RESUMO
Palliative chemotherapy can improve outcomes in most patients with advanced soft tissue sarcoma (STS), but the treatment of elderly patients remains a challenge because of older age, comorbidities and poor performance status. This study retrospectively analyzed the efficacy and safety of the multi-targeted tyrosine kinase inhibitor anlotinib in elderly patients with advanced STS. Eligible patients included those of age at least 60 years, diagnosed with unresectable or metastatic STS, and treated with at least one cycle of anlotinib between June 2018 and September 2020 in our center. Clinical characteristics, treatment response, survival status and adverse events were analyzed by reviewing medical records. The median age of 35 eligible patients was 65 (range, 61-85) years, and the median Charlson Comorbidity Index score was 8 (range, 4-11). Anlotinib as first-line systemic treatment was in 24 (68.6%) patients, and as second-line or third-line treatment in the remaining 11 (31.4%) patients. The objective response rate was 8.6%. The median progression-free survival was 5.5 [95% confidence interval (CI), 1.4-9.6] months and the median overall survival was 14.3 (95% CI, 9.6-19.0) months. Thirteen (37.1%) patients developed at least one grade 3/4 adverse event during anlotinib treatment. Our findings suggest that anlotinib treatment has promising efficacy and an acceptable toxicity profile in elderly patients with unresectable or metastatic STS. Prospective controlled trials are needed to compare the safety and efficacy of anlotinib and chemotherapy as first-line treatment in elderly patients with advanced STS.
Assuntos
Indóis/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Desempenho Físico Funcional , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Estudos Retrospectivos , Sarcoma/patologia , Fatores Sexuais , Neoplasias de Tecidos Moles/patologia , Análise de SobrevidaRESUMO
INTRODUCTION: Psychotherapy is considered part of the standard treatment of cancer in Western countries. However, there is no literature on the attitudes of Chinese cancer patients toward psychotherapy. METHODS: In a multicenter, cross-sectional study in China, a homemade questionnaire was delivered to cancer patients. The targeted population was Chinese hospitalized cancer patients who were informed of their state of illness. RESULTS: Five hundred and fifty cancer patients received our questionnaire, and 83.3% completed the questionnaire. Among the 458 patients, 43.2% indicated that they had never heard of psychotherapy before the survey. However, after a brief introduction of psychotherapy, most (92.1%) cancer patients indicated that psychotherapy is essential for cancer patients, and over half of patients (57.4%) were willing to take psychotherapy on the advice of the oncologist in charge. Participants aged 45 years or younger, had a family income > 10000 yuan per month, and had an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 2-4 were more willing to receive psychotherapy. Of all patients, 59.2% and 57.6% were willing to participate in individual and group psychotherapy clinical trials, respectively. Participants who had a bachelor's degree or higher (odds ratio, OR = 2.09) and were aged 45 years or younger (OR = 1.67) were more willing to participate in individual and group psychotherapy clinical trials, respectively. CONCLUSION: The unmet psychological needs of cancer patients in China remain high, and doctors' advice is likely to positively impact the patients' acceptance of psychotherapy. Psychological education for Chinese cancer patients should be strengthened. More high-quality clinical trials of psychotherapy should be conducted in China to achieve greater benefits for cancer patients and their families.
Assuntos
Neoplasias , Psicoterapia , Povo Asiático , China , Estudos Transversais , Humanos , Neoplasias/tratamento farmacológicoRESUMO
Background Chemotherapy is an important first-line treatment option in patients with advanced soft tissue sarcoma (STS). Whether maintenance therapy improves survival after chemotherapy is still controversial. Methods We retrospectively analyzed the data of 21 adults diagnosed with unresectable or metastatic STS between May 2018 and September 2019 in our center. They achieved an objective response or stable disease after chemotherapy and then received at least one cycle of switch maintenance therapy with anlotinib, a novel multi-targeted tyrosine kinase inhibitor. The objective response rate (ORR), disease control rate (DCR), adverse events, and median progression-free survival (PFS) after anlotinib maintenance (PFSa), and the median PFS after chemotherapy (PFSc) were analyzed. Results Nineteen patients received first-line chemotherapy and 2 received second-line chemotherapy. Five patients achieved a partial response and 16 had stable disease after chemotherapy. The median number of anlotinib maintenance cycles was five (range, 2-31). One patient achieved a complete response and two patients exhibited a partial response during anlotinib maintenance, with an ORR of 14.3%. The DCR was 81.0%. After a median follow-up of 14.0 months, the median PFSa and PFSc were 7.3 and 13.6 months, respectively. Grade 3/4 adverse events occurred in six (28.6%) patients and were managed through symptomatic treatment, dose reduction or anlotinib discontinuance. Conclusion Our results indicate that switch maintenance therapy with anlotinib is a promising strategy for the treatment of patients with unresectable or metastatic STS who have benefited from chemotherapy. Toxicities were manageable. Prospective clinical trials are needed to confirm this finding.
