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Background: Although CDK4/6 inhibitors combined with endocrine therapies have improved outcomes in HR+ HER2-negative metastatic breast cancer, predictive biomarkers for treatment response and adverse effects remain limited. This study assessed the prognostic and predictive value of large unstained cells (LUC), a subset of white blood cells that may reflect immune status or treatment response. Methods: A retrospective analysis of 210 patients with HR+ HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors between 2021 and 2024 was conducted. Clinical data, including demographics, tumor characteristics, and treatment regimens, were analyzed. Based on LUC levels, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. Results: The cohort had a median age of 57, of which 78% were postmenopausal. Common metastatic sites included bone (67%) and liver (24%). At a median follow-up of 18.5 months, the PFS and OS rates were 65% and 83%. Patients with low LUC levels had significantly shorter PFS (OR: 1.91; p = 0.014) and OS (OR: 2.39; p = 0.012), while high LUC levels correlated with a lower incidence of grade 3 neutropenia (OR: 0.49; p = 0.017). Liver metastasis and prior treatments were also linked to shorter survival. Conclusions: LUC levels emerge as a promising biomarker for predicting survival outcomes and the risk of neutropenia in HR+ HER2-negative metastatic breast cancer patients treated with CDK 4/6 inhibitors and endocrine therapy, showing their potential to guide personalized treatment approaches. [ABSTRACT FROM AUTHOR]

The discovery of KRAS mutations, particularly the KRASG12C variant, has been a milestone in understanding the molecular underpinnings of non-small cell lung cancer (NSCLC). These mutations are associated with aggressive tumor behavior and resistance to conventional therapies, highlighting the urgent need for targeted interventions. In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer. Literature search is made from PubMed, Medline ASCO and ESMO Annual Meetings abstracts by using the following search keywords: "sotorasib", "adagrasib", "divarasib" and "KRAS G12C inhibitors." The last search was on 5 June 2024. This review highlights the importance of pharmacokinetics, pharmacodynamics and potential adverse effects for treating individual patients and ensuring the best outcomes. Additionally, the review discusses research identifying biomarkers that can predict therapy responses and mentions the combination strategies to overcome resistance. Results of the studies and ongoing clinical trials are also briefly summarized in this review. KRASG12C inhibitors sotorasib, adagrasib and the newer divarasib, has revolutionized treating patients harboring this mutation. Ongoing studies and future clinical trials will refine our understandings with the ultimate goal of improving survival and quality of life for patients with this challenging disease. Article highlights Advances in targeted therapy Covalent inhibitors like sotorasib, adagrasib and divarasib represent significant advancements in targeted therapy aimed specifically at tumors harboring the KRASG12C mutation. Clinical efficacy Clinical trials have shown that KRAS G12C inhibitors improved objective response rates and progression-free survival compared with standard treatments. These trials have obtained promising results in personalized cancer therapy for non-small cell lung cancer (NSCLC) patients harboring the KRASG12C mutation. Importance of co-mutations Co-mutations in genes like KEAP1, SMARCA4 and CDKN2A can significantly impact patient outcomes and response to KRAS G12C inhibitors, with certain co-mutations associated with poor prognosis. Pharmacokinetics & safety Each KRAS G12C inhibitor comes with its own pharmacokinetics profile. Sotorasib and adagrasib are both well tolerated, though gastrointestinal adverse events are common and can be managed with supportive care. Predictive biomarkers Liquid biopsies show promise in detecting KRAS mutations, monitoring treatment response and predicting overall survival, making them a valuable tool in managing NSCLC. Resistance mechanisms Development of resistance to KRAS inhibitors can occur through various genetic alterations and activation of alternative pathways. Combination therapies may help overcome these resistance mechanisms. Future directions Ongoing and future clinical trials aim to further explore the efficacy of KRAS G12C inhibitors, their combinations with immunotherapies, and other novel compounds to improve treatment outcomes in NSCLC. [ABSTRACT FROM AUTHOR]

Objective: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC). Data sources: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC. Data summary: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress. Conclusion: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background/aim: In this study, we aimed to assess the cancer risk among patients with periodontal disease. Materials and methods: Patients diagnosed with periodontal diseases at Hacettepe University between 2007 and 2012 were included and data on the diagnosis of any cancer after periodontal disease were collected from patient files. The age- and sex-standardized incidence rates (SIRs) were calculated using Turkish National Cancer Registry 2013 data. Results: A total of 5199 patients were included. Median follow-up was 7.2 years. Patients with periodontal diseases had 17% increased risk of cancer compared with the expected counts for the corresponding age and sex groups (SIR: 1.17; 95% CI: 1.04–1.3, P = 0.006). The increased cancer risk was statistically significant in women (SIR: 1.24; 95% CI: 1.05–1.45, P = 0.008) but not in men. Among women with periodontal disease, the risks of breast cancer (SIR: 2.19) and head and neck cancer (SIR: 4.71) were significantly increased. Among men, the risks of prostate cancer (SIR: 1.84), head and neck cancer (SIR: 3.55), and hematological cancers (SIR: 1.76) were significantly increased. Conclusion: This study showed that periodontal diseases were associated with increased risk of several cancers. Besides other wellknown benefits for health, the provision of oral/dental health should be considered and employed as a cancer prevention measure. [ABSTRACT FROM AUTHOR]

