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Publication Metadata only The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study)(Springer Science and Business Media Deutschland Gmbh, 2023) Hizal,M.; Bilgin,B.; Paksoy,N.; Atcı,M.M.; Kahraman,S.; Kılıçkap,S.; Güven,D.C.; Keskinkılıç,M.; Ayhan,M.; Eren,O.; Mustafayev,F.N.A.; Yaman,Ş.; Bayram,E.; Ertürk,İ.; Özcan,E.; Korkmaz,M.; Akagündüz,B.; Erdem,D.; Telli,T.A.; Aksoy,A.; Üskent,N.; Baytemür,N.K.; Gülmez,A.; Aydın,D.; Şakalar,T.; Arak,H.; Tatlı,A.M.; Ergün,Y.; Ak,N.; Ünal,Ç.; Özgün,M.A.; Yalçın,B.; Öztop,İ.; Algın,E.; Sakin,A.; Aydıner,A.; Şendur,M.A.N.; Yumuk, Perran Fulden; School of MedicineIntroduction: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. Materials and methods: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. Results: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25–0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22–0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20–39%, 40–59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. Conclusion: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.Publication Metadata only Prognostic significance of mucinous histology in left‑sided metastatic colorectal cancers with wild‑type RAS and evaluation of backbone chemotherapy regimens(Spandidos Publ Ltd, 2023) Arikan, Rukiye; Atci, Muhammed Mustafa; Ay, Seval; Ayhan, Murat; Demircan, Nazim Can; Telli, Tugba Akin; Celebi, Abdussamet; Yasar, Alper; Isik, Selver; Celikel, Cigdem; Balvan, Ozlem; Bayoglu, Ibrahim Vedat; Kostek, Osman; Dane, Faysal; Yumuk, Perran Fulden; School of MedicineMucinous colorectal adenocarcinoma (MCAC) is a distinct subtype of colorectal carcinoma (CRC). The prognostic and predictive significance of mucinous histology remains controversial. It was aimed to investigate the prognostic and/or predictive role of mucinous histology in left-sided metastatic CRC (mCRC) with wild-type RAS. This is a retrospective multicenter study of mCRC treated with first line anti-EGFR combined 5-fluorouracil based chemotherapy (CT). Patients were stratified according to presence (>50% extracellular mucin) or absence of mucinous histology. Survival analyses were performed firstly regardless of treatment options and then performed as separating according to CT regimens. Additional analyses were performed for MCAC patients considering backbone CT regimens. A total of 125 patients were included, consisting of 40 (32.0%) patients with MCAC and 85 (68.0%) patients with non-MCAC. Median follow-up time was 19.7 months. Median progression-free survival (PFS) was 10.7 months in all patients, and PFS was lower in MCAC than non-MCAC (9.9 vs. 12.0 months, respectively, P=0.005). Median overall survival (OS) was 25.7 months in all patients. OS was lower in MCAC than non-MCAC (22.8 vs. 29.7 months, respectively, P=0.005). When considering backbone CT regimens, in multivariate analyses, mucinous histology was an independent prognostic factor for OS in both for mFOLFOX6 (HR: 1.92, P=0.04) and FOLFIRI (HR: 2.04, P=0.04) groups and was associated with poor PFS in only mFOLFOX6 (HR: 3.86, P<0.001) group. When outcomes were analyzed for the MCAC group, median OS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 22.47 and 14.22 months, respectively (P=0.41). Median PFS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 10.15 and 8.11 months, respectively (P=0.73). The study revealed poor prognosis of mucinous histology, both in whole study population and in backbone CT groups. Moreover, lower PFS of MCAC patients was revealed in only mFOLFOX6 group and this finding may be a valuable issue for the future research. However, considering all analyses, the present results did not indicate a special benefit of any backbone CT regimen for MCAC patients.Publication Metadata only A population-based validation of the IGCCCG update consortium for survival in metastatic non-seminoma testis cancer(Oxford Univ Press, 2024) Incesu, Reha-Baris; Morra, Simone; Scheipner, Lukas; Barletta, Francesco; Baudo, Andrea; Garcia, Cristina Cano; Tappero, Stefano; Piccinelli, Mattia Luca; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; de Cobelli, Ottavio; Terrone, Carlo; Chun, Felix