Publications by authors named "Sercan Aksoy"

171 Publications

Upper limb sensory evaluations and ultrasonographic skin measurements in breast cancer-related lymphedema receiving complex decongestive physiotherapy.

Support Care Cancer 2021 Apr 29. Epub 2021 Apr 29.

Faculty of Physical Therapy and Rehabilitation, Hacettepe University, 06100, Samanpazari, Ankara, Turkey.

Purpose: The aims of this study were to investigate if/how the presence of lymphedema affects the sensation of the upper limb and to assess whether complex decongestive physiotherapy (CDP) has a favorable impact on sensory testing.

Methods: A total of 27 patients with unilateral stage 2 breast cancer-related lymphedema (BCRL) were included in the study. Bilateral circumferential measurements were taken with a tape measure at different levels. Based on these measurements, limb volumes were determined by summing segment volumes derived from the truncated cone formula. Circumferential measurements and ultrasonographic evaluations (epidermis, dermis, and subcutaneous fat thicknesses) were performed at 10 cm distal to the elbow crease. The Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination, pressure pain threshold (PPT), and tactile localization tests were also applied at the same site. After an initial evaluation, all patients underwent CDP phase 1 program. All the evaluations were repeated at the end of the treatment period.

Results: Before CDP, affected sides had significantly higher values than the unaffected sides in terms of SWM (p < 0.001), static (p = 0.002) and moving (p = 0.011) two-point discrimination, PPT (p = 0.001), and tactile localization (p < 0.001) values. After CDP, SWM (p = 0.002), static (p = 0.009) and moving (p = 0.024) two-point discrimination, PPT (p = 0.014), and tactile localization (p < 0.001) values decreased significantly on the affected sides.

Conclusion: BCRL seems to reduce light touch, static and moving two-point discrimination, PPT, and tactile localization sensations, whereas CDP seems to improve these sensory perceptions in women with BCRL. Ultrasonographic measurements also appear to be promising for prompt and convenient follow-up in the management of BCRL.

Trial Registration: Clinical Trial Registration Number: NCT04296929 (date of registration: March 5, 2020).
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http://dx.doi.org/10.1007/s00520-021-06235-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081563PMC
April 2021

Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment.

Prostate 2021 Apr 27. Epub 2021 Apr 27.

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

Background: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed.

Materials And Methods: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS.

Results: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis.

Conclusions: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.
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http://dx.doi.org/10.1002/pros.24132DOI Listing
April 2021

The burden of polypharmacy and drug-drug interactions in older cancer patients treated with immunotherapy.

J Oncol Pharm Pract 2021 Apr 20:10781552211012038. Epub 2021 Apr 20.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Introduction: Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs.

Methods: A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions.

Results: The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038).

Conclusion: In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.
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http://dx.doi.org/10.1177/10781552211012038DOI Listing
April 2021

Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES.

Breast Cancer Res Treat 2021 Mar 16. Epub 2021 Mar 16.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC).

Methods: The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 - ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2 - ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day) + EXE (25 mg/day) orally.

Results: A total of 235 patients received ≥ 1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥ 20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

Conclusion: The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE + EXE could be a viable treatment option for the postmenopausal women with HR+, HER2 - ABC in Asian region.
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http://dx.doi.org/10.1007/s10549-021-06173-zDOI Listing
March 2021

Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy.

Support Care Cancer 2021 Mar 11. Epub 2021 Mar 11.

Department of Medical Oncology, Hacettepe University Cancer Institute, 06100 Sıhhıye, Ankara, Turkey.

Purpose: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors.

Methods: A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses.

Results: The median age was 60 (interquartile range (IQR) 48-66) years, and the median follow-up was 10.1 (IQR 5.8-18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011-9.039, p=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk.

Conclusions: In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.
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http://dx.doi.org/10.1007/s00520-021-06139-3DOI Listing
March 2021

Investigation of Intestinal Protozoon Prevalence in Immunocompromised Patients at a University Hospital

Turkiye Parazitol Derg 2021 03;45(1):39-44

Hacettepe University Faculty of Medicine, Department of Medical Microbiology, Ankara, Turkey

Objective: Immunocompromised patients are at a greater risk of developing intestinal parasite infections. In this study, we examined the presence of and other intestinal protozoa in stool samples of immunosuppressed patients.

