Nurullah Ilhan

Background The Excision Repair Cross-Complementation (ERCC) gene family is critical for the Nucleotide Excision Repair (NER) pathway, yet its clinical utility in solid tumors remains underexplored. Impaired DNA repair via ERCC alterations drives tumorigenesis and influences response to DNA-damaging therapies. This study maps the clinical and genomic landscape of ERCC mutations to highlight their potential as predictive biomarkers. Methods A retrospective analysis of cancer patients (2017–2024) was conducted utilizing a hereditary cancer Next-Generation Sequencing (NGS) panel. Excluding dominant variants like BRCA1/2, the study analyzed tumor characteristics, metastatic status, and receptor expression in patients harboring ERCC mutations. Results ERCC gene mutations were identified in 5.8% (32/550) of the cohort. The predominant malignancies were breast (40.7%), endometrial (22.2%), and ovarian cancers (7.4%), with metastasis present in 15.6% of cases. Mutations were most frequent in ERCC2 (43.8%) and ERCC4 (25%), primarily presenting as missense variants (68.8%). Notably, 87.5% of the identified alterations were classified as Variants of Uncertain Significance (VUS). Conclusions ERCC alterations represent a critical, yet clinically underutilized, genetic factor in breast and gynecological malignancies. The remarkably high VUS rate in this cohort underscores an urgent need for international database updates and functional reclassification. Accurately profiling ERCC mutations offers a promising avenue for expanding personalized treatment strategies, particularly in leveraging platinum-based therapies and PARP inhibitors for non-BRCA carriers.

Background and Objectives: Sarcopenia is a common yet underrecognized condition in cancer patients and is associated with increased treatment-related toxicity, functional decline, and poor clinical outcomes. Practical, rapid, and bedside-applicable tools are needed to detect sarcopenia early in routine oncology practice. This study aimed to evaluate the diagnostic value of rectus femoris muscle ultrasonography within an integrated clinical assessment combining handgrip strength and bioelectrical impedance analysis for the detection of sarcopenia in cancer patients. Materials and Methods: In this prospective cross-sectional study, 147 adult patients with malignancy were evaluated using a multimodal sarcopenia assessment framework. Muscle strength was assessed by handgrip dynamometry, muscle mass was estimated using bioelectrical impedance analysis (BIA)-derived appendicular skeletal muscle mass index (ASMI), and muscle morphology was evaluated using ultrasonographic measurements of the rectus femoris and biceps brachii muscles. Sarcopenia was defined and classified according to the EWGSOP2 criteria. Associations between clinical variables, BIA parameters, and ultrasonographic measurements were analyzed. Receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of muscle ultrasonography for sarcopenia detection. Results: The mean age of the study population was 60.2 ± 11.2 years, and 51% of participants were male. Confirmed sarcopenia was identified in 12.2% of patients, while 27.2% were classified as having probable sarcopenia. Sarcopenic patients were significantly older (68.5 ± 7.6 vs. 59.0 ± 11.2 years, p = 0.001) and had lower handgrip strength (15.8 ± 6.0 vs. 24.3 ± 8.4 kg, p < 0.001) and ASMI values (5.96 ± 0.64 vs. 7.23 ± 1.18 kg/m², p < 0.001). Rectus femoris muscle thickness was significantly reduced in patients with sarcopenia (6.40 ± 1.42 vs. 8.19 ± 2.21 mm, p = 0.001). Rectus femoris muscle thickness demonstrated good diagnostic performance for sarcopenia detection (AUC = 0.752; 95% CI: 0.650–0.853; p = 0.001), with an optimal cut-off value of ≤7.59 mm (sensitivity 83.3%, specificity 61.2%). Conclusions: Rectus femoris muscle ultrasonography is a practical, rapid bedside assessment for detecting sarcopenia in cancer patients. When integrated with handgrip strength and BIA, this multimodal approach provides a feasible, radiation-free strategy for early sarcopenia screening in routine oncology practice.