Assuntos
Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Neoplasias de Tecidos Moles/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Intervalo Livre de Progressão , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Estudos Retrospectivos , Adulto JovemRESUMO
Treatment options for unresectable local recurrence or metastatic well-differentiated/dedifferentiated liposarcoma (WDLS/DDLS) remain limited. Different liposarcoma subtypes have varying clinical features and sensitivities to treatment regimens. The multitarget tyrosine kinase inhibitors (TKIs), such as pazopanib and regorafenib, have been approved for use in nonadipocytic soft tissue sarcomas (STS). Anlotinib, another TKI, has been approved in China for treating metastatic STS that has progressed after the use of anthracycline-based regimens. In this study, we aimed to evaluate the role of anlotinib in the treatment of local recurrence or metastatic WDLS/DDLS. From August 2018 to June 2020, 17 patients with unresectable local recurrence or metastatic WDLS/DDLS treated with anlotinib in our center were included. The follow-up cutoff time was set as 20 October 2020. Baseline and observation indicators were collected and analyzed. Estimated median progression-free survival (PFS) was 27.9 weeks, the PFS rate at 24 weeks was 58.8%, overall survival (OS) was 56.6 weeks, the disease control rate was 64.7% and no complete response or partial response was detected. Grade 3/4 adverse events occurred in four cases and could be managed. Anlotinib is a potential treatment option for unresectable local recurrence or metastatic WDLS/DDLS.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Indóis/uso terapêutico , Lipossarcoma/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Neoplasias Retroperitoneais/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Intervalo Livre de Progressão , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Neoplasias Retroperitoneais/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: The objective of the study is to develop a novel tool-the Burnout Battery-for briefly screening burnout among oncology professionals in China and assessing its validity. METHODS: A multicenter study was conducted in doctors and nurses of the oncology departments in China from November 2014 to May 2015. The Burnout Battery was administered with the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) and the Doctors' Job Burnout Questionnaire. RESULTS: Of 538 oncology doctors and nurses who completed all the survey, using MBI-HSS as the standard tool for measuring burnout, 52% had emotional exhaustion, 39.4% had depersonalization, and 59.3% had a low sense of personal accomplishment. Receiver operating characteristic curve analyses showed that the best cut-off of the Burnout Battery was the battery with 3 bars, which yielded best sensitivity and specificity against all the 3 subscales of MBI-HSS. With this cut-off, nearly half of Chinese oncology professionals (46.8%) had burnout. The Burnout Battery correlated significantly with subscales of the MBI-HSS and the Doctors' Job Burnout Questionnaire. In multiple logistic regression analysis, those who worked more than 60 hours per week and who thought clinical work was the most stressful part of their job were more likely to experience burnout. CONCLUSION: Chinese oncology professionals exhibit high levels of burnout. The Burnout Battery appears to be a simple and useful tool for screening burnout. Working long hours and perceiving clinical work as the most stressful part of the job were the main factors associated with burnout.
Assuntos
Esgotamento Profissional/psicologia , Satisfação no Emprego , Corpo Clínico/psicologia , Inquéritos e Questionários/normas , Logro , Adulto , China , Despersonalização/psicologia , Feminino , Humanos , Masculino , Oncologia/organização & administração , Pessoa de Meia-Idade , Escala Visual AnalógicaRESUMO
OBJECTIVE: In China, not only patients and physicians are involved in medical decision-making (MDM) but also the patients' family members. The objective is to investigate the willingness and actual situation of cancer patients and their family members participating in the MDM process. METHODS: In this cross-sectional study, questionnaires were administered to 247 pairs of cancer inpatients and their relatives. Information regarding participants' willingness and actual experience during the decision-making process was documented. Eligible participants were cancer inpatients or their relatives, 18 years of age or older, and informed of the cancer diagnosis. All the patients should have received chemotherapy. RESULTS: The effective response rate was 72.9% (180/247). Over half of the patients (53.3%) and family members (57.8%) were willing to be part of the MDM process. In contrast, only 35.0% of patients and 46.1% of family members actually experienced this process (p = 0.001 and p = 0.011, respectively). Fewer family members (42.2%) than patients (53.3%) believed that patients should be involved in the MDM process (p < 0.001). Patients who were the head of their family (odds ratio 2.577, 95% CI 1.198-5.556, p = 0.015) experienced more involvement in MDM. CONCLUSIONS: Although more than half of Chinese cancer patients and family members wanted to be part of MDM, the actual participation was below their expectation. Majority of family members do not want the patients to be involved in the process of MDM.