Methods: A total of 100 stool samples were obtained from patients receiving chemotherapy because of solid organ tumour with haematological malignancies and those receiving immunosuppressive treatment because of rheumatic diseases, organ transplant patients and patients receiving treatment for HIV-related infections. Stool samples were examined by using the native-lugol method in which the stool concentration, modified Kinyoun acid-fast and trichrome staining methods and parasite presence were analysed. The stool samples were also examined for the presence of and using an indirect fluorescent antibody method.

Results: Intestinal parasites were detected in 12% of all patients. The distribution of intestinal parasites in patients were 7% spp., 2% spp. + , 1% spp. + , 1% spp. + and 1% spp. were detected in 4% of all patients by the IFAT method and in 8% of all patients by calcoflour staining method.

Conclusion: In our study, the most prevalent parasite detected in the immunosuppressed patients was spp. The pathogenesis of spp. remains to be controversial, and their role in immunocompromised patients continues to remain unknown. Although these rates detected in our study are similar to the prevalence in the normal population, it is important to study these microorganisms in immunocompromised patients in terms of the associated decreasing morbidity and mortality rates.
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http://dx.doi.org/10.4274/tpd.galenos.2020.6819DOI Listing
March 2021

Clinical features and outcomes of COVID-19 in patients with solid tumors: Turkish National Registry Data.

Int J Cancer 2020 Dec 7. Epub 2020 Dec 7.

Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range: 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3-13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6-6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5-8,1, P = .005) were found to be associated with increased 30-day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.
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http://dx.doi.org/10.1002/ijc.33426DOI Listing
December 2020

The use of CDK 4/6 inhibitors in the adjuvant treatment of breast cancer: Timing matters.

Breast J 2021 Jan 4;27(1):104. Epub 2020 Dec 4.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

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http://dx.doi.org/10.1111/tbj.14126DOI Listing
January 2021

Perspectives, Knowledge, and Fears of Cancer Patients About COVID-19.

Front Oncol 2020 28;10:1553. Epub 2020 Aug 28.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Coronavirus disease 2019 (COVID-19) is expected to significantly affect cancer patients due to adverse outcomes with COVID-19 and disruptions in cancer care. Another important point is the stress and anxiety burden of COVID-19, which could affect quality of life. Patient education is vital due to the vulnerability of the topic to disinformation. To determine the areas needing improvements in patient education, and coping with stress, the burden of the problem should be pictured. From this point, we aimed to assess the perspectives and fears of cancer patients about COVID-19 with resources of COVID-19 knowledge with a questionnaire. A total of 250 adult cancer patients applied to the outpatient chemotherapy unit of Hacettepe University Cancer Center between May 27, 2020, and June 9, 2020, invited to answer a questionnaire of 13 multiple-choice questions with a return rate of 78% (195/250). Most patients acquired their knowledge about COVID-19 from television (91.9%). Social media were the second most common source of knowledge (43.8%) with a predilection in younger patients, nonsmokers, targeted therapy- or immunotherapy-treated patients, and breast cancer patients (>65 vs. <65 years of age, = 0.057; nonsmoker vs. ever-smoker, = 0.036; targeted therapy and immunotherapy vs. chemotherapy, = 0.004; breast cancer vs. other cancers, = 0.019). The percentage of patients seeing the information about COVID-19 as adequate (38.9%) or inadequate (35.1%) was similar. More than 90% of the patients had a moderate to severe degree of COVID-19 fear. In addition, 27.6% of patients had false knowledge of glove using as a protective measure for COVID-19. More than half of the patients had another wrong knowledge as the need for the supplements for COVID-19 protection. A significant percentage of patients (84.7%) expected some level of disruption in oncological care with the expectation of a moderate-to-severe disruption was more common in the advanced-stage patients ( = 0.026). In our experience, most cancer patients had a significant degree of fear about both infecting COVID-19 and the disruption of cancer care by COVID-19. A significant amount of our patients had wrong information about the protection necessities, which denotes the need for better patient education about COVID-19.
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http://dx.doi.org/10.3389/fonc.2020.01553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493662PMC
August 2020

Evaluation of emergency departments visits in patients treated with immune checkpoint inhibitors.

