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OBJECTIVE: To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy. METHODS: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival. RESULTS: The median cumulative cisplatin dose was 210 mg (range 40-320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1-150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin <10 g/dL before chemoradiotherapy as poor prognostic factors for both progression free survival and overall survival in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose <200 mg was found to be a significant poor prognostic factor in overall survival (hazard ratio 1.79, 95% confidence interval 1.1 to 3.0, p=0.031). CONCLUSION: Our study showed that a cumulative cisplatin dose >200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.
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The fact that the human epidermal growth factor receptor 2 (HER2)-low group, historically classified as HER2 negative in breast cancer histology, benefited from HER2-targeted treatments similarly to the HER2-positive group indicates that this group has a distinct histology from the HER2-0 group. The effectiveness of cyclin-dependent kinase 4/6 inhibitors, which are the standard first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer, in this newly defined histological subgroup remains a topic of debate. In our study, we examined the impact of HER2 status on the efficacy of CDK4/6 inhibitors. Our study is a retrospective, multicenter, real-world data analysis. One hundred sixty patients were included in the study. The relationship between HER2 status and other clinical-pathological features, as well as progression-free survival, was examined. Median follow-up was 20.33â ±â 0.98 months. The mPFS could not be reached. All patients exhibited positive estrogen receptor expression. Among the patients, 111 (69.4%) were categorized as HER2-0, and 49 (30.6%) as HER2-low. The 24-month progression-free survival rates were similar between HER2-0 and HER2-low patients (60.6% vs 65.3%, hormone receptor: 1.18, CI: 0.67-2.20, Pâ =â .554). We established that the mPFS achieved with cyclin-dependent kinase 4/6 inhibitors as a first-line therapy for patients with advanced breast cancer is unaffected by HER2 status.
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Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Estudios Retrospectivos , Persona de Mediana Edad , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Adulto , Supervivencia sin Progresión , Receptores de Estrógenos/metabolismoRESUMEN
This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor (VEGF)-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.
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Bevacizumab , Carcinoma de Células Escamosas , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias del Cuello Uterino , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/farmacología , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/metabolismo , Persona de Mediana Edad , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Estudios Retrospectivos , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Metástasis de la Neoplasia , Pronóstico , Supervivencia sin ProgresiónRESUMEN
AIM: Sirolimus, a mammalian target of rapamycin inhibitor, inhibits cell growth and proliferation by controlling ribosome biogenesis and protein synthesis in vascular anomalies and cancers. However, most sirolimus studies on vascular anomalies were conducted in the pediatric population, with limited data in adults. In this study, we assessed the effectiveness and safety of sirolimus in adult patients with vascular malformation, a subtype of vascular anomaly. METHODS: We conducted a retrospective analysis of adult vascular malformation patients aged over 16, treated at Hacettepe University Cancer Institute from January 2013 to September 2022. Patient demographics and clinical characteristics were recorded. The primary outcome was the efficacy of sirolimus evaluated by response and disease control rates. The disease control rate was defined as the cumulative percentage of complete or partial responses, along with stable disease. The secondary endpoint was toxicity and safety. RESULTS: 38 patients with a median age of 21 (IQR: 18-33) were recruited. Prior to sirolimus treatment, 57.9% of patients had undergone other therapeutic interventions, predominantly sclerotherapy and surgery. The median follow-up time during sirolimus treatment was 18.5 (IQR: 11.3-74.5) months. The disease control rate was 92.1% (35/38). Head-neck localization was associated with better response rates (p = .001). Sirolimus was generally well tolerated and grade 1 or 2 oral mucositis (n = 4) and skin rash (n = 3) were the most common side effects. CONCLUSION: In this study, we found sirolimus was efficacious and well tolerated in adult patients with vascular malformation.
