Publications by authors named "Berrin Pehlivan"

28 Publications

  • Page 1 of 1

Comparison of Total Body Irradiation-based Versus Chemotherapy-based Conditionings for Early Complications of Allogeneic Hematopoietic Stem Cell Transplantation in Children With ALL.

J Pediatr Hematol Oncol 2021 Mar 31. Epub 2021 Mar 31.

MedicalPark Goztepe Hospital, Pediatric Bone Marrow Transplantation Unit Bahcesehir University Faculty of Medicine, Radiation Oncology Bahcesehir University Faculty of Medicine MedicalPark Antalya Hospital, Pediatric Bone Marrow Transplantation Unit, Istanbul, Turkey.

Background: Total body irradiation (TBI) is the cornerstone of conditioning regimens in pediatric hematopoietic stem cell transplantation for acute lymphoblastic leukemia. As the late effects and survival comparison between TBI and chemotherapy were well analyzed before, in this study, we aim to focus on the first 100 days and early complications of transplantation.

Methods: This retrospective study involves 72 pediatric patients (0 to 18 y) underwent first hematopoietic stem cell transplantation for acute lymphoblastic leukemia between October 2015 and May 2019. Patients are divided into 2 groups regarding conditioning regimens. Conditionings includes either TBI 1200 cGy/6 fractions/3 days and etoposide phosphate or busulfan, fludarabine, and thiotepa. Busulfan was administered IV and according to body weight.

Results: The incidences of acute graft versus host disease grade 2 to 4, veno-occlusive disease, capillary leakage syndrome, thrombotic microangiopathy, blood stream infection, hemorrhagic cystitis and posterior reversible encephalopathy syndrome before day 100 were similar for both conditioning regimens; however, patients received TBI-based conditioning had significantly longer neutrophil engraftment time (17.5 vs. 13 d, P=0.001) and tended to have more engraftment syndrome (ES) (45.5% for TBI vs. 24.0% for chemotherapy, P=0.069). Multivariate analysis showed that TBI-based conditioning was associated with a longer neutrophil engraftment time (hazard ratio [HR]=1.20, P=0.006), more cytomegalovirus (CMV) reactivation (HR=3.65, P=0.038) and more ES (HR=3.18, P=0.078).

Conclusions: Our findings support chemotherapy-based regimens with early neutrophil engraftment, less ES and CMV reactivation compared with TBI. Although there is no impact on survival rates, increased incidence of ES and CMV reactivation should be considered in TBI-based regimens.
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http://dx.doi.org/10.1097/MPH.0000000000002055DOI Listing
March 2021

Prechemoradiotherapy Systemic Inflammation Response Index Stratifies Stage IIIB/C Non-Small-Cell Lung Cancer Patients into Three Prognostic Groups: A Propensity Score-Matching Analysis.

J Oncol 2021 23;2021:6688138. Epub 2021 Jan 23.

Department of Radiation Oncology, Bahcesehir University, Istanbul, Turkey.

Purpose: We explored the prognostic influence of the systemic inflammation response index (SIRI) on the survival outcomes of stage IIIB/C non-small-cell lung cancer (NSCLC) patients who underwent concurrent chemoradiotherapy.

Methods: Present propensity score-matching (PSM) analysis comprised 876 stage IIIB/C NSCLC patients who received 1-3 cycles of platinum-based doublets concurrent with thoracic radiotherapy from 2007 to 2017. The primary and secondary objectives were the relationships between the SIRI values and overall (OS) and progression-free survival, respectively. Propensity scores were calculated for SIRI groups to adjust for confounders and to facilitate well-balanced comparability between the SIRI groups by creating 1 : 1 matched study groups.

Results: The receiver operating characteristic curve analysis identified an optimal SIRI cutoff at 1.9 for OS (AUC: 78.8%; sensitivity: 73.7%; specificity: 70.7%) and PFS (AUC: 80.5%; sensitivity: 75.8%; specificity: 72.9%) and we grouped the patients into two PSM cohorts: SIRI < 1.9 ( = 304) and SIRI ≥ 1.9 ( = 304), respectively. The SIRI ≥ 1.9 cohort had significantly worse median OS ( < 0.001) and PFS ( < 0.001) than their SIRI < 1.9 companions. The further combination of SIRI with disease stage exhibited that the SIRI-1 (IIIB and SIRI < 1.9) and SIRI-3 (IIIC and SIRI ≥ 1.9) cohorts had the best and worst outcomes, respectively, with SIRI-2 cohort (IIIB and SIRI ≥ 1.9 or IIIC and SIRI < 1.9) being remained in between ( < 0.001 for OS and PFS, separately). In multivariate analysis, the two- and three-laddered stratifications per the 1.9 cutoffs and SIRI groups retained their independent significance, individually.

Conclusions: The SIRI ≥ 1.9 independently prognosticated significantly worse OS and PFS results and plated the stage IIIB/C patients into three fundamentally distinct prognostic groups.
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http://dx.doi.org/10.1155/2021/6688138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847338PMC
January 2021

The Influence of Systemic Inflammation Response Index on Survival Outcomes of Limited-Stage Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy.

J Oncol 2020 16;2020:8832145. Epub 2020 Dec 16.