Support Care Cancer 2021 Apr 26;29(4):2029-2035. Epub 2020 Aug 26.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Background: The emergency department (ED) is a crucial encounter point in cancer care. Yet, data on the causes of ED visits are limited in patients treated with immune checkpoint inhibitors (ICI). Therefore, we evaluated ED visits in patients treated with ICIs in attempt to determine the predisposing factors.

Methods: We performed a retrospective chart review on adult cancer patients treated with ICIs for any type of cancer in the Hacettepe University Cancer Center. The data on ED visits after the first dose of ICIs to 6 months after the last cycle of ICIs were collected.

Results: A total of 221 patients were included in the study. The mean age was 58.46 ± 13.87 years, and 65.6% of patients were males. Melanoma was the most common diagnosis (27.6%), followed by kidney and lung cancers. Eighty-three of these patients (37.6%) had at least one emergency department (ED) visit. Most of the ED visits were related to symptoms attributable to the disease burden itself, while immune-related adverse events comprised less than 10% of these visits. While baseline Eastern Cooperative Oncology Group performance status, age, polypharmacy, concomitant chemotherapy, eosinophilia, and lactate dehydrogenase levels did not significantly increase the risk, patients with regular opioid use and baseline neutrophilia (> 8000/mm) had a statistically significant increased risk of visiting the ED (p = 0.001 and 0.19, respectively). These two factors remained significant in the multivariate analyses.

Conclusion: In this study, almost 40% of ICI-treated patients had ED visits. Collaboration with other specialties like emergency medicine is vital for improving the care of patients receiving immunotherapy.
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http://dx.doi.org/10.1007/s00520-020-05702-8DOI Listing
April 2021

The use of CDK 4/6 inhibitors in the adjuvant treatment of breast cancer: Timing matters.

Breast J 2020 12 19;26(12):2435-2436. Epub 2020 Aug 19.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

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http://dx.doi.org/10.1111/tbj.14027DOI Listing
December 2020

COVID-19 pandemic: changes in cancer admissions.

BMJ Support Palliat Care 2020 Jul 14. Epub 2020 Jul 14.

Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara, Turkey.

Background: COVID-19 pandemic could create a collateral damage to cancer care denoting disruptions in care due to a significant burden on healthcare and resource allocations. Herein, we evaluate the early changes in the inpatient and outpatient oncology clinics to take a snapshot of this collateral damage at Hacettepe University Cancer Institute.

Methods: Patients applying the outpatient clinic and outpatient palliative care (OPC) clinic for the first time and patients admitted to inpatient wards in the first 30 days after the first case of COVID-19 in Turkey were evaluated. These data were compared with data from the same time frame in the previous 3 years.

Results: The mean number of daily new patient applications to the outpatient clinic (9.87±3.87 vs 6.43±4.03, p<0.001) and OPC clinic (3.87±1.49 vs 1.13±1.46, p<0.001) was significantly reduced compared with the previous years. While the number of inpatient admissions was similar for a month frame, the median duration of hospitalisation was significantly reduced. The frequency of hospitalisations for chemotherapy was higher than in previous years (p<0.001). By comparison, the rate of hospitalisations for palliative care (p=0.028) or elective interventional procedures (p=0.001) was significantly reduced.

Conclusion: In our experience, almost all domains of care were affected during the pandemic other than patients' systemic treatments. There were significant drops in the numbers of newly diagnosed patients, patients having interventional procedures and palliative care services, and these problems should be the focus points for the risk mitigation efforts for prevention of care disruptions.
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http://dx.doi.org/10.1136/bmjspcare-2020-002468DOI Listing
July 2020

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412.

Future Oncol 2020 Jun 3;16(18):1235-1243. Epub 2020 Jun 3.

Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.

Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-0184DOI Listing
June 2020

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.

Nat Commun 2020 05 15;11(1):2416. Epub 2020 May 15.

Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC, 29208, USA.

Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy. Similarly, inhibiting FAK/Src results in chemosensitization. These effects are observed in 3D-cultured cell lines, tumor organoids, chemoresistant xenografts, syngeneic tumors and PDX models. Re-expressing the hypoxia-repressed miR-142-3p, which targets HIF1A, LOX and ITGA5, causes further suppression of the HIF-1α/LOX/ITGA5/FN1 axis. Notably, higher LOX, ITGA5, or FN1, or lower miR-142-3p levels are associated with shorter survival in chemotherapy-treated TNBC patients. These results provide strong pre-clinical rationale for developing and testing LOX inhibitors to overcome chemoresistance in TNBC patients.
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http://dx.doi.org/10.1038/s41467-020-16199-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229173PMC
May 2020

Gut microbiota and cancer immunotherapy: prognostic and therapeutic implications.

Future Oncol 2020 Mar 26;16(9):497-506. Epub 2020 Feb 26.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara 06100, Turkey.

The immune checkpoint inhibitors have opened new horizons in oncology. Although the indications for the use of Immune checkpoint inhibitors in cancer patients are expanding, there is still a need for markers that can aid in patient selection. Gastrointestinal microbiota can be among these markers. Recently, gastrointestinal microbiota stated to have a bidirectional relation with cancer immunotherapy with roles in both prognostic and therapeutic sides. Preclinical data suggest that modulation of the microbiota could become a novel strategy for improving the efficacy of immunotherapy. However, its labile structure prone to be affected by many factors. Further research can delineate the mechanisms of the relationship between microbiota and immunotherapy can have clinical implications.
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http://dx.doi.org/10.2217/fon-2019-0783DOI Listing
March 2020

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

The Reliability and Validity of the Turkish Version of the Lymphedema Life Impact Scale in Patients With Breast Cancer-Related Lymphedema.

Cancer Nurs 2020 Sep/Oct;43(5):375-383

Author Affiliations: Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences (Drs Orhan, Özgül and Akbayrak and Mss Üzelpasaci, Baran, and Nakip) and Cancer Institute (Dr Aksoy), Hacettepe University, Ankara, Turkey.

Background: Health-related quality of life is measured to detect the influence of lymphedema on physical, functional, and social aspects of life in patients with breast cancer-related lymphedema (BCRL).

Objective: This study aimed to perform the psychometric evaluation of the Lymphedema Life Impact Scale (LLIS) in Turkish patients with BCRL.

Methods: Patients with BCRL (n = 78) filled out the Turkish LLIS, Lymphedema Quality of Life, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and Quick Disability of Arm, Shoulder and Hand scales. Breast cancer survivors without BCRL (n = 35) completed only the Turkish LLIS. Psychometric properties were analyzed with the internal consistency, test-rest reliability, construct, criterion, and discriminant validity.

Results: The internal consistency of the Turkish LLIS was strong (Cronbach's α coefficient >.70). Test-retest reliability was strong to very strong (intraclass correlation coefficients from 0.88 to 0.93; P < .001). Similar to the original structure of the scale, exploratory factor analysis identified 3 factors. Criterion validity was supported by moderate to strong correlations between the LLIS, Lymphedema Quality of Life, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and quick Disability of Arm, Shoulder and Hand. There were significant differences in the total and subscale scores of the LLIS between participants with and without BCRL (P < .05).

Conclusions: The present study provided the evidence to confirm reliability and clinical validity of the Turkish LLIS.

Implications Of Practice: The Turkish LLIS is a reliable and valid condition-specific scale to measure the physical, functional, and psychological aspects of health-related quality of life in patients with BCRL.
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http://dx.doi.org/10.1097/NCC.0000000000000709DOI Listing
April 2021

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.

N Engl J Med 2019 03;380(10):985-986

Hacettepe Cancer Institute, Ankara, Turkey

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http://dx.doi.org/10.1056/NEJMc1900150DOI Listing
March 2019

The investigation of Strongyloides stercoralis seroprevalence in immunosupressed patients in Turkey

Turk J Med Sci 2019 Feb 11;49(1):16-19. Epub 2019 Feb 11.

Background/aim: In immunosuppressed patients, strongyloidiasis can be lifethreatening because of hyperinfection or dissemination. Therefore, diagnosis of S. stercoralis is important in immunosuppressed patients with chronic strongyloidiasis. In this study, our objective was to investigate the presence of S. stercoralis antibodies by an ELISA method in immunosuppressed patients.

