RESUMO
OBJECTIVE: A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS: Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS: A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION: The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.
Assuntos
Albuminas, Protocolos de Quimioterapia Combinada Antineoplásica, Quimiorradioterapia, Cisplatino, Paclitaxel, Neoplasias do Colo do Útero, Humanos, Feminino, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/tratamento farmacológico, Cisplatino/administração & dosagem, Cisplatino/efeitos adversos, Cisplatino/uso terapêutico, Paclitaxel/administração & dosagem, Paclitaxel/efeitos adversos, Paclitaxel/uso terapêutico, Pessoa de Meia-Idade, Quimiorradioterapia/métodos, Quimiorradioterapia/efeitos adversos, Estudos Retrospectivos, Albuminas/administração & dosagem, Albuminas/uso terapêutico, Albuminas/efeitos adversos, Adulto, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos, Estadiamento de Neoplasias, IdosoRESUMO
Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P = .042), and the 3-year DFS rates were 70.4% and 47.4% (P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5â cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.
Assuntos
Quimiorradioterapia, Estadiamento de Neoplasias, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/mortalidade, Feminino, Pessoa de Meia-Idade, Prognóstico, Adulto, Idoso, Estudos Retrospectivos, Metástase Linfática, Estimativa de Kaplan-Meier, Resultado do Tratamento, Modelos de Riscos Proporcionais, Taxa de SobrevidaRESUMO
Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists.
Assuntos
Papillomaviridae, Infecções por Papillomavirus, Receptores Toll-Like, Humanos, Receptores Toll-Like/metabolismo, Receptores Toll-Like/agonistas, Receptores Toll-Like/imunologia, Infecções por Papillomavirus/imunologia, Infecções por Papillomavirus/terapia, Infecções por Papillomavirus/virologia, Papillomaviridae/fisiologia, Papillomaviridae/imunologia, Transdução de Sinais, Neoplasias/terapia, Neoplasias/imunologia, Animais, Imunoterapia/métodos, Feminino, Neoplasias do Colo do Útero/virologia, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/imunologia, Interações Hospedeiro-Patógeno/imunologiaRESUMO
Objective: To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49 years in Uganda, and to analyse the programme data. Methods: The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. Findings: The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. Conclusion: We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.
Assuntos
Detecção Precoce de Câncer, Infecções por HIV, Neoplasias do Colo do Útero, Humanos, Feminino, Neoplasias do Colo do Útero/diagnóstico, Neoplasias do Colo do Útero/terapia, Uganda/epidemiologia, Pessoa de Meia-Idade, Infecções por HIV/epidemiologia, Infecções por HIV/diagnóstico, Adulto, Infecções por Papillomavirus/diagnóstico, Infecções por Papillomavirus/epidemiologia, Programas de RastreamentoRESUMO
Cervical cancer patients commonly experience psychological supportive care needs, necessitating diverse interventions to enhance psychological well-being and alleviate physical symptoms. This systematic review, covering English-published articles from January 1999 to April 2023, assessed the impact of psychological supportive care interventions on anxiety and depression. Twenty-Six studies, including 11,638 patients, were analyzed, comprising randomized controlled trials; quasi-experimental, and pre-post-test designs from PubMed; Science Direct; Wiley online library; Google Scholar; Cochrane Library; and JSTOR. The extraction of data was done by two independent authors and a third independent author checked the data extraction. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 2020 statement was adopted. The population, intervention, comparator, and outcomes (PICO) search strategy was applied. Effective Public Health Practice Project (EPHPP) tool was used to assess the quality of selected articles. Various interventions, such as psychological nursing, exercise, counselling, psycho-curative approaches, peer and family education, psychotherapy, and medication, were identified. Two studies incorporated homework sessions, predominantly administered by nursing staff. Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were commonly used instruments. Statistical analysis revealed a significant difference in anxiety and depression scores between treatment and control groups (p < 0.005) post-intervention across all studies. A subsequent meta-analysis of eight homogeneous studies, utilizing a random-effects model, showed a moderate-to-high overall effect size (1.35, 95% CI: 0.75 to 1.94), indicating a statistically significant positive impact. Various studies exhibited variability in effect sizes ranging from low to high. While the meta-analysis included 936 participants, the forest plot visually represents individual study effect sizes and the combined effect size. Preliminary evidence supports the positive impact of psychological supportive care interventions on cervical cancer outcomes, urging further research, especially exploring long-term effects and employing rigorous study designs.
Assuntos
Ansiedade, Intervenção Psicossocial, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/psicologia, Neoplasias do Colo do Útero/terapia, Feminino, Intervenção Psicossocial/métodos, Ansiedade/terapia, Depressão/terapia, Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.