Baskent University Medical Faculty, Department of Radiation Oncology, Adana, Turkey.

Background: Recent studies have indicated that the systemic inflammation response index (SIRI) can efficiently predict survival outcomes in various tumor types. Thusly, in absence of comparable investigations in limited-stage small-cell lung cancers (LS-SCLCs), we aimed to retrospectively evaluate the prognostic utility of SIRI in LS-SCLC patients treated with concurrent chemoradiotherapy (CRT). . Present multi-institutional retrospective analysis incorporated LS-SCLC patients treated with CRT at three academic radiation oncology centers between January 2007 and December 2018. The SIRI was calculated by using the peripheral blood neutrophil (N), monocyte (M), and lymphocyte (L) counts acquired in the last ≤7 days before the commencement of the CRT: SIRI = N × M/L. Accessibility of pretreatment SIRI cutoff that may stratify the study population into two gatherings with distinctive overall survival (OS) results was evaluated by utilizing the receiver operating characteristic (ROC) curve analysis. Primary objective was the association between the SIRI values and the OS results.

Results: Search for the availability of an ideal SIRI cutoff that may stratify the entire patients' population into two particular groups with distinctive OS outcomes identified the 1.93 value (area under the curve (AUC): 72.9%; sensitivity: 74.6%; specificity: 70.1%): Group 1: SIRI <1.93 ( = 71) and Group 2: SIRI ≥1.93 ( = 110), respectively. At a median follow-up of 17.9 (95% CI: 13.2-22.6) months, 47 (26.0%) patients were still alive (47.9% for SIRI <1.93 versus 18.3% for SIRI ≥1.93; < 0.001). Kaplan-Meier comparisons between the two SIRI groups showed that the SIRI <1.93 cohort had significantly longer median OS (40.5 versus 14.2 months; < 0.001) than the SIRI ≥1.93 cohort. Similarly, the 3- (54% versus 12.6%) and 5-year (33% versus 9.9%) OS rates were also numerically superior in the SIRI <1.93 cohort. Results of the multivariate analyses uncovered that the prognostic significance of the SIRI on OS outcomes was independent of the other confounding variables.

Conclusions: The results of this retrospective multi-institutional cohort analysis suggested that a pre-CRT SIRI was a strong and independent prognostic biomarker that reliably stratified LS-SCLC patients into two cohorts with significantly different OS outcomes.
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http://dx.doi.org/10.1155/2020/8832145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759417PMC
December 2020

Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol.

J Immunol Res 2020 14;2020:8628540. Epub 2020 Nov 14.

Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey.

Objectives: We endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol.

Methods: The records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SIRI = Neutrophils × Monocytes/Lymphocytes. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively.

Results: The ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1: SIRI ≤ 1.78 ( = 96) and SIRI > 1.78 ( = 85)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the SIRI ≤ 1.78 cohort had altogether significantly superior median PFS (16.2 versus 6.6 months; < 0.001) and OS (22.9 versus 12.2 months; < 0.001) than its SIRI > 1.78 counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS ( < 0.001) and OS ( < 0.001) durations, respectively.

Conclusions: Present results firmly counseled the pretreatment SIRI as a novel, sound, and independent predictor of survival outcomes in newly diagnosed GBM patients intended to undergo postoperative Stupp protocol.
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http://dx.doi.org/10.1155/2020/8628540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683150PMC
November 2020

Low Advanced Lung Cancer Inflammation Index Predicts Poor Prognosis in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Definitive Concurrent Chemoradiotherapy.

J Oncol 2020 7;2020:3127275. Epub 2020 Oct 7.

Bahcesehir University, Department of Radiation Oncology, Istanbul, Turkey.

Purpose: We aimed to retrospectively investigate the prognostic worth of pretreatment advanced lung cancer inflammation index (ALI) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients treated with concurrent chemoradiotherapy (C-CRT). . A total of 164 LA-NPC patients treated with cisplatinum-based definitive C-CRT were included in this retrospective cohort analysis. The convenience of ideal pre-C-CRT ALI cut-offs affecting survival results was searched by employing the receiver operating characteristic (ROC) curve analyses. The primary endpoint was the link between the ALI groups and overall survival (OS), while cancer-specific survival (CSS), locoregional progression-free survival [LR(PFS)], distant metastasis-free survival (DMFS), and PFS comprised the secondary endpoints.

Results: The ROC curve analyses distinguished a rounded ALI cut-off score of 24.2 that arranged the patients into two cohorts [ALI ≥ 24.2 ( = 94) versus < 24.2 ( = 70)] with significantly distinct CSS, OS, DMFS, and PFS outcomes, except for the LRPFS. At a median follow-up time of 79.2 months (range: 6-141), the comparative analyses showed that ALI < 24.2 cohort had significantly shorter median CSS, OS, DMFS, and PFS time than the ALI ≥ 24.2 cohort ( < 0.001for each), which retained significance at 5- ( < 0.001) and 10-year ( < 0.001) time points. In multivariate analyses, ALI < 24.2 was asserted to be an independent predictor of the worse prognosis for each endpoint ( < 0.001for each) in addition to the tumor stage (T-stage) ( < 0.05 for all endpoints) and nodal stage (N-stage) ( < 0.05 for all endpoints).