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The objective of this study was to explore the possible association between low skeletal muscle mass (SMM)-assessed by computed tomography (CT) and ultrasound (US)-and hematologic toxicity in cancer patients. A prospective cohort study was conducted in cancer patients who received anthracycline-based chemotherapy between 2018 and 2020 and who had baseline abdominal CT including L3 level for measuring SMM. Regional muscle measurements were carried out using US. A total of 65 patients (14 males, 51 females) were included. ROC (receiver operating characteristic) analysis identified threshold values of 18.0 mm [AUC (area under the curve) = 0.765] for females and 20.0 mm (AUC = 0.813) for males, predicting severe neutropenia. Using these cut-offs, females with low rectus femoris (RF) thickness (<18.0 mm) had a significantly higher incidence of grade ≥3 neutropenia (50.0% vs. 10.8%, p = 0.005), and males with low RF values (<20.0 mm) had a higher incidence (80.0% vs. 22.2%, p = 0.063). A regression analysis, irrespective of age, gender, and body mass index, revealed that only low RF muscle thickness increased the risk of grade 3-4 neutropenia by 9.210 times (95% CI = 2.401-35.326, p = 0.001). Utilizing US to measure RF muscle thickness aids in identifying cancer patients at an elevated risk of developing neutropenia. Needless to say, US can serve as a convenient and easily accessible tool for assessing low SMM, providing repeat point-of-care evaluations in clinical practice.
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The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.
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INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.
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Aminopiridinas , Neoplasias de la Mama Masculina , Neoplasias de la Mama , Piperazinas , Purinas , Piridinas , Anciano , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama Masculina/etiología , Receptor ErbB-2/metabolismo , Estudios RetrospectivosRESUMEN
Tyrosine kinase inhibitors (TKIs) have transformed cancer treatment but are associated with cardiovascular toxicity, including heart failure. This review examines the cardiotoxicity of pazopanib, a VEGFR-TKI, through two case reports and explores potential mechanisms. The importance of vigilant clinical monitoring to prevent cardiac dysfunction in cancer patients receiving pazopanib is emphasized. We present two cases of acute heart failure following pazopanib treatment. Case 1 involves a comorbidity-free, 62-year-old woman with metastatic renal cell carcinoma who experienced irreversible heart failure. In case 2, a 40-year-old woman with a history of anthracycline-containing chemotherapy developed reversible left ventricular systolic dysfunction following pazopanib discontinuation. Both patients received appropriate management for their heart failure symptoms. Case 1's condition rapidly deteriorated, leading to her unfortunate demise 3 months after starting pazopanib. In contrast, case 2's cardiac function improved after discontinuing pazopanib. The advent of TKIs has revolutionized cancer treatment, but their association with cardiovascular toxicity necessitates meticulous monitoring of patients. The cases presented here highlight the importance of recognizing and managing cardiotoxicity, particularly in patients without prior cardiovascular risk factors. Understanding the underlying mechanisms and risk factors for TKI-induced heart failure is crucial to optimize patient care and treatment outcomes. Oncologists should be vigilant in identifying clinical symptoms and closely monitoring cardiac function throughout TKI therapy.
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Carcinoma de Células Renales , Insuficiencia Cardíaca , Neoplasias Renales , Pirimidinas , Sulfonamidas , Humanos , Femenino , Persona de Mediana Edad , Adulto , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Cardiotoxicidad/etiología , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Indazoles/efectos adversosRESUMEN
Introduction: Although immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, identifying factors that predict treatment response remains a challenge in clinical practice. There is a need for biomarkers to identify patients who may not benefit from these treatments. It is crucial to identify a simple and cost-effective biomarker that can be easily incorporated into clinical practice. This study aims to investigate the mean platelet volume to lymphocyte ratio (MPVLR), as measured by a hemogram test, and median overall survival (mOS) in patients with cancer treated with nivolumab. Methods: A total of 131 adult patients with metastatic cancer, including malignant melanoma (MM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and head and neck cancer (HNC), were included in this study. Baseline demographics, ECOG (Eastern Cooperative Oncology Group) performance status, tumor type, and blood count parameters were recorded. Univariate and multivariate analyses were conducted to evaluate potential risk factors. Results: The median age of the patients was 59.87 ± 11.97 years, and the median follow-up period was 20.20 months (IQR, 12.80-27.60). RCC (43.5%) and MM (25.9%) were the most common diagnoses. Patients with ECOG scores of 0-1 had a longer mOS than those with scores of 2-3 (mOS: 20.60 months [95% CI, 14.94-25.29] vs. 5.24 months [95% CI, 0-16.42], p < 0.001). Additionally, patients with lactate dehydrogenase (LDH) levels within the normal range had a longer mOS than those with high LDH levels (mOS: 24.54 months [95% CI, 14.13-34.96] vs. 13.10 months [95% CI, 4.49-21.72], p = 0.038). Patients with low MPVLR also had a longer mOS than those with high MPVLR (mOS: 33.70 months [95% CI, 25.99-41.42] vs. 11.07 months [95% CI, 6.89-15.24], p < 0.001). In the multivariate Cox regression analysis, high MPVLR, ECOG score of 2-3, and high LDH level were associated with shorter mOS (p < 0.001, p = 0.001, and p = 0.046, respectively). Conclusion: This study demonstrates that MPVLR could serve as a novel biomarker for predicting response to nivolumab treatment. Incorporating MPVLR into clinical practice may aid in identifying patients who are less likely to benefit from the treatment.
