Publications by authors named "Ugur Selek"

85 Publications

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Preliminary Simulation Study of Carotid Artery and Pharyngeal Constrictor Muscle Sparing-Radiotherapy in Glottic Carcinoma.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820956989

Department of Radiation Oncology, 175695Baskent University Medical Faculty, Adana, Turkey.

Background: This preliminary simulation study aimed to compare the dosimetric outcomes of carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) in patients with T1N0M0 glottic carcinoma undergoing helical tomotherapy-intensity modulated radiotherapy (HT-IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) plans.

Methods: In addition to the clinical target volume (CTV) which was defined as the entire larynx, the CAs and PCM of 11 glottic carcinoma patients were delineated. The CTV was uniformly expanded 5 mm to create a planning target volume (PTV) relative to the PCM and at a distance of 2 mm from the CA. The dosimetric characteristics in HT-IMRT and lateral opposed fields-based 3D-CRT plans were analyzed.

Results: Median Dand V of PTV were significantly higher in HT-IMRT (p < 0.001) compared to 3D-CRT. The right/left CA dosimetric outcomes, including the mean doses (20.7/21.5 Gy versus 48.7/50.5 Gy), D (53.6/52.0 Gy versus 67.4/67.7 Gy), V (25.0/27.1% versus 77.6/80.3%), V (8.0/7.9% versus 74.6/71.9%), and V (2.0/1.2% versus 70.0/71.6%) were also significantly lower in HT-IMRT (p < 0.05), similar to the mean PCM doses (49.6 Gy versus 62.6 Gy for 3D-CRT;p < 0.001), respectively.

Conclusions: Our present results demonstrated the feasibility of simultaneous sparing of the CAs and PCM in HT-IMRT- compared to 3D-CRT plans in glottic carcinoma patients undergoing definitive radiotherapy.
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http://dx.doi.org/10.1177/1533033820956989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549151PMC
October 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

Clin Respir J 2020 Nov 17;14(11):1050-1059. Epub 2020 Aug 17.

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

Objective: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey.

Materials And Methods: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/β ratio of 10 (BED ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity.

Results: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]).

Conclusion: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.
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http://dx.doi.org/10.1111/crj.13240DOI Listing
November 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Low Prognostic Nutritional Index Predicts Poor Clinical Outcomes in Patients with Stage IIIB Non-small-cell Lung Carcinoma Undergoing Chemoradiotherapy.

Cancer Manag Res 2020 16;12:1959-1967. Epub 2020 Mar 16.

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

Purpose: To investigate the prognostic utility of the prognostic nutritional index (PNI) in stage IIIB non-small-cell lung carcinoma (NSCLC) patients undergoing concurrent chemoradiotherapy (CRT).

Methods: A total of 358 stage IIIB NSCLC patients who received a total dose of 60-66 Gy (2 Gy/fraction) radiotherapy and ≥1 cycle(s) of platinum-based chemotherapy were analyzed. The receiver operating curve analysis was utilized to identify the optimal PNI cut-off value demonstrating a significant connection with the overall survival (OS), locoregional progression-free survival (LRPFS), and progression-free survival (PFS).

Results: At a median follow-up time of 22.5 months (range: 2.4-123.5), 30.2% and 14% of the patients were still alive and free of disease progression, respectively.The median OS, LRPFS, and PFS were 25.2 [95% confidence interval (CI): 36.3-46.6 months], 15.4 (95% CI: 26.6-35.3 months), and 10.7 (95% CI: 36.8-69.9 months), individually, for the whole study accomplice. The ROC analysis revealed an optimum rounded cut-off that associated meaningfully with each of the OS [area under the curve (AUC): 84.1%; sensitivity: 75.9%;72.4% specificity], LRPFS (AUC: 92.4%; sensitivity: 87.9%; 85.1% specificity), and PFS (AUC: 80.1%; sensitivity: 73.7%; 71.6% specificity) at a value of 40.5. Comparative analyses revealed that the patients presenting with PNI≤40.5 had significantly inferior OS (16.8 vs 36.7; P<0.001), LRPFS (11.5 vs 19.5; P<0.001), and PFS (8.6 vs 13.6; P<0.001) outcomes compared to patients with PNI>40.5. In univariate analyses, lower T-stage (1-2 vs 3-4; P< 0.001), lower N-stage (N2 vs N3; P< 0.001), anemia status (absent vs present; P< 0.001), weight loss status (<5% vs ≥5%; P< 0.001), and PNI group (≤40.5 vs >40.5; P<0.001) were the factors found to be associated with OS, LRPFS and PFS results. The results of multivariate analysis exhibited that the PNI was independently associated with each of the OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001) outcomes.