Conclusion: As a novel prognostic index, the pretreatment ALI < 24.2 appeared to be strongly associated with significantly diminished survival outcomes in LA-NPC patients treated with C-CRT independent of the universally recognized T- and N-stages.
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http://dx.doi.org/10.1155/2020/3127275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563083PMC
October 2020

Comparison of Involved Field Radiotherapy versus Elective Nodal Irradiation in Stage IIIB/C Non-Small-Cell Lung Carcinoma Patients Treated with Concurrent Chemoradiotherapy: A Propensity Score Matching Study.

J Oncol 2020 4;2020:7083149. Epub 2020 Sep 4.

Koc University, School of Medicine, Radiation Oncology Department, Istanbul, Turkey.

Background: We retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT).

Methods: Our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1 : 1 matched study groups.

Results: The median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1 : 1 matched 646 patients for the ENI ( = 323) and IFRT ( = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%; =0.52) and median overall survival (25.2 versus 24.6 months; =0.69), locoregional progression-free survival (15.3 versus 15.1 months; =0.52), and progression-free survival (11.7 versus 11.2 months; =0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (=0.0012), grade 3 nausea-vomiting (=0.006), esophagitis (=0.003), pneumonitis (=0.002), late grade 3-4 esophageal toxicity (=0.038), and the need for hospitalization ( < 0.001) were all significantly higher in the ENI than in the IFRT group, respectively.

Conclusion: Results of the present large-scale PSM cohort established the absence of meaningful IENF or survival differences between the IFRT and ENI cohorts and, consequently, counseled the IFRT as the elected RT technique for such patients since ENI increased the toxicity rates.
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http://dx.doi.org/10.1155/2020/7083149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487114PMC
September 2020

Low Systemic Inflammation Response Index Predicts Good Prognosis in Locally Advanced Pancreatic Carcinoma Patients Treated with Concurrent Chemoradiotherapy.

Gastroenterol Res Pract 2020 30;2020:5701949. Epub 2020 Jul 30.

Department of Radiation Oncology, Bahcesehir University, Istanbul/, Turkey.

Background: We investigated the prognostic significance of pretreatment systemic inflammation response index (SIRI) in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (CRT).

Methods: Present retrospective cohort analysis investigated consecutive 154 LAPC patients who received radical CRT. The SIRI was defined as: SIRI = neutrophil × monocyte/lymphocyte counts. Ideal SIRI cutoff(s) influencing overall survival (OS) and progression-free survival (PFS) results were sought by using receiver operating characteristic (ROC) curve analysis. The primary endpoint was the interaction between the SIRI and OS results.

Results: The median follow-up, PFS, and OS durations were 14.3 (range: 2.9-74.6), 7.9 [%95 confidence interval (CI): 5.7-10.1), and 14.7 months (%95 CI: 11.4-18.0) for the entire cohort, respectively. ROC curve analyses determined the ideal SIRI cutoff that exhibiting a significant link with OS and PFS outcomes at the rounded 1.6 point (AUC: 74.3%; sensitivity: 73.8%; specificity: 70.1%).The SIRI <1.6 patients ( = 58) had significantly superior median PFS (13.8 versus 6.7 months; < 0.001) and OS (28.6 versus 12.6 months; < 0.001) lengths than SIRI ≥1.6 patients ( = 96), respectively. Although the N0 (versus N1; < 0.05) and CA 19-9 ≤90 U/mL (versus >90 U/mL) appeared as the other significant associates of better OS and PFS in univariate analyses, yet the results of multivariate analyses confirmed the SIRI <1.6 as the independent indicator of superior OS and PFS ( < 0.001 for each).

Conclusion: Pretreatment SIRI is a novel independent prognosticator that may further enhance the conventional tumor-node-metastases staging system in a more precise prediction of the OS and PFS outcomes of LAPC patients after radical CRT.
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http://dx.doi.org/10.1155/2020/5701949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414371PMC
July 2020

Prognostic Value of C-Reactive Protein to Albumin Ratio in Glioblastoma Multiforme Patients Treated with Concurrent Radiotherapy and Temozolomide.

Int J Inflam 2020 8;2020:6947382. Epub 2020 Jun 8.

Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey.

Objective: We investigated the prognostic impact of C-reactive protein to albumin ratio (CRP/Alb) on the survival outcomes of newly diagnosed glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ).

Methods: The pretreatment CRP and Alb records of GBM patients who underwent RT and concurrent plus adjuvant TMZ were retrospectively analyzed. The CRP/Alb was calculated by dividing serum CRP level by serum Alb level obtained prior to RT. The availability of significant cutoff value for CRP/Alb that interacts with survival was assessed with the receiver-operating characteristic (ROC) curve analysis. The primary endpoint was the association between the CRP/Alb and the overall survival (OS).

Results: A total of 153 patients were analyzed. At a median follow-up of 14.7 months, median and 5-year OS rates were 16.2 months (95% CI: 12.5-19.7) and 9.5%, respectively, for the entire cohort. The ROC curve analysis identified a significant cutoff value at 0.75 point (area under the curve: 74.9%; sensitivity: 70.9%; specificity: 67.7%; < 0.001) for CRP/Alb that interacts with OS and grouped the patients into two: CRP/Alb <0.75 ( = 61) and ≥0.75 ( = 92), respectively. Survival comparisons revealed that the CRP/Alb <0.75 was associated with a significantly superior median (22.5 versus 15.7 months; < 0.001) and 5-year (20% versus 0%) rates than the CRP/Alb ≥0.75, which retained its independent significance in multivariate analysis ( < 0.001).

