Publications by authors named "Yasemin Bolukbasi"

26 Publications

  • Page 1 of 1

Vaginal cuff brachytherapy practice in endometrial cancer patients: a report from the Turkish Oncology Group.

J Contemp Brachytherapy 2021 Apr 14;13(2):152-157. Epub 2021 Apr 14.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University Ankara, Turkey.

Purpose: The American Brachytherapy Association is attempting to develop standards for delivering brachytherapy, although differences in practice have been reported in the literature. This study evaluated vaginal cuff brachytherapy (VBT) practice and quality of life-related recommendations among Turkish radiation oncologists.

Material And Methods: A nationwide web-based 17-item survey was distributed to the members of the Turkish Society for Radiation Oncology. These members received e-mail notifications, and a link was posted on the Turkish Society for Radiation Oncology internet site to solicit voluntary responses The survey addressed the simulation processes, target volume, prescribed dose, delivery schedules, and recommendations related to vaginal side effects.

Results: Fifty-seven radiation oncologists responded to the survey. The most used dose fraction schemes for adjuvant VBT were 7 Gy × 3 fractions (30%), 5.5 Gy × 5 fractions (26%), and 6 Gy × 5 fractions (28%). The preferred VBT scheme was 5 Gy × 3 fractions (50%) when the external beam radiotherapy (EBRT) dose was 45 Gy external radiotherapy, while the preferred schemes were 6 Gy × 3 fractions (30%) or 5 Gy × 3 fractions (32%) when the external radiotherapy dose was increased to 50.4 Gy. One-half of the respondents delivered VBT twice a week, and the dose was prescribed to 0.5 cm from vaginal mucosa by 86% of the respondents. There was no common definition for the dose prescription length, which was defined as 3 cm from the vaginal cuff in 33% of responses and as 4 cm in 35% of responses. For serous and clear cell histological types, 38% of the respondents targeted "full cylinder length". To prevent vaginal side effects, 78% of the respondents recommended using a vaginal dilator and/or sexual intercourse after VBT.

Conclusions: This survey revealed variations in the clinical practice of VBT among Turkish radiation oncologists, which suggests that standardization is necessary.
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http://dx.doi.org/10.5114/jcb.2021.105282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060958PMC
April 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

Bortezomib induced pulmonary toxicity: a case report and review of the literature.

Am J Blood Res 2020 15;10(6):407-415. Epub 2020 Dec 15.

Department of Hematology, School of Medicine, Koç University Istanbul, Turkey.

Bortezomib is widely used in the treatment of Multiple Myeloma. While the most common side effects are neurological and gastrointestinal related complications, severe pulmonary problems are rarely described. The present case is a 72-year old male with multiple myeloma, who received Lenalidomide, Bortezomib, and Dexamethasone (RVD) combination regimen. He underwent 30 Gy palliative radiotherapy to the thoracic 5-9 and lumbar L1-3 vertebra due to pain and fracture risk. During the third cycle, he was admitted to hospital with dyspnea and dizziness. The thoracic CT revealed bilateral pleural effusions, a diffuse reticular pattern on the parenchyma, and ground-glass opacities that were compatible with drug-induced lung injury. The microbiological and molecular analysis excluded infectious disease, and lung biopsy confirmed the diagnosis of Bortezomib Lung Injury. The time from the first dose of Bortezomib to the lung injury was 57 days, and it was five days from the last dose of Bortezomib. His symptoms were refractory to IV steroids and supportive care. Our patient was lost despite steroids and intensive care support. Even Bortezomib induced lung injury is a rare adverse effect, based on high mortality rate, we would like to emphasize the clinical importance of this clinical scenario in light of the published literature and our presented case.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811899PMC
December 2020

Hypofractionated frameless gamma knife radiosurgery for large metastatic brain tumors.

Clin Exp Metastasis 2021 Feb 3;38(1):31-46. Epub 2021 Jan 3.