Conclusion: The pretreatment PNI appears to be a robust novel prognostic factor that stratifies patients with stage IIIB NSCLC into two significantly distinct survival groups after CRT.
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http://dx.doi.org/10.2147/CMAR.S248034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083637PMC
March 2020

Pretreatment Photopenia on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Scans Predicts Poor Prognosis in Nasopharyngeal Cancer Patients Undergoing Concurrent Chemoradiotherapy.

Clin Exp Otorhinolaryngol 2020 Nov 21;13(4):407-414. Epub 2020 Feb 21.

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

Objectives: To investigate the influence of pretreatment primary tumor or nodal photopenia (PP) on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT), an indicator of tumor ischemia, on survival results of nasopharyngeal cancers (NPCs) treated with concurrent chemoradiotherapy (C-CRT).

Methods: The pre-C-CRT FDG PET-CT scans of 104 patients with NPC (cT1-4 N0-3 M0) were retrospectively examined to determine the presence of PP (PP+). Our primary endpoint was the influence of PP+ on overall survival (OS), while the progression-free survival (PFS) and locoregional PFS (LRPFS) constituted the secondary endpoints.

Results: The PP+ was detected in 29 (27.9%): nine (8.7%), seven (6.7%), and 13 (12.5%) in the primary tumor alone, primary tumor plus neck nodes, and neck nodes alone, respectively. Because the PP+ cases were small by count per location, all comparative analyses were performed according to overall PP+/ PP- status instead of per detected site. At a median follow-up of 67.8 months (range, 9 to 130 months), the median survival times were not reached (NR) for the entire population, while 5-year OS, LRPFS, and PFS rates were 73.3%, 68.2%, and 63.4%, respectively. Comparatively the PP+ patients exhibited significantly poorer median OS (49.8 months vs. NR, P<0.001), LRPFS (40.7 months vs. NR, P=0.001), and PFS (31.8 months vs. NR, P=0.002) durations than their PP- counterparts. Furthermore, the PP+ retained its independent prognostic significance in multivariate analysis (P<0.001).

Conclusion: Present results uncovered the pre-C-CRT PP as an independent predictor of poor prognosis for NPC patients, which underscore the requirement for the fortification of the local and systemic treatments in hypoxic NPCs.
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http://dx.doi.org/10.21053/ceo.2019.01298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669310PMC
November 2020

Prognostic Usefulness Of Advanced Lung Cancer Inflammation Index In Locally-Advanced Pancreatic Carcinoma Patients Treated With Radical Chemoradiotherapy.

Cancer Manag Res 2019 7;11:8807-8815. Epub 2019 Oct 7.

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

Background/aims: Previously advanced lung cancer inflammation index (ALI) has been demonstrated to have prognostic utility in the stratification of patients into distinctive survival groups, but the prognostic value of ALI has never been explored in the setting of locally advanced pancreatic carcinomas (LAPC) treated with concurrent chemoradiotherapy (CCRT). Hence, we aimed to investigate the prognostic value of pre-treatment ALI in LAPC patients who underwent radical CCRT.

Methods: Present retrospective cohort analysis incorporated 141 LAPC patients who received radical CCRT. Accessibility of baseline ALI cutoff(s) impacting survival outcomes was sought by receiver operating characteristic (ROC) curve analysis. Interaction between the ALI and overall- (OS) and progression-free survival (PFS) comprised our primary and secondary endpoints, respectively.

Results: At a median follow-up of 14.4 months (range: 3.2-74.2), the median PFS and OS were 7.5 (%95 CI: 5.9-9.1) and 14.6 months (%95 CI: 11.6-17.6), respectively. ROC curve analyses set the ideal ALI cutoff value at 25.3 (AUC: 75.6%; sensitivity: 72.7%; specificity: 70.3%) that exhibited significant associations with both the OS and PFS results. Patient stratification into two groups per ALI [≤25.3 (N=75) versus>25.3 (N=66)] showed that the ALI>25.3 group had significantly superior median OS (25.8 versus 11.4 months; P<0.001) and PFS (15.9 versus 6.0 months; P<0.001) durations than its ALI≤25.3 counterpart. Other factors exhibiting significantly better OS and PFS rates were N stage (versus N1; P<0.05 for each endpoint) and CA 19-9 ≤90 U/mL (versus >90 U/mL; P<0.05 for each endpoint), respectively. These three factors were additionally asserted to be independent indicators of longer OS (P<0.05 for each) and PFS (P<0.05 for each) in multivariate analyses.