Conclusion: Present results suggested the pretreatment CRP/Alb as a significant and independent inflammation-based index which can be utilized for further prognostic lamination of GBM patients.
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http://dx.doi.org/10.1155/2020/6947382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298277PMC
June 2020

Prognostic Value of Pretreatment Systemic Immune-Inflammation Index in Glioblastoma Multiforme Patients Undergoing Postneurosurgical Radiotherapy Plus Concurrent and Adjuvant Temozolomide.

Mediators Inflamm 2020 23;2020:4392189. Epub 2020 May 23.

Department of Radiation Oncology, Koc University, School of Medicine, Istanbul, Turkey.

Objectives: To evaluate the potential prognostic utility of pretreatment systemic immune-inflammation index (SII) in newly diagnosed glioblastoma multiforme (GBM) patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.

Methods: The retrospective data of GBM patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide were analyzed. For each patient, SII was calculated using the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SII = platelets × neutrophils/lymphocytes. The receiver operating characteristic (ROC) curve analysis was utilized for the evaluation of optimal cut-off values for SII those linked with the outcomes. Primary and secondary endpoints constituted the overall (OS) and progression-free survival (PFS) per conveyance SII group.

Results: A total of 167 patients were included. The ROC curve analysis identified the optimum SII cut-off at a rounded 565 value that significantly interacted with the PFS and OS and stratified patients into two groups: low-SII (SII < 565; = 71) and high-SII (SII ≥ 565; = 96), respectively. Comparative survival analyses exhibited that the high-SII cohort had significantly shorter median PFS (6.0 versus 16.6 months; < 0.001) and OS (11.1 versus 22.9 months; < 0.001) than the low-SII cohort. The relationship between the high-SII and poorer PFS ( < 0.001) and OS ( < 0.001) further retained its independent significance in multivariate analysis, as well.

Conclusions: The outcomes displayed here qualified the pretreatment SII as a novel independent prognostic index for predicting survival outcomes of newly diagnosed GBM patients undergoing postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.
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http://dx.doi.org/10.1155/2020/4392189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262659PMC
May 2020

Dosimetric Comparison of Lung-Sparing Radiation Therapy between Volumetric Arc Therapy and Helical Tomotherapy for Unresectable Malignant Pleural Mesothelioma.

Biomed Res Int 2019 20;2019:4568958. Epub 2019 Dec 20.

Baskent University Medical Faculty, Department of Radiation Oncology, Adana, Turkey.

Objective: To compare volumetric arc therapy (VMAT) and helical tomotherapy (HT) plans in terms of dosimetric parameters in positron emission tomography- (PET-) computerized tomography- (CT-) based radiation therapy planning in unresectable malignant pleural mesothelioma (MPM).

Methods: CT and coregistered PET-CT data from seven patients with histologically-proven MPM were utilized for VMAT and HT plans. Target volumes and organs at risk (OARs) were delineated. The prescription doses for planning target volume 1 (PTV) and PTV were 45.0 Gy and 54 Gy in 1.8 Gy/fr, respectively. Each technique was evaluated in terms of target volume coverage and OAR doses.

Findings: Although the maximum (=0.001) and mean ( < 0.001) doses of PTV, and PTV ( < 0.001 for maximum and =0.001 for mean doses) favored the HT technique over VMAT, both techniques efficiently covered the target volumes. Additionally, HT also provided more homogeneous dose distribution ( < 0.001) and numerically lower doses received by most OARs, but again both rotational techniques were successful in keeping the OAR doses below the universally accepted limits. The major disadvantage of the HT technique was the requirement for longer treatment times (7.4 versus 2.5 minutes/fr; < 0.001) to accomplish the intended treatment.

Conclusion: Results of this dosimetric comparison clearly demonstrated the possibility of safe hemithoracic irradiation of medically/technically unresectable MPM patients with either of the two rotational RT techniques, namely the VMAT and HT. Clinically, considering their poor prognosis, these promising findings may open a potential new window for curative treatment of unresectable MPM patients, if further confirmed by future clinical studies.
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http://dx.doi.org/10.1155/2019/4568958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942749PMC
June 2020

Evidence for the approach to the diagnostic evaluation of squamous cell carcinoma occult primary tumors of the head and neck.

Oral Oncol 2019 01 30;88:145-152. Epub 2018 Nov 30.

Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address:

Metastases to the cervical lymph nodes from a occult primary (CUP) of head and neck squamous carcinomas has been increasing in presentation (HNSCC). Modern diagnostic workup, including clinical evaluation, conventional imaging, FDG-PET/CT and panendoscopy/tonsillectomy enables detection of the primary site in over half of all cases, and is associated with significantly improved survival rates. Recent studies have demonstrated the utility of novel molecular pathology and transoral surgical techniques in improving diagnosis and treatment. We present a new, evidence-based protocol incorporating these novel diagnostic modalities. It aims to identify the site of the primary tumor, and determine the stage of the disease, including extranodal extension. This information can personalise treatment recommendations, rationalise combinations of treatment modalities, and thereby potentially minimise toxicity and improving functional outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2018.11.020DOI Listing
January 2019

Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients.