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INTRODUCTION: In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated. MATERIALS AND METHODS: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics. RESULTS: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were ≥ 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of ≥2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity. DISCUSSION: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged ≥75 years and/or with an ECOG performance status ≥2.
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Neoplasias de la Mama , Fragilidad , Neutropenia , Humanos , Anciano , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.
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INTRODUCTION: The therapeutic armamentarium for the neoadjuvant treatment of triple-negative breast cancer (TNBC) has significantly expanded with the hopes of improving pathological complete response (pCR) rates and the possibility of a cure. However, the data on optimal adjuvant treatment strategies for patients with residual disease after neoadjuvant treatment is limited. AREAS COVERED: We discuss the available data on adjuvant treatment for residual TNBC after neoadjuvant treatment considering clinical trials. Additionally, we discuss ongoing trials to give perspectives on how the field may evolve in the next decade. EXPERT OPINION: The available data support the use of adjuvant capecitabine for all patients and either adjuvant capecitabine or olaparib for patients with germline BRCA1 and BRCA2 mutations, according to availability. The CREATE-X study of capecitabine and OlympiA study of olaparib demonstrated disease-free and overall survival benefits. There is an unmet need for studies comparing these two options for patients with germline BRCA mutations. Further research is needed to delineate the use of immunotherapy in the adjuvant setting, molecular targeted therapy for patients with molecular alterations other than germline BRCA mutation, combinations, and antibody-drug conjugates to further improve outcomes.
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Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas , Humanos , Capecitabina , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Mutación de Línea GerminalRESUMEN
Human epidermal growth factor receptor 2 (HER2)-targeting therapies have become crucial in the management of HER2-positive breast cancer. Trastuzumab emtansine (T-DM1) is a microtubule inhibitor and HER2-targeted antibody conjugate. T-DM1 resistance is most likely influenced by factors involved in the biological mechanisms of T-DM1 action. This study aimed to examine the efficacy of statins, which influence HER-2-based therapies via the caveolin-1 (CAV-1) protein, in female breast cancer patients receiving T-DM1. Our study included 105 patients with HER2-positive metastatic breast cancer treated with T-DM1. The progression-free survival (PFS) and overall survival (OS) of patients who received statins concurrently with T-DM1 versus those who did not were compared. During the median 39.5 (95% confidence interval [CI]: 35.6-43.5) months of follow-up, 16 (15.2%) patients received statins, and 89 (84.8%) patients did not. Median OS was significantly higher in patients using statins than in patients not using statins (58.8 vs 26.5 months, P = .016). The association between statin use and PFS did not reach statistical significance (34.7 vs 9.9 months, P = .159). Multivariate Cox regression analysis showed that better performance status (hormone receptor [HR]: 0.30, 95% CI: 0.13-0.71, P = .006), use of trastuzumab plus pertuzumab prior to T-DM1 (HR: 0.37, 95% CI: 0.18-0.76, P = .007) and use of statins with T-DM1 (HR: 0.29, 95% CI: 0.12-0.70, P = .006) were independent factors that prolong OS duration. Our study showed that T-DM1 is more effective at treating HER2-positive breast cancer in people who receive statins concurrently with T-DM1 than those who do not.
