RESUMEN
PURPOSE: Breast cancer progression varies across molecular subtypes, and treatment options for human epidermal growth factor receptor 2 (HER2)-low expression tumors are limited compared with those of HER2 overexpression tumors. Comprehensive information regarding the epidemiology and clinical outcomes of metastatic HER2-low expression breast cancer in a Southeast Asian population is lacking. METHODS: This retrospective cohort study was performed to analyze data from patients with de novo advanced breast cancer, including HER2 expression, tumor stage, and metastatic pattern. Statistical analyses, including chi-square tests and survival analyses, were used to compare HER2-low expression and HER2-negative groups. RESULTS: Of the 491 patients, 21.2% had HER2-low expression, 30% had HER2 overexpression, and 50% had HER2-negative expression. Among the hormone receptor (HR)-positive patients, 34% had HER2-low expression; in the triple-negative patients, the HER2-low incidence was 20.6%. No significant differences in clinical characteristics between HER2-low and HER2-negative groups were observed, except for more HR-positive patients in the HER2-low group. HER2-low patients had a longer overall survival (OS) than HER2-negative patients (43 v 23 months; hazard ratio, 0.7; P < .001), especially in HR-positive patients. After adjusting for HR status, HER2-low patients maintained improved outcomes. HR-positive HER2-low patients showed nonsignificant OS gains compared with HR-positive HER2-negative patients, regardless of first-line chemotherapy or endocrine therapy. CONCLUSION: This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.
Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Femenino , Estudios Retrospectivos , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Persona de Mediana Edad , Pronóstico , Incidencia , Adulto , Anciano , Asia Sudoriental/epidemiología , Metástasis de la Neoplasia , Biomarcadores de Tumor/metabolismo , Pueblos del Sudeste AsiáticoRESUMEN
BACKGROUND: The current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 -) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib. METHODS: This multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 - ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events. RESULTS: Of the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55-1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29-1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%). CONCLUSION: This preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 - ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted.
Asunto(s)
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Piperazinas , Purinas , Piridinas , Receptor ErbB-2 , Receptores de Estrógenos , Humanos , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Femenino , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Purinas/administración & dosificación , Purinas/efectos adversos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Tailandia/epidemiología , Anciano , Receptor ErbB-2/metabolismo , Adulto , Receptores de Estrógenos/metabolismo , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/uso terapéutico , Receptores de Progesterona/metabolismo , Supervivencia sin ProgresiónRESUMEN
Chemoradiotherapy (CRT) remains the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), based on numerous randomized controlled trials and meta-analyses demonstrating that CRT improved locoregional control and overall survival. Achieving locoregional control is a crucial outcome for the treatment of HNSCC, as it directly affects patient quality of life and survival. Cisplatin is the recommended standard-of-care radiosensitizing agent for LA-HNSCC patients undergoing CRT, whereas cetuximab-radiotherapy is reserved for cisplatin-ineligible patients. Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of recurrent or metastatic HNSCC. However, the combination of ICIs with standard-of-care radiotherapy or chemoradiotherapy in LA-HNSCC has not demonstrated significant improvement in survivals. Over the past few decades, significant advancements in radiotherapy techniques have allowed for more precise and effective radiation delivery while minimizing toxicity to surrounding normal tissues. These advances have led to improved treatment outcomes and quality of life for patients with LA-HNSCC. Despite these advancements, the development of novel radiosensitizing agents remains an unmet need. This review discusses the mechanism of radiotherapy and its impact on the immune system. We summarize the latest clinical development of novel radiosensitizing agents, such as SMAC mimetics, DDR pathway inhibitors, and CDK4/6 inhibitor. We also elucidate the emerging evidence of combining ICIs with radiotherapy or chemoradiotherapy in curative settings for LA-HNSCC, using both concurrent and sequential approaches. Lastly, we discuss the future direction of systemic therapy in combination with radiotherapy in treatment for LA-HNSCC.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Fármacos Sensibilizantes a Radiaciones , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Cisplatino/uso terapéutico , Calidad de Vida , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Quimioradioterapia/métodosRESUMEN
OPINION STATEMENT: Sarcoma describes a rare and heterogeneous group of diseases. Current treatment options for metastatic sarcoma are quite limited. Conventional treatments with chemotherapy or anti-angiogenic agents result in a non-durable response and a survival rate of approximately 12 to 18 months. In addition, the benefits of such treatments remain limited in some sarcoma subtypes only. Immunotherapy is an emerging treatment for several cancer types with promising outcomes. Studies at the cellular level have shown a relatively high immunogenicity in some subtypes of sarcoma. It is therefore hypothesized that sarcoma may respond to immunotherapy. However, sarcoma is a heterogeneous disease and differences in terms of immunogenicity exist. A multitude of immune-based treatment approaches for sarcoma have been explored. This includes immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapy. Single-agent immunotherapy has exhibited efficacy against some sarcoma subtypes, including alveolar soft-part sarcoma, angiosarcoma, and undifferentiated pleomorphic sarcoma. Combination immunotherapy appears superior to single-agent immunotherapy in terms of response, and several ongoing studies of immunotherapy using single/combination immune checkpoint inhibitors and combination with anti-angiogenesis have begun to report beneficial results. Predictive and prognostic biomarkers are also under active investigations, with particular interest in tumor-infiltrating lymphocytes or high tumor mutational burden levels. However, the information is still limited and further studies are needed.
Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Biomarcadores de Tumor , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia/métodos , Sarcoma/diagnóstico , Sarcoma/etiología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/tratamiento farmacológicoRESUMEN
BACKGROUND: Multi-drug resistant organisms have been emerging among kidney transplant (KT) recipients with bloodstream infections (BSI). The investigation for epidemiology, risk factors and outcome of these infections following KT was initiated. MATERIALS AND METHODS: A retrospective study of all adult KT recipients who developed a BSI within the first year after KT in 2016 at a single transplant center was conducted. The cumulative incidence of BSI was estimated with Kaplan-Meier methodology. Clinical characteristics and outcome were extracted. Risk factors were analyzed with Cox proportional hazards models. RESULTS: Among 171 KT recipients, there were 26 (15.2%) episodes of BSI. Fifty-nine percent were men and the mean ± SD age was 43 ± 12 years. The cumulative incidence of BSIs was 10.1% at 1 month, 13.5% at 6 months, and 15.2% at 12 months. Gram-negative bacteria were responsible for 92% of BSIs, Escherichia coli was the most common pathogen (65%) followed by Klebsiella pneumoniae (11%). Among those, 71% were resistant to extended-spectrum cephalosporins. The genitourinary tracts were the predominant source of BSIs (85%). The second kidney transplantation (HR, 4.55; 95% CI, 1.24-16.79 [P = 0.02]) and receiving induction therapy (HR, 3.05; 95% CI, 1.15-8.10 [P < 0.03]) were associated with BSI in a multivariate analysis. One patient (4%) developed allograft rejection, allograft failure and death from septic shock. CONCLUSIONS: One out of six KT recipients could develop BSI from gram-negative bacteria within the first year after transplant, particularly in those that received the second transplantation or induction therapy.
Asunto(s)
Fenómenos Fisiológicos Bacterianos , Farmacorresistencia Bacteriana Múltiple , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Sepsis/epidemiología , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Tailandia/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Cytomegalovirus (CMV) infection is one of the leading causes of morbidity and mortality in kidney transplantation (KT) recipients. We investigated the association of CMV serostatus and patient outcomes within the first year after KT. METHODS: All KT recipients between January 1, 2007 and December 31, 2017 were identified from the Thai Transplant Registry. The prevalence rates of allograft loss and mortality within the first year after KT were estimated by the Kaplan-Meier method. The CMV serostatus in donors (D) and recipients (R) was assessed as a prognostic factor for allograft loss and mortality within the first year by the Cox proportional hazards model. RESULTS: During the 10-year study period (2007-2017), there were 4556 KT recipients with a mean ± standard deviation age of 43 ± 14 years, and 63% of the recipients were male. Deceased-donor KT and induction therapy were performed in 52% and 58% of the recipients, respectively. Among the 3907 evaluable patients, the rates of cases with D+/R+, D+/R-, D-/R+, and D-/R- as the CMV serostatus were 88.9%, 6.1%, 2.9%, and 1.9%, respectively. The estimated prevalence rates of allograft loss and mortality within the first year were 3.8% and 2.8%, respectively. In univariate analysis, CMV D+/R- serostatus was significantly associated with mortality (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.18-3.75; P = .01) but not with an allograft loss (HR, 1.51; 95% CI, 0.85-2.66; P = .16) within the first year after KT. In multivariate analysis, CMV D+/R- serostatus of D+/R- was associated with mortality within the first year after KT (HR, 2.04; 95% CI, 1.05-3.95; P = .04). Other independent prognostic factors for mortality were old recipient age, deceased-donor KT, and hemodialysis after KT. CONCLUSIONS: In a national setting with predominant CMV seropositivity in both D and R, CMV seromismatch was associated with poor patient survival within the first year after KT.