Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration

Determining the Factors Affecting the Beliefs of Patients with Cancer on Immunotherapy Medications

Amaç: Bu çalışmanın amacı immünoterapi tedavisi alan kanser hastalarında ilaç inancı ve etkileyen faktörlerin belirlenmesidir. Hastalar ve Yöntemler: Tanımlayıcı tipteki bu çalışmanın örneklemini Aralık 2018-Mayıs 2019 tarihleri arasında bir eğitim ve araştırma hastanesinin tıbbi onkoloji kliniğine ayaktan başvuran, immünoterapi tedavisi alan ve araştırmaya katılmayı kabul eden hastalar (N=85) oluşturdu. Verilerin toplanmasında hasta tanıtıcı bilgi formu ve İlaçlar Hakkında İnançlar Anketi kullanıldı. Veriler bilgisayar ortamında SPSS for Windows 22.00 paket programında değerlendirildi. Verilerin normal dağılıma uygunluğu Shapiro-Wilk Testi ile değerlendirildi. p ≤ 0.05 istatistiksel olarak anlamlı kabul edildi. Bulgular: Katılımcıların yaş ortalaması 58.80±14.23 yıl, %50.6’sı kadın, %56.5’i evre IV kanser hastasıydı ve %74.1’inin metastazı vardı. İmmünoterapinin yan etkilerinden etkilenen hastalar katılımcıların %54.1’ini oluşturdu. Yaşa göre İlaç İnanç Anketinin alt ölçek puan ortalamaları karşılaştırıldığında 65 yaş üzeri hastaların “Spesifik Endişe” puan ortalamalarının genç hastalara göre daha düşük olduğu saptandı (t=2.175, p=0.032). Metastaz varlığına göre alt ölçek puan ortalamaları karşılaştırıldığında, metastazı olan hastaların “Spesifik Gereklilik” alt ölçeğinden aldıkları puan ortalamalarının metastazı olmayanlara göre daha yüksek olduğu bulundu (z=-2.185, p=0.029). İlaçların yan etki oluşturmasına göre ilaç yan etkisi olan hastaların “Genel Aşırı Kullanım” ve “Genel Zarar” alt ölçeklerinden aldıkları puan ortalamalarının yan etki yaşamayan hastalara göre daha yüksek olduğu saptandı (sırasıyla; z=-2.599, p=0.009; z=-1.966, p=0.049). Sonuç: Sonuç olarak yaşlı kanser hastalarının immünoterapi ilaçları konusunda daha az endişe duyduğu, metastazı olan hastaların kullandıkları ilaçların gerekli olduğuna daha fazla inandığı, yan etki yaşayan hastaların yaşamayanlara göre genel zarar ve genel aşırı kullanım inançlarının daha yüksek olduğu değerlendirildi.Anahtar Kelimeler: İmmünoterapi, tedavi, ilaç inancı, kanserObjectives: The aim of this study was to determine the beliefs about medications and the affecting factors in patients with cancer having immunotherapy treatment. Patients and Methods: The sample of this descriptive study consisted of patients (N = 85) who were admitted to the outpatient medical oncology clinic of an education and research hospital between December 2018-May 2019. Data were collected using the patient information form and the Beliefs about Medications Questionnaire (BMQ). Data were analysed by SPSS for Windows 22.00 package program. p ≤ 0.05 was considered statistically significant. Results: The mean age of the participants was 58.80±14.23 years, 50.6% were female, 56.5% had stage IV cancer and 74.1% had metastasis. More than half of the patients (54.1%) experienced adverse effects of immunotherapy. It was found that the “Specific Concern” subscale scores of the patients over 65 years were lower than the younger patients (t = 2.175, p = 0.032). The mean “Specific Necessity” subscale scores of the patients with metastasis were higher than those without metastasis (z = -2.185, p = 0.029). It was found that the mean “General Harm” and “General Overuse” subscale scores of the patients who had adverse effects were higher than the patients who did not experience adverse effects (z = -1.966, p = 0.049; z = -2.599, p = 0.009, respectively). Conclusion: Elderly patients with cancer were less concerned about immunotherapy; patients with metastasis believed that immunotherapy medications were necessary, and patients who had adverse effects during immunotherapy treatment believed that medications were harmful and overused.Keywords: Immunotherapy, treatment, medication belief, cance

Kikuchi-Fujimoto Disease as a Cause of Fever of Unknown Origin: A Case Report

Histiocytic necrotizing lymphadenitis also known as Kikuchi-Fujimoto disease (KFD) is a benign, rare and self-limiting disease. A thirty-six years old woman had high fever and cervical and axillary lymphadenopathy for three months. Her symptoms prompted antibiotic therapy failure and extensive evaluations of fever of unknown origin (FUO). At admission there were several enlarged cervical and axillary lymph nodes and fever of 40°C. Laboratory findings and imaging studies did not show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an excisional lymph node biopsy revealed histiocytic necrotizing lymphadenitis as the underlying disease. After spontaneous resolution without specific therapy the patient is now symptomless 12 months after diagnosis. KFD which presents with fever and lymphadenopathy, should be considered in differential diagnosis of FUO. Physicians should be aware of this uncommon entity since early histologic recognition will minimize unnecessary evaluations and treatments

