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1.
Eur Rev Med Pharmacol Sci ; 28(4): 1562-1574, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436189

RESUMO

OBJECTIVE: The objective of this study was to assess treatment outcomes of intensity-modulated radiotherapy with concomitant chemotherapy and to identify prognostic factors on survival in patients with limited-stage small-cell lung cancer. PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of seventy-two patients who received curative treatment between December 2011 and January 2023. Several clinical and biochemical parameters were examined as potential prognostic factors. RESULTS: The median age was 63 years, and 79% of them were males. Concomitant chemotherapy was administered in 83% of patients. Prophylactic cranial irradiation was applied in 61% of the cohort. Two and five-year overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS) rates were 50% and 25%, 38% and 24%, and 44% and 25%, respectively. Univariate analysis revealed that older age, comorbid lung disease, advanced tumor-node-metastasis (TNM) stage, radiotherapy (RT) alone, and the absence of prophylactic cranial irradiation (PCI) were adverse factors affecting OS. The advanced TNM stage emerged as a significant prognostic factor for LRFS and DFS, with a notable trend toward affecting OS. CONCLUSIONS: The TNM staging system is of significance in cases classified as limited-stage small-cell lung cancer due to its prognostic implications. Our results suggest that patients with more advanced TNM stage exhibit less favorable treatment outcomes, which may require individual tailoring of new systemic therapies.


Assuntos
Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias Pulmonares/radioterapia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Intervalo Livre de Doença
2.
Clin Nucl Med ; 49(4): 379-380, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427959

RESUMO

ABSTRACT: Patients with dermatomyositis are prone to have occult malignancy. A previously healthy 68-year-old man with dermatomyositis underwent FDG PET/CT to detect possible malignancy of unknown origin. The images showed not only diffuse increased activity in the muscle, which was related to the known dermatomyositis, but also intense activity in the anterior chest with foci of abnormal activity throughout the body. Pathology examination confirmed small cell carcinoma of the lung with widespread metastases.


Assuntos
Carcinoma de Células Pequenas , Dermatomiosite , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Idoso , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Dermatomiosite/complicações , Dermatomiosite/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão , Tomografia por Emissão de Pósitrons
3.
Pathol Oncol Res ; 30: 1611709, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476352

RESUMO

The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in "fit," operable patients as well, so SBRT would be eligible in place of surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Radiocirurgia/métodos , Pulmão/patologia , Fracionamento da Dose de Radiação , Carcinoma de Pequenas Células do Pulmão/patologia , Estadiamento de Neoplasias
4.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473726

RESUMO

The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in the vast majority of small cell lung cancer (SCLC) tumors. Data support the notion that these two deleterious genetic events represent the initial steps in the development of SCLC, making them essential for a lung epithelial cell to progress toward the acquisition of a malignant phenotype. With the loss of TP53 and RB1, their broad tumor suppressive functions are eliminated and a normal cell is able to proliferate indefinitely, escape entering into cellular senescence, and evade death, no matter the damage it has experienced. Within this setting, lung epithelial cells accumulate further oncogenic mutations and are well on their way to becoming SCLC cells. Understanding the molecular mechanisms of these genetic lesions and their effects within lung epithelial cells is of paramount importance, in order to tackle this aggressive and deadly lung cancer. The present review summarizes the current knowledge on p53 and Rb aberrations, their biological significance, and their prospective therapeutic potential, highlighting completed and ongoing clinical trials with agents that target downstream pathways.


Assuntos
Neoplasias Pulmonares , Neoplasias da Retina , Retinoblastoma , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteína Supressora de Tumor p53/genética
5.
Nat Commun ; 15(1): 2067, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453939

RESUMO

Recent studies have identified a previously uncharacterized protein C11orf53 (now named POU2AF2/OCA-T1), which functions as a robust co-activator of POU2F3, the master transcription factor which is critical for both normal and neoplastic tuft cell identity and viability. Here, we demonstrate that POU2AF2 dictates opposing transcriptional regulation at distal enhance elements. Loss of POU2AF2 leads to an inhibition of active enhancer nearby genes, such as tuft cell identity genes, and a derepression of Polycomb-dependent poised enhancer nearby genes, which are critical for cell viability and differentiation. Mechanistically, depletion of POU2AF2 results in a global redistribution of the chromatin occupancy of the SWI/SNF complex, leading to a significant 3D genome structure change and a subsequent transcriptional reprogramming. Our genome-wide CRISPR screen further demonstrates that POU2AF2 depletion or SWI/SNF inhibition leads to a PTEN-dependent cell growth defect, highlighting a potential role of POU2AF2-SWI/SNF axis in small cell lung cancer (SCLC) pathogenesis. Additionally, pharmacological inhibition of SWI/SNF phenocopies POU2AF2 depletion in terms of gene expression alteration and cell viability decrease in SCLC-P subtype cells. Therefore, impeding POU2AF2-mediated transcriptional regulation represents a potential therapeutic approach for human SCLC therapy.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Regulação da Expressão Gênica , Fatores de Transcrição/metabolismo , Neoplasias Pulmonares/genética , Diferenciação Celular , Sequências Reguladoras de Ácido Nucleico
6.
Clin Respir J ; 18(3): e13740, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497229

