Retrospective evaluation of trabectedin use in metastatic soft tissue sarcomas: A single-center experience

Çalışmada metastatik yumuşak doku sarkomu tanısıyla trabektedin tedavisi alan hastaların tedavi yanıtları, sağkalım sonuçları, ilaç yan etkilerinin değerlendirilmesi amaçlanmıştır. Sarkom tanısıyla trabektedin tedavisi alan 16 hastanın dosyaları retrospektif olarak tarandı. Hastaların demografik özellikleri, tedavi süreleri, tedavi yanıtları, ilaç yan etkileri kaydedildi. 16 hastanın 9’u erkek (%56,2), 7’si kadındı (%43,7). Trabektedin için medyan progresyonsuz sağkalım (progression-free survival, PFS) 2,9 ay, genel sağkalım (overall survival, OS) 6,7 ay saptandı. Sağkalım üzerine etkili olan tek faktör trabektedin tedavi sırası olarak belirlendi. Trabektedini 2. ya da 3.sıra tedavi olarak alan hastalar daha iyi PFS süresine (medyan PFS 10,3 aya karşı 1,6 ay, %95 GA: 0-21.9, p= 0.003) ve OS süresine (medyan 26,7 ay’a karşı 5,7 ay, %95 GA: 16.9-36.5, p= 0.003) sahipti. Sarkom çalışmalarında objektif yanıt değerlendirme kriteri olarak kullanılan büyüme modülasyon indeksi (growth modulation index, GMI) değeri 1,33’ün üzerinde olan hastaların PFS ve OS süreleri istatiksel anlamlı olarak daha iyiydi (medyan PFS 19,8 ay, p=0.002; medyan OS 26,7 ay, p=0.047). Tüm hastalarda yan etki gözlendi, grad 3/4 yan etkiler hematolojik yan etkiler %62,5 ve alanin aminotransferaz (ALT)/ aspartat aminotransferaz (AST) artışı %50 sıklıkta oldu. Çalışmada saptanan PFS, OS, yanıt oranları ve yan etkiler diğer çalışmalar ile benzer saptanmış, trabektedini 2.ve 3.sıra tedavi olarak alan hastaların ilaçtan daha fazla fayda gördüğü belirlenmiştir.This study aimed to evaluate the treatment responses, survival results, and drug side effects of patients treated with trabectedin for metastatic soft tissue sarcoma. The files of 16 patients who received trabectedin treatment with the diagnosis of sarcoma were reviewed retrospectively. Demographic characteristics of the patients, duration of treatment, response to treatment, and drug side effects were recorded. Of 16 patients, 9 (56.2%) were male and 7 (43.7%) were female. Median progression-free survival (PFS) for trabectedin was 2.9 months, and overall survival (OS) was 6.7 months. The only factor effective on survival was determined as trabectedin treatment line. Patients receiving trabectedin as second or third-line therapy had better PFS time (median PFS 10.3 vs 1.6 months, 95% CI: 0-21.9, p= 0.003) and OS time (median 26.7 vs 5.7 months, 95% CI: 16.9-36.5, p= 0.003). Patients with a growth modulation index (GMI) value above 1.33, which is used as an objective response evaluation metric in sarcoma studies, had statistically significantly better PFS and OS times (median PFS 19.8 months, p=0.002; median OS 26.7 months, p=0.047). Any grade side effects were observed in all patients, grade 3/4 side effects were hematological side effects in 62.5% and alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) increase in 50%. The PFS, OS, response rates and side effects detected in the study were found to be similar to other studies, and it was determined that the patients who received trabectedin as the second and third-line treatment benefited more from the drug

The Ki-67 proliferation index predicts recurrence-free survival in patients with dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2−412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019−1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences

Why do some patients with stage 1A and 1B endometrial endometrioid carcinoma experience recurrence? A retrospective study in search of prognostic factors