Assuntos
Tomada de Decisões , Família/psicologia , Neoplasias/terapia , Participação do Paciente/psicologia , Adolescente , Adulto , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
To determine if the radiation sensitivity of cells that survive acute high-dose radiation exposure used in stereotactic body radiation therapy (SBRT), differs from the sensitivity of non-irradiated cells and cells that survive multiple 2 Gy doses of radiation. Isogenic rodent and two human tumor cell lines were exposed to 14 × 2 Gy of radiation, or a single acute dose of 12 Gy. The most resistant cell line was also exposed to an acute dose of 15 Gy. One week after 12 Gy, and 4 days after 14 × 2 Gy, surviving cells were exposed to 0-8 Gy in 2 Gy doses and cell survival was assessed by colony formation. In addition, the colony forming efficiency of 12 Gy survivors was evaluated for 1 month postirradiation. For cells exposed to 15 Gy, the response of surviving cells to 6 Gy was determined for up to 35 days postirradiation and compared to the 6 Gy surviving fraction of control cells. The radiation sensitivity of cells that survived 12 Gy exposure, and cells that survived 14 fractions of 2 Gy irradiation did not differ from the response of unirradiated control cells. However, the growth rate and colony forming efficiency of 12 Gy survivors was transiently reduced for greater than 2 weeks postirradiation. In contrast to the unchanged sensitivity of 12 Gy surviving cells at day 7 postirradiation, 15 Gy survivors exhibited enhanced sensitivity to radiation for up to 21 days postirradiation and suggests a biological basis for SBRT.
Assuntos
Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Doses de Radiação , Tolerância a Radiação , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta à RadiaçãoRESUMO
BACKGROUND: Chronic stress can induce stress-related hormones; norepinephrine (NE) is considered to have the highest potential in cancer. NE can stimulate the expression of hypoxia-inducible factor-1α (HIF-1α), which is associated with vascular endothelial growth factor (VEGF) secretion and tumor angiogenesis. However, the underlying mechanisms are poorly understood. METHODS: Tumor-bearing mice were subjected to chronic restraint stress and treated with normal saline, human monoclonal VEGF-A neutralizing antibody bevacizumab, or ß-adrenergic receptor (ß-AR) antagonist (propranolol). Tumor growth and vessel density were also evaluated. Human colorectal adenocarcinoma cells were treated with NE, propranolol, or the inhibitor of transforming growth factor-ß (TGF-ß) receptor Type I kinase (Ly2157299) in vitro. TGF-ß1 in mouse serum and cell culture supernatants was quantified using ELISA. The expression of HIF-1α was measured using Real time-PCR and western blotting. Cell migration and invasion were tested. RESULTS: Chronic restraint stress attenuated the efficacy of bevacizumab and promoted tumor growth and angiogenesis in a colorectal tumor model. Propranolol blocked this effect and inhibited TGF-ß1 elevation caused by chronic restraint stress or NE. NE upregulated HIF-1α expression, which was reversed by propranolol or Ly2157299. Propranolol and Ly2157199 blocked NE-stimulated cancer cell migration and invasion. CONCLUSIONS: Our results demonstrate the effect of NE on tumor angiogenesis and the critical role of TGF-ß1 signaling during this process. In addition, ß-AR/TGF-ß1 signaling/HIF-1α/VEGF is a potential signaling pathway. This study also indicates that psychosocial stress might be a risk factor which weakens the efficacy of anti-angiogenic therapy.