K. H.; Carmignani, Luca; Briganti, Alberto; Ahyai, Sascha; Longo, Nicola; Tilki, Derya; Graefen, Markus; Karakiewicz, Pierre, I; Tilki, Derya; School of Medicine; Koç University HospitalBackground: In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients. Patients and Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM). Results: Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P < 0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P < 0.001) were independent predictors of higher OM, relative to good prognosis group. Conclusions: The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large.Publication Metadata only Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+ rectal cancer: Istanbul R-02 phase II randomized study(Tech Science Press, 2023) Saglam, Sezer; Saglam, Esra Kaytan; Yanar, Hakan; Gok, Kaan; Tastekin, Didem; Akbas, Canan Koksal; Sakin, Nergiz Dagoglu; Kartal, Gulbiz Dagoglu; Keskin, Metin; Sanli, Yasemin; Gulluoglu, Mine; Akgun, Zuleyha; Şenyürek, Şükran; Balık, Emre; School of Medicine; Koç University HospitalRadiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group. Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module (EORTC QLQ-CR29) was administered at baseline and at three and six months after CRT. A total of 60 patients with LARC randomized to receive IC-CRT (n = 30) or LC-CRT (n = 30) were included in this phase II randomized trial. No significant difference was noted between groups in terms of pathological outcomes, including pathological response rates (ypT0N0-complete response: 23.3% vs. 16.7%, respectively, and ypT0-2N0downstaging: 50% for each; p = 0.809) and Dworak score-based pathological tumor regression grade (Grade 4-complete response: 23.3 vs. 16.7%, p = 0.839). The 5-year overall survival (73.3 vs. 86.7%, p = 0.173) rate was also similar. The acute radiation dermatitis (p < 0.001) and any hematological toxicity (p = 0.004) rates were significantly higher in the LC-CRT group, while no significant difference was noted between treatment groups in terms of baseline, third month, and sixth month EORTC QLQ-CR29 scores.Publication Metadata only Neoadjuvant chemotherapy and pathologic complete response in HR+/HER2-Breast Cancer: impact of Tumor Ki67 and ER status(KARGER, 2024) Akdağ, Goncagül; Yıldırım, Sedat; Doğan, Akif; Yaşar, Zeynep Yuksel; Bal, Hamit; Kınıkoğlu, Oğuzcan; Oksuz, Sila; Ozkerim, Ugur; Tunbekici, Salih; Yildiz, Hacer Sahika; Turkoglu, Ezgi; Kokten, Sermin Coban; Isik, Deniz; Sever, Özlem Nuray; Odabaş, Hatice; Yıldırım, Mahmut Emre; Turan, Nedim; Alan, Özkan; School of Medicine; Koç University HospitalIntroduction: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2)-positive BC and in estrogen receptor-positive (ER+)/HER2- BC with high-risk features. In ER+/HER2- BC, pathological complete rates are much lower (<10%), while axillary dissection rates are higher. This study focuses on hormone receptor-positive (HR+)/HER2- BC patients undergoing NAC, examining its impact on pathological complete response (pCR) rates, with specific attention to tumor Ki67 and ER status. Methods: Retrospective data analysis from Kartal Dr. L & uuml;tfi K & imath;rdar City Hospital included HR+/HER2- BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR. Results: Of 203 patients, 11.8% achieved pCR. Ki67 (p < 0.001) and ER percentage (p < 0.001) significantly correlated with pCR. Higher Ki67 was associated with increased pCR likelihood (HR: 1.03, 95% CI: 1.01-1.05). A Ki67-pCR probability curve revealed a cutoff of 23.5%. ER%-pCR analysis showed decreasing pCR rates with higher ER percentages. Multivariate analysis confirmed Ki67 (p = 0.003, HR: 1.02) and ER percentage (p = 0.019, HR: 0.97) as independent predictors of pCR probability. Conclusion: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2- BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 <= 24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.Publication Metadata only Response to Deantoni et al.