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Neoplasias de la Mama , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Maitansina , Humanos , Femenino , Ado-Trastuzumab Emtansina/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Maitansina/uso terapéutico , Trastuzumab/uso terapéutico , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
BACKGROUND: There are biological distinctions between gastric cancers from Eastern and Western nations, and therapeutic strategies may differ regionally. Perioperative chemotherapy, adjuvant chemotherapy, and adjuvant chemoradiotherapy (CRT) have all been demonstrated to be effective in the treatment of gastric cancer. The goal of this study was to do a meta-analysis of published studies that were eligible to see if adjuvant chemoradiotherapy was helpful for gastric cancer based on the cancer's histology. METHOD: From inception to May 4, 2022, manual searches were conducted to identify all eligible literature using the PubMed database for the published phase III clinical trial and a randomize-controlled trial testing the role of adjuvant chemoradiotherapy in operable gastric cancer. RESULTS: Two trials with a total of 1004 patients were selected as a result. Adjuvant CRT was found to have no effect on disease-free survival (DFS) in gastric cancer patients treated with D2 surgery (HR: 0.70 (0.62-1.02), p: 0.07). However, patients with intestinal-type gastric cancers exhibited significantly longer DFS (HR: 0.58 (0.37-0.92), p = 0.02). DISCUSSION: After D2 dissection, adjuvant CRT improved DFS in patients with intestinal-type gastric cancers but not in those with diffuse-type gastric cancers.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Quimioradioterapia Adyuvante/efectos adversos , Supervivencia sin Enfermedad , Quimioterapia Adyuvante , Escisión del Ganglio Linfático , QuimioradioterapiaRESUMEN
INTRODUCTION: There have been significant advances in the treatment of hepatobiliary cancers, especially for advanced-stage disease. However, data is limited for optimal therapy selection in the first line and sequencing of available options. AREAS COVERED: This review covers the systemic treatment of hepatobiliary cancers with an emphasis on the advanced stage. The previously published and ongoing trials will be discussed to create an algorithm for the current practice and to give future perspectives on how the field could go forward. EXPERT OPINION: While there is no standard-of-care option in the adjuvant treatment of hepatocellular cancer, capecitabine is the standard of care for biliary tract cancer. The efficacy of adjuvant gemcitabine and cisplatin and the added benefit of radiotherapy to chemotherapy are yet to be defined. For the advanced stage, immunotherapy-based combinations became the standard of care for both hepatocellular and biliary tract cancers. The molecularly targeted therapy has profoundly changed the second-line and later treatment for biliary tract cancers, while the optimal second-line treatment for advanced hepatocellular cancer is yet to be defined due to rapid advances in the first-line setting.
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Neoplasias del Sistema Biliar , Neoplasias Hepáticas , Humanos , Neoplasias del Sistema Biliar/tratamiento farmacológico , Gemcitabina , Capecitabina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.
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Lesión Renal Aguda , Carcinoma de Pulmón de Células no Pequeñas , Hipoalbuminemia , Neoplasias Pulmonares , Insuficiencia Renal Crónica , Humanos , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Incidencia , Hipoalbuminemia/complicaciones , Neoplasias Pulmonares/complicaciones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Factores de RiesgoRESUMEN
Pancreatic cancer is mostly metastaticat diagnosis. BR east CA ncer gene (BRCA) mutations are associated with platinum sensitivity in metastatic pancreatic cancer. However, curative surgery and complete remission are infrequent. In this report, we present a 42-year-old female patient diagnosed with BRCA-mutated pancreatic cancer with liver metastases. After 12 cycles of FOLFIRINOX, liver metastases disappeared and the patient underwent pancreaticoduodenectomy. The patient has been followed in complete remission for 5 years. To the best of our knowledge, the presented case is the longest recurrence-free survival after platinum-based therapy in metastatic pancreatic cancer with BRCA mutation. Our case emphasizes that investigating BRCA gene mutations at the time of diagnosis can be life-saving in these patients.