J Oncol 2018 1;2018:4518935. Epub 2018 Nov 1.

Bahcesehir University Medical Faculty, Department of Radiation Oncology, Istanbul, Turkey.

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/TS), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed ≤12 months of C-CRT. All FPHs were diagnosed in patients with TC (N=60): group-specific FPH incidence: 21.6%. TC (P<0.001) was the unique independent factor associated with higher FPH risk in multivariate analysis. Further analysis limited to TC patients exhibited the RCV>0.14 (37.5% versus 11.1% for RCV≤0.14; P<0.001), major RCS group [31.0% versus 19.0% for minor versus 0% for minimum RCS; P=0.008), and baseline hemoptysis (26.3% versus 13.6% for no hemoptysis; P=0.009) as the independent risk factors for higher FPH incidence. FPH was an infrequent (2.6%) complication of C-CRT in stage 3B/C SqCLC patients, but its incidence increased to 37.5% in patients presenting with TC and RCV>0.14. Diagnosis of >90% FPHs ≤12 months of C-CRT stresses the importance of close and careful follow-up of high-risk patients after C-CRT for multidisciplinary discussion of possible invasive preventive measures.
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http://dx.doi.org/10.1155/2018/4518935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236701PMC
November 2018

Safety and palliative efficacy of single-dose 8-Gy reirradiation for painful local failure in patients with stage IV non-small cell lung cancer previously treated with radical chemoradiation therapy.

Int J Radiat Oncol Biol Phys 2015 Mar;91(4):774-80

Medstar Hospital, Department of Radiation Oncology, Antalya, Turkey.

Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal.

Patients And Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors.

Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS.

Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.
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http://dx.doi.org/10.1016/j.ijrobp.2014.12.010DOI Listing
March 2015

History of the rare cancer network and past research.

Rare Tumors 2014 Jul 6;6(3):5462. Epub 2014 Aug 6.

Department of Radiation Oncology, Mayo Clinic , Rochester, MN, USA.

Approximately, twenty years ago, the Rare Cancer Network (RCN) was formed in Lausanne, Switzerland, to support the study of rare malignancies. The RCN has grown over the years and now includes 130 investigators from twenty-four nations on six continents. The network held its first international symposium in Nice, France, on March 21-22, 2014. The proceedings of that meeting are presented in two companion papers. This manuscript reviews the history of the growth of the RCN and contains the abstracts of fourteen oral presentations made at the meeting of prior RCN studies. From 1993 to 2014, 74 RCN studies have been initiated, of which 54 were completed, 10 are in progress or under analysis, and 9 were stopped due to poor accrual. Forty-four peer reviewed publications have been written on behalf of the RCN.
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http://dx.doi.org/10.4081/rt.2014.5462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178278PMC
July 2014

Five-year follow-up results for patients diagnosed with anaplastic astrocytoma and effectiveness of concomitant therapy with temozolomide for recurrent anaplastic astrocytoma.

Asian J Neurosurg 2012 Oct;7(4):181-90

Department of Neurosurgery, Baskent University Faculty of Medicine, Ankara, Turkey.

Background: Anaplastic astrocytoma (AA; WHO grade-III) patients determination of prognostic factors helps generating multimodal therapy protocols. For this purpose, in the Baskent University, Adana Medical Research Center, specific characteristics of AA patients who have surgery were retrospectively investigated and factors which affect prognosis has been determined.

Patients And Methods: Between January 2005 and 2009, 20 patients who have AA have been evaluated retrospectively. Totally, 20 patients had 31 operations. Sixteen patients had only adjuvant radiation therapy (RT). In the postoperative period, 8 patients received adjuvant RT. Nine of 10 patients with tumor recurrence received concomitant therapy with temozolomide (ConcT with TMZ) protocol. No adjuvant therapy protocol could be applied in three patients with poor general condition in the postoperative period.

Results: Median survival for patients died was 16±17 months; one year survival was 75% and five year survival 25%. After univariate analysis, preoperative Karnofsky performance score (KPS) was ≥80 (P=0.005577(*)), postoperative KPS was ≥80 (P=0.003825(*)), type of tumor resection (P=0.001751(*)), multiple operations (P=0.006233(*)), and ConcT with TMZ protocol (P=0,005766(*)) were all positive prognostic factors which extend the survival.

Conclusions: The results of the multivariate analysis did not put forward an independent prognostic factor acting on the survival period (P>0.05).
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http://dx.doi.org/10.4103/1793-5482.106650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613640PMC
October 2012

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer.

BMC Cancer 2012 Oct 31;12:502. Epub 2012 Oct 31.

Department of Radiation Oncology, Baskent University Adana Medical Faculty, Adana, Turkey.

Background: Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities.

Methods: The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation.

Results: Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4-5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively.

Conclusion: In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.
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http://dx.doi.org/10.1186/1471-2407-12-502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529187PMC
October 2012

Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors.