Assuntos
Bevacizumab , Neoplasias Colorretais , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neovascularização Patológica , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Animais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Humanos , Neovascularização Patológica/metabolismo , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Propranolol/farmacologia , Linhagem Celular Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Masculino , Movimento Celular , Norepinefrina/farmacologia , Norepinefrina/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Angiogênese , Pirazóis , QuinolinasRESUMO
Objective: We performed this pooled analysis for the first time to comprehensively explore the prognostic value of tumor-associated high endothelial venules (TA-HEVs) and determine their relationships with clinicopathological features in solid tumors. Methods: Four online databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched to identify studies assessing the effect of TA-HEVs on prognosis or clinicopathological features. Hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate survival outcomes, including overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). The association between TA-HEV status and clinicopathological characteristics was assessed by odds ratios (ORs) combined with 95% CIs. Subgroup analysis was conducted to explore sources of heterogeneity. The sensitivity analysis was performed to evaluate the stability of our findings. Meanwhile, Funnel plots were employed to visually evaluate potential publication bias, and both Begg's and Egger's tests were adopted to quantitatively determine publication bias. Results: A total of 13 retrospective cohort studies, involving 1,933 patients were finally included in this meta-analysis. Effect-size pooling analysis showed that the positivity of TA-HEVs was related to improved OS (pooled HR: 0.75, 95% CI: 0.62-0.93, P<0.01), and DFS (pooled HR = 0.54, 95% CI = 0.41-0.72, P< 0.01). However, TA-HEV positivity in solid tumors was not linked to PFS (pooled HR = 0.75, 95% CI 0.34-1.64, P = 0.47) or CSS (pooled HR: 0.58, 95% CI: 0.04-7.58, P= 0.68). Further subgroup analysis demonstrated that ethnicity and source of HR were the main factors contributing to heterogeneity. Moreover, TA-HEVs were inversely associated with lymph node metastasis and distant metastasis, but were positively related to worse tumor differentiation. However, TA-HEVs were not significantly correlated with sex, LVI, clinical stage, and depth of invasion. Sensitivity analysis suggested that the pooled results were stable and reliable, with no significant publication bias in all included articles. Conclusions: This is the first comprehensive analysis of the prognostic value of TA-HEVs in solid tumors using existing literature. Overall, our study demonstrated a significant correlation between TA-HEVs and prognosis as well as clinicopathological features. TA-HEVs may serve as novel immune-related biomarkers for clinical assessments and prognosis prediction in solid tumors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD42023394998.
Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/mortalidade , Vênulas/patologia , Prognóstico , Microambiente Tumoral , Biomarcadores TumoraisRESUMO
OBJECTIVE: The purpose of this study was to compare the antitumor efficacy of anlotinib with gemcitabine-based chemotherapy as subsequent treatment regimens in patients with advanced non-specific soft tissue sarcoma (STS) after the failure of anthracycline-based chemotherapy. METHODS: Patients diagnosed with advanced STS who were treated with either anlotinib or gemcitabine-based chemotherapy between May 2009 and May 2023 in our center were eligible. All patients experienced disease progression or recurrence after the anthracycline-based chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were disease control rate (DCR), overall survival (OS) and safety. RESULTS: We included 49 patients receiving anlotinib and 45 patients receiving gemcitabine-based chemotherapy. The median follow-up time was 76.9 weeks (range 2.9-678.9 weeks). The DCR (65.3% vs. 57.8%; p = 0.610), PFS (24.0 weeks vs. 18.6 weeks; p = 0.669) and OS (79.4 weeks vs. 87.0 weeks; p = 0.471) of anlotinib and gemcitabine-based chemotherapy indicated similar clinical efficacy. Moreover, exploratory subgroup analyses showed that patients with STS originating from limbs and trunk were inclined to benefit from anlotinib treatment (median PFS: 31.3 weeks vs. 12.4 weeks; p = 0.045). ECOG PS was an independent predictor of the PFS [Hazard Ratio (HR) 0.31; 95% confidence interval (CI) 0.11-0.85; p = 0.023] and OS (HR 0.26, 95%CI 0.10-0.70; p = 0.008) in the anlotinib group. While neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic factor of the PFS (HR 0.33, 95%CI 0.11-0.98; p = 0.045) in the gemcitabine-based chemotherapy group. The incidence of grade 3 or higher related AEs in anlotinib and gemcitabine-based chemotherapy was 20.4% (n = 10) and 20.0% (n = 9), respectively. CONCLUSION: Our research suggested that anlotinib and gemcitabine-based chemotherapy showed similar clinical efficacy and safety in the subsequent treatment of advanced STS after the failure of anthracycline-based chemotherapy.
Assuntos
Policetídeos , Quinolinas , Sarcoma , Humanos , Gencitabina , Antraciclinas , Indóis/efeitos adversos , Antibióticos Antineoplásicos , Sarcoma/tratamento farmacológicoRESUMO
OBJECTIVES: This study evaluates the efficacy of programmed death-1 (PD-1) inhibitors as adjuvant therapy for acral melanoma (AM) and the predictive value of genetic mutations and tertiary lymphoid structures (TLSs). METHODS AND RESULTS: A single-center retrospective longitudinal cohort study was conducted between October 1, 2018, and September 31, 2022. Patients with stages II-III completely resected AM were treated with at least two doses of adjuvant PD-1 inhibitors. A total of 44 participants were included in the final analysis, of which 41 patients with stage III. The median follow-up time, median relapse-free survival (RFS), and median distance metastasis-free survival (DMFS) for all patients were 18.4 months, 21.6 months, and 30.6 months, respectively. 21 (47.7%) and 20 (45.5%) patients were intravenously administered pembrolizumab and toripalimab, respectively. There were no significant differences in RFS (24.4 months vs. 18.9 months, p = 0.432) or DMFS (30.6 months vs. not reached, p = 0.865) between the pembrolizumab and toripalimab groups, respectively. The median DMFS (41.1 months vs. 9.0 months, p < 0.001) in the wild-type NRAS group was significantly longer than that in the NRAS mutation group. Overall, different levels of TLSs infiltration did not significantly affect patient survival. Only three people discontinued treatment due to adverse events. No treatment-related death occurred during the study period. CONCLUSION: Our study suggests that adjuvant toripalimab and pembrolizumab therapy have comparable efficacies in patients with AM and are both well tolerated. Adjuvant monotherapy with PD-1 inhibitors may not be appropriate for AM with NRAS mutations.
