Publications by authors named "Ozan Cem Guler"

49 Publications

Upfront metastasis‑directed therapy in oligorecurrent prostate cancer does not decrease the time from initiation of androgen deprivation therapy to castration resistance: in regard to Triggiani et al.

Med Oncol 2021 Jun 11;38(7):81. Epub 2021 Jun 11.

Department of Radiation Oncology, Adana Dr. Turgut Noyan Research and Treatment Centre, Baskent University Faculty of Medicine, 01120, Adana, Turkey.

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http://dx.doi.org/10.1007/s12032-021-01528-4DOI Listing
June 2021

Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy.

Acta Oncol 2021 May 17:1-7. Epub 2021 May 17.

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

Background: We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT).

Material And Methods: The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS).

Results: Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade ≥2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, =.004). However, no significant difference grade ≥2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; =.15). Acute grade ≥2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade ≥2 GI toxicity. Estimated 3-year late grade ≥3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis.

Conclusion: In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.
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http://dx.doi.org/10.1080/0284186X.2021.1926537DOI Listing
May 2021

In Regard to Hall et al.

Int J Radiat Oncol Biol Phys 2021 Jun;110(2):619-620

Department of Radiation Oncology, Başkent University Faculty of Medicine, Adana Dr Turgut Noyan Research and Treatment Center, Adana, Turkey.

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http://dx.doi.org/10.1016/j.ijrobp.2021.01.040DOI Listing
June 2021

Clinical parameters and nomograms for predicting lymph node metastasis detected with Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

Prostate 2021 Jul 5;81(10):648-656. Epub 2021 May 5.

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

Background: Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients.

Materials And Methods: The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves.

Results: A total of 288 lymph node metastases were identified in 121 patients (27.3%) using Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF.

Conclusion: The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.
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http://dx.doi.org/10.1002/pros.24142DOI Listing
July 2021

Stereotactic radiotherapy to oligoprogressive lesions detected with Ga-PSMA-PET/CT in castration-resistant prostate cancer patients.

Eur J Nucl Med Mol Imaging 2021 Mar 10. Epub 2021 Mar 10.

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

Purpose: We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using gallium prostate-specific membrane antigen-positron emission tomography (Ga-PSMA-PET/CT).

Methods: The clinical data of 67 CRPC patients with 133 lesions treated with Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed.

Results: With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. The PSA response was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. A total of 45 patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after metastasis-directed treatment (MDT). Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed.

Conclusion: This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.
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http://dx.doi.org/10.1007/s00259-021-05298-zDOI Listing
March 2021

Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT: TROD 09-004 Study.

Clin Nucl Med 2021 06;46(6):465-470

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

Purpose: To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients.

Methods: In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed.

Results: The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed.

Conclusions: We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000003558DOI Listing
June 2021

Concurrent versus sandwich treatment in adjuvant treatment in high risk operated gastric cancer: A single center experience.

J BUON 2020 Sep-Oct;25(5):2341-2349

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

Purpose: In this study we compared postoperative early vs sandwich chemoradiotherapy in operated stage IIA-IIIC gastric cancer patients in terms of effectiveness and outcome.

Methods: The data of 201 gastric cancer patients treated in the same center between December 2006 and June 2017 were retrospectively evaluated. One hundred forty nine patients who were eligible for the study criteria were divided into two groups according to the postoperative treatment modality. The first group included 85 patients who were given chemoradiotherapy simultaneously (ETG) and the second group icluded 64 patients who received sandwich (chemotherapy-chemoradiotherapy-chemotherapy) (STG) treatment. Overall survival (OS) and disease-free survival (DFS) were evaluated as primary endpoints.