Department of Neurosurgery, School of Medicine, Koç University, Davutpasa Caddesi No:4, 34010, Zeytinburnu/İstanbul, Turkey.

Hypofractionated stereotactic radiosurgery has become an alternative for metastatic brain tumors (METs). We aimed to analyze the efficacy and safety of frameless hypofractionated Gamma Knife radiosurgery (hfGKRS) in the management of unresected, large METs. All patients who were managed with hfGKRS for unresected, large METs (> 4 cm) between June 2017 and June 2020 at a single center were reviewed in this retrospective study. Local control (LC), progression-free survival (PFS), overall survival (OS), and toxicities were investigated. A total of 58 patients and 76 METs with regular follow-up were analyzed. LC rate was 98.5% at six months, 96.0% at one year, and 90.6% at 2 years during a median follow-up of 12 months (range, 2-37). The log-rank test indicated no difference in the distribution of LC for any clinical or treatment variable. PFS was 86.7% at 6 months, 66.6% at 1 year, and 58.5% at 2 years. OS was 81% at 6 months, 63.6% at one year, and 50.7% at 2 years. On the log-rank test, clinical parameters such as control status of primary cancer, presence of extracranial metastases, RTOG-RPA class, GPA group, and ds-GPA group were significantly associated with PFS and OS. Patients presented with grade 1 (19.0%), grade 2 (3.5%) and grade 3 (5.2%) side effects. Radiation necrosis was not observed in any patients. Our current results suggest that frameless hfGKRS for unresected, large METs is a rational alternative in selected patients with promising results.
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http://dx.doi.org/10.1007/s10585-020-10068-6DOI Listing
February 2021

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

The Use of Treatment Response Assessment Maps in Discriminating Between Radiation Effect and Persistent Tumoral Lesion in Metastatic Brain Tumors Treated with Gamma Knife Radiosurgery.

World Neurosurg 2021 Feb 27;146:e1134-e1146. Epub 2020 Nov 27.

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

Background: Traditional imaging modalities are not useful in the follow-up of irradiated metastatic brain tumors, because radiation can change imaging characteristics. We aimed to assess the ability of treatment response assessment maps (TRAMs) calculated from delayed-contrast magnetic resonance imaging (MRI) in differentiation between radiation effect and persistent tumoral tissue.

Methods: TRAMs were calculated by subtracting three-dimensional T1 MRIs acquired 5 minutes after contrast injection from the images acquired 60-105 minutes later. Red areas were regarded as radiation effect and blue areas as persistent tumoral lesion. Thirty-seven patients with 130 metastatic brain tumors who were treated with Gamma Knife radiosurgery and who underwent TRAMs perfusion-weighted MRI were enrolled in this retrospective study.

Results: The median age was 58 years and the most common primary diagnosis was lung cancer (n = 21). The median follow-up period of patients was 12 months. The overall local control rate was 100% at 1 year and 98.9% at 2 years. The median progression-free survival was 12 months. The mean overall survival was 27.3 months. The radiologic and clinical follow-up showed a clinicoradiologic diagnosis of a persistent tumoral lesion in 3 tumors (2.3%) and radiation effect in 127 tumors (97.7%). There was a fair agreement between clinicoradiologic diagnosis and TRAMs analysis (κ = 0.380). The sensitivity and positive predictive value of TRAMs in diagnosing radiation effect were 96.06% and 99.2%, respectively. TRAMs showed comparable results to perfusion-weighted MRI, with a diagnostic odds ratio of 27.4 versus 20.7, respectively.

Conclusions: The presented results show the ability of TRAMs in differentiating radiation effect and persistent tumoral lesions.
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http://dx.doi.org/10.1016/j.wneu.2020.11.114DOI Listing
February 2021

Primary Retroperitoneal Müllerian Adenocarcinoma: Report of Two Cases Treated With Radical Surgery.

