The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment.
Retrospective analysis of ...T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey.
Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%).
The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death globally. In this study, the effect of complete removal of mediastinal lymph nodes by video-assisted mediastinoscopic ...lymphadenectomy (VAMLA) on natural killer (NK) cell phenotype and functions in patients with NSCLC was evaluated. The study included 21 NSCLC patients (cIA-IVA) undergoing VAMLA staging and 33 healthy controls. Mononuclear cells were isolated from peripheral blood of all participants and mediastinal lymph nodes of the patients. NK cells were analyzed by flow cytometry to define NK subsets, expressions of PD-1, CTLA-4, activating/inhibitory receptors, granzyme A, and CD107a. The plasma levels of soluble PD-1, PDL-1, and CTLA-4 were measured by ELISA. Mediastinal lymph nodes of NSCLC patients had increased ratios of exhausted NK cells, increased expression of PD-1 and IL-10, and impaired cytotoxicity. Mediastinal lymph nodes removal increased CD56
dim
CD16
bright
cytotoxic effector phenotype and reduced exhausted NK cells. PD-1
+
NK cells were significantly more abundant in patients’ blood, and VAMLA significantly reduced their ratio as well. The ratio of IL-10 secreting regulatory NK cells was also reduced after VAMLA. Blood NK cells had increased cytotoxic functions and spontaneous IFN-γ secretion, and these NK cell functions were also recovered by VAMLA. Mediastinal lymph node removal reversed NK cell exhaustion, reduced regulatory NK cells, and improved antitumoral functions of NK cells. Tumor-draining lymph nodes may contribute to tumor evasion from antitumoral immune responses. The role of their removal needs to be further studied both to better understand this mechanism and as a potential immunotherapeutic approach.
Introduction:
Mediastinal lymph node (MLN) removal by video-assisted mediastinoscopic lymphadenectomy (VAMLA) for preoperative cancer staging was reported to be associated with increased survival. ...The aim of this study was to evaluate the immunologic effects of complete MLN removal by VAMLA on cytotoxic T lymphocyte (CTL) phenotype and function.
Methods:
Seventeen patients with non-small cell lung cancer (NSCLC) (stage cT1-4N0-3M0-1A) and 20 healthy participants were included in this study. Blood samples were collected before and 4 weeks after the procedure. Lymphocytes were isolated from the removed MLNs. CTL phenotypes and functions were evaluated by flow cytometry. Plasma levels of soluble programmed cell death protein 1 (sPD-1), soluble programmed cell death protein 1 ligand, and soluble CTL antigen 4 (sCTLA-4) were measured with enzyme-linked immunosorbent assay.
Results:
The ratio of the immunosenescent CTLs (CD3+CD8+CD28−) was increased in peripheral blood and MLNs of the patients with NSCLC compared to controls (p = 0.037), and MLN removal did not change this ratio. PD-1 and CTL antigen 4 expressions were significantly reduced in peripheral blood CTLs after MLN removal by VAMLA (p = 0.01 and p = 0.01, respectively). Granzyme A expression was significantly reduced in the peripheral blood CTLs of the patients compared to controls (p = 0.006) and MLN removal by VAMLA significantly improved Granzyme A expression in CTLs (p = 0.003). Plasma concentrations of sPD-1 and sCTLA-4 remained unchanged after VAMLA.
Conclusion:
CTLs in the MLNs and peripheral blood of the patients with NSCLC had an immunosenescent phenotype, increased immune checkpoint receptor expression, and impaired cytotoxicity. MLN removal by VAMLA improved these phenotypic and functional characteristics of CTLs. These changes may explain the potential contribution of VAMLA to improved survival.
Introduction:
With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the ...spectrum of toxicity, management, and outcomes for irAEs.
Methods:
Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes.
Results:
A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti–programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti–programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments.
Conclusion:
With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.
Purpose
To determine whether inherited thrombophilia affects components of second trimester combined aneuploidy screening test.
Methods
A case–control study was performed between 1 December 2010 and ...1 February 2012, at a tertiary referral hospital. Singleton pregnancies with inherited thrombophilia that underwent second trimester (16–19
+6
week) combined aneuploidy screening test were included in the study. Maternal serum alfa fetoprotein, unconjugated estriol, human chorionic gonadotropin levels and multiple of median (MoM) levels were compared between the study group and controls.