Results: The median follow-up time for all patient groups was 26.7 months (1.3 -136.5 months). Adjuvant chemotherapy and radiotherapy were initiated concurrently in patients receiving concomitant therapy. Half of the planned chemotherapy, then chemoradiotherapy and then the remaining chemotherapy treatments were given to the sandwich treatment group. A total of 50.4 Gy radiotherapy was given to the concurrent chemoradiotherapy group and a total of 45 Gy radiotherapy to the group receiving the sandwich treatment.. OS was 30.6 months (23.7-37.5) in all groups, 30.4 months (23.7-35.0) in concurrent therapy (ETG) and 35.6 months (26.3-45) in sandwich therapy (STG) (p=0.73). DFS was 26.6 months (21.3-32.0) in all groups and 24.5 months (18.1-31.0) in the group receiving ETG, 32.5 months (22.2-42.8) in STG. (p=0.46). The most common grade 3 and above toxicities were; acute upper gastrointestinal toxicity (19.1% in ETG vs. 9.0% in STG, p=0.01) and hematological toxicity (31.8% in ETG vs. 13.9% in STG; p=0.002). Early cessation of treatment was similar in both groups. In multivariate analysis, female gender (p=0.01), stage III disease, grade III disease were seen as negative predictive factors for overall survival. In DFS multivariate analysis, there was no difference between the groups in terms of gender, T stage, N stage, and AJCC stage.

Conclusion: In this study, superiority of sandwich treatment over concurrent treatment was observed in patients with operated stage IIB-IIIC gastric cancer, but the difference was not statistically significant. If this study is performed in larger patient series, the difference of sandwich treatment may become meaningful.
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December 2020

The use of 18F-FDG positron emission tomography to detect mediastinal lymph nodes in metastatic breast cancer.

Breast 2020 Dec 26;54:197-202. Epub 2020 Oct 26.

Baskent University Faculty of Medicine, Adana Dr Turgut Noyan Research and Treatment Center, Department of Nuclear Medicine, Adana, Turkey.

Background: To assess the predictive value of F-fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) in detecting mediastinal lymph node metastasis with histopathologic verification in breast cancer (BC) patients.

Materials And Methods: Between February 2012 and October 2019, 37 BC patients who underwent histopathological verification for FDG-PET positive mediastinal lymph nodes were retrospectively analyzed. Nine patients (24%) were screened before beginning treatment, while 27 (76%) were screened at the time of disease progression, an average of 39 months after completion of initial treatment.

Results: The histopathologic diagnosis revealed lymph node metastasis from BC in 15 patients (40%) and benign disease in 22 patients (60%). The standardized uptake value (SUV) of mediastinal lymph nodes was significantly higher in patients with lymph node metastasis compared to those with benign histology (9.0 ± 3.5 vs. 5.9 ± 2.4; P = 0.007). The cut-off value of SUV after the ROC curve analysis for pathological lymph node metastasis was 6.4. Two of the 15 patients with mediastinal SUV ≤ 6.4 and 13 of the 22 patients with SUV > 6.4 had lymph node metastasis. Age and pathological findings were prognostic factors for overall survival in univariate analysis. The treatment decision was changed in 19 patients (51%) after mediastinoscopic evaluation of the entire cohort.

Conclusions: This is the first study to support the need for pathologic confirmation of a positive PET/CT result following evaluation of mediastinal lymph nodes for staging BC, either at initial diagnosis or at the time of progression. Treatment decisions were consequently altered for nearly half of the patients.
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http://dx.doi.org/10.1016/j.breast.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593617PMC
December 2020

Half-dose bevacizumab experience in relapsed ovarian cancer patients in Turkey due to formal regulations: similar effectiveness with lower rate of hypertension.

J BUON 2020 Jul-Aug;25(4):1928-1934

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

Purpose: Ovarian cancer is the fifth leading cause of cancer related death in women. Platin-based doublet regimens plus bevacizumab is standard treatment in relapse. Due to formal regulation of Turkish Ministry of Health, adjuvant bevacizumab has not been reimbursed and clinicians can use bevacizumab at a dose of 7.5 mg/kg/3wk in platin-resistant and sensitive relapse settings. The primary aim of this study was to evaluate 7.5 mg/kg/3wk bevacizumab dosing in platin-resistant and sensitive relapse ovarian cancer and compare these findings with the current literature.

Methods: A total of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included.