Conclusion: Results of this hypothesis-generating research proposed the pre-CCRT ALI as a novel robust associate of OS and PFS outcomes for LAPC patients undergoing CCRT.
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http://dx.doi.org/10.2147/CMAR.S222297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789411PMC
October 2019

Significance of overall concurrent chemoradiotherapy duration on survival outcomes of stage IIIB/C non-small-cell lung carcinoma patients: Analysis of 956 patients.

PLoS One 2019 22;14(7):e0218627. Epub 2019 Jul 22.

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

Background: To investigate the detrimental effects of prolonged overall radiotherapy duration (ORTD) on survival outcomes of stage IIIB/C NSCLC patients treated with concurrent chemoradiotherapy (C-CRT).

Methods: The study cohort consisted of 956 patients who underwent C-CRT for stage IIIB/C NSCLC. Primary endpoint was the association between the ORTD and overall survival (OS) with locoregional progression-free survival (LRPFS) and PFS comprising the secondary endpoints. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of the cut-off that interacts with survival outcomes. Multivariate Cox model was utilized to identify the independent associates of survival outcomes.

Results: The ROC curve analysis exhibited significance at 49 days of ORTD cut-off that dichotomized patients into ORTD<50 versus ORTD≥50 days groups for OS [area under the curve (AUC): 82.8%; sensitivity: 81.1%; specificity: 74.8%], LRPFS (AUC: 91.9%; sensitivity: 90.6%; specificity: 76.3%), and PFS (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%), respectively. Accordingly, ORTD≥50 days group had significantly shorter median OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001); and 10-year actuarial locoregional control (P<0.001) and distant metastases-free (P<0.011) rates than the ORTD<50 days group. The ORTD retained its significant association with survival outcomes at multivariate analyses independent of the other favorable covariates (p<0.001, for OS, LRPFS, and PFS): Stage IIIB disease (versus IIIC), lymph node bulk <2 cm (versus ≥2 cm), and 2-3 chemotherapy cycles (versus 1). The higher sensitivity for LRPFS (90.6%) than PFS (72.4%) on ROC curve analysis suggested the prolonged ORTD-induced decrements in locoregional control rates as the major cause of the poor survival outcomes.

Conclusions: Longer ORTD beyond ≥50 days was associated with significantly poorer OS, LRPFS and PFS outcomes, where reduced locoregional control rates appeared to be the main causative.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218627PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645460PMC
February 2020

Baseline Low Prognostic Nutritional Index Predicts Poor Survival in Locally Advanced Nasopharyngeal Carcinomas Treated With Radical Concurrent Chemoradiotherapy.

Ear Nose Throat J 2021 Feb 10;100(2):NP69-NP76. Epub 2019 Jun 10.

Department of Radiation Oncology, 52979Koc University, School of Medicine, Istanbul, Turkey.

Background: To retrospectively assess the impact of prognostic nutritional index (PNI) on survival outcomes of patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with concurrent chemoradiotherapy (CCRT).

Methods: This study incorporated 154 patients with LA-NPC who received exclusive cisplatinum-based CCRT. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of pretreatment PNI cutoffs influencing survival results. The primary end point was the interaction between the overall survival (OS) and PNI values, while cancer-specific survival (CSS) locoregional progression-free survival (LR-PFS), distant metastasis-free survival (DMFS), and PFS were the secondary end points.