RESUMO

Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.


Assuntos
Síndrome Miastênica de Lambert-Eaton , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Autoanticorpos
7.
Sci Rep ; 14(1): 6350, 2024 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491108

RESUMO

Lung cancer remains the leading cause of cancer mortality worldwide. Small cell lung cancer (SCLC) accounts for 10-15% of cases and has an overall 5-years survival rate of only 15%. Neuron-specific enolase (NSE) has been identified as a useful biomarker for early SCLC diagnosis and therapeutic monitoring. This work reports an electrochemical immunosensing platform based on a graphene-graphitic carbon nitride (g-C3N4) nanocomposite for ultrasensitive NSE detection. The g-C3N4 nanosheets and graphene nanosheets were synthesized via liquid exfoliation and integrated through self-assembly to form the nanocomposite. This nanocomposite was used to modify screen-printed carbon electrodes followed by covalent immobilization of anti-NSE antibodies. The unique properties of the graphene-g-C3N4 composite facilitated efficient antibody loading while also enhancing electron transfer efficiency and electrochemical response. Systematic optimization of experimental parameters was performed. The immunosensor exhibited a wide linear detection range of 10 pg/mL to 100 ng/mL and low limit of detection of 3 pg/mL for NSE along with excellent selectivity against interferences. Real serum matrix analysis validated the applicability of the developed platform for sensitive and accurate NSE quantifica-tion at clinically relevant levels. This novel graphene-g-C3N4 nanocomposite based electro-chemical immunoassay demonstrates great promise for early diagnosis of SCLC.


Assuntos
Biomarcadores , Técnicas Biossensoriais , Neoplasias Pulmonares , Fosfopiruvato Hidratase , Carcinoma de Pequenas Células do Pulmão , Humanos , Biomarcadores/análise , Técnicas Eletroquímicas , Grafite/química , Imunoensaio , Limite de Detecção , Neoplasias Pulmonares/diagnóstico , Fosfopiruvato Hidratase/análise , Carcinoma de Pequenas Células do Pulmão/diagnóstico
8.
J Cancer Res Clin Oncol ; 150(3): 125, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483588

RESUMO

PURPOSE: Although immune checkpoint inhibitors (ICIs), together with cytotoxic chemotherapy (chemoimmunotherapy), have been adapted for the initial treatment of extensive-disease small-cell lung cancer (ED-SCLC), they have achieved limited success. In ED-SCLC, a subtype of SCLC, the expression of immune-related molecules and clinical data are not well understood in relation to ICI treatment efficiency. METHODS: We examined lung biopsy specimens from patients diagnosed with ED-SCLC treated with chemoimmunotherapy or chemotherapy. SCLC subtype, expression of HLA class I, and infiltration of CD8-positive cells were examined using immunohistochemistry (IHC). Subsequently, the association between clinical factors, IHC results, and progression-free survival or overall survival was assessed. RESULTS: Most of the cases showed the achaete-scute homolog 1 (ASCL1) subtype. Among the 75 SCLC cases, 29 expressed high levels of HLA class I, while 46 showed low levels or a negative result; 33 patients were characterized as CD8-high, whereas 42 were CD8-low. In the chemoimmunotherapy cohort, multivariate analysis revealed a correlation between CD8-high and improved survival. Specifically, patients in the CD8-high group of the chemoimmunotherapy cohort experienced enhanced survival compared to those in the chemotherapy cohort, which was attributed to ICI addition. IHC subtype analysis demonstrated a survival advantage in the SCLC-I and SCLC-A groups when ICI was combined with chemotherapy compared to chemotherapy alone. CONCLUSION: Our study highlights the predictive value of IHC-classified subtypes and CD8-positive cell infiltration in estimating outcomes for patients with ED-SCLC treated with chemoimmunotherapy as a first-line therapy. These findings have practical implications for daily clinical assessments and treatment decisions.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Biópsia
9.
Front Immunol ; 15: 1333850, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487532

RESUMO

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events. Case presentation: A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade. Conclusions: This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.


