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1.
Cancers (Basel) ; 16(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38927957

RESUMEN

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023. This study included 111 patients (54 women, 57 men) with a median age of 58 years. The median progression-free survival (PFS) and overall survival (OS) were 11.7 months and 18.2 months, respectively, whereas the objective response rate (ORR) was 70.3%. Multivariable analyses revealed that previous curative surgery was a favorable independent prognostic factor for both PFS and OS. Conversely, an Eastern Cooperative Oncology Group performance status of 2 emerged as an adverse independent prognostic factor for OS. The safety profile of nivolumab plus chemotherapy was found to be manageable. Our findings support the use of nivolumab plus chemotherapy for the first-line treatment of Turkish patients with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Patient selection based on clinical characteristics is crucial for optimizing treatment outcomes.

2.
J Chemother ; : 1-10, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38803194

RESUMEN

We evaluated the incidence, clinicopathological features, prognostic factors, progression-free survival (PFS) and overall survival (OS) of patients with gastric cancer and bone metastases. The medical records of 110 patients with bone metastases were retrospectively analyzed. In our study, the incidence of bone metastases was 3.2%. The median patient age was 60 years. A total of 68 (61.8%) patients exhibited synchronous metastases, and 42 (38.2%) patients developed metachronous metastases. Alkaline phosphatase (ALP) levels were high in 54 (49%) patients. At the median follow-up time of 9.8 months, median PFS and OS times were 4.7 and 6.3 months, respectively. The median interval from the diagnosis to bone metastases was 9.3 months. Univariate analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, use of zoledronic acid treatment, palliative chemotherapy post-bone metastases and radiotherapy to bone metastases were significant prognostic indicators for PFS. Additionally, ECOG PS ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, zoledronic acid treatment, palliative chemotherapy post-bone metastases, and radiotherapy to bone metastases significantly influenced OS. Moreover, in multivariate analysis, ECOG PS, time of metastases, presence of extra-bone metastases, and the use of palliative chemotherapy after bone metastases were found to be independent prognostic factors for PFS. Moreover, ECOG PS, time of metastases, and use of palliative chemotherapy after bone metastases were significantly independent prognostic indicators for OS. Our findings show that the presence of synchronous metastases, use of palliative chemotherapy, use of zoledronic acid after bone metastases, and ALP level within the normal range were significantly associated with prolonged OS in gastric cancer patients with bone metastases.

3.
Curr Probl Cancer ; 50: 101102, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735211

RESUMEN

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25-30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Neoplasias de la Mama , Terapia Neoadyuvante , Receptor ErbB-2 , Humanos , Femenino , Terapia Neoadyuvante/métodos , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Pronóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Anciano , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/tratamiento farmacológico , Tasa de Supervivencia , Quimioterapia Adyuvante/métodos
4.
Medicine (Baltimore) ; 103(21): e37972, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787994

RESUMEN

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.


Asunto(s)
Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas , Crizotinib , Neoplasias Pulmonares , Humanos , Crizotinib/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Quinasa de Linfoma Anaplásico/genética , Adulto , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Resultado del Tratamiento
5.
Expert Opin Pharmacother ; 25(4): 477-484, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38568074

RESUMEN

BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.


Asunto(s)
Antimetabolitos Antineoplásicos , Capecitabina , Neoplasias de la Mama Triple Negativas , Humanos , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Quimioterapia Adyuvante/métodos , Antimetabolitos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Supervivencia sin Enfermedad , Turquía , Anciano , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasia Residual , Tasa de Supervivencia , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mastectomía
6.
J Chemother ; : 1-9, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38351652

RESUMEN

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

7.
Jpn J Clin Oncol ; 54(5): 562-568, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38271177

RESUMEN

OBJECTIVE: 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.


