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1.
World J Surg Oncol ; 22(1): 153, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38863003

RESUMO

In rectal cancer treatment, the diagnosis and management of lateral pelvic lymph nodes (LLN) are critical for preventing local recurrence. Over time, scholars have reached a consensus: when imaging suggests LLN metastasis, combining neoadjuvant chemoradiotherapy (nCRT) with selective LLN dissection (LLND) can mitigate the risk of recurrence. Selective LLND typically encompasses lymph nodes in the internal iliac and obturator regions. Recent studies emphasize distinctions between internal iliac and obturator lymph nodes regarding prognosis and treatment outcomes, prompting the need for differentiated diagnostic and treatment approaches.


Assuntos
Excisão de Linfonodo , Linfonodos , Metástase Linfática , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Linfonodos/patologia , Linfonodos/cirurgia , Excisão de Linfonodo/métodos , Prognóstico , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Pelve/patologia
2.
Blood Cancer J ; 14(1): 90, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821914

RESUMO

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Imunoterapia Adotiva/métodos , Estudos Retrospectivos , Receptores de Antígenos Quiméricos/uso terapêutico , Adulto , Resultado do Tratamento , Padrão de Cuidado , Recidiva Local de Neoplasia/terapia
3.
Clin Transplant ; 38(5): e15366, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38775798

RESUMO

In children with high-risk childhood acute leukemia who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT), relapse is still the leading cause of treatment failure. The prognosis is poor, yet prospective studies have only limited data on risk factors and outcomes. We aimed to understand the outcomes and prognostic factors for patients with acute lymphoblastic leukemia (ALL) who relapsed following allo-HSCT. We analyzed retrospectively 46 children with childhood acute lymphoblastic leukemia who had relapsed after receiving their first alloHSCT. All these patients received salvage chemotherapy which consisted of fludarabine, cytarabine, and idarubicin before performing a second alloHSCT. The median follow-up of the 46 patients after the first transplantation was 366 days. The median time from first allo-HSCT to relapse was 278.4 ± 238.4 days. Forty-six patients received salvage chemotherapy before the second alloHSCT, and CR was achieved in 32 of 46 patients. However, only 17 (37%) of 46 patients received a second allo-HSCT, and 15 of 46 patients died from disease progression, infections, and bleeding. Twelve patients are still alive after the second allo-HSCT. Two-year overall survival (OS) was 38.9%. Local therapy was given to 10 (21.8%) patients, either as part of systemic therapy or alone. In multivariate analyses, the time of relapse and curative salvage therapy with a second allo-HSCT were identified as significant prognostic factors for OS. Children with leukemia who had relapsed after the first allo-HSCT received salvage chemotherapy. Our statistical analysis showed that the second HSCT could be beneficial for outcomes if patients relapsed beyond 180 days of the first allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Transplante Homólogo , Humanos , Feminino , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Criança , Estudos Retrospectivos , Pré-Escolar , Prognóstico , Seguimentos , Adolescente , Taxa de Sobrevida , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Fatores de Risco , Lactente , Doença Enxerto-Hospedeiro/etiologia , Terapia de Salvação , Condicionamento Pré-Transplante , Recidiva
4.
CNS Oncol ; 13(1): 2345579, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38722227

RESUMO

Background: Treatment for refractory or relapsed primary CNS lymphoma (r/r PCNSL) is challenging. Salvage whole-brain radiation therapy (WBRT) is an option but has a short duration of disease control, so additional treatment modalities are warranted. Case: A 75-year-old female with r/r PCNSL who had multiple progressions after multiple lines of treatment underwent salvage WBRT. The patient received ibrutinib, a Bruton's tyrosine kinase inhibitor, as maintenance therapy for 18 months following WBRT with the intention of increasing survival duration after salvage WBRT. She survived 81 months from diagnosis, including 57 months after completion of WBRT. Conclusion: This case presentation describes the experience of using ibrutinib as maintenance therapy in treating r/r PCNSL after salvage WBRT.