Materials And Methods: A total of 100 immunosuppressed patients’ sera were included in the study. Forty-two of the patients were receiving immunosuppressive therapies for cancer or being treated for hematopoietic malignancies, 38 of the patients were receiving immunosuppressive drugs for rheumatic diseases, 14 were receiving immunosuppressive therapies for liver transplantation. Two of the patients were being treated for HIV infection and 4 were being treated for hypogammaglobulinemia. As control group, 50 individuals without a known disease were included in the study. The presence of IgG antibodies against S. stercoralis was investigated with a commercial ELISA kit.

Results: S. stercoralis antibody test was positive in 4 of 100 (4%) sera from immunosuppressed patients. All control patients were negative for S. stercoralis.

Conclusions: Strongyloidiasis can be a lifelong chronic infection if not treated. In patients who are going to receive immunosuppressive therapy, it should be tested before treatment, as it can become a disseminated and life-threatening infectious disease.
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http://dx.doi.org/10.3906/sag-1804-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350872PMC
February 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

Association between androgen receptor status and prognosis in triple negative breast cancer.

J BUON 2018 Sep-Oct;23(5):1325-1330

Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey.

Purpose: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients.

Methods: A total of 84 TNBC patients treated between 2000 - 2015 in Hacettepe University Cancer Institute were included and their medical records were analyzed retrospectively. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with ≥1% nuclear staining were considered AR-positive, while the ones with <1% staining were considered AR-negative. We analyzed the association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC.

Results: Of the 84 TNBC patients, 25 (29.8%) were AR-positive. The frequency of grade 3 tumors was lower among AR-positive TNBC tumors compared to AR-negative tumors (40 vs 86.4%, p<0.001). In the AR-positive group, invasive ductal carcinoma (IDC) was less prevalent compared to AR-negative group (56 vs 86.4%, p<0.002). However, there were not statistically significant differences between AR positive and negative groups in terms of overall survival (OS) and disease free survival (DFS) (p=0.449, p=0.733, respectively). We found that grade 3 tumors were less frequent in AR-positive TNBC in our study. Nonetheless, we did not detect statistically significant difference in terms of overall survival and disease free survival between AR positive and negative TNBC.

Conclusion: Routine evaluation of AR could contribute to further studies that may enlighten the role of AR targeting therapies in TNBC.
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August 2019

Behçet's disease and breast cancer: A case series study.

J Cancer Res Ther 2018 Oct-Dec;14(6):1184-1190

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

Introduction: The relation between Behçet's disease (BD) and breast cancer (BC) is unclear. Our purpose is to investigate whether BD has an important effect on BC or vice versa.

Patients And Methods: A total of 12 female BC patients with a diagnosis of BD were identified from a cohort including 5050 BC patients. The demographic data of the selected patients including previous chemotherapy (CT), radiotherapy (RT), hormonal therapy (HT), drugs used for BD, history of thrombotic events, and overall survival were examined.

Results: The rate of BD in the entire cohort was found to be 0.25% (12/4800), and all had early BC at the time of BC diagnosis, with a median age of 47 years (range: 38-51). All patients underwent curative surgery for BC. In the adjuvant setting, CT, RT, and HT were administered in 11 (91%), 10 (83.4%), and 9 (75%) patients, respectively. All patients received acetylsalicylic acid and colchicine for BD. No serious adverse event associated with BC and/or BD was observed. Clinical symptoms in 11 patients with BD were observed to be improved following the BC treatment. Only one patient developed disease progression and then expired.

Conclusion: Unlike the natural behavior of BD, which is well-defined to have an increased risk of thrombosis, BC patients with BD in this study did not have any adverse event. However, due to small sample size, it is difficult to drive any definite conclusion regarding the relation between these two pathologies.
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http://dx.doi.org/10.4103/0973-1482.189249DOI Listing
February 2019

The Effect of Total Size of Lesions in Multifocal/Multicentric Breast Cancer on Survival.

Clin Breast Cancer 2018 08 9;18(4):320-327. Epub 2017 Nov 9.