Aims: Androgen receptor pathway inhibitors (ARPIs) have improved outcomes in advanced prostate cancer. Still, evidence regarding their feasibility in older patients with comorbidities and multiple concomitant medications remains limited, as such populations are often underrepresented in clinical trials. Methods: This multicenter, retrospective cohort study included 538 prostate cancer patients diagnosed between January 2021 and November 2023 across seven centers in Turkiye. Demographic, clinical, pathological, and treatment data were extracted from institutional records. Patients were stratified by treatment type [androgen deprivation therapy (ADT), androgen receptor pathway inhibitor (ARPI), chemotherapy (CT)] and by the number of medications used (≥ three vs. <3). The primary outcome was overall survival (OS); secondary outcomes included follow-up duration, tumor grade, and metastatic distribution. Results: The mean age at diagnosis was 70.3 years, and 59.5% of patients had comorbidities. Concomitant medication use of three or more drugs, was observed in 34.4%. Metastatic disease was present in 82.3% of cases, most commonly involving the bone (62.8%). ARPI therapy was administered to 72.7% of patients, ADT alone to 18.6%, and CT to 8.7%. Patients receiving ARPIs had higher comorbidity and concomitant medication rates and more frequent metastases than those receiving ADT. Still, they achieved significantly longer median follow-up (901 vs. 470 days, p<0.001) and prolonged OS. Patients with concomitant medication use of three or more drugs also showed a longer follow-up (1081 vs. 573 days, p<0.001), lower mortality (32.4% vs. 47.3%, p=0.001), and a higher proportion of grade 1 tumors compared with patients using fewer than three medications. Conclusion: In this large real-world cohort, ARPIs were found to be feasible and effective, even in elderly, comorbid, and medication use of three or more patients, supporting their use beyond traditional trial populations.

Aims: It was aimed to evaluate the prevalence of anxiety and depression among cancer patients, and examine their association with quality of life (QoL). Methods: A cross-sectional study was conducted, including 750 adult cancer patients at a tertiary oncology outpatient clinic. Anxiety and depression status were measured using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI), respectively, while QoL was assessed with the EORTC QLQ-C30. Sociodemographic and clinical data were collected through structured forms. Comparative, correlation, and subgroup analyses were performed, with p

Background Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have significantly improved clinical outcomes in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR + /HER2−) metastatic breast cancer. Hepatotoxicity is a known class-related adverse event that may interrupt or modify treatment. However, real-world evidence on its incidence, risk factors, and management strategies—particularly rechallenge approaches—remains limited. This study aimed to evaluate the frequency and clinical characteristics of CDK4/6 inhibitor-associated hepatotoxicity, to identify risk factors, and to assess the outcomes and safety of rechallenge following liver injury. Methods This retrospective multicenter study included 544 patients with HR+ /HER2− metastatic breast cancer who were treated with ribociclib or palbociclib between January 2017 and July 2024 in oncology centers across Turkey. Abemaciclib was not included due to reimbursement limitations during the study period. Patient characteristics, comorbidities, concomitant medications, and herbal or dietary supplement use were recorded. Liver function tests and viral hepatitis serologies were analyzed. Hepatotoxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0), and causality was assessed with the Roussel Uclaf Causality Assessment Method (RUCAM). Management strategies—including dose interruption, dose reduction, switching to another CDK4/6 inhibitor, and outcomes of rechallenge were evaluated. Results Hepatotoxicity occurred in 10.5% of patients, most commonly in a hepatocellular pattern. Ribociclib was the most frequently used agent. Younger age, herbal supplement use, and hepatitis B carrier status were significantly associated with increased risk of hepatotoxicity. All hepatotoxic events were managed conservatively. None of the patients developed acute liver failure or required invasive evaluation. Dose reduction or switching to the alternate agent was attempted in most patients after enzyme normalization and was successful in the majority, with no recurrence of severe hepatotoxicity. Conclusion CDK4/6 inhibitor-related hepatotoxicity is manageable with careful monitoring and individualized strategies. Timely dose interruption, switching agents, or cautious rechallenge allowed most patients to resume therapy safely. These findings support the continued use of CDK4/6 inhibitors in eligible patients, even after hepatotoxicity events.

