping poorly is important for compliance with treatment and control of distress. This study aims to investigate the effect of the childhood trauma experience on the type of reaction and adjustment that the person exhibits to the cancer among the patients with breast cancer. METHODS: This cross-sectional study enrolled 310 patients with breast cancer. The effect of the childhood trauma and the psychological condition on the adjustment to cancer was investigated by assessing the adjustment to cancer, the experiences of childhood trauma and psychological status of the subjects using mental adjustment to cancer scale (MAC), childhood trauma questionnaire (CTQ28), Beck Depression Inventory (BDI) and Beck anxiety inventory (BAI). RESULTS: Majority of the subjects (77.4%) showed positive adjustment to cancer. Fighting spirit (63.9%) was the most commonly seen mechanism of adjustment to cancer. Of the subjects, 54.5% suffered at least one of the childhood trauma types. Among the patients, 47.1% had depression and 58.4% had anxiety. In the multivariate logistic regression analysis, emotional neglect and depression, respectively, have an effect on both positive and negative adjustment to cancer. CONCLUSIONS: Our study demonstrated that childhood trauma, especially emotional neglect, affects coping and adjustment among the patients with breast cancer. It is necessary to determine the childhood experiences to ensure the development of psychosocial interventions that will increase the adjustment and quality of life after the diagnosis of the cancer.


Subject(s)
Adaptation, Psychological , Anxiety/etiology , Breast Neoplasms/psychology , Depression/etiology , Quality of Life , Stress Disorders, Post-Traumatic/physiopathology , Anxiety/psychology , Breast Neoplasms/complications , Child , Cross-Sectional Studies , Depression/psychology , Female , Follow-Up Studies , Humans , Middle Aged , Prognosis , Psychiatric Status Rating Scales , Surveys and Questionnaires
11.
Value Health Reg Issues ; 10: 91-99, 2016 09.
Article in English | MEDLINE | ID: mdl-27881285

ABSTRACT

OBJECTIVES: To compare conventionally fractionationed volumetric arc therapy (VMAT) and hypofractionated stereotactic body radiotherapy (SBRT) modalities in terms of prostate-specific antigen (PSA) kinetics, toxicity, and quality of life (QOL) in patients with localized prostate cancer. METHODS: Patients received radical radiotherapy as either 33.5 Gy/5 fr for SBRT or 75.6 Gy/35 fr for VMAT. International Prostate Symptom Score (IPSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (QLQ-PR25) forms were used to assess QOL. RESULTS: Of the 48 patients (28 in SBRT and 20 in VMAT) included in the study, 40 (20 in SBRT and 20 in VMAT) were evaluated for QOL status. PSA control rate was 100% and PSA nadir value was 0.5 ng/dl in both arms during the median follow-up period of 23 months. The magnitude of PSA bounce was higher in the SBRT arm than in the VMAT arm (P = 0.01). The PSA decline rate in the VMAT arm was higher than in the SBRT arm (P = 0.028). Three (10.7%) patients treated with SBRT who had a history of transurethral resection of the prostate (TURP) experienced grade 3 urinary toxicity. No significant difference was observed concerning sexual activity and sexual functioning scores, whereas scores at 10.5 and 13.5 months were decreased in both arms. The SBRT and VMAT arms had similar urinary incontinence, bowel symptoms, and IPSS obstruction scores. The magnitude of increase in IPSS scores at treatment completion was higher in the VMAT arm than in the SBRT arm (P = 0.046). The decrease in hormonal symptom scores at 4.5, 10.5, and 13.5 months was higher in the VMAT arm than in the SBRT arm (P = 0.007, 0.027, and 0.021, respectively). CONCLUSIONS: Both treatment modalities had similar effectiveness and provided acceptable outcomes in terms of toxicity and QOL. Grade 3 urinary toxicities might be eliminated with careful patient selection for SBRT.


Subject(s)
Prostate-Specific Antigen/analysis , Prostatic Neoplasms/therapy , Quality of Life , Radiosurgery , Transurethral Resection of Prostate , Follow-Up Studies , Humans , Kinetics , Male , Radiosurgery/adverse effects , Transurethral Resection of Prostate/adverse effects , Treatment Outcome
12.
Medicine (Baltimore) ; 95(30): e4280, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27472701

ABSTRACT

Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide-cisplatin (EP) or docetaxel-cisplatin (DP) in this curative setting.Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods.A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32-70 years) and 55 years (range, 37-73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1-132 months) in the EP group and 19 months (range, 1-96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25-0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3-4: 0% vs. 6%, P = 0.024).Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Chemoradiotherapy , Cisplatin/administration & dosage , Docetaxel , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Taxoids/administration & dosage , Treatment Outcome
13.
J Dermatolog Treat ; 27(3): 275-7, 2016.
Article in English | MEDLINE | ID: mdl-26368051

ABSTRACT

BACKGROUND: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. METHODS: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. RESULTS: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28-85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. CONCLUSIONS: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.


Subject(s)
Sarcoma, Kaposi/epidemiology , Sarcoma, Kaposi/therapy , Adult , Aged , Aged, 80 and over , Disease Progression , Disease-Free Survival , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/radiotherapy , HIV Infections/surgery , HIV Infections/therapy , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Sarcoma, Kaposi/drug therapy , Sarcoma, Kaposi/radiotherapy , Sarcoma, Kaposi/surgery
14.
Tumour Biol ; 37(3): 3969-78, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26482616

ABSTRACT

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Head and Neck Neoplasms/blood , RNA, Long Noncoding/blood , Area Under Curve , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , ROC Curve , Treatment Outcome
15.
Medicine (Baltimore) ; 94(52): e2341, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26717372

ABSTRACT

Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ±â€Š9% vs. 82 ±â€Š6%, P = 0.013) and overall survival (OS) (68 ±â€Š8% vs. 94 ±â€Š4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.