Int J Radiat Oncol Biol Phys 2012 Aug 18;83(5):1432-40. Epub 2012 Feb 18.

Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.

Purpose: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT.

Methods And Materials: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1, 2, and 3 cc of brain volume (D(0.5), D(1), D(2), D(3)) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated.

Results: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 ± 5 Gy (RBE) for no toxicity to 74 ± 5 Gy (RBE) for Grade 1 and to 76 ± 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of ≥ 64 Gy (RBE) D(3), ≥ 68 Gy (RBE) D(2), ≥ 72 Gy (RBE) D(1), and ≥ 73 Gy (RBE) D(0.5), respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy.

Conclusions: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of establishing an organ-at-risk maximally permissible dose for BP.
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http://dx.doi.org/10.1016/j.ijrobp.2011.10.042DOI Listing
August 2012

Impact of prophylactic cranial irradiation timing on brain relapse rates in patients with stage IIIB non-small-cell lung carcinoma treated with two different chemoradiotherapy regimens.

Int J Radiat Oncol Biol Phys 2012 Jul 13;83(4):1264-71. Epub 2011 Dec 13.

Baskent University Adana Medical Faculty, Department of Radiation Oncology, Kisla Saglik Yerleskesi, Adana, Turkey.

Purpose: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC).

Methods And Materials: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy.

Results: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001).

Conclusion: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.
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http://dx.doi.org/10.1016/j.ijrobp.2011.09.031DOI Listing
July 2012

Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy.

BMC Gastroenterol 2011 Nov 10;11:123. Epub 2011 Nov 10.

Baskent University Adana Medical Faculty, Department of Radiation Oncology, Adana, Turkey.

Background: We aimed to study the predictive value of combined 18F-fluoro-deoxy-D-glucose positron emission tomography and computerized tomography (FDG-PET-CT), on outcomes in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT).

Methods: Thirty-two unresectable LAPC patients received 50.4 Gy (1.8 Gy/fr) of RT and concurrent 5-FU followed by 4 to 6 cycles of gemcitabine consolidation. Response was evaluated by FDG-PET-CT at post-C-CRT 12-week. Patients were stratified into two groups according to the median difference between pre- and post-treatment maximum standard uptake values (SUVmax) as an indicator of response for comparative analysis.

Results: At a median follow-up of 16.1 months, 16 (50.0%) patients experienced local/regional failures, 6 of which were detected on the first follow-up FDG-PET-CT. There were no marginal or isolated regional failures. Median pre- and post-treatment SUVmax and median difference were 14.5, 3.9, and -63.7%, respectively. Median overall survival (OS), progression-free survival (PFS), and local-regional progression-free survival (LRPFS) were 14.5, 7.3, and 10.3 months, respectively. Median OS, PFS, and LRPFS for those with greater (N = 16) versus lesser (N = 16) SUVmax change were 17.0 versus 9.8 (p = 0.001), 8.4 versus 3.8 (p = 0.005), and 12.3 versus 6.9 months (p = 0.02), respectively. On multivariate analysis, SUVmax difference was predictive of OS, PFS, and LRPFS, independent of existing covariates.

Conclusions: Significantly higher OS, PFS, and LRPFS in patients with greater SUVmax difference suggest that FDG-PET-CT-based metabolic response assessment is an independent predictor of clinical outcomes in LAPC patients treated with definitive C-CRT.
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http://dx.doi.org/10.1186/1471-230X-11-123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224773PMC
November 2011

Pseudoprogression in patients with glioblastoma multiforme after concurrent radiotherapy and temozolomide.

Am J Clin Oncol 2012 Jun;35(3):284-9

Department of Radiation Oncology, Adana Medical and Research Center, Baskent University Medical Faculty, Kisla Saglik Yerleskesi, Adana, Turkey.

Background: To evaluate pathologically confirmed incidence of pseudoprogression and its impact on survival in glioblastoma multiforme (GBM) patients treated with radiotherapy and concurrent temozolomide (TMZ), followed by 6 months of TMZ maintenance therapy.

Materials And Methods: Sixty-three patients with histologic proof of GBM underwent 60 Gy (2 Gy/fr, 30 fractions) of brain radiotherapy concurrent with continuous 75 mg/m/d TMZ, followed by 6 cycles of maintenance TMZ (200 mg/m/d for 5 d, every 28 d). Response assessment was performed by magnetic resonance imaging every 2 months. All patients with radiologic doubt of early tumor progression (≤6 mo) underwent salvage surgery.

Results: All patients underwent surgical resection. Gross total, subtotal resection, and biopsy were performed in 17 (27.0%), 32 (51.6%), and 14 (21.4%) patients, respectively. Lesion enlargement on first follow-up magnetic resonance imaging evidenced in 28 (44.4%) patients. Salvage pathologies revealed pseudoprogression in 12 of 28 (42.8%) patients corresponding to an overall pseudoprogression rate of 19%. Survival analysis revealed that patients with pseudoprogression had superior overall and progression-free survival rates at both 1 and 2 years (P<0.05 for each, respectively).