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Neoplasias Hepáticas , Neoplasias Pancreáticas , Femenino , Humanos , Adulto , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Oxaliplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Proteína BRCA2/genética , Neoplasias PancreáticasRESUMEN
BACKGROUND: People socialize and receive education and training for the first time outside the home at school, where their teachers act as role models. Teachers play a crucial role in instilling sun-protection habits in children. Avoiding the sun between 10 a.m. and 4 p.m., staying in the shade, wearing sun-protective clothing, wearing sunglasses, wearing hats, using sunscreen products, and using an umbrella are some of the sun-protection methods described in the literature. This study sought to assess teachers' skin cancer knowledge and attitudes (SC). METHODS: In this cross-sectional study conducted between 21 September 2020, and 21 October 2020, 647 teachers from 30 schools in Kahramanmaras were included with their consent. The number of teachers employed at Kahramanmaras was 1863. Accordingly, the sample was found to be 641 with a 5% margin of error and a 99% confidence interval. Schools were selected by a simple random method. Teachers' knowledge and behaviors were assessed using a 25-point questionnaire designed by the literature data to gauge the level of SC knowledge. RESULTS: Of the 647 teachers included in this study, 230 (35.5%) were male, and 417 (64.5%) were female. The mean age of the participants was 38.44 ± 8.79 (min = 22, max = 65) years. The knowledge level of the teachers about SC was 13.54 ± 4.48 (min = 0, max = 23). The internet (75.9%) was the most preferred source of information. SC knowledge level was significantly higher in those with SC in their families and birthmarks on their bodies. (p < 0.001, p = 0.042, respectively). The rate of precaution taken to protect from the sun was higher in those with higher knowledge (p = 0.032). Women, primary school teachers, those with skin type 1, those with multiple nevi, and those with a high level of SC knowledge used statistically significantly more sunscreen (p = 0.001, p = 0.003, p < 0.001, p = 0.037, p = 0.002, respectively). CONCLUSIONS: It was found that the knowledge level of teachers about skin cancer and sun-protective behaviors was moderate. Correct behaviors increased as knowledge about SC grew. Information and recommendations made on the Internet should be made by experts. Additionally, health policymakers should implement projects aimed at improving teachers' knowledge and behaviors and, through them, teaching students about SC; as such projects would significantly contribute to both public health and health economics.
RESUMEN
PURPOSE: A significant portion of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) relapse despite multimodality treatment denoting the need for biomarkers. The pan-immune-inflammation value (PIV) is a recently developed blood count-based prognostic biomarker. We evaluated the relationship between PIV and survival in locally advanced HNSCC patients treated with chemoradiotherapy (CRT). METHODS: A total of 199 patients who underwent CRT at Hacettepe University Oncology Hospital were included. The relationship between clinical and laboratory parameters with overall survival (OS) and disease-free survival (DFS) was analyzed by multivariate analyses. RESULTS: The median age was 59 years and 90.5% of the patients were male. 66.8% of the patients had laryngeal primaries, and 78.9% had T3-T4 disease. 84.9% of the patients received CRT with cisplatin. The optimal PIV threshold value was calculated as 404 in ROC analyses. This PIV value had 75.8% sensitivity and 70.4% specificity for OS prediction (AUC 0.781; 95% CI 0.715-0.846; p < 0.001). In multivariate analyses, high PIV levels (≤ 404 vs. > 404, HR 2.862; 95% CI 1.553-5.276; p = 0.001), higher NLR (≤ 2.5 vs. > 2.5, HR 1.827; 95% CI 1.017-3.281; p = 0.044) levels and ECOG performance score of 2 (HR 2.267; 95% CI 1.385-3.711; p = 0.001) were associated with shorter OS. These factors were associated with shorter DFS also (HR for PIV 2.485, 95% CI 1.383-4.467, p = 0.002). CONCLUSIONS: We observed shorter OS and DFS in locally advanced HNSCC patients with high PIV levels. If prospective studies support our findings, the PIV score could be a prognostic biomarker in HNSCC.