Results: A rounded PNI cutoff value of 51 was identified in ROC curve analyses to exhibit significant link with CSS, OS, DMFS, and PFS outcomes, but not LR-PFS. Patients grouping per PNI value (≥51 [N = 95] vs <51 [N = 49]) revealed that PNI < 51 group had significantly shorter median CSS ( < .001), OS ( < .001), DMFS ( < .001), and PFS ( < .001) times than the PNI ≥ 51 group, and the multivariate results confirmed the PNI < 51 as an independent predictor of poor outcomes for each end point ( < .05 for each). The unfavorable impact of the low PNI was also continued at 10-year time point with survival rates of 77.9% versus 42.4%, 73.6% versus 33.9%, 57.9% versus 27.1%, and 52.6% versus 23.7% for CSS, OS, DMFS, and PFS, respectively. Additionally, we found that PNI < 51 was significantly associated with higher rates of weight loss >5% over past 6 months (49.2% versus 11.6%; = .002) compared to PNI < 51 group.

Conclusion: Low pre-CCRT PNI levels were independently associated with significantly reduced CSS, OS, DMFS, and PFS outcomes in patients with LA-NPC treated with definitive CCRT.
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http://dx.doi.org/10.1177/0145561319856327DOI Listing
February 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

Baseline hemoglobin <11.0 g/dL has stronger prognostic value than anemia status in nasopharynx cancers treated with chemoradiotherapy.

Int J Biol Markers 2019 Jun 13;34(2):139-147. Epub 2019 Mar 13.

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

Background: To retrospectively investigate the influence of pretreatment anemia and hemoglobin levels on the survival of nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy (C-CRT).

Methods: A total of 149 nasopharyngeal carcinoma patients who received C-CRT were included. All patients had received 70 Gy to the primary tumor plus the involved lymph nodes, and 59.4 Gy and 54 Gy to the intermediate- and low-risk neck regions concurrent with 1-3 cycles of cisplatin. Patients were dichotomized into non-anemic and anemic (hemoglobin <12 g/dL (women) or <13 g/dL (men)) groups according to their pre-treatment hemoglobin measures. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of a pre-treatment hemoglobin cut-off that impacts outcomes. Potential interactions between baseline anemia status and hemoglobin measures and overall survival, locoregional progression-free survival (LRPFS), and progression-free survival were assessed.

Results: Anemia was evident in 36 patients (24.1%), which was related to significantly shorter overall survival (=0.007), LRPFS (<0.021), and progression-free survival (=0.003) times; all three endpoints retained significance in multivariate analyses (<0.05, for each). A baseline hemoglobin value of 11.0 g/dL exhibited significant association with outcomes in ROC curve analysis: hemoglobin <11.0 g/dL (N=26) was linked with shorter median overall survival (<0.001), LRPFS (=0.004), and progression-free survival (<0.001) times, which also retained significance for all three endpoints in multivariate analyses and suggested a stronger prognostic worth for the hemoglobin <11.0 g/dL cut-off value than the anemia status.

Conclusion: Pre-C-CRT hemoglobin <11.0 g/dL has a stronger prognostic worth than the anemia status with regard to LRPFS, progression-free survival, and overall survival for nasopharyngeal carcinoma patients.
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http://dx.doi.org/10.1177/1724600818821688DOI Listing
June 2019

Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment.

Front Immunol 2019 15;10:193. Epub 2019 Feb 15.

Departments of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.

In recent decades, there has been substantial growth in our understanding of the immune system and its role in tumor growth and overall survival. A central finding has been the cross-talk between tumor cells and the surrounding environment or stroma. This tumor stroma, comprised of various cells, and extracellular matrix (ECM), has been shown to aid in suppressing host immune responses against tumor cells. Through immunosuppressive cytokine secretion, metabolic alterations, and other mechanisms, the tumor stroma provides a complex network of safeguards for tumor proliferation. With recent advances in more effective, localized treatment, radiation therapy (XRT) has allowed for strategies that can effectively alter and ablate tumor stromal tissue. This includes promoting immunogenic cell death through tumor antigen release to increasing immune cell trafficking, XRT has a unique advantage against the tumoral immune evasion mechanisms that are orchestrated by stromal cells. Current studies are underway to elucidate pathways within the tumor stroma as potential targets for immunotherapy and chemoradiation. This review summarizes the effects of tumor stroma in tumor immune evasion, explains how XRT may help overcome these effects, with potential combinatorial approaches for future treatment modalities.
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http://dx.doi.org/10.3389/fimmu.2019.00193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384252PMC
January 2020

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

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

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

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

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials.

Int J Radiat Oncol Biol Phys 2018 08 27;101(5):1141-1148. Epub 2018 Apr 27.

Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: The safety of combined immunotherapy and thoracic radiation therapy (iRT) has been understudied. We evaluated toxicities in patients receiving iRT from 3 single-institutional phase 1/2 trials.

Methods And Materials: Clinical/treatment characteristics and toxicities (per the Common Toxicity Criteria for Adverse Events, version 4.0) were extracted. For purposes of this analysis, groupings were made into (1) patients receiving immunotherapy plus stereotactic body radiation therapy (50 Gy/4 fractions or 60 Gy/10 fractions), (2) immunotherapy plus 45 Gy/15 fractions, and (3) twice-daily chemoimmunoradiotherapy (45 Gy in twice-daily fractions).

Results: None of the 60 patients undergoing immunotherapy plus stereotactic body radiation therapy (50 Gy, n = 49; 60 Gy, n = 11) experienced grade ≥4 events. There were 34 instances of any grade 3 event (in 15 total patients), with 9 pulmonary specific grade 3 events (in 4 patients). In the patients receiving 45 Gy/15 fractions (small cell lung cancers, n = 26; non-small cell lung cancers, n = 27), there were 2 grade 4 events (in the same patient), along with 17 grade 3 toxicities experienced by 10 total patients (2 pulmonary specific). Lastly, in the twice-daily cohort (n = 22), there were 5 grade 4 events (3 of which occurred in 1 patient) and 16 grade 3 toxicities occurring in 8 total patients (half of which were hematologic).

Conclusions: Administration of combined iRT is safe in the short term. Toxicities did not appreciably associate with demographics or dosimetry.
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http://dx.doi.org/10.1016/j.ijrobp.2018.04.054DOI Listing
August 2018

Oncology: Management of Elderly Cancer Patients.

Biomed Res Int 2018;2018:7362585. Epub 2018 Jun 7.

Department of Radiation Oncology, Complejo Hospitalario de Albacete, Albacete, Spain.

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http://dx.doi.org/10.1155/2018/7362585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011156PMC
December 2018

Incidence and Impact of Pretreatment Tumor Cavitation on Survival Outcomes of Stage III Squamous Cell Lung Cancer Patients Treated With Radical Concurrent Chemoradiation Therapy.

Int J Radiat Oncol Biol Phys 2018 08 26;101(5):1123-1132. Epub 2018 Apr 26.

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

Purpose: To investigate the incidence and influence of tumor cavitation (TC) on survival outcomes of locally advanced squamous cell lung cancer (LA-SqCLC) patients treated with concurrent chemoradiation therapy (C-CRT).

Methods And Materials: Records of 789 stages IIIA/B squamous cell lung cancer (SqCLC) patients treated with C-CRT who received 1 to 3 cycles of platinum-based doublet chemotherapy during 60 to 66 Gy radiation therapy (RT) were analyzed retrospectively. Primary endpoint was the association between overall survival (OS) and pretreatment TC status. Secondary endpoints included locoregional progression-free survival (LRPFS), progression-free survival (PFS), and incidence of TC and correlated factors.

Results: Pretreatment TC occurred in 95 patients (12%), being significantly more common in those patients with ever-smoking history (12.6% vs 3.9%; P < .001), weight loss >5% (20.9% vs 7.1%; P < .001), and hemoptysis (27.1% vs 6.4%; P < .001). Rates of acute and late toxicities were similar in patients who presented with and without TC (P > .05 for each). For the whole cohort, at a median follow-up of 22.9 months (range: 2.4-71.1), the respective median OS, LRPFS, and PFS estimates were 23.7, 14.7, and 10.7 months. In multivariate analysis, stage IIIB disease (P < .001; hazard ratio [HR]: 1.33; 95% CI: 1.21-1.45), weight loss >5% (P < .001; HR: 2.10; 95% CI: 1.85-2.35), anemia (P < .001; HR: 1.82; 95% CI: 1.67-1.97), and presence of TC (P < .001; HR: 1.54; 95% CI: 1.37-1.71) appeared to be independently associated with poorer OS durations, likewise the LRPFS (P < .001 for each of these covariates), and PFS (P < .001 for each of these covariates), respectively.

Conclusions: Present results showed that the TC occurred in 12% of LA-SqCLC patients, which was strongly associated with poorer PFS, LRPFS, and OS outcomes after definitive C-CRT.
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http://dx.doi.org/10.1016/j.ijrobp.2018.04.053DOI Listing
August 2018

Chemoradiotherapy-induced hemoglobin nadir values and survival in patients with stage III non-small cell lung cancer.