Results: At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients died. Progression-free survival (PFS) and overall survival (OS) were estimated at 18.8 months (14.4-23.3) vs 29.7 months (24.3-35.1) of the whole group overall survival. We observed that 78.4% of patients treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients with debulking surgery relapsed. A significant number of patients (81%) treated with primary surgery without neoadjuvant treatment and 59 (76.6 %) had secondary debulking surgery at relapse. In relapse, 38 patients were treated with single agent liposomal doxorubicin (LPD) plus bevacizumab. On the other hand, 68 patients were treated with carboplatin and LPD plus bevacizumab. Multivariate analysis failed to show any clinicopathological characteristics with significant effect on PFS. However, cytoreductive surgery at relapse showed significant effect on OS. Bevacizumab-related toxicities were detected in 23 (21.7%) patients; hypertension, pulmonary embolism, perforation, and other toxicities (nephrotic syndrome in 2, osteonecrosis in 2, cerebrovascular and cardiac ischemia in 3 patients) were seen in 12 (11.3%), 3 (2.8%), 1 (0.9%) and 7 (6.6%) patients, respectively.

Conclusions: In conclusion, our findings showed that 7.5 mg/kg/3week dosing of bevacizumab in relapsed ovarian cancer could have similar effectiveness compared to standard 15 mg/kg/3week dosing. Increase of OS and PFS in patients treated with primary and secondary debulking surgery with no-visible disease was more pronounced. No new safety information was observed but lower rate of grade 3 or above hypertension with similar rate of severe vascular and intestinal complications were detected.
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October 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

Role of vaginal brachytherapy boost following adjuvant external beam radiotherapy in cervical cancer: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-002).

Int J Gynecol Cancer 2021 Feb 30;31(2):185-193. Epub 2020 Sep 30.

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

Objective: There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer.

Methods: Patients treated with post-operative external beam radiotherapy ± chemotherapy ± vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy.

Results: A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors.

Conclusion: Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer.
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http://dx.doi.org/10.1136/ijgc-2020-001733DOI Listing
February 2021

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

Definitive concurrent chemoradiotherapy outcomes in Stage IIIB nonsmall cell lung cancer patients younger than 45 years: A retrospective analysis of 145 patients.

J Cancer Res Ther 2020 Jul-Sep;16(4):757-763

Department of Radiation Oncology, Baskent University Adana Treatment and Research Center, Adana, Turkey.

Purpose: To assess the survival outcomes and prognostic factors of young (≤45 years) Stage IIIB nonsmall cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT).

Materials And Methods: Medical records of 145 Stage IIIB NSCLC patients (≤45 years) who received 60-66 Gy thoracic radiotherapy and concurrent 1-3 cycles of cisplatin-based doublet chemotherapy were retrospectively evaluated. The primary endpoint was overall survival (OS), while locoregional progression-free survival (LRPFS), progression-free survival (PFS), and evaluation of potential prognostic factors constituted the secondary endpoints.

Results: At median 21.6 months (range: 7.3-62.5) of follow-up, the median and 4-year survival estimates were 24.8 months and 24.2% for OS, 15.7 months and 18.9%, for LRPFS and 12.0 months and 11.2% for PFS, respectively. On univariate analyses, among all factors, the smaller tumor size (≤7.0 cm; P = 0.03), lower T-stage (T1-T2; P = 0.02), lower N-stage (N2; P = 0.01), absence of anemia before C-CRT (hemoglobin [Hb] ≥12 g/dL; P < 0.001), and lower/no pretreatment weight loss (WL ≤5%; P < 0.001) were found to be associated significantly with longer median OS durations, which also retained their independent significance on multivariate analyses, except for tumor size category.

Conclusions: The encouraging median 24.8 months OS duration observed here in young NSCLC patients accords well with the results of recent landmark locally advanced NSCLC series without age stratification. Other than the well-established T and N stages, extra exhibit of superior OS in patients with initial Hb ≥12 g/dL and ≤5% WL levels suggests a noteworthy prognostic role for these two latter variables in the stratification of such patients.
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http://dx.doi.org/10.4103/jcrt.JCRT_1063_16DOI Listing
November 2020

Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients.

Radiother Oncol 2020 10 28;151:222-227. Epub 2020 Aug 28.