Conclusions: Current results indicates the urgency of need for novel imaging techniques and/or biochemical marker(s) that can better distinguish pseudoprogression from true progression to avoid unnecessary and potentially harmful surgical interventions in almost half of the radiologically progressive GBM patients. Our additional observation which suggests better survival for patients with pseudoprogression warrants to be studied in larger patient cohorts.
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http://dx.doi.org/10.1097/COC.0b013e318210f54aDOI Listing
June 2012

Outcome and prognostic factors in olfactory neuroblastoma: a rare cancer network study.

Int J Radiat Oncol Biol Phys 2010 Nov 16;78(4):992-7. Epub 2010 Mar 16.

Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Purpose: To assess the outcome in patients with olfactory neuroblastoma (ONB).

Methods And Materials: Seventy-seven patients treated for nonmetastatic ONB between 1971 and 2004 were included. According to Kadish classification, there were 11 patients with Stage A, 29 with Stage B, and 37 with Stage C. T-classification included 9 patients with T1, 26 with T2, 16 with T3, 15 with T4a, and 11 with T4b tumors. Sixty-eight patients presented with N0 (88%) disease.

Results: Most of the patients (n = 56, 73%) benefited from surgery (S), and total excision was possible in 44 patients (R0 in 32, R1 in 13, R2 in 11). All but five patients benefited from RT, and chemotherapy was given in 21 (27%). Median follow-up period was 72 months (range, 6-315). The 5-year overall survival (OS), disease-free survival (DFS), locoregional control, and local control were 64%, 57%, 62%, and 70%, respectively. In univariate analyses, favorable factors were Kadish A or B disease, T1-T3 tumors, no nodal involvement, curative surgery, R0/R1 resection, and RT-dose 54 Gy or higher. Multivariate analysis revealed that the best independent factors predicting the outcome were T1-T3, N0, R0/R1 resection, and total RT dose (54 Gy or higher).

Conclusion: In this multicenter retrospective study, patients with ONB treated with R0 or R1 surgical resection followed by at least 54-Gy postoperative RT had the best outcome. Novel strategies including concomitant chemotherapy and/or higher dose RT should be prospectively investigated in this rare disease for which local failure remains a problem.
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http://dx.doi.org/10.1016/j.ijrobp.2009.09.019DOI Listing
November 2010

Bilateral glomus tumor treated with PET-CT based conformal radiotherapy: a case report.

Cases J 2009 Sep 15;2:8402. Epub 2009 Sep 15.

Department of Radiation Oncology, Baskent University Medical Faculty 01120, Adana Turkey.

Introduction: Glomus tumors are benign, slow growing tumors originating from paraganglionic tissue, mostly located at the carotid bifurcation, jugular foramen, cervical portion vagus nerve, and middle ear cavity. Radiotherapy is treatment of choice for patients with intracranial extension, and patients with bilateral and multiple tumors, or patients who are inoperable.

Case Presentation: We present a 53-year-old female patient with a glomus tumor treated with positron emission tomography computed tomography planning and 3D conformal radiotherapy, and the patient has remained free of disease progression 2 years after.

Conclusion: It is suggested that radiotherapy is a good treatment modality in patients with glomus tumor, and metabolic imaging and treatment planning with positron emission tomography computed tomography is superior to other imaging modalities.
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http://dx.doi.org/10.4076/1757-1626-2-8402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769436PMC
September 2009

Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma.

Radiat Oncol 2009 Sep 16;4:35. Epub 2009 Sep 16.

Department of Radiation Oncology, Baskent University Medical Faculty, Adana Medical and Research Center, Kisla Campus, Adana, Turkey.

Background: When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group.

Methods: Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes.

Results: In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% +/- 28.4%, mean CTV decreased by 38.7% +/- 24.7%, mean PTV1 decreased by 31.1% +/- 23.1%, and mean PTV2 decreased by 40.0% +/- 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients.

Conclusion: This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond conventional limits potential clinical benefits in tumor control rates, which needs to be tested in future studies.
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http://dx.doi.org/10.1186/1748-717X-4-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754492PMC
September 2009

Comparison of conventional and CT-based planning for intracavitary brachytherapy for cervical cancer: target volume coverage and organs at risk doses.

J Exp Clin Cancer Res 2009 Jul 1;28:95. Epub 2009 Jul 1.

Department of Radiation Oncology, Baskent University Medical Faculty, Adana, Turkey.

Background: To compare intracavitary brachytherapy (ICBT) planning methods for cervical cancer, based on either orthogonal radiographs (conventional plan) or CT sections (CT plan); the comparison focused on target volume coverage and dose volume analysis of organs at risk (OARs), by representing point doses defined by the International Commission on Radiation Units and Measurement (ICRU) and dose volume histograms (DVHs) from 3D planning.

Methods: We analyzed the dosimetric data for 62 conventional and CT-based ICBT plans. The gross tumor volume (GTV), clinical target volume (CTV) and organs at risk (OAR)s were contoured on the CT-plan. Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images.

Results: Patients were categorized on the basis of whether the >95% isodose line of the point-A prescription dose encompassed the CTV (group 1, n = 24) or not (group 2, n = 38). The mean GTV and CTV (8.1 cc and 20.6 cc) were smaller in group 1 than in group 2 (24.7 cc and 48.4 cc) (P <0.001). The mean percentage of GTV and CTV coverage with the 7 Gy isodose was 93.1% and 88.2% for all patients, and decreased with increasing tumor size and stage. The mean D2 and D5 rectum doses were 1.66 and 1.42 times higher than the corresponding ICRU point doses and the mean D2 and D5 bladder doses were 1.51 and 1.28 times higher. The differences between the ICRU dose and the D2 and D5 doses were significantly higher in group 2 than in group 1 for the bladder, but not for the rectum.