J Obstet Gynaecol Can 2021 02 26;43(2):242-246. Epub 2020 Aug 26.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Koc University School of Medicine, Istanbul, Turkey. Electronic address:

Background: Primary retroperitoneal Müllerian adenocarcinoma (PRMA) is a very rare type of primary retroperitoneal tumour. CASE 1: A 45-year-old woman presented with left lower extremity swelling and pain. Imaging revealed that the tumour had invaded the left common iliac vein and artery, internal and external iliac arteries, sciatic and obturator nerves, and pelvic wall. CASE 2: A 37-year-old was admitted with pelvic pain. Imaging showed the tumor at the left iliac bifurcation infiltrating the internal iliac artery and left sciatic, obturator, and femoral nerves. Both of these patients were treated with radical surgery that achieved no visible tumour at the end of the operation.

Conclusion: There is no guideline for the diagnosis and management of this entity due to its rarity. These cases should be managed at highly specialized centres with expertise in radical surgery.
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http://dx.doi.org/10.1016/j.jogc.2020.08.009DOI Listing
February 2021

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

Efficacy of whole-sellar Gamma Knife Radiosurgery for magnetic resonance imaging-negative Cushing's disease.

J Neurosurg Sci 2020 Sep 28. Epub 2020 Sep 28.

Department of Neurosurgery, School of Medicine, Koç University, Istanbul, Turkey -

Background: Corticotroph adenoma delineation in Cushing's disease (CD) patients with previous surgery can be challenging. This study investigated the outcome of wholesellar Gamma Knife Radiosurgery (GKRS) in MRI-negative, but hormone-active CD patients with prior failed treatment attempts.

Methods: We retrospectively analyzed data of nine CD cases who underwent wholesellar GKRS between April 2008 and April 2020 at a single center. Remission was determined as normal morning serum cortisol, normal 24-hour urinary free cortisol (UFC), or extended postoperative requirement for hydrocortisone replacement.

Results: Median age was 35.0 years, and most of the cases were female (89%). All subjects had undergone previous surgery. The mean pre-GKRS morning serum cortisol and 24-hour UFC was 27.5 mcg/dL and 408.0 mcg, respectively. Target volume varied from 0.6 to 1.8 cc, and the median margin dose was 28 Gy. The median duration of endocrine follow-up was 105 months, and initial endocrine remission was achieved in eight subjects (89%) at a median time of 22 months. The actuarial initial remission was 44% at two years, 67% at four years, and 89% at six years. The mean recurrence-free survival was 128 months. Age and pre-GKRS morning serum cortisol were found to be predictors for initial and durable endocrine remissions. New-onset hypopituitarism was observed in two of five patients (40%). None of the patients developed new neurological deficits and had GKRS-related adverse events during the follow-up.

Conclusions: Whole-sellar GKRS is a safe and efficient method to manage MRInegative CD and provides similar GKRS outcome rates as in MRI-positive CD.
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http://dx.doi.org/10.23736/S0390-5616.20.05048-1DOI Listing
September 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

Radionecrosis: Pandora's box.

Radiother Oncol 2021 02 9;155:e10. Epub 2020 Sep 9.

Koç University, School of Medicine, Department of Neurosurgery, Istanbul, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.radonc.2020.07.058DOI Listing
February 2021

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

The 2018 assisi think tank meeting on breast cancer: International expert panel white paper.

Crit Rev Oncol Hematol 2020 Jul 22;151:102967. Epub 2020 Apr 22.