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

Purpose: To evaluate the distribution of metastatic lymph nodes (LN) detected on Ga-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naïve prostate cancer (PC) patients and to analyze the LN coverage rates of the pelvic fields defined in the GETUG trial and RTOG guidelines and a pelvic field extending superiorly from the L4/L5 interspace.

Materials And Methods: Ga-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retrospectively analyzed. The number and locations of Ga-PSMA-positive LNs were co-registered with one single-planning CT. The numbers, locations, and sizes of LNs located outside the three pelvic volumes were investigated for the entire cohort and for patients with LN metastasis in the pelvic area only.

Results: A total of 441 PSMA-PET-positive LN metastases were identified. The most frequent metastatic LNs were internal iliac LNs (25.2%). Para-aortic and presacral LNs outside the three pelvic fields were present in 20 (14.5%) and 22 patients (15.9%), respectively. The LN coverage rates according to the GETUG trial, the RTOG guidelines, and the pelvic field extending superiorly from L4/L5 were 44.2%, 52.2%, and 71, respectively, in the entire cohort and 51.7%, 61 and 83.1%, respectively, in patients with only pelvic LN metastasis. The number of metastatic LNs was a predictive factor for LNs located outside the three pelvic fields.

Conclusions: Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 increases the accuracy of pelvic field irradiation in approximately 20% of patients, highlighting the importance of proximal common iliac irradiation, particularly in patients with multiple LN metastasis.
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http://dx.doi.org/10.1016/j.radonc.2020.08.021DOI Listing
October 2020

Estimation of secondary cancer risk after radiotherapy in high-risk prostate cancer patients with pelvic irradiation.

J Appl Clin Med Phys 2020 Sep 16;21(9):82-89. Epub 2020 Jul 16.

Department of Radiation and Cellular Oncology, University of Chicago Medicine, Chicago, IL, USA.

We aimed to estimate the risk of secondary cancer after radiotherapy (RT) in high-risk prostate cancer (HRPC) patients with pelvic irradiation. Computed tomography data of five biopsy-proven HRPC patients were selected for this study. Two different planning target volumes (PTV and PTV ) were contoured for each patient. The PTV included the prostate, seminal vesicles, and pelvic lymphatics, while the PTV included only the prostate and seminal vesicles. The prescribed dose was 54 Gy for the PTV with a sequential boost (24 Gy for the PTV ). Intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT) techniques were used to generate treatment plans with 6 and 10 MV photon energies with the flattening filter (FF) or flattening filter-free (FFF) irradiation mode. The excess absolute risks (EARs) were calculated and compared for the bladder, rectum, pelvic bone, and soft tissue based on the linear-exponential, plateau, full mechanistic, and specific mechanistic sarcoma dose-response model. According to the models, all treatment plans resulted in similar risks of secondary bladder or rectal cancer and pelvic bone or soft tissue sarcoma except for the estimated risk of the bladder according to the full mechanistic model using IMRT technique compared with VMAT techniques with FFF options. The overall estimation of EAR indicated that the radiation-induced cancer risk due to RT in HRPC was lower for bladder than the rectum. EAR values ranged from 1.47 to 5.82 for bladder and 6.36 to 7.94 for rectum, depending on the dose-response models used. The absolute risks of the secondary pelvic bone and soft tissue sarcoma were small for the plans examined. We theoretically predicted the radiation-induced secondary cancer risk in HRPC patients with pelvic irradiation. Nevertheless, prospective clinical trials, with larger patient cohorts with a long-term follow-up, are needed to validate these model predictions.
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http://dx.doi.org/10.1002/acm2.12972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497909PMC
September 2020

Treatment outcomes of metastasis-directed treatment using Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

Strahlenther Onkol 2020 Nov 2;196(11):1034-1043. Epub 2020 Jul 2.

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

Purpose: The aim of this study was to evaluate the outcomes of Ga prostate-specific membrane antigen (Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC).

Methods: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation.

Results: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2‑year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2‑year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT.