Kanser hastaları, gerek kanserin neden olduğu gerekse kanser tedavilerine bağlı gelişen yan etkilerin yol açtığı solunum yolu rahatsızlıkları ile çok sık karşılaşmaktadır. Bu durum, mevcut kanser hastalığı dışında ek sağlık sorunlarına neden olmakta, hastaların yaşam kalitesini ve tedavi devamlılığını düşürmekte, bazen de beklenen yaşam sürelerinde kısalmalara yol açmaktadır. Bu durumları yönetmek için hastaların, gerek primer kanser hastalığı gerekse aldığı tedavilere bağlı gelişebilecek yan etkilerin multidisipliner yaklaşımlar ile yakın takibi, anamnez, fizik muayene, laboratuvar ve radyolojik değerlendirmelerin periyodik olarak yapılması hayati önem taşımaktadır. Bu durumları hastaların primer kanser tipine göre veya aldığı tedavi türüne göre sınıflandırmak mümkündür.Kanser tedavisinde süregelen konvansiyonel yöntemler dışında çok fazla yeni gelişen ilaç ve tedavi yöntemi mevcuttur. Her gün literatüre eklenen yeni bilgiler eşliğinde geliştirilen ve kullanımı onaylanan kanser ilaçları, girişimsel yöntemler, cerrahi yenilikler, nükleer tıp ve radyasyon onkolojisi alanındaki yenilikler nedeniyle kanser hastalığının multidisipliner tedavisinde yer alan hekimler, bilgilerini güncellemek ve yeni tedavi modalitelerini, bunların yan etkilerini, güncel kılavuzlar ve yayınları çok yakından takip ederek hasta takip yönetimlerini belirlemek zorundadırlar. Cancer patients frequently encounter respiratory disorders caused by cancer itself or as side effects of cancer treatments. These conditions can lead to additional health issues beyond the primary cancer diagnosis, reducing patients' quality of life, treatment adherence, and, in some cases, even shortening their expected survival times. To manage these issues, it is crucial to closely monitor patients using a multidisciplinary approach, which includes regular anamnesis, physical examinations, laboratory tests, and radiological evaluations. These assessments should be conducted periodically to address side effects related to both the primary cancer and the treatments received. It is also possible to classify these conditions based on the type of primary cancer or the nature of the treatments administered.In addition to conventional cancer treatment methods, numerous newly developed drugs and therapeutic approaches have emerged. With the continuous influx of new information into the literature, cancer drugs, interventional techniques, surgical advancements, and innovations in nuclear medicine and radiation oncology are being developed and approved for use. Physicians involved in the multidisciplinary treatment of cancer must update their knowledge and closely follow new treatment modalities, their side effects, and the latest guidelines and publications to determine effective patient management strategies.

Background and Objectives: KRAS genes are among the most prominent oncogenes that trigger tumor formation in colorectal cancer (CRC) and serve as predictive biomarkers for resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. However, the prevalence and mutation spectrum of the KRAS gene family in mCRC patients in Turkey have not been sufficiently analyzed. This study investigates the frequency and distribution of mutations in the KRAS gene family across different regions of Turkey and examines gender-related variations. Materials and Methods: This multicenter observational study included 2458 histologically confirmed mCRC patients collected from 52 centers across Turkey. In a central laboratory, KRAS mutations in codons 12 and 13 were analyzed using polymerase chain reaction (PCR). Statistical analyses were performed using chi-square tests and Monte Carlo simulations, with a significance threshold set at p < 0.05. Results: Depending on the region, KRAS mutations were detected in 45% of patients, ranging from 39.6% to 47.5%. The mutation rate was significantly higher in female patients (48.8%) compared to male patients (42.6%) (p = 0.002). Codon 12 mutations were more frequent than codon 13 mutations. G12D, G12V, and G13D mutations accounted for 80% of all detected mutations. The G12V mutation was prevalent in female patients (p = 0.007). Based on region, mutation diversity was similar, and no statistically significant difference was found (p > 0.05). Conclusions: This large-scale, multicenter study provides the most comprehensive dataset of KRAS mutations in mCRC patients in Turkey. This study revealed regional trends, as well as gender differences. The findings highlight the importance of routine KRAS genotyping in guiding personalized treatment strategies, especially regarding candidate selection for anti-EGFR therapies. Further research is required to elucidate the prognostic and therapeutic implications of specific KRAS mutations.