Conclusion: The CT-plan is superior to the conventional plan in target volume coverage and appropriate evaluation of OARs, as the conventional plan overestimates tumor doses and underestimates OAR doses.
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http://dx.doi.org/10.1186/1756-9966-28-95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711061PMC
July 2009

Feasibility and efficacy of accelerated weekly concomitant boost postoperative radiation therapy combined with concomitant chemotherapy in patients with locally advanced head and neck cancer.

Ann Surg Oncol 2009 May 12;16(5):1337-43. Epub 2009 Mar 12.

Department of Radiation Oncology, University Hospital Center, University of Lausanne, Lausanne, Switzerland.

Background: The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC).

Methods And Materials: Conformal or intensity-modulated 66-Gy RT was performed in 5.5 weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36 months.

Results And Discussion: Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6 months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status.

Conclusion: Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidity.
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http://dx.doi.org/10.1245/s10434-009-0426-4DOI Listing
May 2009

Decrease in hemoglobin levels following surgery influences the outcome in head and neck cancer patients treated with accelerated postoperative radiotherapy.

Ann Surg Oncol 2009 May 14;16(5):1331-6. Epub 2009 Feb 14.

Radiation Oncology, University Hospital Center, University of Lausanne, Lausanne, Switzerland.

Aim: To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT).

Material And Methods: Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52 months (range 12-95 months).

Results And Discussion: Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (<120 or 130 g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38 g/l (quartile value) compared with those with Hb decrease 38 g/l or more (61% versus 16%, P = 0.008).

Conclusion: Decrease in Hb level by more than 38 g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicated.
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http://dx.doi.org/10.1245/s10434-009-0355-2DOI Listing
May 2009

Sarcomatoid carcinoma of the urinary bladder treated with adjuvant radiotherapy: a case report.

Clin Med Case Rep 2009 30;2:39-42. Epub 2009 Jul 30.

Assistant Professor, Department of Radiation Oncology, Baskent University Medical Faculty, Adana, Turkey.

Sarcomatoid carcinoma is a rare tumor of the urinary bladder accounting for less than 0.5% of all primary urinary bladder tumors. Since the patients were presented with large tumor with extended stages, outcome was found to be poor. In order to improve local control, adjuvant local treatment may be practical. We report a rare case with sarcomatoid carcinoma of the urinary bladder diagnosed with immunuhistochemical (IHC) study and treated with 3D-conformal radiotherapy (3DCRT) post-operatively. A 55-year old female patient complained about painless hematuria for 2 months. Computed tomography of the pelvic region revealed tumor and wall thickening at the left posterolateral side of the bladder. Total cystectomy with lymph node dissection and total abdominal hysterectomy and bilateral salphingo-oopherectomy was performed and histopathological and immunohistochemical findings strongly correlate with sarcomatoid carcinoma. The patient was treated with 3D conformal radiotherapy (3DCRT) with a total dose of 59.4 Gy with 1.8 Gy fractional daily doses. Patient was alive without any local recurrence and distant metastasis 10 months after surgery.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785343PMC
http://dx.doi.org/10.4137/ccrep.s3126DOI Listing
November 2013

Interfractional set-up errors evaluation by daily electronic portal imaging of IMRT in head and neck cancer patients.

Acta Oncol 2009 ;48(3):440-5

Department of Radiation Oncology, Institut Gustave-Roussy, Villejuif, France.

Introduction: Interfractional set-up errors were assessed from daily portal images (PI) registration for head and neck cancer patients. We aimed to evaluate whether a daily PI is worthwhile and we derived the Planning Target Volume (PTV) margins from the estimation of systematic and random errors.

Material And Methods: Twenty patients were treated in supine position with a fixed 5-point mask immobilisation system and head-and-knee supports. DRRs (Digitally Reconstructed Radiograph) were obtained from the planning CT-scan and considered the reference images to be compared with two orthogonal PI by matching bone anatomy landmarks. A total of 567 PI were done. For the set-up errors analysis, we determined the systematic, random, and overall standard deviations (SD), as well as the overall means in three directions (cranio caudal CC, medio lateral ML and anterior posterior AP). PTV-margins were calculated according to three methods. Differences of SD regarding the overall displacements among portals performed every day and each 2, 3, or 4 days were tested.

Results: The systematic set-up errors were less than 1 mm in the three directions whereas the random set-up errors were around 2 mm. PTV margins varied from 3 to 4 mm in the 3 directions. Corrections were significant in the CC direction only, in which the set-up error increased significantly when the scenario of one PI every 3 fractions was adopted.

Conclusions: It is of practical importance to apply on-line protocols with contouring of the bony landmarks on the PI in order to decrease the systematic mean error in this patient group. This study suggested that a PI in AP and ML directions once a week and every two days in the CC direction would be adequate to overcome the problem of set-up errors.
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http://dx.doi.org/10.1080/02841860802400610DOI Listing
April 2009