Objectives: Endometrial endometrioid carcinoma (EEC) is the most encountered subtype of endometrial cancer (EC). Our study aimed to investigate the factors affecting recurrence in patients with stage 1A and 1B EEC. Material and methods: Our study included 284 patients diagnosed with the International Federation of Gynecology and Obstetrics stage 1A/1B EEC in our center from 2010 to 2018. The clinicopathological characteristics of the patients were obtained retrospectively from their electronic files. Results: The median age of the patients was 60 years (range 31–89). The median follow-up time of the patients was 63.6 months (range 3.3–185.6). Twenty-two (7.74%) patients relapsed during follow-up. Among the relapsed patients, 59.1% were at stage 1A ECC, and 40.9% were at stage 1B. In our study, the one-, three-, and five-year recurrence-free survival (RFS) rates were 98.9%, 95.4%, and 92.9%, respectively. In the multivariate analysis, grade and tumor size were found to be independent parameters of RFS in all stage 1 EEC patients. Furthermore, the Ki-67 index was found to affect RFS in stage 1A EEC patients, and tumor grade affected RFS in stage 1B EEC patients. In the time-dependent receiver operating characteristic curve analysis, the statistically significant cut-off values were determined for tumor size and Ki-67 index in stage 1 EEC patients. Conclusions: Stage 1-EEC patients in the higher risk group in terms of tumor size, Ki-67, and grade should be closely monitored for recurrence. Defining the prognostic factors for recurrence in stage 1 EEC patients may lead to changes in follow-up algorithms

The impact of Ki-67 index, squamous differentiation, and several clinicopathologic parameters on the recurrence of low and intermediate-risk endometrial cancer

Endometrial endometrioid carcinoma (EEC) represents approximately 75-80% of endometrial carcinoma cases. Three hundred and thirty-six patients with EEC followed-up in the authors’ medical center between 2010 and 2018 were included in our study. Two hundred and seventy-two low and intermediate EEC patients were identified using the European Society for Medical Oncology criteria and confirmed by histopathological examination. Recurrence was reported in 17 of these patients. The study group consisted of patients with relapse. A control group of 51 patients was formed at a ratio of 3:1 according to age, stage, and grade, similar to that in the study group. Of the 17 patients with recurrent disease, 13 patients (76.5%) were Stage 1A, and 4 patients (23.5%) were Stage 1B. No significant difference was found in age, stage, and grade between the case and control groups (p > 0.05). Body mass index, parity, tumor size, lower uterine segment involvement, SqD, and Ki-67 index with p<0.25 in the univariate logistic regression analysis were included in the multivariate analysis. Ki-67 was statistically significant in multivariate analysis (p = 0.018); however, there was no statistical significance in SqD and other parameters. Our data suggest that the Ki-67 index rather than SqD needs to be assessed for recurrence in patients with low- and intermediate-risk EEC

Metastatik meme kanseri tedavisinde lapatinib kapesitabin kombinasyonun etkinliğinin retrospektif değerlendirilmesi.

Tüm dünyada meme kanseri kadınlarda kanserin ve kanser ilişkili ölümlerin en sık nedenidir. Meme kanserli hastaların %17-30 HER2overekspresyonu olup hastalık, kötü prognoz, hastalık progresyon riskinde artış, genel sağkalım ve progresyona kadar geçen sürenin herikisinde azalma ile birliktedir. Lapatinib, HER2 ve epidermal büyüme faktör reseptör(EGFR) ün ilk dual tirozin kinaz inhibitörüdür. Buçalışma da antrasiklin, taksan ve trastuzumab tedavisi sonrasında progrese olan metastatik meme kanserli hastalarda kapesitabin ve lapatinibkombinasyonunun etkisini ve tolerabilitesini inceledik. Medyan yaş 56 (34-76) olan toplam 24 hasta dosyası Eylül 2010-Mayıs 2018 arasında3 merkezde retrospektif olarak incelendi. Tüm hastalar taksan ve antrasiklin içeren kemoterapi ve trastuzumab sonrası progrese olanHER2 pozitif metastatik meme kanseri hastalardı. Genel cevap oranı %29.1, 2 komplet yanıt (CR, 8.3%), 5 parsiyel yanıt (PR, 20.8%) ve 7stabil hastalık (SD, 29.1%) olmak üzere sağlandı. Kapesitabin ve lapatinib kombinasyon tedavisi antrasiklin, taksan ve trastuzumab tedavisisonrasında progrese olan metastatik meme kanserli hastalarda etkili ve iyi tolere edilmiştir.Worldwide, breast cancer is the most common malignancy and cause of cancer-related death in women. In the 17%–30% of breast cancer patients who overexpress ErbB2 (HER2), the disease is associated with poorer prognosis, greater risk for disease progression and reductions in both progression free survival (PFS) and overall survival (OS). Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 24 patients with a median age of 56 (34-76) were evaluated retrospectively in 3 centers between September 2010 and May 2018. All the patients had HER2 positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. An overall response rate (ORR) of 29.1% was achieved including 2 complete responses (CR, 8.3%), 5 partial responses (PR, 20.8%), and 7 stable disease (SD, 29.1%). Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy

Retrospective evaluation of the efficacy of lapatinib capecitabine in the treatment of metastatic breast cancer

Tüm dünyada meme kanseri kadınlarda kanserin ve kanser ilişkili ölümlerin en sık nedenidir. Meme kanserli hastaların %17-30 HER2overekspresyonu olup hastalık, kötü prognoz, hastalık progresyon riskinde artış, genel sağkalım ve progresyona kadar geçen sürenin herikisinde azalma ile birliktedir. Lapatinib, HER2 ve epidermal büyüme faktör reseptör(EGFR) ün ilk dual tirozin kinaz inhibitörüdür. Buçalışma da antrasiklin, taksan ve trastuzumab tedavisi sonrasında progrese olan metastatik meme kanserli hastalarda kapesitabin ve lapatinibkombinasyonunun etkisini ve tolerabilitesini inceledik. Medyan yaş 56 (34-76) olan toplam 24 hasta dosyası Eylül 2010-Mayıs 2018 arasında3 merkezde retrospektif olarak incelendi. Tüm hastalar taksan ve antrasiklin içeren kemoterapi ve trastuzumab sonrası progrese olanHER2 pozitif metastatik meme kanseri hastalardı. Genel cevap oranı %29.1, 2 komplet yanıt (CR, 8.3%), 5 parsiyel yanıt (PR, 20.8%) ve 7stabil hastalık (SD, 29.1%) olmak üzere sağlandı. Kapesitabin ve lapatinib kombinasyon tedavisi antrasiklin, taksan ve trastuzumab tedavisisonrasında progrese olan metastatik meme kanserli hastalarda etkili ve iyi tolere edilmiştir.Worldwide, breast cancer is the most common malignancy and cause of cancer-related death in women. In the 17%–30% of breast cancer patients who overexpress ErbB2 (HER2), the disease is associated with poorer prognosis, greater risk for disease progression and reductions in both progression free survival (PFS) and overall survival (OS). Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 24 patients with a median age of 56 (34-76) were evaluated retrospectively in 3 centers between September 2010 and May 2018. All the patients had HER2 positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. An overall response rate (ORR) of 29.1% was achieved including 2 complete responses (CR, 8.3%), 5 partial responses (PR, 20.8%), and 7 stable disease (SD, 29.1%). Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy

Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data

Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4–85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan–Meier analysis, the PFS was 39.9 months (95% CI, 7.7–72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, p = 0.033). The OS was 66.1 months (95% CI, 30.2–102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients

The predictive importance of body mass index on response to neoadjuvant chemotherapy in patients with breast cancer

Purpose: The aim of the study was to investigate the effects of body mass index (BMI) on the response to neoadjuvant chemotherapy (NACT) in Turkish patients with local and locally advanced breast cancer. Methods: The pathological responses for the breast and axilla were assessed according to the Miller-Payne grading (MPG) system. Tumors were grouped into molecular phenotypes and classified as response rates according to the MPG system after the completion of NACT. A 90% or greater reduction in tumor cellularity was considered a good response to treatment. Additionally, patients were grouped according to BMI into <25 (group A) and ≥25 (group B). Results: In total, 647 Turkish women with breast cancer were included in the study. In the univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and BMI were assessed to determine which of these factors were associated with a ≥90% response rate. Stage, HER2 positivity, triple-negative breast cancer (TNBC; ER-negative, PR-negative, and HER2-negative breast cancer), grade, Ki-67 levels, and BMI were found to be the statistically significant factors for a ≥90% response rate. In the multivariate analysis, grade III disease, HER2 positivity, and TNBC were found to be the factors associated with a high pathological response. Meanwhile, hormone receptor (HR) positivity and a higher BMI were associated with a decreased pathological response in patients receiving NACT for breast cancer. Conclusion: Our results show that a high BMI and HR positivity are associated with a poor response to NACT in Turkish patients with breast cancer. The findings presented in this study may guide novel studies to examine the NACT response in obese patients with and without insulin resistance