Background/Aims: The treatment of hepatocellular carcinoma (HCC), which accounts for 90% of all liver cancers, is highly varied. The use of second-line treatments following progression on first-line atezolizumab and bevacizumab (Atez/Bev) for advanced HCC remains controversial. The aim of this study was to analyze the real-world clinical results of second-line treatments in progression after Atez/Bev and to determine the factors affecting prognosis. Materials and Methods: Fifty-eight patients treated with second-line sorafenib, regorafenib, and cabozantinib for progression after first-line Atez/Bev for advanced/metastatic HCC from 20 centers in Türkiye between October 2020 and June 2024 were retrospectively analyzed. Responses were evaluated by Response criteria, specifically Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Median overall survival (OS) and progression-free survival (PFS) were computed with the Kaplan–Meier method. The Cox regression model was utilized to analyze multivariate analyses. Results: About 82.8% of the patients were male and the median age of the whole group was 62 (range, 18-78) years. All patients progressed after first-line Atez/Bev and were given second-line treatment. The most commonly used second-line treatment option was sorafenib (70.7%), followed by regorafenib (12.1%) and cabozantinib (10.3%). Both median PFS (4.1 months) and median OS (7.8 months) were longer in patients treated with sorafenib compared to other treatments. In univariate analyses, Child–Pugh score B, alpha-fetoprotein (AFP) levels (>200 ng/mL), extrahepatic spread, and Prognostic Nutritional Index (PNI) < 47.6 substantially raised the risk of overall mortality. Multivariate analysis showed that extrahepatic spread (HR (Hazard ratio): 0.41, P = .012), PNI level (HR: 0.24, P =.005), and AFP level (HR:1.97, P = .049) were independent predictors of OS. Conclusion: Although second-line therapies after Atez/Bev show different degrees of efficacy, survival rates are consistent with the literature. Extrahepatic spread, AFP level, and PNI level are the main prognostic factors. In light of this information, personalized treatment strategies may improve outcomes for this challenging patient group. Cite this article as: Majidova N, Yaslıkaya S, Mıldanoglu MM, et al. Efficacy of second-line treatments after atezolizumab and bevacizumab in advanced hepatocellular carcinoma and related prognostic factors: A multicenter study by the turkish oncology group (TOG). Turk J Gastroenterol. 2025;36(5):293-301.

Background and Objectives: CDK4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone receptor-positive HER2 negative (HR(+)/HER2(-)) breast cancer. Despite their efficacy, interstitial lung disease (ILD) remains a rare but potentially fatal adverse effect. This study aims to evaluate the incidence and clinical characteristics of ILD associated with CDK4/6 inhibitors in breast cancer patients in Turkey. Materials and Methods: A retrospective multicenter analysis included 464 breast cancer patients treated with CDK4/6 inhibitors between January 2017 and April 2024. Patients receiving ribociclib or palbociclib were evaluated for the development of ILD. Radiological assessments were performed to confirm ILD and exclude other conditions. Clinical characteristics, treatment regimens, and outcomes were analyzed. Results: ILD was identified in 10 patients (2.1%). The average age of the affected patients was 62.5 ± 9.85 years. Hypersensitivity pneumonitis and nonspecific interstitial pneumonia (NSIP) were the most common radiological patterns. Palbociclib was implicated in six cases, while ribociclib was associated with four cases. Grade 3 pulmonary toxicity was observed in eight patients, and Grade 4 toxicity in two patients. One patient who was on palbociclib died due to ILD. No significant correlation was found between ILD and age, smoking status, lung metastases, or prior thoracic radiotherapy. Conclusions: The incidence of CDK4/6 inhibitor-associated ILD in Turkish breast cancer patients appears higher than previously reported in clinical trials. More robust, long-term studies are necessary to identify potential risk factors and mitigate ILD-related mortality.