Radiation Oncology, University of Perugia and Perugia General Hospital, Perugia, Italy. Electronic address:

We report on the second Assisi Think Tank Meeting (ATTM) on breast cancer which was held under the auspices of the European Society for RadioTherapy & Oncology (ESTRO). In discussing in-depth current evidence and practice it was designed to identify grey areas in diverse forms of the disease. It aimed at addressing uncertainties and proposing future trials to improve patient care. Before the meeting, three key topics were selected: 1) primary systemic therapy, mastectomy, breast reconstruction and post-mastectomy radiation therapy, 2) therapeutic options in ductal carcinoma in situ, and 3) therapy de-escalation in early stage breast cancer. Clinical practice in these areas was investigated by means of an online questionnaire. The time lapse period between the survey and the meeting was used to review the literature and on-going clinical trials. At the ATTM both were discussed in depth and research protocols were proposed.
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http://dx.doi.org/10.1016/j.critrevonc.2020.102967DOI Listing
July 2020

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

J Obstet Gynaecol 2021 Apr 29;41(3):414-420. Epub 2020 Apr 29.

Department of Radiation Oncology, Hacettepe University Medical School, Ankara, Turkey.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statement The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous. This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups. Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.
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http://dx.doi.org/10.1080/01443615.2020.1737661DOI Listing
April 2021

Prognostic value of pretreatment Glasgow prognostic score in stage IIIB geriatric non-small cell lung cancer patients undergoing radical chemoradiotherapy.

J Geriatr Oncol 2019 07 26;10(4):567-572. Epub 2018 Oct 26.

Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey; The University Of Texas, MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX, USA.

Objectives: To investigate the prognostic significance of pre-treatment Glasgow prognostic score (GPS) in stage IIIB non-small-cell lung cancer (NSCLC) older patients treated with radical concurrent chemoradiotherapy (C-CRT).

Materials And Methods: We included 83 stage IIIB NSCLC older patients (age > 70 years) treated with C-CRT consisting of 60-66 Gy (2 Gy/fx) thoracic radiotherapy and at least 1 cycle of platinum-based chemotherapy. Patients were grouped into three: GPS-0: c-reactive protein (CRP) ≤ 10 mg/L and albumin >35 g/L, GPS-1: CRP ≤ 10 mg/L and albumin ≤35 g/L or CRP > 10 mg/L and albumin >35 g/L, GPS-2: CRP > 10 mg/L and albumin ≤35 g/L according to the definition. The relationship between GPS groups and overall survival (OS) was the primary objective, while locoregional- (LRPFS) and progression-free survival (PFS) were secondary objectives.

Results: For the whole cohort, the median OS, LRPFS, and OS were 19.7 (95% confidence interval [CI]: 16.8-22.6), 13.2 (95% CI: 8.7-17.7), and 8.3 months (95% CI: 6.6-10.0), respectively. Comparisons between the GPS-0, GPS-1, and GPS -2 groups revealed that the lower GPS was associated with significantly superior median OS (25.8 versus 16.3 versus 9.4 months; p < .001) which retained its independent significance in multivariate analysis (p < .001), as well. Similarly, the respective median LRPFS (20.0 versus 10.4 versus 6.3 months; p < .001), and PFS (11.3 versus 7.3 versus 4.1 months; p < .001) durations were also significantly longer in the earlier GPS groups.

Discussion: The present results suggested that the GPS was useful in three layered stratification of older stage IIIB NSCLC patients undergoing C-CRT in terms of OS, LRPS, and PFS times.
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http://dx.doi.org/10.1016/j.jgo.2018.10.014DOI Listing
July 2019

Dealing with the gray zones in the management of gastric cancer: The consensus statement of the İstanbul Group.

Turk J Gastroenterol 2019 Jul;30(7):584-598

Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey.

