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1.
Oncologist ; 29(5): e580-e600, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38309719

RESUMO

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites/efeitos dos fármacos
2.
Breast Cancer Res Treat ; 204(3): 443-452, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240935

RESUMO

PURPOSE: The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However, biomarkers predicting long-term benefit and early progression are yet to be defined. Several studies suggested the possibility of diminished efficacy in patients with HER2-low disease. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between low-level HER2 expression and efficacy outcomes (PFS, OS, ORR) with CDK 4/6 inhibitors. METHODS: The Pubmed, Web of Science, and Scopus databases were used to systematically filter the published studies from inception to 08 August 2023 for this systemic review. Studies including MBC patients treated with CDK 4/6 inhibitors and reported survival outcomes according to HER2 expression were included. We performed the meta-analyses with the generic inverse-variance method with a fixed-effects model and used HRs with 95% two-sided CIs as the principal summary measure. RESULTS: Nine studies encompassing 2705 patients were included in the analyses. In the pooled analysis of nine studies, the risk of progression and/or death was higher in patients with HER2-low tumors compared to HER2-zero (HR: 1.22, 95% CI 1.10-1.35, p < 0.001). In the pooled analysis of five studies, although the median follow-up was short, the risk of death was higher in the HER2-low group compared to the HER2-zero group (HR: 1.22, 95% CI 1.04-1.44, p = 0.010). CONCLUSION: The available evidence demonstrates a significantly higher risk of progression or death with CDK 4/6 inhibitors in HER2-low tumors. Further research is needed to improve outcomes in patients with HR+-HER2-low tumors.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Quinase 4 Dependente de Ciclina , Ciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
BMC Cancer ; 24(1): 1218, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354432

RESUMO

BACKGROUND: Despite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients. METHODS: The study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m2 every two weeks, following progression after platinum-etoposide treatment. RESULTS: One hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction. CONCLUSIONS: Irinotecan 180 mg/m2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration.


Assuntos
Irinotecano , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Carcinoma de Pequenas Células do Pulmão , Humanos , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Irinotecano/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Esquema de Medicação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia de Salvação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Resultado do Tratamento
4.
Future Oncol ; 20(20): 1427-1434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38864297

RESUMO

Aim: There is limited data available regarding the comparison of Sacituzumab govitecan (SG) vs. chemotherapy in metastatic breast cancer patients.Materials & methods: We performed a systematic review and meta-analysis aimed to assess the safety profile of SG vs. chemotherapy for metastatic breast cancer (mBC) clinical trials.Results: The pooled odds ratio for outcomes such as grade 3-4 and all grade neutropenia, leukopenia, anemia and other non-hematological adverse events showed a higher risk for patients receiving SG. No statistically significant differences were reported in terms of grade 3-4 fatigue, all grade nausea, febrile neutropenia and treatment discontinuation due to adverse events.Conclusion: Our data, coupled with a statistically and clinically meaningful survival benefit, support the use of SG for mBC.


[Box: see text].


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Camptotecina , Feminino , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/efeitos adversos , Camptotecina/administração & dosagem , Imunoconjugados , Metástase Neoplásica , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Resultado do Tratamento
5.
Future Oncol ; 20(4): 207-214, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38328890

RESUMO

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Bevacizumab/efeitos adversos , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Neoplasias Peritoneais/tratamento farmacológico
6.
Jpn J Clin Oncol ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39385508

RESUMO

BACKGROUND: Trastuzumab emtansine (T-DM1) is a novel therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, combining the targeted action of trastuzumab with the cytotoxic effects of emtansine. Although T-DM1 has demonstrated greater efficacy and safety compared to traditional therapies, concerns about hepatotoxicity and spleen-related complications have arisen. METHODS: We conducted a retrospective study of 64 HER2-positive metastatic breast cancer patients treated with T-DM1 at our institution. Patients underwent computed tomography or magnetic resonance imaging at baseline and during treatment cycles. Spleen volume, portal vein diameter, and laboratory values were compared between baseline and 12 months after T-DM1 treatment. RESULTS: Median spleen volume significantly increased from 201 cm3 (IQR, 157-275) at baseline to 291 cm3 (IQR, 215-420) after 12 months of T-DM1 treatment (P < 0.001). Spleen enlargement was observed in 87.5% of patients, while no significant alteration was detected in portal vein diameter. The change in spleen volume was positively correlated with changes in serum globulin levels, liver enzymes, and bilirubin levels, but did not impact survival outcomes. CONCLUSIONS: T-DM1 therapy in HER2-positive metastatic breast cancer leads to significant spleen enlargement and systemic biochemical changes. Future studies should focus on elucidating the long-term implications of these findings and optimizing monitoring strategies for spleen-related complications.

7.
Support Care Cancer ; 32(7): 467, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937345

RESUMO

PURPOSE: This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). METHODS: In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023. RESULTS: Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001). CONCLUSIONS: Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.