(Sage Publications Ltd, 2024) Topkan, Erkan; Somay, Efsun; N/A; Selek, Uğur; School of MedicineN/APublication Metadata only Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study(Taylor & Francis Ltd, 2024) Dulgar, Özgecan; Türker, Sema; Başaran, Gül; Araz, Murat; Sümbül, Ahmet Taner; Çağglayan, Dilek; Gümüşay, Özge; Biter, Sedat; Konca, Ahmet; Özen, Miraç; Demir, Hacer; Özdemir, Melek; Karatas, Fatih; Sahin, Elif; Cavdar, Eyyup; Yasin, Ayse Irem; Yasar, Alper; Derin, Suemeyra; Pehlivan, Metin; Uyeturk, Ummugul; Ozdemir, Ozlem; Kayikcioglu, Erkan; Ak, Naziye; Sakalar, Teoman; Sakin, Abdullah; Buyuksimsek, Mahmut; Ay, Seval; Erturk, Ismail; Yucel, Kadriye Bir; Gumus, Mahmut; Akbaş, Sinem; Koç University HospitalWe aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2);this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.Publication Metadata only Timing of chemotherapy after diagnosis of small cell lung cancer(Taylor & Francis Ltd, 2024) Tas, Faruk; Ozturk, Akin; Ertürk, Kayhan; School of MedicineSystemic chemotherapy is the backbone of therapeutic management in small cell lung cancer (SCLC) and delay of treatment may lead to adverse patient outcomes. This study was conducted to determine the time elapsed between pathological diagnosis and initiation of chemotherapy in SCLC patients and to evaluate its clinical significance. A total of 323 pathologically confirmed SCLC patients were enrolled in the study and analyzed retrospectively. The median value of the patients' time to treatment was used as the cut-off value in distinguishing between early and late chemotherapy. The median (range) of the time interval between the pathological diagnosis and the initiation of chemotherapy was 18 days (1-257). Compared with other clinical variables, only the performance status of patients was significantly associated with the time from diagnosis to initiation of chemotherapy;patients with poor prognostic factors received chemotherapy earlier than other patients (32.9 vs 18.9%, p = 0.004, and 14.5 vs 19 days, p = 0.006). Although patients who received early treatment were found to live less, there was no statistically significant difference in overall survival in patients according to the timing of chemotherapy administration (p = 0.08). In conclusion, there are controversial results about the timing of chemotherapy administration to SCLC patients. More standardized definitions and guides for calculation of the time interval between diagnosis and treatment are needed to better understand the delays in the treatment of patients with clinically rapidly disseminating SCLC.Publication Metadata only Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?(Springer, 2023) Guner, Gurkan; Aktas, Burak Yasin; Basal, Fatma Bugdayci; Demirkazik, Ahmet; Gursoy, Pinar; Demirci, Umut; Erman, Mustafa; Senler, Filiz Cay; Cakar, Burcu; Cicin, Irfan; Ozturk, Akin; Coskun, Hasan Senol; Cubukcu, Erdem; Isikdogan, Abdurrahman; Olmez, Omer Fatih; Tatli, Ali Murat; Karaagac, Mustafa; Sakalar, Teoman; Eralp, Yesim; Korkmaz, Taner; Kilickap, Saadettin; Yumuk, Perran Fulden; School of MedicinePurposeAnaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E.MethodsIn this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC.ResultsOf the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008;19.1% vs 4.8%, p = 0.001;20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051).ConclusionBrain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.Publication Metadata only Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study(Oxford University Press, 2024) Olmez, Omer Fatih; Bilici, Ahmet; Er, Ozlem; Bisgin, Atil; Sevinc, Alper; Akman, Tulay; Uslu, Ruchan; Mandel, Nil Molinas; Yalcin, Suayib; Teomete, Mehmet; Gorumlu, Gurbuz; Demir, Atakan; Namal, Esat; Alici, Suleyman; Bavbek, Sevil; Paksoy, Fatma; Basaran, Gul; Ozer, Leyla; Sener, Nur; Harputluoglu, Hakan; Selçukbiricik, Fatih; School of MedicineObjective The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes.Methods The study encompassed 234 adult patients (mean age: 52.7 +/- 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response.Results Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16).Conclusion Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates. Our real-world study reveals complex molecular profiling significantly impacts treatment decisions for advanced solid tumour patients, though without significant differences in treatment responses.