Asunto(s)
Neoplasias , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/patología , Turquía , Adulto , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Medicina de Precisión , Resultado del Tratamiento , Relevancia Clínica
8.
Cancer Chemother Pharmacol ; 93(1): 71-78, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37773537

RESUMEN

BACKGROUND: Prostate cancer is a prevalent cancer in men worldwide, and castration-resistant prostate cancer (CRPC) is characterized by disease progression despite androgen deprivation therapy. While clinical and prognostic biomarkers have been identified in CRPC, the significance of serum inflammatory markers remains unclear. MATERIALS AND METHODS: This retrospective study included 79 CRPC patients treated with abiraterone or enzalutamide. Inflammatory markers, including the modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR), were assessed as predictive tools for treatment response. Patient data were obtained from medical charts, and statistical analyses were performed. RESULTS: The median age of the patients was 67 years, with most having a Gleason score of 8-10. The median values for NLR, PLR, and SII were 2.9, 168.5, and 713.5, respectively. The objective response rate (ORR) to abiraterone or enzalutamide therapy was 55.1%. mGPS showed a significant association with ORR, with the mGPS 0 group having the highest response rate (59.5%). Median progression-free survival (PFS) was 12.8 months, and median overall survival (OS) was 35.4 months. Palliative radiotherapy during therapy and PSA doubling time were independent prognostic factors for PFS. CONCLUSIONS: mGPS and PSA doubling time significantly impacted survival, and mGPS significantly predicted the treatment response in mCRPC, which may lead to further prospective studies.


Asunto(s)
Androstenos , Benzamidas , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Anciano , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Antagonistas de Andrógenos , Estudios Retrospectivos , Estudios Prospectivos , Nitrilos , Biomarcadores , Resultado del Tratamiento , Acetato de Abiraterona/uso terapéutico
9.
Turk J Med Sci ; 53(4): 949-961, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38031948

RESUMEN

BACKGROUND: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. METHODS: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5-48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. DISCUSSION: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Pronóstico
10.
J Chemother ; 35(7): 662-670, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37599454

RESUMEN

To evaluate the tumour-infiltrating lymphocyte (TIL) rates in breast tissue before and after neoadjuvant chemotherapy (NAC) and their impact on survival, eighty-four patients with locally advanced breast cancer (LABC) were assessed. Pre- and post-NAC TIL levels were determined using biopsy and surgical specimens, respectively. The median TIL rate was significantly different before (17.5%) and after (5%) NAC. Pre- and postoperative Ki-67 index, molecular subtype, pre- and post-NAC TIL concentration, and preoperative residual-cancer-burden TIL were significantly associated with pathological complete response (pCR). Specifically, higher pre-NAC TIL levels were associated with higher pCR rates. Postoperative Ki-67 index and pCR, and postoperative Ki-67 index were significant predictors of disease-free (DFS) and overall survival, respectively. The independent prognostic factors for DFS were postoperative Ki-67 score (hazard ratio [HR]: 6.16; p = 0.012), post-NAC TIL score (HR: 0.42; P = 0.041), and pCR (HR: 0.10; P = 0.038). Our study confirms that higher pre-NAC and lower postoperative TIL levels may be surrogate factors for longer DFS, and postoperative TIL rate may predict post-NAC pCR in patients with LABC.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Terapia Neoadyuvante , Antígeno Ki-67 , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
11.
J Cancer Res Clin Oncol ; 149(14): 13271-13277, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37480524

RESUMEN

PURPOSE: Anaplastic 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. METHODS: In 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. RESULTS: Of 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). CONCLUSION: Brain, 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.

12.
Artículo en Inglés | MEDLINE | ID: mdl-37347353

RESUMEN

OBJECTIVE: Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. METHODS: A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. RESULTS: One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS. CONCLUSION: CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

13.
Biomol Biomed ; 23(6): 1089-1095, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37289436

RESUMEN

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Masculino , Femenino , Neoplasias Colorrectales/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Compuestos de Fenilurea , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico
14.
J Coll Physicians Surg Pak ; 33(6): 666-672, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37300263