The geographical location and differences in tumor biology significantly change the management of gastric cancer. The prevalence of gastric cancer ranks fifth and sixth among men and women, respectively, in Turkey. The international guidelines from the Eastern and Western countries fail to manage a considerable amount of inconclusive issues in the management of gastric cancer. The uncertainties lead to significant heterogeneities in clinical practice, lack of homogeneous data collection, and subsequently, diverse outcomes. The physicians who are professionally involved in the management of gastric cancer at two institutions in Istanbul, Turkey, organized a consensus meeting to address current problems and plan feasible, logical, measurable, and collective solutions in their clinical practice for this challenging disease. The evidence-based data and current guidelines were reviewed. The gray zones in the management of gastric cancer were determined in the first session of this consensus meeting. The second session was constructed to discuss, vote, and ratify the ultimate decisions. The identification of the T stage, the esophagogastric area, imaging algorithm for proper staging and follow-up, timing and patient selection for neoadjuvant treatment, and management of advanced and metastatic disease have been accepted as the major issues in the management of gastric cancer. The recommendations are presented with the percentage of supporting votes in the results section with related data.
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http://dx.doi.org/10.5152/tjg.2018.18737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629281PMC
July 2019

Use of fluorodeoxyglucose positron emission tomography for diagnosis of bleomycin-induced pneumonitis in Hodgkin lymphoma.

Leuk Lymphoma 2017 05 13;58(5):1114-1122. Epub 2016 Oct 13.

b Koç University, School of Medicine , Department of Hematology , Istanbul , Turkey.

Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity. Early diagnosis of bleomycin-induced pneumonitis is crucial to prevent irreversible damage. Pulmonary function tests are unreliable for identifying risk of bleomycin toxicity. Fluorodeoxyglucose PET/CT scanning can reveal inflammation secondary to pneumonitis but is not sufficiently specific for diagnosis. We retrospectively analyzed scans from 77 patients with Hodgkin lymphoma (median age 41 years, mean bleomycin dose 134 mg) to evaluate bleomycin-induced pneumonitis. We identified 13 patients with abnormal lung uptake of fluorodeoxyglucose. Tracer activity was predominantly diffuse, bilateral, in the lower lobes and subpleural areas. Interim scanning during treatment revealed pneumonitis in eight of 13 patients (asymptomatic in six). One asymptomatic patient died of bleomycin toxicity. For remaining 12 patients, bleomycin was discontinued and methylprednisolone given, all showed resolution of the pneumonitis. These findings suggest that routine interim or end-of-treatment FDG-PET/CT scanning could be beneficial for alerting clinicians to asymptomatic bleomycin-induced toxicity.
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http://dx.doi.org/10.1080/10428194.2016.1236379DOI Listing
May 2017

Outcome and Predictive Factors in Uterine Carcinosarcoma Using Postoperative Radiotherapy: A Rare Cancer Network Study.

Rare Tumors 2016 Jun 29;8(2):6052. Epub 2016 Jun 29.

Department of Radiation Oncology, University Hospital Geneva , Switzerland.

Uterine carcinosarcomas (UCS) are rare tumors. Consensus regarding therapeutic management in non-metastatic disease is lacking. This study reports on outcome and predictive factors when using postoperative radiotherapy. We analyzed a retrospective analysis in 124 women treated between 1987-2007 in the framework of the Rare-Cancer-Network. Median follow-up was 27 months. Postoperative pelvic EBRT was administered in 105 women (85%) and 92 patients (74%) received exclusive or additional vaginal brachytherapy. Five-year overall survival (OS), disease-free survival (DFS), cancer specific survival (CSS) and locoregional control (LRC) were 51.6% (95% CI 35-73%), 53.7% (39-71%), 58.6% (38-74%) and 48% (38-67%). Multivariate analysis showed that external beam radiation therapy (EBRT) >50Gy was an independent prognostic factor for better OS (P=0.03), CSS (P=0.02) and LRC (P=0.01). Relative risks (RR) for better OS (P=0.02), DFS (P=0.04) and LRC (P=0.01) were significantly associated with younger age (≤60 years). Higher brachytherapy (BT)-dose (>9Gy) improved DFS (P=0.04) and LRC (P=0.008). We concluded that UCS has high systemic failure rate. Local relapse was reduced by a relative risk factor of over three in all stages of diseases when using higher doses for EBRT and brachytherapy. Postoperative RT was most effective in UCS stage I/II-diseases.
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http://dx.doi.org/10.4081/rt.2016.6052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935818PMC
June 2016

Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer.