Lung Cancer 2018 07 21;121:30-36. Epub 2018 Apr 21.

Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: We investigated the influence of change in hemoglobin (Hgb) levels during concurrent chemoradiotherapy (C-CRT) on outcomes of non-anemic patients with stage IIIA/B non-small cell lung cancer (NSCLC).

Methods: We identified 722 patients with stage IIIA/B NSCLC without anemia at baseline [hemoglobin (Hgb) <12 g/dL for women or <13 g/dL for men], either nonsmokers or ex-smokers, who received C-CRT between 2007 and 2012. All patients had received 1-3 cycles of platinum-based doublet chemotherapy during radiotherapy to 60-66 Gy and had documented Hgb measurements before treatment and at weekly intervals for 6 weeks during the C-CRT. Potential associations were assessed between baseline, nadir, extent of change in Hgb level, and anemia and overall survival (OS), locoregional progression-free survival (LRPFS), and PFS.

Results: The median baseline Hgb level was 13.9 g/dL (range 12.0-16.8) and declined to a median 12.4 g/dL (range 7.9-16.1) during treatment. Anemia appeared in 237 patients (32.8%) and was more common among women (44.8% vs. 26.5%, P < 0.001). Neither baseline Hgb level nor change during treatment nor anemia emergence influenced any survival endpoint. Receiver operating curve analysis revealed an Hgb nadir of 11.1 g/dL to be associated with outcomes, in that a nadir Hgb <11.1 g/dL (in 156 patients) was linked with shorter median OS time (P < 0.001), LRPFS time (P < 0.001), and PFS time (P < 0.001); retained significance for all three endpoints in multivariate analyses; and was more strongly associated with OS in squamous cell carcinoma (P < 0.001) than in adenocarcinoma (P = 0.009).

Conclusion: Nadir Hgb <11.1 g/dL levels during C-CRT were associated with significantly poorer survival times in initially non-anemic patients presenting with locally advanced NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2018.04.016DOI Listing
July 2018

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

J Neurooncol 2018 Sep 25;139(2):411-419. Epub 2018 Apr 25.

Department of Neurosurgery, Baskent University Medical Faculty, Adana, Turkey.

Introduction: To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS).

Methods: Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: 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; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes.

Results: A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001).

Conclusions: The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.
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http://dx.doi.org/10.1007/s11060-018-2879-4DOI Listing
September 2018

Ovarian and Uterine Functions in Female Survivors of Childhood Cancers.

Oncologist 2018 02 20;23(2):214-224. Epub 2017 Nov 20.

Department of Obstetrics and Gynecology, School of Medicine, Koc University, Istanbul, Turkey.

Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically. By contrast, radiation is detrimental to both the ovaries and the uterus, thereby causing a greater magnitude of adverse effects on the female reproductive function. These include infertility, premature ovarian failure, miscarriage, fetal growth restrictions, perinatal deaths, preterm births, delivery of small-for-gestational-age infants, preeclampsia, and abnormal placentation. Regrettably, the majority of these adverse outcomes arise from radiation-induced uterine injury and are reported at higher incidence in the adult survivors of childhood cancers who were exposed to uterine radiation during childhood in the form of pelvic, spinal, or total-body irradiation. Recent findings of long-term follow-up studies evaluating reproductive performance of female survivors provided some reassurance to female cancer survivors by documenting that pregnancy and live birth rates were not significantly compromised in survivors, including those who had been treated with alkylating agents and had not received pelvic, cranial, and total-body irradiation. We aimed in this narrative review article to provide an update on the impact of chemotherapy and radiation on the ovarian and uterine function in female survivors of childhood cancer.

Implications For Practice: Adult survivors of childhood cancers are more prone to developing a number of poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. The impact of radiation therapy on the female genital system is greater than chemotherapy regimens because radiation is detrimental to both the uterus and the ovaries, whereas toxic effects of chemotherapy drugs are confined to the ovaries. Therefore, radiation-induced uterine damage accounts for most poor obstetrical outcomes in the survivors. These include infertility, miscarriages, stillbirths, fetal growth restrictions, preeclampsia, and preterm deliveries.
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http://dx.doi.org/10.1634/theoncologist.2017-0201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813745PMC
February 2018