Assuntos
Melanoma , Neoplasias Cutâneas , Estruturas Linfoides Terciárias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Estudos Longitudinais , Estruturas Linfoides Terciárias/tratamento farmacológico , Melanoma/tratamento farmacológico , Melanoma/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Adjuvantes Imunológicos/uso terapêutico , Recidiva , Mutação , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genética , Melanoma Maligno CutâneoRESUMO
OBJECTIVES: To assess the occurrence of cardiotoxicity in patients with tumors receiving anthracycline-based chemotherapy, especially for sarcomas. METHODS: This study summarized the types and frequency of adverse events (AEs) for three anthracyclines from the FDA adverse event reporting system (FAERS) database. FAERS data from January 2004 to June 2022 were collected and analyzed. Disproportionality analyses, logistic regression, and descriptive analysis were used to compare the differences in cardiac disorders. A retrospective cohort study was conducted in a single center between December 2008 and May 2022. Our hospital-treated patients with bone and soft tissue sarcomas (BSTSs) with anthracycline-containing chemotherapy were analyzed. Serum markers, echocardiography, and electrocardiography have been used to evaluate cardiotoxic events. RESULTS: One hundred thousand and seventy-five AE reports were obtained for doxorubicin (ADM), epirubicin (EPI), and liposome doxorubicin (L-ADM) from the FAERS database. ADM (OR = 3.1, p < 0.001), EPI (OR = 1.5, p < 0.001), and sarcomas (OR = 1.8, p < 0.001) may increase the probability of cardiac disorders. Cardiac failure, cardiotoxicity, and cardiomyopathy were anthracyclines' top 3 frequent AEs. Among patients receiving ADM-containing therapy, those with ADM applied at doses ≥75 mg/m2 /cycle were more likely to develop cardiac disorders than the other subgroups (OR = 3.5, p < 0.001). Patients younger than 18 are more likely to benefit from dexrazoxane prevention of cardiac failure. Six hundred and eighty-three patients with BSTSs receiving anthracycline-based chemotherapy were analyzed in our center. Patients receiving ADM-containing chemotherapy were likelier to experience abnormalities in serum troponin-T and left ventricular ejection fraction (p < 0.05). 2.0% (6/300) of patients receiving ADM-containing chemotherapy required adjustment of the chemotherapy regimen because of cardiotoxicity, whereas none were in the EPI or L-ADM groups. CONCLUSIONS AND RELEVANCE: Among patients receiving anthracycline-containing therapy, patients with BSTSs were more likely to develop cardiac disorders than other tumors. In addition, patients with BSTSs receiving ADM chemotherapy had a higher likelihood of cardiotoxic events than those receiving EPI or L-ADM.
Assuntos
Cardiopatias , Insuficiência Cardíaca , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Antraciclinas/uso terapêutico , Cardiotoxicidade/etiologia , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Antibióticos Antineoplásicos/efeitos adversos , Cardiopatias/induzido quimicamente , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Doxorrubicina/uso terapêutico , Epirubicina , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológicoRESUMO
Leiomyosarcoma occurring in the bone as primary tumor localization is extremely scarce with limited cases described in the literature, accounting for less than 0.7% of all primary bone malignancies. Once distant metastasis occurs, patients have limited treatments and often a somber prognosis, which underscore the need for innovative and effective treatment approaches. The emerging evidence suggests that anti-angiogenic therapy could inhibit angiogenesis and normalize vascular permeability in the tumor microenvironment, which, in turn, would increase immune effector cell infiltration into tumors. Immunotherapy depends on the accumulation and activity of immune effector cells within the tumor microenvironment, and immune responses and vascular normalization seem to be reciprocally regulated. Immunotherapy combined with anti-angiogenic therapy has recently made great progress in the treatment of various types of tumors. However, the effectiveness of the combination treatment in metastatic leiomyosarcoma is undetermined. In this study, we presented a rare case of primary leiomyosarcoma of the bone located in the trochanteric region of the femur, accompanied by multiple distant metastases. After the failure of multi-line therapies including AI regiments as the adjuvant chemotherapy, anlotinib as the first-line therapy, GT regiment as the second-line therapy, and eribulin as the third-line therapy, the patient received combinational therapy with penpulimab plus lenvatinib. The best efficacy for this regimen was a partial response, with a progression-free survival of 8.4 months according to the iRECIST criteria. After a dissociated response was detected without severe toxicities, the patient received local radiotherapy and continued treatment on penpulimab plus lenvatinib and eventually achieved long-term survival benefits with a total of over 60 months of overall survival with good quality of life and ongoing treatment. As our previous retrospective study found that one-third of advanced STS patients could still achieve clinical benefits from rechallenge with multi-targeted tyrosine kinase inhibitors (TKIs), after the failure of previous TKI therapy, this case provided the potential clinical activity of immunotherapy combined with anti-angiogenic TKI rechallenge in metastatic leiomyosarcoma.