Conclusion: Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.
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http://dx.doi.org/10.1007/s00066-020-01660-6DOI Listing
November 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

Stereotactic radiotherapy in patients with oligometastatic or oligoprogressive gynecological malignancies: a multi-institutional analysis.

Int J Gynecol Cancer 2020 06 8;30(6):865-872. Epub 2020 Apr 8.

Department of Radiation Oncology, Hacettepe Universitesi Tip Fakultesi, Ankara, Turkey.

Introduction: Data supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer.

Methods: The clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival.

Results: A total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9-95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0-16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities.

Conclusions: Patients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival.
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http://dx.doi.org/10.1136/ijgc-2019-001115DOI Listing
June 2020

Incidental testicular doses during volumetric-modulated arc radiotherapy in prostate cancer patients.

Radiol Med 2020 Aug 3;125(8):777-783. Epub 2020 Mar 3.

Adana Dr. Turgut Noyan Research and Treatment Center, Department of Radiation Oncology, Baskent University Faculty of Medicine, 01120, Adana, Turkey.

Purpose: To compare the incidental testicular doses during volumetric-modulated arc therapy (VMAT) in patients receiving prostate-only and pelvic lymphatic irradiation.

Materials And Methods: Testicular doses in 40 intermediate- and high-risk prostate cancer patients were determined on treatment planning system (TPS) using the VMAT technique at 6 MV. Scattered testicular doses were also measured by MOSFET detectors placed on testis surface. The testicular doses of patients treated with prostate-only and pelvic field irradiation were compared.

Results: The median testicular doses measured per 200 cGy fraction by TPS and MOSFET detectors were 1.7 cGy (0.7-4.1 cGy) and 4.8 cGy (3.6-8.8 cGy), respectively. The TPS doses and MOSFET readings showed a significant strong correlation (Pearson r = 0.848, p < 0.001). The testicular doses measured by TPS (1.34 ± 0.36 cGy vs. 2.60 ± 0.95 cGy; p < 0.001) and MOSFET (4.52 ± 0.64 cGy vs. 6.56 ± 1.23 cGy; p < 0.001) were significantly lower in patients with prostate-only irradiation than in those with pelvic field irradiation. The mean cumulative scattered dose for prostate-only field delivering 78 Gy was 1.8 Gy and that for pelvic field irradiation was 2.6 Gy, consistent with the reported findings.

Conclusions: The patients with prostate-only irradiation received lower testicular doses than those with additional pelvic field irradiation possibly due to the increased scattered doses in large field irradiation using the VMAT technique. The clinical response to increased incidental testicular doses due to pelvic field irradiation remains unknown, and it warrants further investigation.
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http://dx.doi.org/10.1007/s11547-020-01158-2DOI Listing
August 2020

Is there any benefit of paraaortic field irradiation in pelvic lymph node positive endometrial cancer patients? A propensity match analysis.

J Obstet Gynaecol 2020 Oct 3;40(7):1012-1019. Epub 2019 Dec 3.

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

We evaluated the survival outcomes and recurrence patterns of endometrial cancer (EC) patients with pelvic lymph node metastases who received postoperative radiotherapy (RT) to the pelvis (P-RT) or to the pelvis plus paraaortic lymph nodes (PA-RT) with or without systemic chemotherapy (ChT). The data from 167 patients with stage IIIC1 EC treated with postoperative RT or RT and ChT were collected retrospectively. Those patients with pelvic lymph node metastases were treated with either P-RT (106 patients, 63%) or PA-RT (61 patients, 37%). The median follow-up time for the entire cohort was 49 (range = 5-199) months. The patients receiving adjuvant ChT and RT had significantly higher 5-year OS rates (77% vs. 33%,  < .001) and 5-year PFS rates (71% vs. 30%,  < .001) when compared to those receiving adjuvant RT alone. The patients receiving P-RT and ChT had significantly higher 5-year OS rates and 5-year PFS rates when compared to those treated with adjuvant PA-RT in the entire cohort and matched cohort. Adjuvant ChT together with RT is the strongest predictor of the OS and PFS. Prophylactic PA-RT is unnecessary, even if ChT is used together with P-RT in EC patients with pelvic lymph node metastasis.Impact statement Local and distant recurrence risks are relatively higher in patients with stage IIIC disease, postoperative adjuvant treatment is required to reduce the recurrence risk. Adjuvant RT is a common approach for patients with locally advanced EC. Optimal target volume for RT in patients with stage IIIC EC remains controversial. We demonstrated that extended field RT is unnecessary, even if ChT is used together with pelvic RT in stage IIIC EC patients. We demonstrated that adjuvant ChT together with RT is the strongest predictor of the OS and PFS for EC patients with pelvic lymph node metastases. Extended field RT is unnecessary, even if ChT is used together with pelvic RT in EC patients with pelvic lymph node metastases. Although adjuvant treatment modalities are associated with improvements in survival, distant metastasis still remains the most common site of recurrence in advanced EC patients. Thus, further research is warranted to identify improved combined modality strategies to optimise the outcomes for EC patients with pelvic lymph node metastasis.
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http://dx.doi.org/10.1080/01443615.2019.1679742DOI Listing
October 2020