Assuntos
Analgésicos Opioides , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Feminino , Estudos Retrospectivos , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Idoso , Intervalo Livre de Progressão , Adulto , Idoso de 80 Anos ou mais
8.
Int J Clin Oncol ; 29(6): 822-831, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565751

RESUMO

BACKGROUND: Sarcopenia and myosteatosis have been associated with a poor prognosis for several cancers. The albumin-myosteatosis gauge (AMG) is a novel integrated measure proposed to assess myosteatosis along with serum albumin level as a surrogate of systemic inflammation and malnutrition. The aim of this study was to investigate the prognostic value of AMG in patients with advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with advanced PDAC treated with chemotherapy between 2013 and 2022 were evaluated. Skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) were calculated using computed tomography at the level of the L3 vertebra. The AMG was defined as albumin x SMD and expressed as an arbitrary unit (AU). Patients were first categorized by sex-specific quartiles and then dichotomized at the sex-specific median value of the AMG. RESULTS: A total of 196 patients were included. The median age (interquartile range) was 62 (54-67), and 128 (65.3%) were male. With regard to AMG, 142.86 and 114.15 AU were identified as cutoff values for males and females, respectively. In multivariable analyses, lower AMG values (G1-G2 vs. G3-G4) (HR: 1.61, 95% CI 1.17-2.21, p = 0.003), higher ECOG performance score (> 0 vs. 0) (HR: 1.51, 95% CI 1.10-2.06, p = 0.009) and metastatic disease (vs. locally advanced) (HR: 1.88, 95% CI 1.27-2.79, p = 0.001) were associated with OS. CONCLUSION: The study findings suggest the prognostic value of AMG in patients with advanced PDAC undergoing first-line chemotherapy. Further studies are warranted to validate these findings and assess potential predictive role of AMG in guiding treatment selection.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sarcopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Idoso , Prognóstico , Sarcopenia/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Músculo Esquelético/patologia , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Albumina Sérica/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
9.
Int J Clin Oncol ; 29(3): 258-265, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310597

RESUMO

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.


Assuntos
Aminopiridinas , Neoplasias da Mama Masculina , Neoplasias da Mama , Piperazinas , Purinas , Piridinas , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/etiologia , Receptor ErbB-2/metabolismo , Estudos Retrospectivos
10.
Vascular ; : 17085381241241853, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38523367

RESUMO

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.

11.
Eur Arch Otorhinolaryngol ; 281(9): 4991-4999, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38795147

RESUMO

OBJECTIVES: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. DESIGN: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. RESULTS: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.


Assuntos
Antineoplásicos Imunológicos , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Nivolumabe , Humanos , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Turquia , Idoso , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Antineoplásicos Imunológicos/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento
12.
Int J Cancer ; 152(4): 679-685, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36082448

RESUMO

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.


Assuntos
COVID-19 , Neoplasias , Humanos , Vacinas contra COVID-19 , Vacina BNT162 , COVID-19/prevenção & controle , Neoplasias/terapia , Anticorpos Antivirais , Imunoglobulina G , RNA Mensageiro/genética , Vacinas de mRNA
13.
Strahlenther Onkol ; 199(8): 761-772, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36862156

RESUMO

BACKGROUND: PD-L1 and VISTA are thought to play a role in escape from the immune system, tumor progression, and treatment response in tumoral tissue. The current study aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on PD-L1 and VISTA expression in head and neck cancers. METHODS: PD-L1 and VISTA expression were compared between the primary biopsy taken at the time of diagnosis and refractory tissue biopsies of patients who received definitive CRT or recurrent tissue biopsies of patients who had surgery followed by adjuvant RT or CRT. RESULTS: In total, 47 patients were included. Radiotherapy had no effect on the expression levels of PD-L1 and VISTA in patients with head and neck cancer (p = 0.542 and p = 0.425, respectively). A positive correlation was found between PD-L1 and VISTA expression (p < 0.001; r = 0.560). PD-L1 and VISTA expression in the first biopsy were found to be significantly higher in clinical lymph node-positive patients compared to node-negative patients (PD-L1 p = 0.038; VISTA p = 0.018). The median overall survival of patients with ≥ 1% VISTA expression in the initial biopsy was significantly shorter than that of patients with < 1% VISTA expression (52.4 vs. 110.1 months, respectively; p = 0.048). CONCLUSION: It was found that PD-L1 and VISTA expression did not change with RT or CRT. Further studies are needed to evaluate the relationship of PD-L1 and VISTA expression with RT and CRT.


Assuntos
Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Humanos , Prognóstico , Neoplasias de Cabeça e Pescoço/terapia , Quimiorradioterapia , Intervalo Livre de Doença , Biomarcadores Tumorais/metabolismo
14.
Anticancer Drugs ; 34(10): 1190-1192, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729128

RESUMO

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.