Treatment for refractory or relapsed primary CNS lymphoma (r/r PCNSL) is difficult. Salvage whole-brain radiation therapy (WBRT) is one treatment choice, but the effects do not last very long. Therefore, additional treatment regimens are needed. The authors report a 75-year-old female with r/r PCNSL who had several progressions after multiple lines of treatment and underwent salvage WBRT. Following WBRT, the patient received ibrutinib, a Bruton's tyrosine kinase inhibitor, as maintenance therapy for 18 months to increase the duration of survival after salvage WBRT. She survived 81 months from diagnosis, including 57 months after completion of WBRT. This case reflects the experience of using ibrutinib as maintenance therapy in treating r/r PCNSL after salvage WBRT.


Assuntos
Adenina , Neoplasias do Sistema Nervoso Central , Recidiva Local de Neoplasia , Piperidinas , Pirazóis , Pirimidinas , Humanos , Piperidinas/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Feminino , Idoso , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Terapia de Salvação , Indução de Remissão , Linfoma/tratamento farmacológico , Linfoma/terapia , Linfoma/radioterapia
5.
J Cancer Res Clin Oncol ; 150(5): 224, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693452

RESUMO

BACKGROUND: Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy. PATIENTS: Twenty-nine consecutive adult patients receiving tisagenlecleucel (tisa-cel) for rr LBCL from December 2019 to February 2023 at Jena University Hospital were analyzed. RESULTS: The median age was 63, with a median of 3 prior treatments. Twenty patients (69%) were refractory to any systemic therapy before CAR-T cell treatment. Following leukapheresis, 25 patients (86%) received bridging therapy with the majority undergoing chemotherapy (52%) or combined modality therapy (32%). Radiotherapy (RT) was part of the bridging strategy in 44%, with moderately hypofractionated involved site RT (30.0 Gy/2.5 Gy) being applied most frequently (64%). Post-CAR-T infusion, the objective response rate at 30 days was 83%, with 55% achieving complete response. Twelve-month progression-free (PFS) and overall survival (OS) were 60% and 74%, respectively, with a median follow up of 11.1 months for PFS and 17.9 months for OS. Factors significantly associated with PFS were chemotherapy sensitivity pre-leukapheresis and response to bridging. CONCLUSION: The study underscores the importance of minimal tumor burden at CAR-T initiation, emphasizing the need for suitable bridging regimens. The findings advocate for clinical trials and further real-world analyses to optimize CAR-T cell therapy outcomes by identifying the most effective bridging strategies.


Assuntos
Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Adulto , Indução de Remissão , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Alemanha , Receptores de Antígenos de Linfócitos T/uso terapêutico , Estudos Retrospectivos , Terapia Combinada
6.
Crit Rev Oncol Hematol ; 199: 104390, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782146

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment approach for patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). However, the long-term prognosis has been discouraging. Moreover, the urgent resolution of two critical issues is necessary: minimize tumor burden before CAR-T infusion and control fatal toxicities post CAR-T therapy. By combining radiotherapy (RT), the safety and efficacy of CAR-T can be improved. RT can serve as bridging therapy, reducing the tumor burden before CAR-T infusion, thus enabling safe and successful CAR-T infusion, and as salvage therapy in cases of CAR-T therapy failure. This review aims to discuss the current evidence supporting the use of RT in CAR-T therapy for patients with R/R NHL. Although most studies have shown a positive role of RT in combined modality treatments for patients undergoing CAR-T therapy, the synergy gained from these remains uncertain. Furthermore, the optimal dose/fraction and radiation response require further investigation.