Assuntos
Carcinoma de Células Escamosas, Quimiorradioterapia, Terapia Neoadjuvante, Estadiamento de Neoplasias, Neoplasias do Colo do Útero, Humanos, Feminino, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/mortalidade, Estudos Retrospectivos, Terapia Neoadjuvante/métodos, Pessoa de Meia-Idade, Quimiorradioterapia/métodos, Carcinoma de Células Escamosas/terapia, Carcinoma de Células Escamosas/patologia, Carcinoma de Células Escamosas/mortalidade, Adulto, Idoso, Pontuação de Propensão, Resultado do TratamentoRESUMO
BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica, Quimiorradioterapia, Cisplatino, Paclitaxel, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/radioterapia, Neoplasias do Colo do Útero/mortalidade, Neoplasias do Colo do Útero/tratamento farmacológico, Neoplasias do Colo do Útero/patologia, Feminino, Pessoa de Meia-Idade, Quimiorradioterapia/métodos, Quimiorradioterapia/efeitos adversos, Paclitaxel/administração & dosagem, Paclitaxel/uso terapêutico, Paclitaxel/efeitos adversos, Estudos Retrospectivos, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos, Cisplatino/uso terapêutico, Cisplatino/administração & dosagem, Cisplatino/efeitos adversos, Adulto, Idoso, Resultado do Tratamento, Intervalo Livre de ProgressãoRESUMO
PURPOSE: Shared decision making (SDM) is an approach where clinicians and patients make decisions together using the best available evidence. Although much studied, recognized to be ethically imperative, and recommended in international health policies, it remains poorly implemented. In the Philippines, there are limited studies on patient decision making preferences and SDM. Practical guidance on the implementation of SDM or use of patient decision aids (PtDAs) is often not detailed in existing national clinical practice guidelines in oncology. METHODS: We performed a systematic search of Philippine literature on SDM in oncology and an iterative review of international literature on the philosophy and methods of SDM, the utility and effectiveness of PtDAs, and the facilitators and barriers to implementation or usage. We contextualized our review to the cervical cancer management and health service delivery in the Philippines. RESULTS: Local literature is limited to five scientific publications and two registered studies. International literature encompasses patient decisional preferences, the role of PtDAs and the standards for their development and evaluation, their effectiveness, and barriers and facilitators to their use in cancer-related decision making. We discussed the implications on the management of cervical cancer in the Philippines, challenges in health service delivery and standards, and SDM research. CONCLUSION: Local SDM research is limited. Our preliminary experience in a multicenter clinical trial in Manila on PtDA use in the framework of SDM in cervical cancer suggest good patient and clinician acceptability. Challenges to implementation such as unfavorable financial situations, urgency of clinical decisions, low patient or caregiver educational attainment, and poor integration of multidisciplinary and SDM in organizational workflows will be important when implementing SDM in different settings.
Assuntos
Tomada de Decisão Compartilhada, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/terapia, Filipinas, Feminino, Participação do Paciente, Oncologia/organização & administração, Oncologia/normas, Técnicas de Apoio para a DecisãoRESUMO
The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca2+, Mn2+, and H2S in response to the tumor microenvironment. H2S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H2S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H2S acted as an important synergist between Mn2+ and Ca2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H2S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.
Assuntos
Imunoterapia, Proteínas de Membrana, Piroptose, Microambiente Tumoral, Neoplasias do Colo do Útero, Microambiente Tumoral/efeitos dos fármacos, Microambiente Tumoral/imunologia, Neoplasias do Colo do Útero/imunologia, Neoplasias do Colo do Útero/tratamento farmacológico, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/metabolismo, Neoplasias do Colo do Útero/terapia, Feminino, Humanos, Camundongos, Animais, Piroptose/efeitos dos fármacos, Proteínas de Membrana/metabolismo, Manganês/química, Manganês/farmacologia, Antineoplásicos/farmacologia, Antineoplásicos/química, Nanopartículas/química, Transdução de Sinais/efeitos dos fármacos, Proliferação de Células/efeitos dos fármacos, Cálcio/metabolismo, Camundongos Endogâmicos BALB C, Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).
Assuntos
Imageamento por Ressonância Magnética, Neoplasias do Colo do Útero, Humanos, Feminino, Neoplasias do Colo do Útero/diagnóstico por imagem, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/patologia, Prognóstico, Pessoa de Meia-Idade, Estudos Retrospectivos, Imageamento por Ressonância Magnética/métodos, Adulto, Idoso, RadiômicaRESUMO
Cervical cancer is the 4th most diagnosed cancer in women. At a locally advanced stage, standard treatment combines chemotherapy, radiotherapy and a brachytherapy boost. Brachytherapy is a radiotherapy modality, often unknown, which allows the delivery of a very targeted high dose because it's given directly in contact with the tumor. This technique has proven its effectiveness in the treatment of locally advanced cervical cancer. It represents a major advantage because, despite technical advances, there is currently no alternative yielding equivalent results.