Balkan Med J 2014 Dec 13;31(4):286-94. Epub 2014 Sep 13.

Department of Radiation Oncology, Başkent University Adana Faculty of Medicine, Adana, Turkey.

Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC). Three-dimensional radiotherapy (3DCRT) has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT). IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques), treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.
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http://dx.doi.org/10.5152/balkanmedj.2014.14529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318398PMC
December 2014

Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

Tumori 2014 Mar-Apr;100(2):169-78

Aims And Background: To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure.

Methods And Study Design: Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset.

Results: Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively.

Conclusions: We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.
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http://dx.doi.org/10.1700/1491.16405DOI Listing
July 2014

Preoperative treatment planning with intraoperative optimization can achieve consistent high-quality implants in prostate brachytherapy.

Med Dosim 2012 3;37(4):387-90. Epub 2012 May 3.

Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Advances in brachytherapy treatment planning systems have allowed the opportunity for brachytherapy to be planned intraoperatively as well as preoperatively. The relative advantages and disadvantages of each approach have been the subject of extensive debate, and some contend that the intraoperative approach is vital to the delivery of optimal therapy. The purpose of this study was to determine whether high-quality permanent prostate implants can be achieved consistently using a preoperative planning approach that allows for, but does not necessitate, intraoperative optimization. To achieve this purpose, we reviewed the records of 100 men with intermediate-risk prostate cancer who had been prospectively treated with brachytherapy monotherapy between 2006 and 2009 at our institution. All patients were treated with iodine-125 stranded seeds; the planned target dose was 145 Gy. Only 8 patients required adjustments to the plan on the basis of intraoperative findings. Consistency and quality were assessed by calculating the correlation coefficient between the planned and implanted amounts of radioactivity and by examining the mean values of the dosimetric parameters obtained on preoperative and 30 days postoperative treatment planning. The amount of radioactivity implanted was essentially identical to that planned (mean planned radioactivity, 41.27 U vs. mean delivered radioactivity, 41.36 U; R(2) = 0.99). The mean planned and day 30 prostate V100 values were 99.9% and 98.6%, respectively. The mean planned and day 30 prostate D90 values were 186.3 and 185.1 Gy, respectively. Consistent, high-quality prostate brachytherapy treatment plans can be achieved using a preoperative planning approach, mostly without the need for intraoperative optimization. Good quality assurance measures during simulation, treatment planning, implantation, and postimplant evaluation are paramount for achieving a high level of quality and consistency.
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http://dx.doi.org/10.1016/j.meddos.2012.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935513PMC
April 2013

Postoperative radiotherapy in rectal cancer: long-term results of 290 patients.

Hepatogastroenterology 2010 Sep-Oct;57(102-103):1099-105

Ege University School of Medicine, Department of Radiation Oncology, Izmir, Turkey.

Background/aims: To evaluate treatment results and to identify prognostic factors affecting local-relapse-free (LRFS), disease-free (DFS) and overall survival (OS) in patients treated with postoperative radiotherapy (RT) for rectal cancer.

Methodology: A retrospective review was performed in 290 patients treated between January 1990 and December 2005. Median RT dose was 54 Gy. A total of 220 (75.8%) patients also received 5-fluorouracil based chemotherapy.

Results: During a median follow-up of 56 months (range 9-216 months), 68 patients (23.4%) developed local recurrence and 96 patients (33.1%) developed distant metastases. Five-year LRFS, DFS, and OS rates were 74.6%, 52.6%, and 53.7%, respectively. On multivariate analysis, significant prognostic factors for LRFS were age, pathologic T stage (pT), and distance from anal verge; for DFS were pT stage, and positive surgical margin; for OS were pT and pathologic N (pN) stages. One hundred and fifty-two node-positive patients whose number of retrieved and metastatic nodes are known were evaluated according to the lymph node ratio (LNR). OS and DFS rates significantly decreased with increasing LNR (p = 0.005, and p = 0.023 respectively). RT related Grade 3-4 late morbidity rate was 3.1%. A second primary malignancy developed in 4.8% of patients.