The effect of androgen deprivation therapy on Ga-PSMA tracer uptake in non-metastatic prostate cancer patients.

Eur J Nucl Med Mol Imaging 2020 03 15;47(3):632-641. Epub 2019 Nov 15.

Adana Dr. Turgut Noyan Research and Treatment Center, Department of Nuclear Medicine, Başkent University Faculty of Medicine, Adana, Turkey.

Purpose: To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate-specific membrane antigen (PSMA) tracer uptake demonstrated in Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer (PC) patients.

Materials And Methods: The clinical data of 108 PC patients who received neoadjuvant ADT were retrospectively analyzed. All patients had a baseline Ga-PSMA-PET/CT scan, and a second scan was delivered median of 2.9 months after the initiation of ADT. The maximum standardized uptake value (SUV) of primary tumor (SUV) and metastatic lymph nodes (SUV) as well as PSA response were assessed between pre- and post-ADT Ga-PSMA-PET/CT scans.

Results: There were significant decreases in posttreatment serum PSA, SUV, and SUV. A decrease in SUV was seen in 91 patients (84%) with a median value of 66% (range, 5-100%), while 17 patients (16%) had no change in or an increase in PSMA tracer uptake with a median value of 24% (range, 0-198%). Patients with Gleason score (GS) of 7 had significantly higher metabolic response rates compared to other patients. The disease progression was significantly higher only in patients with GS > 7 disease compared to GS 7 disease. The PSA response to ADT was the lowest in patients with ISUP high-grade tumors. A total of 16 patients (15%) had progressive disease, and in 9 patients (8%), radiotherapy decisions were modified according to posttreatment Ga-PSMA-PET/CT scans.

Conclusions: The current study includes the largest number of patients analyzed to date and demonstrates that ADT causes a significant decrease in serum PSA values and SUV and SUV. The authors demonstrate that Ga-PSMA-PET/CT may be used as a quantitative imaging modality after neoadjuvant ADT in hormone-naïve non-metastatic PC patients.
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http://dx.doi.org/10.1007/s00259-019-04581-4DOI Listing
March 2020

Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients.

Clin Nucl Med 2019 Sep;44(9):e510-e516

Departments of Radiation Oncology.

To assess the role of Gallium-labeled-prostate-specific membrane antigen PET/CT (Ga-PSMA-PET/CT) in risk group definition and radiotherapy planning in the initially planned definitive radiotherapy (RT) for prostate cancer patients.

Methods: The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes.

Results: After staging with Ga-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-PSMA-PET/CT.

Conclusions: We found that Ga-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.
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http://dx.doi.org/10.1097/RLU.0000000000002691DOI Listing
September 2019

Radiotherapy After Skin-Sparing Mastectomy and Implant-Based Breast Reconstruction.

Clin Breast Cancer 2019 10 11;19(5):e611-e616. Epub 2019 Apr 11.

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

Introduction: We evaluated the cosmetic results of radiotherapy (RT) after implant-based reconstruction (IBR).