RESUMO
Background: Tertiary lymphoid structures (TLSs) have been proven to be predictive biomarkers of favorable clinical outcomes and response to immunotherapies in several solid malignancies. Nevertheless, the effect of TLSs in patients with breast cancer (BC) remains controversial. The objective of the current study is to investigate the clinicopathological and prognostic significance of TLSs in BC. Given the unique difficulties for detecting and quantifying TLSs, a TLS-associated gene signature based on The Cancer Genome Atlas (TCGA) BC cohort was used to validate and supplement our results. Methods: Electronic platforms (PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and Wanfang) were searched systematically to identify relevant studies as of January 11, 2022. We calculated combined odds ratios (ORs) with 95% confidence intervals (CIs) to determine the relationship between clinicopathological parameters and TLSs. The pooled hazard ratios (HRs) and 95% CIs were also calculated to evaluate the prognostic significance of TLSs. The TLS signature based on the TCGA BC cohort was applied to validate and supplement our results. Results: Fifteen studies with 3,898 patients were eligible for enrollment in our study. The combined analysis indicated that the presence of TLSs was related to improved disease-free survival (DFS) (HR = 0.61, 95% CI: 0.41-0.90, p < 0.05) and overall survival (OS) (HR = 1.66, 95% CI: 1.26-2.20, p < 0.001). Additionally, the presence of TLSs was positively correlated with early tumor TNM stage and high tumor-infiltrating lymphocytes. TLS presence was positively related to human epidermal growth factor receptor 2 (HER-2) and Ki-67 but inversely correlated with the status of estrogen and progesterone receptor. Simultaneously, our study found that tumor immune microenvironment was more favorable in the high-TLS signature group than in the low-TLS signature group. Consistently, BC patients in the high-TLS signature group exhibited better survival outcomes compared to those in the low-TLS signature group, suggesting that TLSs might be favorable prognostic biomarkers. Conclusions: TLS presence provides new insight into the clinicopathological features and prognosis of patients with BC, whereas the factors discussed limited the evidence quality of this study. We look forward to consistent methods to define and characterize TLSs, and more high-quality prospective clinical trials designed to validate the value of TLSs alone or in combination with other markers.
Assuntos
Neoplasias da Mama , Estruturas Linfoides Terciárias , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Humanos , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Estudos Prospectivos , Microambiente TumoralRESUMO
BACKGROUND: The ALTER0203 clinical trial showed that anlotinib, a multitargeted tyrosine kinase inhibitor, had antitumor effects on advanced soft tissue sarcoma (STS) after the failure of standard chemotherapy. We aimed to evaluate the real-world efficacy and explore prognostic factors and treatment patterns of anlotinib in patients with advanced STS. METHODS: We retrospectively analyzed the data of patients with unresectable locally advanced or metastatic STS who received at least one dose of anlotinib from June 2018 to March 2021. The survival data were analyzed using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was performed for multivariate analysis. RESULTS: A total of 209 patients were included. The median age was 48 (range 11-85) years. The median follow-up, progression-free survival, and overall survival were 18.7 months, 6.1 months [95% confidence interval (CI): 4.9-7.2], and 16.4 months (95% CI: 13.6-19.1), respectively. The objective response rate was 13.4%. Nutritional status, Eastern Cooperative Oncology Group (ECOG) performance status, and anlotinib treatment patterns (combination therapy or switch maintenance therapy vs. monotherapy) were significantly associated with progression-free survival. Besides, pathological grade, nutritional status, ECOG performance status, and anlotinib treatment patterns were predictive of overall survival. Due to anlotinib-related toxicity, 31 (14.8%) patients, and 25 (12.0%) patients experienced dose reduction and treatment discontinuation, respectively. CONCLUSION: These findings confirmed the efficacy of anlotinib in patients with advanced STS in a real-world setting. The patterns of anlotinib treatment deserve further exploration.