Mustafa Kadri Altundag (MKA) Breast Cancer Clinic, Ankara, Turkey. Electronic address:

Background: In this study, we aimed to assess the prognostic performance of determining the T stage according to the total size of lesions compared with the size of the largest lesion in the breast in patients with multifocal/multicentric (MF/MC) breast cancer.

Patients And Methods: The charts of the patients with MF/MC breast cancer who were diagnosed between 2003 and 2014 were reviewed. The T stage of MF/MC tumors was determined according to the largest lesion size (T) as well as the sum of the longest diameters of the lesions (T) in the breast.

Results: Multifocal/multicentric tumors were identified in 323 of 3890 patients (8.3%) with breast cancer. Ten-year rates of overall survival (OS; 75% and 74%; P = .965) and disease-free survival (DFS; 66% and 61%; P = .817) were similar in patients with unifocal and MF/MC tumors, respectively. When the T stage was determined by summing the sizes of the lesions, the T stage of 67 (20.7%) and 63 (19.5%) patients advanced from T1 to T2 and from T2 to T3, respectively. Thus, the T stage increased in 130 patients (40.2%) according to American Joint Committee on Cancer. Discriminatory ability of T was better than T in terms of OS and DFS, as shown with higher Royston D and Harrel C statistics and Schemper V values.

Conclusion: The new T classification proposed in this report stands out as a better predictive classification particularly in patients with low disease burden.
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http://dx.doi.org/10.1016/j.clbc.2017.11.002DOI Listing
August 2018

Comparison of prognosis and clinical features between synchronous bilateral and unilateral breast cancers.

J BUON 2017 May-Jun;22(3):623-627

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Purpose: The clinical significance of synchronous bilateral breast cancer (SBBC) is unclear and its influence on prognosis is controversial. Our study objective was to determine the epidemiological features, tumor characteristics, and prognosis of SBBC in comparison with those of unilateral breast cancer (UBC).

Methods: A total of 3675 breast cancer patients diagnosed and treated between 2000 and 2014 were evaluated. Of these patients, 132 (3.6%) had bilateral breast cancer, including 55 patients (1.5%) with SBBC and 77 (2.1%) with metachronous bilateral breast cancer (MBBC). The patient demographic characteristics, including survival data and clinicopathological tumor characteristics, were obtained from medical charts and compared between the patients with SBBC and those with UBC.

Results: The median age in the SBBC group was 51 years (range 32-77). The mastectomy rate was higher in the SBBC group (72.7%) than in the UBC group (66.6%) (p=0.08). In both the SBBC and UBC groups, the baseline clinicopathological features and the history of treatment with radiotherapy and chemotherapy were similar. Infiltrating ductal carcinoma was the most common histology in both groups. Lobular histology was more frequent in the SBBC group (36.3%) than in the UBC group (17.1%; p<0.001). Stage IV disease at initial presentation was more frequent in the SBBC group than in the UBC group (34.5 vs 8.7%, p<0.001). The 5-year disease-free survival (DFS) rates were 90% and 82% in the SBBC and UBC groups, respectively (p=0.99). The 5-year overall survival (OS) rates were 83% and 88%, respectively (p=0.357). The multivariate Cox regression analysis, including stage, hormone receptor status, grade, and SBBC, revealed that the presence of SBBC was not associated with OS (hazard ratio 0.929; 95% confidence interval, 0.455-0.1894, p=0.839).

Conclusion: Despite the differences in histology, initial stage, and other characteristics, the prognoses of UBC and SBBC were similar.
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July 2019

Modified docetaxel, cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study.

Curr Med Res Opin 2017 03 8;33(3):401-407. Epub 2016 Dec 8.

b Hacettepe University, Cancer Institute , Department of Medical Oncology , Ankara , Turkey.

Aim: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC).

Methods: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2-6 cycles of mDCF chemotherapy which consisted of docetaxel 60 mg/m intravenously (IV) on day 1, cisplatin 60 mg/m IV on day 1, and 5-fluorouracil 600 mg/m IV for 5 days of continuous infusion, with cycles repeated every 21 days.

Results: The most common grade 3-4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3-8.6) and 11.5 (95% CI: 9.4-13.7) months, respectively.