RESUMEN

OBJECTIVE: To evaluate the clinicopathological characteristics of mismatch repair (MMR) deficiency and its clinical outcomes by performing immunohistochemistry (IHC) for MMR genes in the serous ovarian cancer (SOC) tumour sections. STUDY DESIGN: A retrospective case-control study. Place and Duration of the Study: Gynecology Department of Kanuni Sultan Süleyman Training and Research Hospital, and Department of Medical Oncology of Medipol University, between March 2001 and January 2020. METHODOLOGY: IHC was carried out for MLH1, MSH2, MSH6, and PMS2 on full-section slides from 127 SOCs to evaluate the MMR status. MMR-negative and MMR-low groups together were defined as MMR deficient and called microsatellite instability-high (MSI-H). The MSI status and expression of programmed cell death-1 (PD-1) were compared in SOCs with different MMR statuses. RESULTS: A significantly higher frequency of MMR-deficient SOCs was diagnosed at early stages compared with the patients in the MSS group (38.6% and 20.6%, respectively, p=0.022). The frequency of cases with PD-1 expression was significantly higher in the MSI-H group (76.2%) than in the MSS counterparts (58.8%, p=0.028). Patients in the MSI-H group had significantly longer DFS (25.6 months) and OS (not reached) than those in the MSS group (16 months and 48.9 months, p=0.039 and p=0.026, respectively). CONCLUSION: MSI-H SOCs were diagnosed at an earlier stage as compared to MMR proficient cases. The presence of PD-1 expression was significantly higher in cases presenting MMR deficiency compared with MMR-proficient cases. MSI status was significantly associated with DFS and OS. KEY WORDS: Serous ovarian cancer, Microsatellite instability, Mismatch repair deficiency.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Reparación de la Incompatibilidad de ADN/genética , Inestabilidad de Microsatélites , Receptor de Muerte Celular Programada 1/genética , Estudios Retrospectivos , Estudios de Casos y Controles , Carcinoma Epitelial de Ovario , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Cistadenocarcinoma Seroso/genética
15.
Medicine (Baltimore) ; 102(15): e33432, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37058061

RESUMEN

Atezolizumab is now the standard treatment for extensive-stage small cell lung cancer (ES-SCLC). Herein, we investigated the prognostic role of inflammatory markers in patients treated with atezolizumab plus chemotherapy and evaluated the efficacy and safety of adding atezolizumab to chemotherapy for patients with ES-SCLC and prognostic and predictive factors as a real-life experience. This retrospective study included 55 patients who received front-line atezolizumab with etoposide plus platin regimen for ES-SCLC. We analyzed the survival outcomes and factors that may predict response and survival. The objective response rate (ORR) was 81.8%. At a median follow-up of 23.5 months, the median progression-free survival (PFS) time was 10.8 months, and the median overall survival (OS) time was 15.2 months. In univariate analysis for PFS, limited-stage disease at the time of diagnosis, the presence of prophylactic cranial irradiation (PCI), the presence of liver metastasis, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were found to be prognostic factors (P = .041, P = .034, P = .031, P = .004, and P = <.001, respectively). In other words, while the median PFS time was 14.1 months in patients with PLR ≤ 135.7, it was 7.5 months in patients with > 135.7. Similarly, median PFS was 14.9 months in patients with NLR ≤ 3.43, while it was 9.6 months in patients with > 3.43. Univariate analysis for OS revealed that limited stage at the time of diagnosis, NLR and PLR were significant prognostic indicators (P = .01, P = .006, and P = .007, respectively). Median OS time for patients with both NLR ≤ 3.43 and PLR ≤ 135.7 was significantly better than that of patients with NLR > 3.43 and PLR > 135.7 (16.9 vs 11.3 and 16.9 vs 11.5 months, respectively). Logistic regression analysis demonstrated that PLR was an independent significant predictive factor for the response to atezolizumab plus chemotherapy (OR: 0.07, P = .028). The patients with PLR ≤ 135.7 were significantly good responders to atezolizumab plus chemotherapy treatment. Real-life data demonstrated a significant correlation between survival and NLR and, PLR in ES-SCLC patients treated with atezolizumab. In addition, PLR was a significant predictive indicator of response to atezolizumab plus chemotherapy.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neutrófilos/patología , Neoplasias Pulmonares/patología , Pronóstico , Estudios Retrospectivos , Linfocitos/patología , Plaquetas/patología
16.
Head Neck ; 45(7): 1643-1653, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37084179