Assuntos
Segunda Neoplasia Primária , Quinolinas , Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Indóis , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Quinolinas/efeitos adversos , Estudos Retrospectivos , Sarcoma/patologia , Adulto JovemRESUMO
Background: Melanoma is the most lethal skin malignant tumor with a short survival once stepping into the metastatic status and poses a therapeutic challenge. Apatinib (a tyrosine kinase inhibitor) is a promising antiangiogenic agent for the treatment of metastatic melanoma. However, antiangiogenic monotherapy is prone to acquired drug resistance and has a limited therapeutic effect. The persistence dependence of glycolytic metabolism in antiangiogenic therapy-resistant cells provides evidence that glycolysis inhibitors may enhance the effect of antiangiogenic therapy. So, this study aimed to investigate whether WZB117 (a specific GLUT1 inhibitor) could enhance the anti-tumor effect of apatinib against melanoma and its potential mechanisms. Methods: We investigated the anti-tumor effects of apatinib alone or in combination with WZB117 on human melanoma cell lines (A375 and SK-MEL-28). The MTT assay determined cell viability and the half-maximal inhibitory concentration (IC50). Multiple drug effect/combination indexes (CI) analysis was conducted to assess interactions between apatinib and WZB117. Signal transducer and activator of transcription 3 (STAT3) pathway measured by western blotting and immunofluorescence staining. RNA expression analyses were performed using the reverse transcription-quantitative PCR method. Results: Apatinib and WZB117 showed dose and time-dependent growth inhibitory effects in both melanoma cells. The IC50 of apatinib at 48 h in A375 and SK-MEL-28 cells was 62.58 and 59.61 µM, respectively, while the IC50 of WZB117 was 116.85 and 113.91 µM, respectively. The CI values of the two drugs were 0.538 and 0.544, respectively, indicating a synergistic effect of apatinib combined with WZB117. We also found that glucose consumption and lactate production were suppressed by apatinib plus WZB117 in a dose-dependent manner, paralleled by reducing glycolytic enzyme pyruvate kinase M2 (PKM2). The potential mechanism of the combination was to suppress the phosphorylation of STAT3. Knockdown of STAT3 by siRNA inhibited the expression of PKM2, while the activation of STAT3 by IL-6 increased the expression of PKM2. The effects of IL-6 were attenuated by apatinib combined with WZB117 treatment. Conclusion: WZB117 enhanced the anti-tumor effect of apatinib against melanoma via modulating glycolysis by blocking the STAT3/PKM2 axis, which suggested the combination of apatinib with WZB117 could be a potential therapeutic candidate for melanoma.
RESUMO
PURPOSE: Chemotherapy and multi-targeted tyrosine kinase inhibitors (TKI) are important treatments for advanced soft tissue sarcomas, but the following treatment remains unclear after the failure of these drugs. This retrospective study investigated the efficacy and safety of multi-targeted TKI rechallenge in patients with advanced soft tissue sarcoma after the failure of previous TKI treatment. PATIENTS AND METHODS: Gastrointestinal stromal tumors, dermatofibrosarcoma protuberans and anaplastic lymphoma kinase translocation-positive inflammatory myofibroblastic tumor were excluded. Eligible patients included those diagnosed with advanced soft tissue sarcoma, progressed after the initial TKI treatment, and received the same or other TKI therapies. Treatment response, adverse events, median progression-free survival and overall survival were analyzed. RESULTS: Twenty-six eligible patients were included. Nineteen patients had previously received chemotherapy, and all patients had received at least 1.5 months of initial TKI treatment. During the TKI rechallenge, patients were treated with anlotinib (n =16), lenvatinib (n =3), apatinib (n =2), pazopanib (n =2), axitinib (n =2) or regorafenib (n =1). No patients achieved responses. Nine (34.6%) patients had stable disease confirmed by a second imaging scan, and 5 (19.2%) patients had stable disease that was not confirmed by a second scan. The estimated median progression-free survival and overall survival were 3.3 months and 11.7 months, respectively. Grade 3/4 adverse events occurred in 6 (23.1%) patients and were manageable. CONCLUSION: Our findings suggest that multi-targeted TKI rechallenge may provide potential clinical benefits for patients with advanced soft tissue sarcoma after their previous TKI treatment.