Assuntos
Neoplasias Hepáticas , Neoplasias Pancreáticas , Feminino , Humanos , Adulto , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Oxaliplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Proteína BRCA2/genética , Neoplasias Pancreáticas
15.
Anticancer Drugs ; 34(6): 783-790, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729111

RESUMO

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.


Assuntos
Injúria Renal Aguda , Carcinoma Pulmonar de Células não Pequenas , Hipoalbuminemia , Neoplasias Pulmonares , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Incidência , Hipoalbuminemia/complicações , Neoplasias Pulmonares/complicações , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Fatores de Risco
16.
Future Oncol ; 19(10): 727-736, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37133230

RESUMO

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Letrozol/uso terapêutico , Neoplasias da Mama/patologia , Estudos Retrospectivos , Aminopiridinas/uso terapêutico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor ErbB-2
17.
Support Care Cancer ; 31(12): 624, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37819422

RESUMO

PURPOSE: Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies. METHODS: We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were "hearing loss" OR "hearing impairment" OR "ototoxicity" OR "vestibular toxicity" OR "audiovestibular toxicity" AND "immune checkpoint inhibitor" OR "immunotherapy." RESULTS: A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively. CONCLUSION: We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.


Assuntos
Antineoplásicos Imunológicos , Perda Auditiva , Melanoma , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Melanoma/tratamento farmacológico , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia , Estudos Retrospectivos
18.
Eur Arch Otorhinolaryngol ; 280(8): 3541-3556, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37188907

RESUMO

PURPOSE: The purpose of this article is to provide an up-to-date summary of sarcopenia and its clinical implications for patients with head and neck cancer (HNC). METHODS: We conducted a literature review of recent studies investigating the prevalence of sarcopenia in HNC patients, its detection using MRI or CT scans, and its association with clinical outcomes such as disease-free and overall survival time, radiotherapy-related side effects, cisplatin toxicity, and surgical complications. RESULTS: Sarcopenia, characterized by low skeletal muscle mass (SMM), is a prevalent condition in HNC patients and can be effectively detected using routine MRI or CT scans. Low SMM in HNC patients is associated with increased risks of shorter disease-free and overall survival times, as well as radiotherapy-related side effects such as mucositis, dysphagia, and xerostomia. In addition, cisplatin toxicity is more severe in HNC patients with low SMM, leading to higher dose-limiting toxicity and treatment interruptions. Low SMM may also predict higher risks of surgical complications in head and neck surgery. Identifying sarcopenic patients can aid physicians in better riskstratifying HNC patients for therapeutic or nutritional interventions to improve clinical outcomes. CONCLUSIONS: Sarcopenia is a significant concern for HNC patients and can impact their clinical outcomes. Routine MRI or CT scans can effectively detect low SMM in HNC patients. Identifying sarcopenic patients can aid physicians in better risk-stratifying HNC patients for therapeutic or nutritional interventions to improve clinical outcomes. Further research is needed to explore the potential of interventions to mitigate the negative effects of sarcopenia in HNC patients.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias de Cabeça e Pescoço , Lesões por Radiação , Sarcopenia , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Cisplatino , Neoplasias de Cabeça e Pescoço/patologia , Músculo Esquelético , Estudos Retrospectivos
19.
Eur Arch Otorhinolaryngol ; 280(5): 2471-2478, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36565325

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas/patologia , Estudos Prospectivos , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia , Intervalo Livre de Doença , Quimiorradioterapia , Inflamação , Prognóstico
20.
Anticancer Drugs ; 33(1): e477-e485, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261917

RESUMO

We aimed to compare the efficacy and the safety of the FOLFOX and the FLOT regimens in metastatic gastric cancer (mGC) as first-line treatment. It was a retrospective multicenter observational study. The comparisons between groups were conducted in terms of progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and hematologic adverse events. Seventy-nine patients, diagnosed with mGC between March 2012 and December 2019, treated with FOLFOX (n = 43) or FLOT (n = 36) regimens as first-line treatment were included in the study. The mPFS was 10.9 months [95% confidence interval (CI), 5.8-16.1] in the FLOT arm and 7.1 months (95% CI, 5.1-9.1) in the FOLFOX arm (P < 0.001). The ORR was 63.9% in the FLOT arm and 30.2% in the FOLFOX arm (P = 0.003). The mOS was 13.3 months (95% CI, 11.3-15.4) in the FLOT arm and 10.9 months (95% CI, 8.2-13.5) in the FOLFOX arm (P = 0.103). The hematologic adverse events in all grades were 88.4% (n = 38) in the FOLFOX arm compared with 80.6% (n = 29) in the FLOT arm (P = 0.335). The FLOT regimen might be a preferred option in mGC with an improved PFS and ORR compared with the FOLFOX regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Junção Esofagogástrica/patologia , Feminino , Fluoruracila/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise de Sobrevida
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