Introduction: Although, immune check-point inhibitors changed the course of many cancers, the outcomes in sarcomas were rather disappointing with less than 10% response rates. Ewing sarcoma is a poorly differentiated and aggressive tumor mostly seen in the children and adolescents. It's a distinct type of sarcoma with prominent chemosensitivity in the early stages. However, the relapsing disease has a poor prognosis with limited treatment options. Case report: Herein, we represent a case of relapsed Ewing sarcoma treated with multiple lines of chemotherapy. Management & outcome: The patient had a very good response to salvage treatment with a combination of paclitaxel and nivolumab which lasted for twelve months after the cessation of treatment. Discussion: We think that chemotherapy plus immunotherapy can be an option for Ewing sarcoma patients treated with multiple lines of chemotherapy. [ABSTRACT FROM AUTHOR]

Amaç: Romatoid artrit (RA) en sık rastlanılan sistemik otoim-mün hastalıktır. RA eklem bulguları dışında %5() vakada sistemik tutulum gösterir. Gastrointestinal sistem en sık tutulan sistemlerdendir. Karaciğer tutulumu çoğu zaman transaminazlar-da ılımlı non-spesifik yükselme şeklindedir. RA tedavisinde kul-lanlan ilaçlardan sülfasalazin, metotreksat, leflunomidin hepa-totoksik etkileri en sık non spesifik transaminaz yüksekliği şeklinde olup bu ilaçlarla ilişkili granülomatöz hepatit tablosu daha önce bildirilmemiştir. Bu yazının amacı leflunomidin granülomatöz hepatite neden olduğunu gösteren ilk yazı olmasıdır. Olgu: 7 yıldır seropozitif (RF+, CCP+) RA ile takip edilen 38 yaşında kadın hasta Hidroksiklorokin 1x200 mg, Leflunomid 20 mg/gün aşırı, Metotreksat 4tb/hf tedavisi alünda izlenirken, ani başlayan kanıt ağrısı şikayetiyle acile başvuran hastanın vital bulgularında bir anormallik saptanmadı. Fizik muayenede sağ üst kadranda hassasiyet dışında patoloji saptanmadı. Flemogram ve biyokimyasında patoloji saptanmadı. Flepatobilier USG'de karaciğerde multipl düzensiz hiperekoik lezyonlar gözlenen hastanın Abdomen MRG'si en büyüğü segement 7 de 30×28 mm boyutunda Tl A sekanslarda düşük, T2A sekanslarda yüksek sinyal yoğunlukta, kontrast madde sonrası düzensiz çevresel kontrast madde tutulumu gösteren multipl kitle lezyonu olarak değerlendirildi (Sekil PS-189). Toraks-Abdomen BT, mamogra-fik görüntüleme endoskopi ve kolonoskopisi yapıldı. Malignite saptanmadı. BruceUa agglütinasyonu, AMA, hepatit markerları negatif, ACE düzeyi 17.5 U/L (8-52 U/L) geldi. Quantiferon pozitif gelmesine rağmen anlamlı kabul edilmedi.Karaciğer biyopsisi 'geniş fibrinoid nekroz alanları ve çevresinde palizatik dizilim gösteren lenfohistiyositik hücrelerden oluşan granülomatöz reaksiyon odakları ' şeklinde raporlandı. Malignite ve infeksiyoz sebeplerin dışlamnasıyla ön planda ilaç ilişkili granülomatöz hepatit düşünüldü. Hastamn ilaçlarından tedavisine en yakın tarihte eklenen (2.5 ay önce) leflunomid kesildi ve prednizolon dozu 30 mg/gün'e çıkarıldı. Hastanın 3 ve 9 ay sonraki abdominal MR görüntülemelerinde kitle lezyonlarında minimal ve tamamen gerileme olduğu gözlendi. Prednizolon 1 yıl içinde azaltılarak 5 mg/gün'e düşüldü. Tedaviye Metotreksat 4 tb/hf, Prednizolon 5 mg/gün, Hidroksik-lorokin 200 mg/gün şeklinde devam edilmektedir. Sonuç: Granülomatöz hepatite ilaçların neden olduğu bilinmektedir. Vakada ilk kez leflunomidin granülomatöz hepatite neden olduğu gösterilmiştir. [ABSTRACT FROM AUTHOR]