RESUMEN

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias de las Glándulas Salivales , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Neoplasias de las Glándulas Salivales/epidemiología , Neoplasias de las Glándulas Salivales/terapia , Glándulas Salivales Menores/patología
17.
Acta Oncol ; 62(4): 381-390, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37083566

RESUMEN

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Trastuzumab/uso terapéutico , Neoplasias de la Mama/patología , Terapia Neoadyuvante/métodos , Docetaxel , Estudios Retrospectivos , Receptor ErbB-2 , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Paclitaxel , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
18.
Mol Biol Rep ; 50(4): 3489-3492, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36781608

RESUMEN

BACKGROUND: In vitro studies have shown that the functional - 1478CA > del polymorphism (rs33989964) of the suppressor of cytokine signaling (SOCS)-1 gene is associated with an altered trascriptional activity. Here, we sought to examine the potential association of this polymorphism with the risk of gastric cancer (GC) and to analyze its prognostic impact on overall survival (OS). MATERIALS AND METHODS: The study cohort consisted of 74 Turkish patients with GC and 52 healthy controls. Genotyping of the SOCS-1 -1478CA > del polymorphism was carried out using restriction fragment length polymorphism analysis. RESULTS: After allowance of age and sex, multivariable logistic regression analysis revealed that the carriage of the del allele of the SOCS-1 -1478CA > del polymorphism was independently associated with an increased risk of GC (odds ratio = 6.78, 95% confidence interval = 3.24-10.99, P < 0.001). Kaplan-Meier analysis revealed no significant differences in OS for patients harboring at least one del allele of rs33989964 compared with CA/CA homozygotes (log-rank test, P = 0.17). CONCLUSION: While the SOCS-1 -1478CA > del polymorphism is significantly associated with the risk of GC in the Turkish population, it does not affect OS.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Polimorfismo Genético , Proteínas Supresoras de la Señalización de Citocinas/genética , Homocigoto , Alelos , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo
19.
Clin Genitourin Cancer ; 21(3): 334-341, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36641357

RESUMEN

BACKGROUND: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). PATIENTS AND METHODS: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. RESULTS: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. CONCLUSION: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Supervivencia sin Progresión , Estimación de Kaplan-Meier
20.
Anticancer Drugs ; 33(10): 1150-1155, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36206103

RESUMEN

The aim of this study was to investigate the predictive value of PLR and NLR as an indicator of pathological complete response (pCR) in patients with breast cancer after NACT. One hundred thirty-nine patients with early or LABC and candidates to NACT were retrospectively analyzed. The prognostic significance of PLR and NLR was analyzed. In addition, predictive indicators of pCR to NACT were also evaluated. pCR was obtained in 48.9% of patients. Significant difference was detected between pCR and PLR, tumor grade, clinical lymph node status and molecular subgroup. The higher rate of pCR was significantly achieved for patients with PLR low ( < 181.7) compared with those with PLR high (>181.7) (68.6% vs. 33.4%; P < 0.001). PLR, tumor grade and pCR to NACT for disease-free survival (DFS), and PLR, NLR, tumor grade and pCR to NACT for overall survival were detected to be prognostic factors by univariate analysis. On the other hand, a logistic regression analysis indicated that PLR and NLR were found to be an independent factors for predicting pCR to NACT ( P < 0.001; OR, 0.07; 95% CI, 0.02-0.25 and P = 0.016; OR, 4.66; 95% CI, 1.33-16.2, respectively), as were molecular subtypes ( P = 0.001; OR, 0.23; 95% CI, 0.09-0.56). Our results showed that PLR low and NLR low before NACT are readily feasible and simple and also inexpensive biomarkers predicting pCR to NACT for patients with LABC.


Asunto(s)
Neoplasias de la Mama , Neutrófilos , Biomarcadores de Tumor , Plaquetas/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Linfocitos/patología , Terapia Neoadyuvante , Neutrófilos/patología , Pronóstico , Estudios Retrospectivos , Turquía
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