Assuntos
Imunoterapia Adotiva , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Humanos , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/radioterapia , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Terapia Combinada/métodos , Recidiva Local de Neoplasia/terapia
7.
Leuk Res ; 142: 107519, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761562

RESUMO

Although follicular lymphoma (FL) is traditionally classified as an indolent subtype of B cell non-Hodgkin lymphoma, clinical trajectories are often diverse based on unique disease biology, and many patients will eventually experience relapse of their disease. Furthermore, progression of disease within 24 months is associated with increased mortality rates for FL. In the last five years, we have witnessed an upsurge in the commercial availability of targeted therapies for relapsed/refractory (R/R) FL, including chimeric antigen receptor-T (CAR-T) products, bispecific T cell engagers (BiTEs), epigenetic modifier therapies, and next-generation Bruton tyrosine kinase (BTK) inhibitors. Furthermore, clinical trial options have increased tremendously and now include combinatorial strategies that exert synergy against malignant germinal center B cells. Here, we provide a 2024 update of novel therapeutic agents whose development has been informed by recent advances in the genetics and immunobiology of R/R FL. Specifically, we emphasize high-value targeted therapeutics, including anti-CD3 x anti-CD20 BiTEs and adoptive T cell therapies. We discuss prospects on selection and sequencing of BiTEs and CAR-T therapies for patients with R/R FL. We underscore the principles of FL pathobiology that are paving way for future drug discovery and shed insight into therapeutic targeting within nodal basins based on our increasing understanding of the FL microenvironment. Finally, we summarize how a greater knowledge of FL immunobiology can inform risk stratification and therapy selection on a personalized basis for R/R FL in 2025.


Assuntos
Linfoma Folicular , Humanos , Linfoma Folicular/terapia , Linfoma Folicular/genética , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Imunoterapia Adotiva/métodos , Resistencia a Medicamentos Antineoplásicos/genética , Pesquisa Translacional Biomédica , Terapia de Alvo Molecular/métodos
8.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(5): 480-484, 2024 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-38706073

RESUMO

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated non-small cell lung cancer (NSCLC) that contains sarcomatoid components or sarcomatoid differentiation, and accounts for less than 1% of all lung tumors. Compared to other types of NSCLC, PSC has more invasive biological behavior, is prone to metastasis, and has a higher recurrence rate after early surgery. Its greater resistance to traditional treatments leads to a poorer prognosis compared to other NSCLCs. Immunotherapy offers the possibility of long-term survival for PSC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Imunoterapia/métodos , Carcinoma Pulmonar de Células não Pequenas/terapia , Prognóstico , Recidiva Local de Neoplasia/terapia
9.
Int J Mol Sci ; 25(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732213

RESUMO

Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento , Qualidade de Vida , Recidiva Local de Neoplasia/terapia , Síndrome da Liberação de Citocina/etiologia
10.
Technol Cancer Res Treat ; 23: 15330338241249026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38693845

RESUMO

Laser Interstitial Thermotherapy is a minimally invasive treatment option in neurosurgery for intracranial tumors, including recurrent gliomas. The technique employs the thermal ablation of target tissue to achieve tumor control with real-time monitoring of the extent by magnetic resonance thermometry, allowing targeted thermal injury to the lesion. Laser Interstitial Thermotherapy has gained interest as a treatment option for recurrent gliomas due to its minimally invasive nature, shorter recovery times, ability to be used even in patients with numerous comorbidities, and potential to provide local tumor control. It can be used as a standalone treatment or combined with other therapies, such as chemotherapy or radiation therapy. We describe the most recent updates regarding several studies and case reports that have evaluated the efficacy and safety of Laser Interstitial Thermotherapy for recurrent gliomas. These studies have reported different outcomes, with some demonstrating promising results in terms of tumor control and patient survival, while others have shown mixed outcomes. The success of Laser Interstitial Thermotherapy depends on various factors, including tumor characteristics, patient selection, and the experience of the surgical team, but the future direction of treatment of recurrent gliomas will include a combined approach, comprising Laser Interstitial Thermotherapy, particularly in deep-seated brain regions. Well-designed prospective studies will be needed to establish with certainty the role of Laser Interstitial Thermotherapy in the treatment of recurrent glioma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Hipertermia Induzida , Terapia a Laser , Recidiva Local de Neoplasia , Humanos , Glioblastoma/terapia , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/terapia , Terapia a Laser/métodos , Neoplasias Encefálicas/terapia , Resultado do Tratamento , Terapia Combinada
11.
Cancer Treat Rev ; 127: 102736, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38696903