Patients And Methods: We retrospectively evaluated 170 patients with 171 breast cancers treated between December 2004 and January 2016 in 2 university hospitals. RT fields were reconstructed breast (RB) only in 24 (14%), and RB and regional lymphatics in 147 (86%) breasts, respectively. All but 1 patient received a total 50 Gy with conventional fractionation. All patients received systemic chemotherapy. One hundred thirty-eight (81%) patients received hormonal therapy; 118 tamoxifen and 20 aromatase inhibitor.

Results: Median follow-up time was 46.8 months (range, 1-163 months). The 5-year disease-free and overall survival rate was 83% and 93%, respectively. Cosmetic results were considered excellent in 111 (65%), fair in 46 (27%), and bad in 14 (8%) RB by patients. Thirty-four (20%) RB had restorative surgery; because of surgeons' preference because of implant natural life time span in 5, and contracture, fibrosis, deformation, or dislocation of the implant, or cellulitis in the remaining. Statistically significant adverse factors in univariate analysis for impaired cosmetic outcome were bolus use on the RB, lymphatic irradiation, and volume that received at least 110% of the prescribed dose being > 1%. The use of bolus material was the only prognostic factor for deterioration of the cosmetic result in multivariate analysis.

Conclusion: RT after IBR yields acceptable cosmetic results. Although only 111 (65%) of RBs were considered to have excellent cosmetic results, only a small percentage of patients needed reoperation because of bad cosmetic outcome.
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http://dx.doi.org/10.1016/j.clbc.2019.04.002DOI Listing
October 2019

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

Strahlenther Onkol 2019 Oct 29;195(10):882-893. Epub 2019 May 29.

Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, 06100, Ankara, Turkey.

Purpose: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era.

Methods: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT.

Results: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5‑year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10.

Conclusions: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.
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http://dx.doi.org/10.1007/s00066-019-01476-zDOI Listing
October 2019

The prognostic value of haematologic parameter changes during treatment in cervical cancer patients treated with definitive chemoradiotherapy.

J Obstet Gynaecol 2019 Jul 25;39(5):695-701. Epub 2019 Apr 25.

a Department of Radiation Oncology , Baskent University Faculty of Medicine , Adana , Turkey.

We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. IMPACT STATEMENT What is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group. What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.
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http://dx.doi.org/10.1080/01443615.2019.1586852DOI Listing
July 2019

The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Future Oncol 2019 May 12;15(13):1469-1479. Epub 2019 Apr 12.

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

Currently, there are no predictive markers of response to abiraterone. We calculated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks in 102 metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone either pre- or postchemotherapy. With a median follow-up was 24.0 months (range: 0.3-54.9), median overall survival (OS) was 20.8 months. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. NLR and prostate-specific antigen response to abiraterone was a significant predictor of OS and progression-free survival (PFS) in metastatic castration-resistant prostate cancer patients treated with abiraterone delivered either pre- or postchemotherapy.
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http://dx.doi.org/10.2217/fon-2018-0635DOI Listing
May 2019

Retrospective comparison of standard and escalated doses of radiotherapy in newly diagnosed glioblastoma patients treated with concurrent and adjuvant temozolomide.

Indian J Cancer 2019 Jan-Mar;56(1):59-64

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

Background: To compare the efficacies of standard dose-(SDRT) and escalated dose radiotherapy (EDRT) in newly diagnosed glioblastoma (GBM) with concurrent and adjuvant temozolomide (TMZ).

Materials And Methods: Outcomes of 126 newly diagnosed GBM patients who received SDRT (60 Gy, 30 fractions) or EDRT (70 Gy, 30 fractions) with concurrent plus adjuvant TMZ were retrospectively analyzed. Both groups received concurrent TMZ (75 mg/m) during the course of RT and at least one course of adjuvant TMZ (150-200 mg/m), thereafter. Overall survival (OS) and local progression free survival (LPFS) constituted the primary and secondary endpoints, respectively.