Conclusions: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.
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http://dx.doi.org/10.1080/03007995.2016.1257984DOI Listing
March 2017

Efficacy and safety of eribulin monotherapy in patients with heavily pretreated metastatic breast cancer.

J BUON 2016 Mar-Apr;21(2):375-81

Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey.

Purpose: Eribulin is a non-taxane microtubule inhibitor, which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated MBC patients.

Methods: In this single-center trial, a total of 66 MBC patients who received eribulin monotherapy in Hacettepe University Cancer Institute between 2013 and 2015 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values <0.05 were considered as statistically significant.

Results: Sixty-six patients who received at least one cycle of eribulin were registered. Most patients were heavily pretreated with a median of 4 (range 2-7) previous chemotherapy lines prior to eribulin. Median patient age was 50 years (range 28-67). Most patients were treated with eribulin at 4th or 5th line (33.3 and 27.3%, respectively). Brain metastases were present in 19 (28.8%) patients at the time of initial eribulin administration. Median PFS was 5 (95% CI 4.1-5.8) and median OS was 8 (95% CI 6-9.9) months. Fifteen patients (22.7%) responded to treatment with partial remission (PR) and 36 (54%) had stable disease (SD). No hypersensitivity reactions and no toxic deaths were observed. Three (5%) patients experienced grade 4 neurotoxicity. Fourteen (21.5%) patients developed grade 3-4 neutropenia.

Conclusion: Eribulin monotherapy is an effective and safe regimen for MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease in its intravenous administration make this agent a preferable option for both physicians and patients.
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July 2016

Effect of body mass index on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.

J BUON 2016 Jan-Feb;21(1):27-34

Yildirim Beyazit University, Faculty of Medicine, Department of Medical Oncology, Ankara, Turkey.

Purpose: Obesity has been confirmed to be an adverse prognostic factor in patients who were treated with aromatase inhibitors; however, such relationship has never been thoroughly investigated in patients treated with tamoxifen. The purpose of this study was to examine the effect of body mass index (BMI) on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.

Methods: Newly diagnosed premenopausal and non-metastatic hormone receptor-positive breast cancer patients were enrolled in the study. Patients with BMI ranging between 18.5 and 24.9 kg/m(2) were considered as normal weight patients (Arm A, n = 408), and/patients with a BMI ≥ 25 kg/m(2) were considered as overweight and obese patients (Arm B, n = 418).

Results: In both normal weight and overweight patients, the baseline clinicopathologic properties and the treatment history with radiotherapy and chemotherapy were similar and no statistical significant difference could be detected. Tamoxifen in combination with luteinizing hormone-releasing hormone (LHRH) agonist was used in 33% (136/408) of the patients in Arm A and in 22% (91/418) of patients in Arm B (p<0.001). Three-year disease free survival (DFS) rates were 89% and 87% in arm A and arm B, respectively (p=0.39). Three-year overall survival (OS) rates were 99% in arm A and 94% in arm B which appeared to be of significance (p=0.028). In univariate analysis no statistical significant effect of LHRH agonist usage on DFS (p=0.58) and OS (p=0.96) was found.

Conclusion: Although BMI had no negative effect on recurrence risk, poor OS was observed in overweight and obese premenopausal breast cancer patients with hormone-receptor positive tumors who were treated with tamoxifen.
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May 2016

Analysis of the Adjuvant Hormone Therapy Randomized Trial.

J Clin Oncol 2016 06 21;34(17):2070. Epub 2016 Mar 21.

Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.1200/JCO.2015.65.4277DOI Listing
June 2016

Squamous cell and neuroendocrine carcinoma of esophagus: Collision versus composite tumor: A case report and review of literature.

Indian J Cancer 2015 Oct-Dec;52(4):603-4

Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey.

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http://dx.doi.org/10.4103/0019-509X.178436DOI Listing
December 2016

Targeted therapies in gastric cancer and future perspectives.

World J Gastroenterol 2016 Jan;22(2):471-89

Ozan Yazici, Nuriye Ozdemir, Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara 06100, Turkey.

Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.
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http://dx.doi.org/10.3748/wjg.v22.i2.471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716053PMC
January 2016