Conclusion: Among several prognostic factors, pT stage significantly predicted for LRFS, DFS and OS on multivariate analysis, while pN stage was significant for all three only on univariate analysis. LNR which affected DFS and OS could be an important tool for prognostic prediction for node-positive patients.
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April 2011

Postoperative radiotherapy in the management of resected non-small-cell lung carcinoma: 10 years' experience in a single institute.

Int J Radiat Oncol Biol Phys 2010 Feb 20;76(2):433-9. Epub 2009 Apr 20.

Department of Radiation Oncology, Celal Bayar University Medical School, Manisa, Turkey.

Purpose: This study reports the long term outcomes of postoperative radiotherapy in patients with resection for non-small-cell lung cancer (NSCLC).

Methods And Materials: A total of 98 patients with resected NSCLC who received postoperative radiotherapy (PORT) between January 1994 and December 2004 were retrospectively analyzed. The most frequently performed surgical procedure was lobectomy (59 patients), followed by pneumonectomy (25), wedge resection (8), and bilobectomy (6). Postoperative radiotherapy was delivered as an adjuvant treatment in 71 patients, after a wedge resection in 8 patients, and after an R1 resection in 19 patients. The PORT was administered using a Co-60 source in 86 patients and 6-MV photons in 12 patients. A Kaplan-Meier estimate of overall survival, locoregional control, and distant metastasis-free survival were calculated.

Results: Stages included I (n =13), II (n = 50), IIIA (n = 29), and IIIB (n = 6). After a median follow-up of 52 months median survival was 61 months. The 5-year overall survival, locoregional control, and distant metastasis-free survival rates for the whole group were 50%, 78%, and 55% respectively. The RT dose, Karnofsky performance status, age, lateralization of the tumor, and pneumonectomy were independent prognostic factors for OAS; anemia and the number of involved lymph nodes were independent prognostic factors for LC.

Conclusions: Doses of PORT of greater than 54 Gy were associated with higher death rate in patients with left-sided tumor, which may indicate a risk of radiation-induced cardiac mortality.
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http://dx.doi.org/10.1016/j.ijrobp.2009.02.010DOI Listing
February 2010

High dose rate endobronchial brachytherapy in the management of lung cancer: response and toxicity evaluation in 158 patients.

Lung Cancer 2008 Dec 14;62(3):326-33. Epub 2008 May 14.

Ege University, Faculty of Medicine, Department of Radiation Oncology, Izmir, Turkey.

The aim of this study was to evaluate the symptomatic and endoscopic responses as well as the toxicities in 158 patients with endobronchial lung cancer treated with high dose rate endobronchial brachytherapy (HDR-EB). Forty-three patients with stage III NSCLC were treated with 60Gy external beam radiotherapy (ERT) and three applications of 5Gy each of HDR-EB (group A). Seventy-four patients who did not receive previous RT were treated with 30Gy ERT and two applications of 7.5Gy HDR-EB with palliative intent (group B). Forty-one patients with recurrent tumor who were irradiated previously were treated with three applications of 7.5Gy HDR-EB, with palliative intent (group C). In group A, bronchoscopic complete (CR) and overall response rates (ORR) were 67% and 86%, respectively. Symptomatic improvement was obtained in 58% of patients with cough, 77% of patients with dyspnea and 100% of patients with hemoptysis. Two and 5-year survival rates were 25.5% and 9.5%, respectively and the median survival time (MST) was 11 months. In group B, the bronchoscopic CR and ORR were 39% and 77%, respectively and 28% and 72% in group C. The symptomatic response rates were 57% and 55% for cough, 90% and 78% for dyspnea and 94% and 77% for hemoptysis, with a MST of 7 and 6 months in Groups B and C, respectively. Eighteen patients (11%) died of fatal hemoptysis (FH) with the median time to this event of 7 months. Treatment intent (p<0.001), total BED (p<0.001) and the number of HDR-EB fractions (p<0.001) were significant prognostic factors for FH. HDR-EB provides effective palliation in relieving the symptoms of patients with endobronchial lung cancer, however, there is a risk of developing FH that is associated with a high BED and multiple HDR-EB applications.
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http://dx.doi.org/10.1016/j.lungcan.2008.03.018DOI Listing
December 2008