RESUMO

Due to improvements in treatment for primary rectal cancer, the incidence of LRRC has decreased. However, 6-12% of patients will still develop a local recurrence. Treatment of patients with LRRC can be challenging, because of complex and heterogeneous disease presentation and scarce - often low-grade - data steering clinical decisions. Previous consensus guidelines have provided some direction regarding diagnosis and treatment, but no comprehensive guidelines encompassing all aspects of the clinical management of patients with LRRC are available to date. The treatment of LRRC requires a multidisciplinary approach and overarching expertise in all domains. This broad expertise is often limited to specific expert centres, with dedicated multidisciplinary teams treating LRRC. A comprehensive, narrative literature review was performed and used to develop the Dutch National Guideline for management of LRRC, in an attempt to guide decision making for clinicians, regarding the complete clinical pathway from diagnosis to surgery.


Assuntos
Recidiva Local de Neoplasia , Guias de Prática Clínica como Assunto , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/diagnóstico , Recidiva Local de Neoplasia/terapia , Países Baixos
12.
Curr Oncol Rep ; 26(5): 496-503, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38602581

RESUMO

PURPOSE OF REVIEW: To summarize and evaluate the literature on treatment approaches for oligometastatic and locally recurrent urothelial cancer. RECENT FINDINGS: There is no clear definition for oligometastatic urothelial cancers due to limited data. Studies focusing on oligometastatic and locally recurrent urothelial cancer have been primarily retrospective. Treatment options include local therapy with surgery or radiation, and generalized systemic therapy such as chemotherapy or immunotherapy. Oligometastatic and locally recurrent urothelial cancers remain challenging to manage, and treatment requires an interdisciplinary approach. Systemic therapy is nearly always a component of current care in the form of chemotherapy, but the role of immunotherapy has not been explored. Consideration of surgical and radiation options may improve outcomes, and no studies have compared directly between the two localized treatment options. The development of new prognostic and predictive biomarkers may also enhance the treatment landscape in the future.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/terapia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Metástase Neoplásica , Imunoterapia , Terapia Combinada , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia , Prognóstico
13.
Pediatr Blood Cancer ; 71(7): e31026, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38679864

RESUMO

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Sarcoma de Ewing/patologia , Feminino , Masculino , Criança , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/secundário , Estudos Retrospectivos , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/patologia , Pré-Escolar , Taxa de Sobrevida , Prognóstico , Seguimentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto Jovem , Indução de Remissão , Lactente , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Quimioterapia de Indução
14.
Pediatr Blood Cancer ; 71(7): e31038, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38679840

RESUMO

PURPOSE: Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma. PATIENTS AND METHODS: The study included 41 patients <21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities. RESULTS: The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse. CONCLUSION: Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials.


Assuntos
Recidiva Local de Neoplasia , Sarcoma Sinovial , Humanos , Sarcoma Sinovial/terapia , Sarcoma Sinovial/mortalidade , Sarcoma Sinovial/patologia , Estudos Retrospectivos , Masculino , Feminino , Criança , Adolescente , Pré-Escolar , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Europa (Continente) , Taxa de Sobrevida , Terapia Combinada , Seguimentos , Adulto Jovem , Adulto , Lactente
17.
J Immunother Cancer ; 12(4)2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631712

RESUMO

BACKGROUND: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL. METHODS: Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells. RESULTS: A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy. CONCLUSIONS: The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile. TRIAL REGISTRATION NUMBERS: ChiCTR1900025419 and NCT04690192.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Humanos , Leucócitos Mononucleares , Recidiva Local de Neoplasia/terapia , Transplante Autólogo , Linfoma Difuso de Grandes Células B/terapia , Resultado do Tratamento , Linfócitos T
18.
BMJ Open ; 14(4): e084488, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643011