Assuntos
Anticorpos Monoclonais Humanizados , Asma , Indóis , Neoplasias Pulmonares , Quinolinas , Carcinoma de Pequenas Células do Pulmão , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Terapia Combinada , Asma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Microambiente Tumoral
10.
Gan To Kagaku Ryoho ; 51(2): 167-169, 2024 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-38449403

RESUMO

A 47-year-old woman with general malaise and abdominal pain presented with multiple liver tumors and lymph node metastasis. She was diagnosed with small cell carcinoma on the basis of a lymph node biopsy; however, the primary lesion was not identified. Finally, we diagnosed her with cancer of unknown primary lesion and placed her in the poor prognosis group. Although her general condition was poor, she experienced a relatively good response to treatment for small cell carcinoma.


Assuntos
Carcinoma de Células Pequenas , Neoplasias Pulmonares , Neoplasias Primárias Desconhecidas , Carcinoma de Pequenas Células do Pulmão , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Prognóstico
11.
Diagn Pathol ; 19(1): 27, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326851

RESUMO

INTRODUCTION: NUT carcinoma is a rare cancer associated with a poor prognosis. Because of its rarity, its diagnosis is challenging and is usually made by excluding other diagnoses. Immunohistochemical analysis is a reliable technique that contributes to a correct diagnosis, but overestimating the expression of neuroendocrine (NE) markers may result in an incorrect diagnosis. In this study, we established the immunohistochemical phenotypes of NUT carcinoma compared with tumors that mimic its phenotype to identify potential diagnostic pitfalls. METHODS: Eight cases of NUT carcinoma were examined along with eight basaloid squamous cell carcinomas and thirteen cases of small cell carcinoma using an immunohistochemical panel consisting of various antibodies. RESULTS: Of the eight NUT carcinomas, three patients had a smoking history. All the cases examined for INSM1 were positive (6/6, 100%), although the staining was somewhat weak. Among the NE markers, synaptophysin was variably positive in two NUT carcinomas (2/6, 33%); however, all cases were negative for ASCL1, chromogranin A, and CD56. Moreover, the squamous cell markers, p40 and CK5/6, were weakly expressed in 4/6 (67%) and 3/6 (50%) of the NUT carcinomas, respectively. CONCLUSIONS: For tumors with an ambiguous morphology, applying the neuroendocrine phenotype of NUT carcinoma may be misleading; particularly, when distinguishing it from small-cell carcinoma. Similarly, null or weak expression of squamous cell markers may be observed in NUT carcinoma, but this differs from squamous cell carcinoma, which consistently demonstrates strong positivity for squamous cell markers.


Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Biomarcadores Tumorais/análise , Sinaptofisina/análise , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Células Epiteliais/patologia , Fenótipo , Carcinoma Neuroendócrino/patologia , Proteínas Repressoras/análise
12.
Pathol Oncol Res ; 30: 1611589, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414671

RESUMO

Aim: This single institute prospective study aimed to evaluate the feasibility of LINAC-based stereotactic body radiotherapy (SBRT) in treating patients with early-stage non-small cell lung cancer (NSLSC). We focused on the survival data with the local and distant control profiles and the cancer- and non-cancer-specific survival. Treatment-related side effects were also collected and analyzed. Methods: Patients with early-stage NSCLC between January 2018 and October 2021 were included in our prospective study; a total of 77 patients receiving LINAC-based SBRT were analyzed. All patients had pretreatment multidisciplinary tumor board decisions on SBRT. The average patient age was 68.8 years (median: 70 years, range: 52-82); 70 patients were in ECOG 0 status (91%), while seven patients were in ECOG 1-2 status (9%). 52% of the patients (40) had histologically verified NSCLC, and the other 48% were verified based on PETCT results. We applied the SBRT scheme 8 x 7.5 Gy for central tumors (74%) or 4 x 12 Gy for peripheral tumors (26%). Results: The mean follow-up time was 25.4 months (median 23, range 18-50). The Kaplan-Meier estimation for overall survival in patients receiving LINAC-based SBRT was 41.67 months. Of the 77 patients treated by SBRT, death was reported for 17 patients (9 cases cancer-specific, 8 cases non-cancer specific reason). The mean local tumor control was 34.25 months (range 8.4-41), and the mean systemic control was 24.24 months (range 7-25). During the treatments, no Grade I-II were reported; in 30 cases, Grade I non-symptomatic treatment-related lung fibrosis and two asymptomatic rib fractures were reported. Conclusion: In the treatment of early-stage NSCLC, LINAC-based SBRT can be a feasible alternative to surgery. Although we reported worse OS data in our patient cohort compared to the literature, the higher older average age and the initial worse general condition (ECOG1-2) in our patient cohort appear to be the reason for this difference. With the comparable local control and survival data and the favorable side effect profile, SBRT might be preferable over surgery in selected cases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Radiocirurgia/efeitos adversos , Estudos Prospectivos , Análise de Sobrevida , Carcinoma de Pequenas Células do Pulmão/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
13.
Mol Cancer ; 23(1): 41, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38395864