Results: At median 14.2 months follow-up, 26 (20.6%) patients were alive. Median LPFS and OS were 9.2 [95% confidence interval (CI); 8.4-10.0] and 15.4 months (95% CI; 12.1-18.8), respectively, for the entire cohort. Although the median OS was numerically superior in the EDRT this difference could not reach statistical significance (22.0 vs. 14.9 months; P = 0.45), Likewise, LPFS was also (9.9 vs. 8.9 months; P = 0.89) not different between the two treatment groups. In multivariate analysis, better recursive partitioning analysis class (3-4 vs. 5; P = 0.044) and extensive surgery (gross total resection vs. subtotal resection/biopsy only; P= 0.021) were identified to associate significantly with superior OS times, irrespective of the RT protocol.

Conclusions: Although the current median OS of 22 months of the EDRT group is promising, no statistically significant survival advantage for EDRT was observed even in the presence of TMZ. Randomized studies with larger population sizes and available genetic markers are warranted to conclude more reliably on the fate of EDRT plus TMZ.
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http://dx.doi.org/10.4103/ijc.IJC_128_18DOI Listing
August 2019

A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma.

J Gynecol Oncol 2019 May;30(3):e28

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

Objective: To analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC).

Methods: Data from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed.

Results: The 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5-167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS.

Conclusion: Postoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.
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http://dx.doi.org/10.3802/jgo.2019.30.e28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424855PMC
May 2019

Local control and vertebral compression fractures following stereotactic body radiotherapy for spine metastases.

J Bone Oncol 2019 Apr 24;15:100218. Epub 2019 Jan 24.

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

Purpose: We aimed to retrospectively assess the incidence of vertebral compression fractures (VCF), examine clinicopathologic factors potentially associated with VCF, and evaluate treatment response in patients who received stereotactic body radiotherapy (SBRT) for spine metastases (spMets).

Methods And Materials: We identified 78 patients with 125 spMets at baseline and subsequent assessments. Patients received SBRT doses of 16 or 18 Gy. Patients with pre-existing VCF and co-existing local progression were excluded. Spine instability neoplastic score (SINS) was used for spMets categorization. Response to SBRT and VCF were assessed according to the Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) and Genant scores, respectively. Kaplan-Meier analyses were used to assess local control of disease and vertebral compression fracture-free survival (FFS).

Results: We treated 103 cases with single spMets and 11 cases involving double spMets with SBRT. Progressive disease was reported in 3.2% and 8.2% of the cases in the first and last PET/CT reports, respectively. The distribution of treatment response in the remaining patients was: complete response in 30.6% of patients, partial response in 47.1% of patients, and stable disease in 22.3% of patients in the first PET/CT; complete response in 62.3% of patients, partial response in 16.7% of patients, and stable disease in 21% of patients at the last monitoring. Local failures were observed in 15 (12%) of cases. Median SINS was 5 (range: 1-13); majority of patients in our cohort (70.4%) were categorized as stable according to SINS, five (4%) patients had Grade 3 VCF at a median time of 16 months after SBRT (range: 2-22 months), and 60% of VCF occurred after an interval of at least 12 months after SBRT. No bisphosphonate usage was significantly associated with VCF ( = -0.204;  = 0.022). Median FFS was 21 months. Univariate analyses indicated that female gender ( < 0.001), bisphosphonate use ( = 0.005), >6 months of bisphosphonates use ( = 0.002), and the lowest vertebral body collapse score ( = 0.023) were associated with higher FFS. Female gender ( = 0.007), >6 months of bisphosphonates usage ( = 0.018), and the lowest vertebral body collapse score ( = 0.044) retained independent significance.

Conclusions: This study demonstrated that spine SBRT with doses of 16-18 Gy promises good local control of disease with acceptable VCF rates. Lowest vertebral body collapse score, female gender, and >6 months of bisphosphonate use were significantly associated with longer FFS.
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http://dx.doi.org/10.1016/j.jbo.2019.100218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378905PMC
April 2019

Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Strahlenther Onkol 2019 Oct 30;195(10):872-881. Epub 2019 Jan 30.

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

Purpose: To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone.

Materials And Methods: The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed.

Resultsn: Median follow-up time was 14.2 months (range: 2.3-54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

Conclusions: Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.
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http://dx.doi.org/10.1007/s00066-019-01429-6DOI Listing
October 2019