RESUMO
Preoperative diagnosis of solitary fibrous tumour (SFT) may not provide a complete tumour picture and may be inaccurate. There is no standard treatment for locally advanced or metastasised malignant SFT (MSFT). Here, the case of a 17-year-old male patient with final pathology diagnosis of MSFT is reported. Preoperative biopsy pathology results suggested an Ewing sarcoma that was positive for CD99 antigen, vimentin, friend leukaemia integration 1 transcription factor, apoptosis regulator Bcl-2, and synaptophysin; and negative for CD34 antigen, S-100 protein (S-100), smooth muscle antigen, cytokeratin, and Wilms tumour 1 associated protein. The Ki67 positive rate was 8%, so the patient initially received eight cycles of conversion chemotherapy (vincristine, etoposide, ifosfamide and pirarubicin for one cycle, and vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide for 7 cycles in total). The tumour shrunk significantly and was surgically removed. The final pathology diagnosis was MSFT that was positive for CD99 and signal transducer and activator of transcription 6, and negative for CD34, tumour protein 63, S-100, desmin, and epithelial membrane antigen. Fluorescence in situ hybridization showed no gene translocation in EWS RNA binding protein 1, SS18 subunit of BAF chromatin remodelling complex or FUS RNA binding protein. The patient finally accepted adjuvant radiotherapy of 5600 cGy. Disease-free survival has been > 1 year, with no recurrence or metastasis detected to date. MSFT is rare and treatment for locally advanced or metastatic MSFT remains controversial. The efficacy of the present therapeutic strategy requires further research.
Assuntos
Recidiva Local de Neoplasia , Tumores Fibrosos Solitários , Adolescente , Intervalo Livre de Doença , Humanos , Ifosfamida , Hibridização in Situ Fluorescente , Masculino , Tumores Fibrosos Solitários/tratamento farmacológicoRESUMO
Chronic stress could induce cancer metastasis by constant activation of the sympathetic nervous system, while cellular mechanism remains obscure. The aim of this research is to explore the metastasis associated negative effect of chronic stress. The analysis of transcriptome sequencing implied that activation of STAT3 signaling pathway by downregulated miR-337-3p might be a potential mechanism to induce epithelial to mesenchymal transition (EMT) of cancer cell and promote metastasis under chronic stress. We also verified this biological process in further experiments. Downregulation of miR-337-3p could downregulate E-cadherin expression and upregulate vimentin expression in vitro and in vivo. STAT3, related signal pathways of which are involved in metastasis regulation, was directly targeted by miR-337-3p. In conclusion, the above results denoted that activation of miR-337-3p/STAT3 axis might be a potential pathway for the increasing metastasis of breast cancer under chronic stress.
Assuntos
Neoplasias Mamárias Experimentais/metabolismo , MicroRNAs/metabolismo , Fator de Transcrição STAT3/metabolismo , Estresse Psicológico/metabolismo , Animais , Doença Crônica , Transição Epitelial-Mesenquimal , Feminino , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Metástase Neoplásica , Fator de Transcrição STAT3/genética , Transdução de Sinais , Estresse Psicológico/genética , Estresse Psicológico/patologiaRESUMO
PURPOSE: This study aimed to determine the potential of positron emission tomography/computed tomography (PET/CT) in replacing routine bone-marrow biopsies (BMB) in newly diagnosed extranodal natural killer/T-cell lymphoma (ENKTCL). METHODS: Newly diagnosed patients underwent PET/CT imaging and routine BMB to assess bone/bone marrow involvement (BMI). Clinical stage and treatment plan were determined, and survival was compared. RESULTS: In a total of 101 patients, 78 were diagnosed as stage I/II and 23 as stage III/IV without using the BMB results. No BMB-positive patients were identified in stages I/II, and therefore, the BMB results did not alter the stage and treatment choice in any patients. The sensitivity and specificity of focal skeletal PET/CT lesion(s) in assessing BMI was 100% and 92.8%, respectively, taking routine BMB as the reference standard. The overall survival (OS) and progression-free survival (PFS) of BMB-positive patients was significantly inferior (P = 0.0011 and 0.0465, respectively, in advanced-stage patients; both P < 0.0001 in all patients), and this was corroborated by the PET/CT findings (P = 0.0006 and 0.0116, respectively, in advanced-stage patients; both P < 0.0001 in all patients). CONCLUSIONS: Based on the results, PET/CT demonstrated satisfactory predictive performance in terms of staging and prognosis in ENKTCL. BMB did not influence staging and treatment in newly diagnosed ENKTCL, and routine non-targeted BMB is not obligatory for early stage patients undergoing PET/CT. Targeted BMB is recommended to confirm BMI in advanced-stage patients.