Tokur, Oguzhan; Aydin, Sonay; Kilinc, Funda; Degirmenci, Tulin; Oztekin, Pelin Seher

Background: The evaluation of axillary lymph nodes (ALNs) using ultrasound (US) plays a crucial role in the diagnosis and management of breast cancer. This study aims to assess the diagnostic performance of both quantitative and qualitative features of suspicious ALNs using superb microvascular imaging (SMI). To the best of our knowledge, this is the first prospective study in the literature to evaluate the largest number of suspicious ALNs using SMI and to analyze the combined diagnostic value of these findings. Methods: Our prospective study involved 102 patients with suspicious lymph nodes in the axilla. SMI method was employed individually to assess distribution, appearance, and number of vascular structures. After histopathological or follow-up confimation, images were re-evaluated. We also examined the diagnostic value of various combinations of these vascular features. Lastly, two radiologists, each with 22 and 4 years of experience, independently reviewed the images, blinded to clinical and pathological data, to assess interobserver agreement. Results: A total of 108 lymph nodes were evaluated in 102 patients, including 67 benign and 41 malignant cases. The diagnostic performance of various combinations in receiver operating characteristic (ROC) analysis revealed that the highest accuracy (78.70%) and area under the curve (AUC) value in ROC analysis were achieved by distribution-appearance combinations (AUC: 0.776, p < 0.001). Interobserver agreement was significant for both the SMI and PDUS methods. In patients diagnosed with breast cancer, the diagnostic accuracy for suspicious axillary lymph nodes reached 92.76%, with an AUC value of 0.855. Conclusion: In conclusion, our findings suggest that SMI facilitates more accurate identification of suspicious axillary lymph nodes prior to surgical intervention.

Taşçı, Elif Şenocak; Oyan, Başak; Sönmez, Özlem; Mutlu, Arda Ulaş; Atcı, Muhammed Mustafa; Sakin, Abdullah; Öner, İrem; Çınkır, Havva Yeşil; Eryılmaz, Melek Karakurt; Çağlayan, Dilek

Background: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. Methods: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. Results: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49–14.49) and 8.08 months (95% CI, 6.88–9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. Conclusion: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Taşçı, Elif Şenocak; Oyan, Başak; Sönmez, Özlem; Mutlu, Arda Ulaş; Atcı, Muhammed Mustafa; Sakin, Abdullah; Öner, İrem; Çınkır, Havva Yeşil; Eryılmaz, Melek Karakurt; Çağlayan, Dilek

Following publication of the original article [1], the authors reported an error in the affiliations of authors Başak Oyan, Özlem Sönmez, Leyla Özer, Ali Arıcan, Özlem Er and Mustafa Bozkurt. These authors are all affiliated to institution 2. The original article [1] has been corrected.

Karacin, Cengiz; Oksuzoglu, Berna; Demirci, Ayşe; Keskinkılıç, Merve; Baytemür, Naziyet Köse; Yılmaz, Funda; Selvi, Oğuzhan; Erdem, Dilek; Avşar, Esin; Paksoy, Nail

Following publication of the original article [1], the authors reported an error in the author name of Enes Erul. Incorrect: Enes Urul Correct: Enes Erul, The original article [1] has been corrected.

Karacin, Cengiz; Oksuzoglu, Berna; Demirci, Ayşe; Keskinkılıç, Merve; Baytemür, Naziyet Köse; Yılmaz, Funda; Selvi, Oğuzhan; Erdem, Dilek; Avşar, Esin; Paksoy, Nail

Background: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Mustufa, Muhammad Ayaz; Ozen, Cigdem; Hashmi, Imran Ali; Aslam, Afshan; Baig, Jameel Ahmed; Yildiz, Gokhan; Muhammad, Shoaib; Solangi, Imam Bakhsh; ul Hasan Naqvi, Naim; Ozturk, Mehmet

Background: The purpose of present work is to synthesize novel (+)-Dehydroabietylamine derivatives (DAAD) using N-acetyl-α-amino acid conjugates and determine its cytotoxic effects on hepatocellular carcinoma cells. Methods: An analytical study was conducted to explore cytotoxic activity of DAAD on hepatocellular carcinoma cell lines. The cytotoxicity effect was recorded using sulforhodamine B technique. Cell cycle analysis was performed using Propidium Iodide (PI) staining. Based on cell morphology, anti growth activity and microarray findings of DAAD2 treatment, Comet assay, Annexin V/PI staining, Immunoperoxidase assay and western blots were performed accoringly. Results: Hep3B cells were found to be the most sensitive with IC50 of 2.00 ± 0.4 μM against (+)-N-(N-Acetyl-L-Cysteine)-dehydroabietylamine as DAAD2. In compliance to time dependent morphological changes of low cellular confluence, detachment and rounding of DAAD2 treated cells; noticeable changes in G2/M phase were recorded may be leading to cell cycle cessation. Up-regulation (5folds) of TUBA1A gene in Hep3B cells was determined in microarray experiments. Apoptotic mode of cell death was evaluated using standardized staining procedures including comet assay and annexin V/PI staining, Immuno-peroxidase assay. Using western blotting technique, caspase dependant apoptotic mode of cell death was recorded against Hep3B cell line. Conclusion: It is concluded that a novel DAAD2 with IC50 values less than 8 μM can induce massive cell attenuation following caspase dependent apoptotic cell death in Hep3B cells. Moreover, the corelation study indicated that DAAD2 may have vital influence on cell prolifration properties.