Le cancer du col utérin est le 4ème cancer féminin le plus diagnostiqué. à un stade localement avancé, la prise en charge standard relève d'un traitement associant de la chimiothérapie, de la radiothérapie et une curiethérapie de clôture. La curiethérapie est une modalité de radiothérapie, souvent méconnue du grand public, qui permet de délivrer une dose élevée de façon très ciblée, car celle-ci est donnée directement au contact de la tumeur. Cette technique a prouvé son efficacité et son caractère indispensable dans le traitement du cancer du col utérin localement avancé. Elle représente un atout majeur car, malgré l'évolution des techniques de radiothérapie externe plus modernes, il n'y a, à ce jour, aucune alternative équivalente.
Assuntos
Braquiterapia, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/radioterapia, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/terapia, Braquiterapia/métodos, Feminino, Estadiamento de NeoplasiasRESUMO
Tumor-associated macrophages (TAM) can be differentiated into M1-type and M2-type macrophage phenotypes in the tumor microenvironment (TME), with M2-type macrophages playing a crucial role in malignant tumors. In cervical cancer, TAM exacerbates human papilloma virus (HPV) infection, promotes the proliferation, invasion, and metastasis of tumor cells, stimulates angiogenesis, and induces immune tolerance. TAM targeting strategies have emerged as a hot topic in cervical cancer immunotherapy.
Assuntos
Microambiente Tumoral, Macrófagos Associados a Tumor, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/imunologia, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/virologia, Feminino, Macrófagos Associados a Tumor/imunologia, Microambiente Tumoral/imunologia, Imunoterapia/métodos, Infecções por Papillomavirus/imunologia, Infecções por Papillomavirus/virologia, Animais, Macrófagos/imunologiaRESUMO
Positron emission tomography (PET) and computed tomography (CT) have evolved as a pivotal diagnostic modality in the field of oncology. With its increasing application in staging and ready availability, it becomes imperative for committed radiation oncologists to possess a complete analysis and understanding of integration of molecular imaging, which can be helpful for radiation planning, while also acknowledging its possible limitations and challenges. A significant obstacle lies in the synthesis and design of tumor-specific bmolecules for diagnosing and treating cancer. The utilization of radiation in medical biochemistry and biotechnology, encompassing diagnosis, therapy, and control of biological systems, is encapsulated under the umbrella term "nuclear medicine". Notably, the application of various radioisotopes in pharmaceutics has garnered significant attention, particularly in the realm of delivery systems for drugs, DNA, and imaging agents. The present article provides a comprehensive review of use of novel techniques PET and CT with major positron-emitting radiopharmaceuticals currently in progress or utilized in clinical practice with their integration into imaging and radiation therapy.
Assuntos
Fluordesoxiglucose F18, Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/diagnóstico por imagem, Neoplasias do Colo do Útero/terapia, Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos, Feminino, Fluordesoxiglucose F18/uso terapêutico, Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO). In total, 34 practitioners from eight provinces responded, including 17 GO, 13 RO and four MO. During staging and diagnosis, 74% of respondents used a trimodality imaging approach, and 85% tested for neuroendocrine markers. In early-stage (1A1-1B2) SCNECC, 87% of practitioners used a surgical-based approach with various adjuvant and neoadjuvant treatments. In locally advanced (1B3-IVA) SCNECC, 53% favored primary chemoradiation, with cisplatin and etoposide, with the remainder using surgical or radiation-based approaches. In metastatic and recurrent SCNECC, the most common first-line regimen was etoposide and platinum, and 63% of practitioners considered clinical trials in the first line setting or beyond. This survey highlights diverse practice patterns in the treatment of SCNECC. Interdisciplinary input is crucial to individualizing multimodality treatment, and there is a need for prospective trials and intergroup collaboration to define the optimal approach towards managing this rare cancer type.