RESUMO

Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain inflammatory characteristics. The role of the transcription regulator YAP1 in defining a unique SCLC subset remains to be established. Although preclinical analyses have described numerous subtype-specific characteristics and vulnerabilities, the so far non-existing clinical subtype distinction may be a contributor to negative clinical trial outcomes. This comprehensive review aims to provide a framework for the development of novel personalized therapeutic approaches by compiling the most recent discoveries achieved by preclinical SCLC research. We highlight the challenges faced due to limited access to patient material as well as the advances accomplished by implementing state-of-the-art models and methodologies.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imunoterapia , Fatores de Transcrição
14.
J Toxicol Environ Health B Crit Rev ; 27(3): 91-105, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38369511

RESUMO

The relationship of occupational exposure to endotoxins with different histologic subtypes of lung cancer has not been established. Our objective was to conduct a systematic review with meta-analysis to assess the effect of exposure to endotoxins on the development of small cell lung cancer (SCLC). A bibliographic search was conducted using MEDLINE, Embase, CENTRAL, and Web of Science databases until December 2022, including all cohort and/or case-control studies that examined occupational exposure to endotoxins and SCLC. Risk of bias was assessed using the U.S. Office of Health Assessment and Translation tool. A random effects model was applied, publication bias were assessed, and a sensitivity analysis was conducted. Four papers were selected for meta-analysis purposes. A total of 144 incident cases of SCLC and 897 population or hospital controls were included. Occupational exposure to endotoxins was considered for textile/leather industry and agricultural sector workers exposed to endotoxins originating from wool, cotton, or leather dust. Except for one study, all investigations were classified as having a low probability of risk of biases. The results of the meta-analysis were not statistically significant (pooled OR: 0.86; 95% CI:0.69-1.08). In addition, neither between-study heterogeneity (I2=0%;p=0.92) nor publication bias was observed (p=0.49). The results of the sensitivity analysis, after including five studies that assessed the risk of SCLC among textile industry and crop/livestock farm workers (not specifically exposed to endotoxins), showed a negative statistically non-significant association and low between-study heterogeneity (pooled OR: 0.90; 95% CI:0.79-1.02; I2=22%;p=0.23). Subjects exposed to occupational exposure to endotoxins seem to exhibit a negative association with the development of SCLC, although the results are not conclusive.


Assuntos
Neoplasias Pulmonares , Doenças Profissionais , Exposição Ocupacional , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/induzido quimicamente , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Endotoxinas , Têxteis , Exposição Ocupacional/efeitos adversos , Poeira , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia
15.
Radiat Oncol ; 19(1): 25, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413988

RESUMO

BACKGROUND: Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT). METHODS: Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects. RESULTS: A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis. CONCLUSION: Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Etoposídeo/uso terapêutico , Estudos Retrospectivos , Pontuação de Propensão , Platina/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapia , Imunoterapia
16.
Anticancer Res ; 44(2): 659-664, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307551

