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Öğe Adjuvant radiotherapy in the management of porocarcinoma with lymphatic micrometastasis(Via Medica, 2023) Kahvecioglu, Alper; Elcin, Gonca; Kilickap, Saadettin; Gokoz, Ozay; Yazici, GozdeBackground. Porocarcinoma is a rare skin tumor originating from dermal sweat glands. Surgical procedures are the first choice of treatment, but the role of adjuvant therapies, such as chemotherapy and radiotherapy (RT), is not clear. In this case report and review of the literature, we aimed to present a patient who underwent adjuvant RT for the diagnosis of porocarcinoma with lymphatic micrometastasis and a review of the current literature. Case summary. A 61-year-old male was admitted to the dermatology department for a nodular lesion on the left knee skin. An excisional biopsy was performed, and the pathology result was reported as porocarcinoma. The closest surgical margin of the tumor was 0.2 cm. In the inguinal sentinel lymph node sampling, two of the three removed lymph nodes had micrometastases. Then, adjuvant RT was applied to the left inguinofemoral lymphat- ics and primary tumor bed. No recurrence was observed in the patient with a follow-up period of 24 months. No acute or late toxicity was observed including lymphedema, subcutaneous fibrosis, or stiffness of the knee joint. Conclusions. Although adjuvant RT is not a routinely recommended treatment, it can be applied to increase lo- cal and regional control in patients with high-risk factors for recurrence or with lymph node metastases. There is a great need for clinical studies clarifying the role of RT, but for now, all patients should undergo multidisciplinary evaluation when a decision on adjuvant therapies is made.Öğe Circulating tumor DNA (ctDNA) dynamics and survival outcomes in patients (pts) with advanced non-small cell lung cancer (aNSCLC) and high (>50%) programmed cell death-ligand 1 (PD-L1) expression, randomized to cemiplimab (cemi) vs chemotherapy (chemo)(Lippincott Williams & Wilkins, 2023) Vokes, Natalie I.; Gandara, David R.; Sezer, Ahmet; Kilickap, Saadettin; Gumus, Mahmut; Bondarenko, Igor; Ozguroglu, Mustafa[Abstract Not Available]Öğe Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multicenter Study from the Turkish Oncology Group Kidney Cancer Consortium(Karger, 2023) Erol, Cihan; Yekeduz, Emre; Tural, Deniz; Karakaya, Serdar; Oztas, Nihan Senturk; Ucar, Gokhan; Kilickap, SaadettinIntroduction: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). Methods: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. Results: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56-69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7-71.8), the median OS was 19.3 months (95% CI: 14.1-24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23-3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01-5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47-22.61 for poor risk) were found to be independent prognostic factors. Conclusion: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.Öğe The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer(Mdpi, 2024) Guven, Deniz Can; Sahin, Taha Koray; Kilickap, SaadettinBackground: After the success of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), the benefit of neoadjuvant chemoimmunotherapy was compared with chemotherapy for localized NSCLC in several trials. However, the available studies had variable study designs, and study cohorts had limited follow-up times. Therefore, we conducted a systematic review and meta-analysis to evaluate the benefit of adding immunotherapy to neoadjuvant chemotherapy in patients with localized NSCLC. Methods: We conducted a systematic review using Pubmed, Web of Science, and Scopus databases for studies published until 5 December 2023. This protocol was registered in the PROSPERO database (Registration Number: CRD42023466337). We performed the meta-analyses with the generic inverse-variance method with a fixed effects model. Results: Overall, 7 studies encompassing 2993 patients were included in the analyses. The use of neoadjuvant chemoimmunotherapy was associated with a 41% reduction in the risk of progression or death compared to neoadjuvant chemotherapy (HR: 0.59, 95% CI: 0.52-0.66, p < 0.0001) and a lower risk of death (HR: 0.67, 95% CI: 0.55-0.82, p < 0.0001). The neoadjuvant chemoimmunotherapy improved pCR rates compared to chemotherapy (21.8% vs. 3.8%, OR: 7.04, 95% CI: 5.23-9.47, p < 0.0001), while high-grade adverse events were higher with neoadjuvant chemoimmunotherapy (OR: 1.18, 95% CI: 1.02-1.36, p = 0.0300). Conclusions: The available evidence demonstrates a statistically significant and clinically meaningful event-free survival benefit and possibly an overall survival benefit with neoadjuvant chemoimmunotherapy with a slight increase in high-grade toxicities.Öğe Efficacy/safety of entrectinib in patients (pts) with ROS1-positive (ROS1 +) advanced/metastatic NSCLC from the Blood First Assay Screening Trial (BFAST)(Lippincott Williams & Wilkins, 2022) Peters, Solange; Gadgeel, Shirish M.; Mok, Tony S. K.; Nadal, Ernest; Kilickap, Saadettin; Perol, Maurice; Cadranel, Jacques[Abstract Not Available]Öğe Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group(Mosby-Elsevier, 2023) Kaplan, Muhammet Ali; Sendur, Mehmet Ali Nahit; Cangir, Ayten Kayi; Firat, Pinar; Goker, Erdem; Kilickap, Saadettin; Oyan, BasakPleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fa-tal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant im-provements in diagnoses and treatments of many malignancies; however, there are still therapeutic chal-lenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncolo-gists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Öğe First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a multicentre, open-label, randomised, phase 3 trial(Elsevier Science Inc, 2023) Ozguroglu, Mustafa; Kilickap, Saadettin; Sezer, Ahmet; Gumus, Mahmut; Bondarenko, Igor; Gogishvili, Miranda; Nechaeva, MarinaBackground: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.Methods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged >= 18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.Findings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 261 months (95% CI 221-318; 149 [52%] of 284 died) versus 133 months (105-162; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 057, 95% CI 046-071; p<00001), median progression-free survival was 81 months (95% CI 62-88; 214 events occurred) in the cemiplimab group versus 53 months (43-61; 236 events occurred) in the chemotherapy group (HR 051, 95% CI 042-062; p<00001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 66 months (61-93) and overall survival of 151 months (113-187). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signalsINTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.Copyright (c) 2023 Elsevier Ltd. All rights reserved.Öğe A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004)(Cell Press, 2024) Zhou, Caicun; Hu, Yanping; Arkania, Ekaterine; Kilickap, Saadettin; Ying, Kejing; Xu, Fei; Wu, LinCombining immunotherapy with chemotherapy can provide improved survival in advanced squamous nonsmall -cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3 -week cycles. The primary endpoint of progression -free survival (PFS) was met at the first interim analysis. At the second interim analysis, PFS benefit was maintained in serplulimab-chemotherapy group (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.42-0.67). At the final analysis, serplulimab-chemotherapy significantly improved median OS compared to placebo -chemotherapy (HR 0.73, 95% CI 0.58-0.93; p = 0.010). Grade R3 serplulimab or placebo -related adverse events occurred in 126 (35.2%) and 58 (32.4%) patients, respectively. Our results demonstrate that adding serplulimab to chemotherapy significantly improves survival in advanced squamous NSCLC patients, with manageable safety.Öğe Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data(Springer, 2023) Guven, Deniz Can; Erul, Enes; Kaygusuz, Yunus; Akagunduz, Baran; Kilickap, Saadettin; De Luca, Raffaele; Rizzo, AlessandroPurposeImmune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies.MethodsWe conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were hearing loss OR hearing impairment OR ototoxicity OR vestibular toxicity OR audiovestibular toxicity AND immune checkpoint inhibitor OR immunotherapy.ResultsA total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively.ConclusionWe observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.Öğe Impact of pharmacist-led educational intervention on pneumococcal vaccination rates in cancer patients: a randomized controlled study(Springer, 2023) Ozdemir, Nesligul; Aktas, Burak Y. Y.; Gulmez, Ahmet; Inkaya, Ahmet C. C.; Bayraktar-Ekincioglu, Aygin; Kilickap, Saadettin; Unal, SerhatPurpose This study aimed to evaluate clinical pharmacist's contribution to the pneumococcal vaccination rate by providing education to cancer patients in hospital settings. Methods This study was conducted in 2 tertiary-care hospitals' medical oncology outpatient clinics. Patients over 18 years of age and diagnosed with cancer for less than 2 years, in remission stage, and have not previously received the pneumococcal vaccine were included. Patients were randomized to intervention and control groups. The intervention group was provided vaccination education and recommended to receive the PCV13 vaccine. The control group received routine care. Patients' knowledge about pneumonia/pneumococcal vaccine, Vaccine Attitude Examination Scale (VAX) score, and vaccination rates were evaluated at baseline and 3 months after the education. Results A total of 235 patients (intervention: 117, control: 118) were included. The mean age +/- SD was 57.86 +/- 11.88 years in the control and 60.68 +/- 11.18 years in the intervention groups. The numbers of correct answers about pneumonia/pneumococcal vaccine (p = 0.482) and VAX scores (p = 0.244) of the groups were similar at baseline. After the intervention, the median (IQR) number of correct answers in intervention group [10(3)] was higher than control group [8(4)] (p < 0.001). After the education, the total VAX score (mean +/- SD) was less in intervention group (33.09 +/- 7.018) than the control group (36.07 +/- 6.548) (p = 0.007). Three months after the education, 20.2% of the patients in the intervention and 6.1% in the control groups were vaccinated with pneumococcal vaccine (p = 0.003). Conclusions The pneumococcal vaccination rate in cancer patients has increased significantly by the education provided by a clinical pharmacist in hospital settings.Öğe Prevalence of EGFR mutations in patients with resected stage I-III non-squamous NSCLC: Results from the EARLY-EGFR study.(Lippincott Williams & Wilkins, 2023) Soo, Ross A.; Reungwetwattana, Thanyanan; Perroud, Herman Andres; Batra, Ullas; Kilickap, Saadettin; Gallegos, Luis Fernando Tejado; Donner, Natalia[Abstract Not Available]Öğe Safety of lorlatinib in ALK-positive non-small-cell lung cancer and management of central nervous system adverse events(Future Medicine Ltd, 2023) Kilickap, Saadettin; Ak, Sertac; Dursun, Oldac U.; Sendur, Mehmet A. N.; Karadurmus, Nuri; Demirci, UmutThe use of tyrosine kinase inhibitors has made a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Recently, lorlatinib, a third-generation tyrosine kinase inhibitor, has demonstrated significant systemic and intracranial activity in both first-line and subsequent-line therapy in ALK-positive NSCLC patients. In this review, general characteristics of lorlatinib, its efficacy in the treatment of ALK-positive NSCLC patients and the safety of lorlatinib, particularly addressing CNS adverse events, are discussed. Management of CNS adverse events, which seem to be specific to lorlatinib therapy, is outlined. Plain language summary - Safety of lorlatinib in ALK-positive non-small-cell lung cancer and management of central nervous system adverse eventsLung cancer is a common disease and affects patients badly. Lorlatinib is a new and useful drug for this disease. But this drug has also some undesirable effects for the brain. These effects are generally mild and can be treated. This article discusses the undesirable effects of this drug on the brain and how to cope with these effects.