RESUMO

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Resultado do Tratamento , Neoplasias da Mama/terapia , Qualidade de Vida , Projetos de Pesquisa , Técnica Delphi , Determinação de Ponto Final , Recidiva Local de Neoplasia/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Revisões Sistemáticas como Assunto
19.
J Cancer Res Ther ; 20(2): 584-591, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687928

RESUMO

PURPOSE: We evaluated the potential role of intravoxel incoherent motion (IVIM) in predicting the therapeutic response and peritumoral invasion in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS: We enrolled 47 patients previously treated with TACE between January 2018 and December 2021. We evaluated the IVIM-derived metrics [apparent diffusion coefficient (ADC), D, D*, f] in the TACE-treated, peritumoral, and parenchymal areas of the liver. RESULTS: The ADCtace and Dtace values (1.13 ± 0.22 × 10-3 m2/s vs 0.95 ± 0.13 × 10-3 mm2/s, 1.28 ± 0.27 × 10-3 mm2/s vs 1.07 ± 0.3 × 10-3 mm2/s, P < 0.05) were higher in the non-progressing groups than in the progressing groups in the TACE-treated areas. Dpt represented the D values in the peritumoral area, which can distinguish between the progressive and non-progressive groups with an AUC of 0.73. The Dstd values, which represent the D values in the peritumoral area normalized by the D values in the liver parenchyma in the non-progressing groups (1.10 ± 0.14 × 10-3 mm2/s), were higher than those of the progressing groups (0.93 ± 0.17 × 10-3 mm2/s). CONCLUSION: The ADCtace, Dtace, Dpt, and Dstd values reflect the changes in the microstructure of the progressive and non-progressive groups after TACE treatment, showing robust diagnostic performances in predicting the therapeutic response and peritumoral invasion.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Quimioembolização Terapêutica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Idoso , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Fígado/patologia , Fígado/diagnóstico por imagem , Curva ROC
20.
J Neurooncol ; 168(1): 13-25, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38587609

RESUMO

PURPOSE: In patients with acromegaly, secondary treatment options in cases of hormonal non-remission or tumor progression include repeat transsphenoidal surgery (TSS), radiation-based treatment (RT), or medical therapy (MT). In this study, we aim to evaluate the clinical effectiveness of various second-line treatment options for acromegaly. METHODS: Using the PRISMA guideline, a systematic review was performed by searching MEDLINE (PubMed), Web of Science, Scopus, and Cochrane electronic bibliographic databases from conception to the end of 2022. Outcomes of interest included hormonal remission rate, complications, and mortality associated with each treatment modality for refractory acromegaly. RESULTS: A total of 79 studies including 3,208 refractory acromegaly patients (44.90% males) were analyzed, with a mean patient age of 43.89 years. There was a statistically significant difference between various therapeutic modalities in terms of remission rate, with MT offering the highest remission rate (62.55%), followed by RT (50.15%) and TSS (37.39%). Subgroup analysis of radiotherapeutic and medical modalities did not show a significant difference in remission rate between different kinds of sub-modalities in each treatment approach. Recurrence following secondary treatment was not different in patients treated with reoperation TSS compared to other modalities. CONCLUSIONS: The management of persistent and recurrent acromegaly optimally requires a multimodal approach. In different scenarios of refractory acromegaly based on previous treatment, secondary treatments may vary in terms of remission rate and complications. Medical agents provide considerable effectiveness as a second-line therapy for recurrent or persistent disease. In selected cases, however, reoperation still provides an opportunity for cure or freedom from medications. The findings of this study may help clinicians to prioritize varying options involved in this multifaceted decision-making process.


Assuntos
Acromegalia , Humanos , Acromegalia/terapia , Terapia Combinada , Recidiva Local de Neoplasia/terapia
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