RESUMO

BACKGROUND/AIM: Progesterone receptor antagonists have been found to provide significant extension of life and considerable palliative benefits in a large variety of very advanced cancers. Most of these treated cancers lack the classical nuclear progesterone receptor (nPR). The hypothesized targets are membrane (m) PRs to inhibit progesterone induced blocking factor (PIBF). To date, there have been no case reports documenting the efficacy of PR antagonists for small cell lung cancer (SCLC) confirmed by pathological analysis. The case reported here demonstrates the efficacy of the single oral agent mifepristone in treating resistant SCLC. CASE REPORT: A 58-year-old man, presenting with a persistent cough, dyspnea on exertion, and marked weakness, was diagnosed with stage IV non-SCLC (NSCLC) that tested positive for the EGFR mutation. He was treated with the single agent osimertinib. When symptoms returned eight months later, along with radiographic evidence of marked cancer progression, a lung biopsy showed SCLC. He failed to respond to pembrolizumab and subsequently to atezolizumab. He was then treated with the single agent mifepristone 200 mg per day orally. He showed marked clinical improvement associated with marked radiographic improvement. Though clinically doing very well, after one year, his dominant lesion increased in size. His oncologist elected to stop mifepristone and treat with camrelizumab with anlototinib. His clinical condition deteriorated on these drugs, and he died five months later. CONCLUSION: SCLC can be added to the long list of very advanced cancers that are treatment resistant to standard therapy, but respond well to PR antagonists.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Mifepristona/uso terapêutico , Mifepristona/farmacologia , Receptores de Progesterona , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Progesterona/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
17.
Anticancer Res ; 44(2): 845-851, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307561

RESUMO

BACKGROUND/AIM: Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. PATIENTS AND METHODS: We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. RESULTS: A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. CONCLUSION: Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Queratina-19 , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Platina/uso terapêutico , Recidiva Local de Neoplasia , Antígenos de Neoplasias , Biomarcadores Tumorais
18.
Front Immunol ; 15: 1353889, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322260

RESUMO

Background: Recent clinical trials demonstrated longer survival in extended small cell lung cancer (SCLC) patients treated with immunotherapy in addition to chemotherapy. However, the magnitude of benefit is modest and the impact in real-world setting has to be fully established. Methods: We collected clinical data and radiological imaging of patients affected by extended or relapsing SCLC and consecutively treated according to clinical practice between 2016 and 2023. As primary end-point, we compared pre-defined outcome indicators before and after the introduction of chemo-immunotherapy (May 2020): 6-month and 12-month progression free survival (PFS) rate, 12-month and 18-month overall survival (OS). Among those who were treated after May 2020, patients who did not receive immunotherapy according to treating physician's choice were included in the analysis to minimize clinical selection bias. Results: The analysis included 214 patients: 132 (61.7%) were treated in an Academic cancer center and 82 (38.3%) in two community hospitals; 104 were treated before May 2020. Median PFS of the overall study population was 4.8 months (95% confidence interval [95% CI]: 4.4-5.4), median OS was 7.1 months (95% CI: 6.3-7.7). Estimated PFS and OS were significantly longer in patients treated after May 2020 with hazard ratio (HR) for PFS and OS of 0.61 (95% CI: 0.46-0.81, p < 0.001) and 0.70 (95% CI: 0.52-0.93, p = 0.015), respectively. 6-month PFS rate increased from 27% to 40% (p = 0.04) while 12-months PFS raised from 1% to 11% (p = 0.003). 12-month and 18-month OS rate increased from 15% to 28% (p = 0.03) and from 2.1% to 12% (p = 0.009), respectively. After May 2020 the median number of hospitalization days per patient decreased significantly and the incidence of severe AEs was similar. Among patients treated with chemo-immunotherapy, the onset of immune-related AEs was associated with improved PFS and OS (HR 0.55, 95% CI: 0.35-0.89, p = 0.012 and HR 0.47, 95%CI 0.28-0.77, p = 0.002, respectively). Conclusions: The real-world analysis shows a meaningful improvement of outcome indicators after the introduction of chemo-immunotherapy, with reduction of the duration of hospitalization, thus supporting the use of chemo-immunotherapy and the need for further biomarker research.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia
19.
Science ; 383(6683): eadj1415, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38330136

RESUMO

Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial cell types in the lung. Intriguingly, LUAD can histologically transform into SCLC after treatment with targeted therapies. In this study, we designed models to follow the conversion of LUAD to SCLC and found that the barrier to histological transformation converges on tolerance to Myc, which we implicate as a lineage-specific driver of the pulmonary neuroendocrine cell. Histological transformations are frequently accompanied by activation of the Akt pathway. Manipulating this pathway permitted tolerance to Myc as an oncogenic driver, producing rare, stem-like cells that transcriptionally resemble the pulmonary basal lineage. These findings suggest that histological transformation may require the plasticity inherent to the basal stem cell, enabling tolerance to previously incompatible oncogenic driver programs.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-myc , Carcinoma de Pequenas Células do Pulmão , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Células Epiteliais/patologia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Oncogenes , Linhagem da Célula , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-akt/genética , Terapia de Alvo Molecular
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