Retrospective analysis of long-term survival after combination treatment with gemcitabine, oxaliplatin and paclitaxel in patients with refractory or relapsed testicular cancers

Aims: Testicular tumors are one of the most common malignancies in males, between 15 and 35 years of age. Testicular cancer patients are treated with the combination of gemcitabine, oxaliplatin and paclitaxel (GOP) in relapsed and refractory disease, but the literature about the GOP treatment is limited. We aimed to demonstrate the real-life data of progressive testicular cancer patients who received GOP treatment. Methods: Medical records of 17 patients who received GOP treatment at the Gulhane Training and Research Hospital were reviewed retrospectively. Overall response rate (ORR), overall survival (OS) rate and progression-free survival (PFS) of the patients were evaluated. Results: Overall response was obtained in 58.8% (n=10), and a complete response was achieved in 11.2% (n=2) of the cases. OS time was 14.2 months and the OS rate in the first year was 73.1%. The PFS time was 7.6 months. In most of the patients, thrombocytopenia, anemia and leukopenia were observed during GOP treatment. Conclusions: GOP is a safe and effective treatment option for relapsed refractory testicular cancer patients with an acceptable ORR, OS and PFS time. Additionally, GOP treatment was associated with cognitive side effects in patients

Long-term outcome and safety in patients treated with immune checkpoint blockade therapies for urothelial carcinoma: Experience from real-world clinical practice

Background: Anti-tumor activity and manageable safety profile of immune checkpoint blockade therapies (ICT) have been demonstrated in previous clinical trials in patients with metastatic urothelial carcinoma. To the best of our knowledge, very limited real-life data is available with the long follow-up time that confirms the durable antitumor activity and safety of ICT. In this study, we reported the real-life results of 56 months follow-up data of urothelial carcinoma patients who were treated with ICT. Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT included in the study. The primary endpoint was the overall response rate (ORR); secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of the ICT treatment, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 185 eligible patients were analyzed, 11.9% of these patients received the ICT as the first line, 76.8 % as the second line, and 11.3 % as the third or more line of treatment. The median age of the patients was 66 years, and 156 (84.3%) were male (37-86). The majority of patients (93.5%) had ECOG PS scores of 0–1 and primary tumor in the bladder was predominant (86.7%). The median follow-up time was 47(1.15-56) months. The complete response rate to ICT, partial response rate, and ORR were 10.3% (n = 19), 19.5% (n = 36), and 29.8% (n = 55), respectively. The median duration of response was 33.1 months (95% CI, 16.5–49.7). Of the fifty-five patients who responded to treatment, 28 (51%) had an ongoing response at the time of the analysis. Median PFS and OS was 3.8 (2.6–5.1) months and 8.9 (6.8–11.1) months, respectively. 56-month PFS and OS rate was 9.2% and 11.4%, respectively. 56-month PFS and OS rate for CR and PR was 56.2% and 20%, respectively. Fifty-nine percent of patients experienced a treatment-related adverse event of any grade, and 32 (17.3%) of patients had a grade 3–4 treatment-related adverse event. Because of treatment-related side effects, treatment was discontinued in 8 (4.3%) patients and adverse event that required systemic steroid use was reported in only 13 (7%) patients. Four patients (2.2%) died due to treatment-related causes. Conclusions: This 56-month analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients. The safety profile was consistent with prior reports, and no new safety signals emerged

Five-year outcome and safety in patients treated with immune checkpoint blockade therapies for urothelial carcinoma: Experience from real-world clinical practice

This 5-year analysis of real-world data confirms the durable response and long-term survival with ICTs in a broader range of patients with metastatic urothelial carcinoma. After 24 months, PFS and OS curves remained nearly flat. The safety profile was consistent with previous reports, and no new safety signals were observed. Background: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). Patients and Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. Conclusion: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients

Retrospective analysis of patients with relapsed or refractory germ cell tumors treated with autologous hematopoietic stem cell transplantation

Aims: Germ cell tumors (GCT) are the most common malignancies, especially in males of 15 to 35 years of age. Tandem autologous hematopoietic stem cell transplantation (AHSCT) with carboplatin and etoposide (CE) has been performed for many years in relapsed and refractory germ cell patients, but information about AHSCT in patients with germ cell tumors is limited. We aimed to demonstrate some real-life data about patients who underwent AHSCT due to germ cell tumors. Methods: In this retrospective study, medical records of 20 patients who received CE as high-dose chemotherapy for AHSCT betweeen November 2016 and April 2018 were reviewed. Response rates at 12th month and toxicity profiles were evaluated. Results: A complete response was obtained in 15% (n=3) and a partial response was obtained in 20% (n=4) of the cases after AHSCT. The survival rate during AHSCT was calculated as 95%. When the progression-free survival time of the patients was examined, the median recurrence time was 6 months (95% CI: 5.08-6.91). The rate of recurrence was 57% in 6 months. Neutropenia, thrombocytopenia and anemia were observed during AHSCT in all patients. Conclusions: High dose chemotherapy as CE in AHSCT is a safe and effective treatment option in relapsed refractory GCT with an acceptable PFS and mortality rate. Also, highdose CE was associated with low treatment-related mortality and reasonable side effects in patients with poor prognosis