Subject(s)
Bridged-Ring Compounds/therapeutic use , Carcinoma, Ductal, Breast , Mastectomy , Taxoids/therapeutic use , Triple Negative Breast Neoplasms , Adult , Antineoplastic Agents/therapeutic use , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/therapy , Disease-Free Survival , Female , Humans , Incidence , Mastectomy/adverse effects , Mastectomy/methods , Mastectomy/statistics & numerical data , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Triple Negative Breast Neoplasms/epidemiology , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/therapy , Turkey/epidemiology
17.
Tumour Biol ; 36(2): 1039-44, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25326440

ABSTRACT

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5% and a specificity of 73.9% (area under the curve (AUC) = 0.592, 95% confidence interval (CI) 35.3-83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1% and a specificity of 65.6% (AUC = 0.562, 95 % CI 36.0-76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.


Subject(s)
Keratin-18/blood , Nasopharyngeal Neoplasms/blood , Peptide Fragments/blood , Adolescent , Adult , Aged , Aged, 80 and over , Apoptosis/genetics , Biomarkers, Tumor/blood , Carcinoma , Disease-Free Survival , Female , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , Predictive Value of Tests , Prognosis
18.
Tumour Biol ; 35(12): 11871-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25142230

ABSTRACT

The synuclein gamma (SNCG) protein, a member of neuronal protein family synuclein, has been considered as a promising potential biomarker as an indicator of cancer stage and survival in patients with cancer. The present study was conducted to evaluate the prognostic value of SNCG in patients with esophageal carcinoma (EC). SNCG levels were assessed immunohistochemically in cancer tissues from 73 EC patients. Median age was 57 (range, 29-78) years old. Forty-seven percent of the patients were male. Thirty-seven percent of the patients had upper or middle localized tumor whereas 59 % had epidermoid carcinoma. More than half of the patients (61 %) had undergone operation where 57 % received adjuvant treatment including chemotherapy or chemotherapy plus radiotherapy. Median overall survival was 11.3 ± 1.8 months (95% confidence interval (CI): 7.7-14.9 months). SNCG positivity was significantly associated with the histological type of EC and inoperability (for SNCG positive vs. negative group; epidermoid 80 vs. 53 %; p = 0.05 and inoperable 59 vs.32 %; p = 0.04, respectively). Lymph node metastasis, inoperability and receiving no adjuvant treatment had significantly adverse effect on survival in the univariate analysis (p = 0.01, p < 0.001, and p = 0.001, respectively). SNCG positivity had significantly adverse effect on survival in both univariate and multivariate analysis (p = 0.02 and p = 0.01, respectively). Our results are the first to suggest that SNCG is a new independent predictor for poor prognosis in EC patients in the literature.


Subject(s)
Esophageal Neoplasms/metabolism , gamma-Synuclein/metabolism , Adult , Aged , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Female , Gene Expression , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Metastasis , Patient Outcome Assessment , Prognosis , gamma-Synuclein/genetics
19.
Invest New Drugs ; 32(6): 1295-300, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24930136

ABSTRACT

This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/adverse effects , Drug Eruptions/drug therapy , Pistacia , Soaps/therapeutic use , Adult , Aged , Cetuximab , Colorectal Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Female , Humans , Male , Middle Aged , Treatment Outcome
20.
Auris Nasus Larynx ; 41(5): 436-40, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24746667

ABSTRACT

OBJECTIVE: Radiotherapy is the primary method of treatment for nasopharyngeal cancer (NPC) and many side effects were reported in patients receiving radiation to this area. This study was conducted to evaluate the long-term effects of radiotherapy following NPC on olfactory bulb (OB) volume and olfactory function. METHODS: Twenty-four patients with NPC who received radiotherapy at least 12 months ago were recruited. Fourteen healthy subjects with similar demographical characteristics were recruited as the healthy control group. All volunteers were subjected to a nasoendoscopical examination, and abnormalities that could potentially cause olfactory dysfunction were the exclusion criteria from the study. An experienced radiologist segmented the MRI coronal, axial and sagittal slices manually for three-dimensional OB volume measurement in a blinded manner. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, and average score (0: worst, 7: best) was calculated as the total CCCRC olfactory score. RESULTS: The mean CCCRC score was 5.5 ± 1.1 for the nasopharyngeal cancer patients, whereas the mean score of healthy control group was 6.4 ± 0.4. There was a significant difference in the olfactory scores (p=0.003). The mean OB volume in the NPC group was 46.7 ± 12.1mm(3). Among the patients with NPC, the cisplatin receiving group had a mean OB volume of 47.2mm(3), whereas the cisplatin+docetaxel receiving group had a mean OB volume of 46.5mm(3), and they were similar. The MRI measurement of the healthy control group was 58.6 ± 13.8mm(3). The OB volumes of the healthy control group were significantly higher (p<0.05). CONCLUSION: Radiotherapy following nasopharyngeal cancer results in a diminished OB volume and deteriorated olfactory function. Chemosensory olfactory dysfunction might be a contributing factor to lack of appetite, cancer cachexia and consequent lowered quality of life in NPC patients.


Subject(s)
Nasopharyngeal Neoplasms/radiotherapy , Olfaction Disorders/etiology , Olfactory Bulb/radiation effects , Radiotherapy/adverse effects , Smell/radiation effects , Adult , Carcinoma , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nasopharyngeal Carcinoma , Olfaction Disorders/pathology , Olfactory Bulb/pathology , Organ Size , Quality of Life , Sensory Thresholds
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