Results
Within the study period, 18,943 women with singleton pregnancies had a combined second trimester aneuploidy screening test at our institution. Among these, 26 women met the criteria of thrombophilia. A control group that comprised 275 women with similar gestational age was generated, using a 1:1 ratio. Unconjugated estriol MoM levels were significantly lower in women with inherited thrombophilia (
p
= 0.02). But there was no statistically significant difference for unconjugated estriol levels, human chorionic gonadotropin, alfa fetoprotein and their MoM levels.
Conclusions
Our study suggest that in patients with hereditary thrombophilia a new correction factor should be used, when calculating unconjugated estriol MoM value, which is one of the markers of second trimester aneuploidy screening test.
Objective. Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related morbidity and mortality. Diverse functions of innate lymphoid cells (ILCs) and NK cell subsets are ...investigated thoroughly in cancer immunotherapy. ILC and recently described NK cell subsets in NSCLC patients’ blood samples and tumor draining lymph nodes were investigated.
Methods. The study included chemotherapy and/or radiotherapy-naive NSCLC patients with clinical stage T1-4N0-2M0 who underwent video-assisted mediastinal lymphadenectomy and 14 healthy controls. Mononuclear cells were isolated from peripheral blood of both groups and mediastinal lymph nodes of NSCLC patients. NK cells and ILC subsets were analyzed by flow cytometry.
Results. Total NK cells are shown to be increased in peripheral blood of NSCLC patients compared to lymph nodes while the ratio of CD56dimCD16- exhausted NK cells is higher in lymph nodes than in blood samples of NSCLC patients. Compared to control group, peripheral blood ILC1 cells were lower in NSCLC patients, however ILC2 and ILC3 cells were significantly increased. However, mediastinal lymph nodes of NSCLC patients had decreased ratio of ILC2 and increased ratio of ILC3 cells than in peripheral blood of patients. NSCLC patients had significantly increased ratio of NKp44-ILC3 cells and decreased ratio of NKp44+ILC3 in lymph nodes.
Conclusion. Decreased ratio of ILC1 cells is an important indicator of impaired anti-tumoral response. Increased in the ratio of NKp44-ILC3 cells in NSCLC patients may potentially contribute to tumor progression. These findings highlight the distinct roles of ILCs, which play a pivotal role in the pathogenesis of lung cancer.
Giriş: Küçük hücre dışı akciğer kanseri (KHDAK) tüm dünyada ciddi morbidite ve mortaliteye neden olmaktadır. Özellikle son yıllarda önemi daha iyi anlaşılan ILC (doğal lenfoid hücreler) alt gruplarındaki değişikliklerin tümör gelişiminde önemli rol oynayabileceği öne sürülmüştür. Bu çalışmada KHDAK hastalarında periferik kan ve tümörü drene eden mediastinal lenf nodlarındaki ILC alt grupları incelenmiştir.
Gereç ve Yöntemler: Çalışmamıza video yardımlı mediastinal lenfadenektomi uygulanan T1-4N0-2M0 evreli ve daha önce sistemik kemoterapi/radyoterapi almamış 13 KHDAK hastası ve 14 sağlıklı kontrol incelenmiştir. Periferik kan ve mediastinal lenf nodundan izole edilen lenfositlerde NK hücre ile ILC alt grupları akan hücre ölçer ile analiz edilmiştir.
Sonuç: KHDAK olguların kan örneklerinde total NK hücre oranı tümör drene eden lenf noduna kıyasla artmıştır. CD56dimCD16- tükenmiş NK hücrelerin oranı ise lenf nodu örneklerinde KHDAK hastaların kan örneklerine kıyasla daha yüksek saptanmıştır. KHDAK olguların kanında ILC1 oranı kontrol grubuna kıyasla daha düşük, ILC2 ve ILC3 alt gruplarının oranı ise daha yüksek bulunmuştur. Buna karşın KHDAK olguların mediastinal lenf nodunda aynı hastaların kan örneklerine göre ILC2 oranı düşük, ILC3 oranı ise yüksektir. KHDAK hastaların lenf nodunda NKp44-ILC3 oranı artmışken, NKp44+ILC3 oranı azalmıştır.
Tartışma: KHDAK hastalarında ILC1 hücre oranındaki azalma bozulmuş anti-tümöral immünitenin önemli bir göstergesidir. Tümör büyümesinde rol oynadığı düşünülen IL-17’yi salgılayan NKp44-ILC-3 hücre grubunun bu hastalarda artmış olması, bu hücrelerin tümör gelişiminde rolü olabileceğini düşündürmektedir. Bu bulgular ILC hücre ailesinin akciğer kanseri patogenezinde önemli rollere sahip olduğunun altını çizmektedir.
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