Evaluation of the weaning process in COPD patients with acute respiratory failure.

Tuberk Toraks 2008 ;56(1):64-73

Respiratory Intensive Care Unit, Süreyyapaşa Chest Diseases and Chest Surgery Teaching Hospital, Istanbul, Turkey.

Based on our observations in chronic obstructive pulmonary disease (COPD) patients admitted to our respiratory intensive care unit due to acute respiratory failure suggesting a significant variation in weaning duration (WD), we conducted a retrospective cohort study in such patients. Fifty-nine patients successfully extubated following invasive mechanical ventilation were included. Syncronized intermittent mandatory ventilation plus pressure support ventilation was used as the weaning mode in mostly. Study population was divided into two groups. Group 1: patients with a WD < or = 24 hours (n= 32), Group 2: patients with a WD > 24 hours (n= 27). Groups were compared with respect to demographics, vital signs, arterial blood gases, laboratory values, and the treatment characteristics. The average WD was 13 +/- 8 and 58 +/- 34 hours in group 1 and group 2, respectively (p< 0.001). In the logistic regression analysis, the following factors were found to have a predictive value for a WD > 24 hours: elevated baseline heart rate, alkaline pH at the day of weaning, duration of midazolam infusion, and emphysematous findings on chest X-ray. In conclusion, whether the WD in COPD patients is less or greater than 24 hours is not only determined by the medical treatment administered, but also by the patient and disease characteristics.
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April 2009

Mature results of neoadjuvant chemotherapy followed by radiotherapy in nasopharyngeal cancer: is it really old fashioned?

Med Oncol 2008 11;25(1):93-9. Epub 2007 Aug 11.

Faculty of Medicine, Department of Radiation Oncology, Ege University, Bornova, Izmir, 35100, Turkey.

Nasopharyngeal carcinoma (NPC) is known as a radiosensitive and chemosensitive tumor. The interest in neoadjuvant chemotherapy (NACT) has been refreshed in recent years due to promising results with more effective chemotherapeutic agents in head and neck tumors. The aim of this retrospective study is to evaluate the long-term toxicity and efficacy of NACT followed by radiotherapy (RT). From January 1995 to December 2002, 73 NPC patients were consecutively treated at Ege University Medical School Department of Radiation Oncology and the results were analyzed retrospectively. The NACT consisted of cisplatin 100 mg/m(2)/day and epirubicine 100 mg/m(2)/day, every 3 weeks. External radiotherapy by conventional fractionation was delivered 3 weeks after NACT. Response evaluated after NACT followed by radiotherapy showed 75% complete response (CR) rate. After a median follow-up time of 74 months, 32 relapses were noted. Most of the local failures were observed in 2 years (median 17 months) and the most common site for distant failure was bone. A total of 27 deaths had occurred due to uncontrolled disease. Xerostomia, soft tissue fibrosis and loss of sensorineural hearing were the most common long-term side effects. Only one treatment related death was observed and this patient died due to temporal lobe necrosis 22 months after the radiotherapy. The 5-year disease-free, distant metastasis-free and overall survival rates were 58, 77 and 68%, respectively. Current study showed that NACT with cisplatin and epirubicine followed by radiotherapy provided promising results with low toxicity in NPC patients.
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http://dx.doi.org/10.1007/s12032-007-0052-6DOI Listing
May 2008