Assuntos
Carcinoma de Células Pequenas, Padrões de Prática Médica, Neoplasias do Colo do Útero, Humanos, Feminino, Canadá, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/patologia, Carcinoma de Células Pequenas/terapia, Padrões de Prática Médica/estatística & dados numéricos, Inquéritos e QuestionáriosRESUMO
The Laparoscopic Approach to Cervical Cancer (LACC) trial was published in 2018 and demonstrated that minimally invasive surgery (MIS) yields inferior survival outcomes in early-stage cervical cancer compared to open surgery. This study investigates how the results of the LACC trial have impacted the selection of the primary treatment modality and adjuvant radiation utilization in early-stage cervical cancer. Using the National Cancer Database (NCDB), we compared patients with stage IA2-IB1 cervical cancer before (1/2016-12/2017) and after (1/2019-12/2020) the LACC trial. A total of 7930 patients were included: 4609 before and 3321 after the LACC trial. There was a decline in MIS usage from 67% pre-LACC to 35% thereafter (p < 0.001). In both the pre- and post-LACC periods, patients undergoing radical MIS more frequently had small volume disease (pre-LACC tumors ≤ 2 cm, 48% MIS vs. 41% open, p = 0.023; post-LACC stage IA2, 22% vs. 15%, p = 0.002). Pre-LACC, MIS radical hysterectomy was associated with White race (82% vs. 77%, p = 0.001) and private insurance (63% vs. 54%, p = 0.004), while there was no difference in socioeconomic factors in the post-LACC period. Although the proportion of patients treated with primary chemoradiation remained stable, the post-LACC cohort had a younger median age (52.47 vs. 56.37, p = 0.005) and more microscopic disease cases (13% vs. 5.4%, p = 0.002). There was no difference in the rate of radiation after radical hysterectomy before and after the trial (26% vs. 24%, p = 0.3). Conclusions: Post-LACC, patients were less likely to undergo MIS but received adjuvant radiation at similar rates, and primary chemoradiation patients were younger and more likely to have microscopic disease.
Assuntos
Bases de Dados Factuais, Estadiamento de Neoplasias, Neoplasias do Colo do Útero, Humanos, Feminino, Neoplasias do Colo do Útero/terapia, Pessoa de Meia-Idade, Estados Unidos, Idoso, Histerectomia/métodos, Adulto, Radioterapia Adjuvante/estatística & dados numéricosRESUMO
Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor ß to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.
Assuntos
Linfócitos T CD8-Positivos, Senescência Celular, Quimiorradioterapia, Recidiva Local de Neoplasia, Neoplasias do Colo do Útero, Humanos, Linfócitos T CD8-Positivos/imunologia, Linfócitos T CD8-Positivos/metabolismo, Feminino, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/genética, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/imunologia, Neoplasias do Colo do Útero/tratamento farmacológico, Quimiorradioterapia/métodos, Recidiva Local de Neoplasia/patologia, Recidiva Local de Neoplasia/genética, Animais, Camundongos, Linhagem Celular Tumoral, Prognóstico, Resistencia a Medicamentos Antineoplásicos/genética, Regulação Neoplásica da Expressão Gênica, Fator de Crescimento Transformador beta/metabolismo, Senescência de Células TRESUMO
PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.
Assuntos
Quimiorradioterapia Adjuvante, Estadiamento de Neoplasias, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/terapia, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/mortalidade, Feminino, Pessoa de Meia-Idade, Estudos Retrospectivos, Quimiorradioterapia Adjuvante/métodos, Quimiorradioterapia Adjuvante/efeitos adversos, Adulto, Fatores de Risco, Idoso, Resultado do Tratamento, HisterectomiaRESUMO
AIMS: Cervical cancer (CC) is a common malignancy in women, predominantly caused by human papillomavirus. The most subtypes are adenocarcinomas (AC) and squamous cell carcinomas (SCC), which show various features and treatment responses. Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) as Immune checkpoint molecules, play a role in immune evasion. We investigated PD-L1 expression in AC and SCC of the cervix and explored its link to clinical characteristics. METHODS AND RESULTS: The present cross-sectional research was done between 2016 and 2022 on samples in Shahid Beheshti University of Medical Sciences-affiliated hospitals in Iran. Histological tissue samples of CCs (16 AC and 48 SCC) were assessed, and clinical information was obtained by reviewing their medical documents. PD-L1 expression was evaluated by immunohistochemistry and we used the combined positive score. SCC cases showed a higher (not significant) PD-L1 expression. The PD-L1 expression and clinical characteristics were not significantly correlated in both subgroups. CONCLUSION: Although SCC cases exhibited higher PD-L1 expression, this difference was non-significant. More investigations should highlight the role of PD-L1 in CC and the potential benefits of immunotherapy.
Assuntos
Adenocarcinoma, Antígeno B7-H1, Carcinoma de Células Escamosas, Neoplasias do Colo do Útero, Humanos, Neoplasias do Colo do Útero/patologia, Neoplasias do Colo do Útero/metabolismo, Neoplasias do Colo do Útero/terapia, Feminino, Antígeno B7-H1/metabolismo, Antígeno B7-H1/análise, Carcinoma de Células Escamosas/patologia, Carcinoma de Células Escamosas/metabolismo, Carcinoma de Células Escamosas/terapia, Estudos Transversais, Adenocarcinoma/patologia, Adenocarcinoma/metabolismo, Pessoa de Meia-Idade, Adulto, Inclusão em Parafina, Biomarcadores Tumorais/metabolismo, Biomarcadores Tumorais/análise, Irã (Geográfico), Idoso, Imuno-HistoquímicaRESUMO
PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.
