Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 8.008
Filter
1.
J Cancer Res Clin Oncol ; 150(5): 224, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693452

ABSTRACT

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.


Subject(s)
Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Middle Aged , Female , Aged , Immunotherapy, Adoptive/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Adult , Remission Induction , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology , Germany , Receptors, Antigen, T-Cell/therapeutic use , Retrospective Studies , Combined Modality Therapy
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(5): 480-484, 2024 May 12.
Article in Chinese | MEDLINE | ID: mdl-38706073

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Humans , Lung Neoplasms/therapy , Immunotherapy/methods , Carcinoma, Non-Small-Cell Lung/therapy , Prognosis , Neoplasm Recurrence, Local/therapy
3.
Clin Transplant ; 38(5): e15366, 2024 May.
Article in English | MEDLINE | ID: mdl-38775798

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Transplantation, Homologous , Humans , Female , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Child , Retrospective Studies , Child, Preschool , Prognosis , Follow-Up Studies , Adolescent , Survival Rate , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Risk Factors , Infant , Graft vs Host Disease/etiology , Salvage Therapy , Transplantation Conditioning , Recurrence
4.
Int J Mol Sci ; 25(9)2024 May 03.
Article in English | MEDLINE | ID: mdl-38732213

ABSTRACT

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.


Subject(s)
Immunotherapy, Adoptive , Multiple Myeloma , Receptors, Chimeric Antigen , Multiple Myeloma/therapy , Multiple Myeloma/immunology , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/immunology , Treatment Outcome , Quality of Life , Neoplasm Recurrence, Local/therapy , Cytokine Release Syndrome/etiology
5.
Blood Cancer J ; 14(1): 90, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38821914

ABSTRACT

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.


Subject(s)
Immunotherapy, Adoptive , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Multiple Myeloma/mortality , Male , Female , Middle Aged , Aged , Immunotherapy, Adoptive/methods , Retrospective Studies , Receptors, Chimeric Antigen/therapeutic use , Adult , Treatment Outcome , Standard of Care , Neoplasm Recurrence, Local/therapy
6.
Technol Cancer Res Treat ; 23: 15330338241249026, 2024.
Article in English | MEDLINE | ID: mdl-38693845

ABSTRACT

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.


Subject(s)
Brain Neoplasms , Glioblastoma , Hyperthermia, Induced , Laser Therapy , Neoplasm Recurrence, Local , Humans , Glioblastoma/therapy , Hyperthermia, Induced/methods , Neoplasm Recurrence, Local/therapy , Laser Therapy/methods , Brain Neoplasms/therapy , Treatment Outcome , Combined Modality Therapy
7.
Cancer Treat Rev ; 127: 102736, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38696903

ABSTRACT

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.


Subject(s)
Neoplasm Recurrence, Local , Practice Guidelines as Topic , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/diagnosis , Neoplasm Recurrence, Local/therapy , Netherlands
9.
J Cancer Res Ther ; 20(2): 584-591, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38687928

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Neoplasm Recurrence, Local , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Chemoembolization, Therapeutic/methods , Male , Female , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Aged , Neoplasm Invasiveness , Prognosis , Retrospective Studies , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Adult , Liver/pathology , Liver/diagnostic imaging , ROC Curve
10.
BMJ Open ; 14(4): e084488, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38643011

ABSTRACT

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).


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Humans , Female , Treatment Outcome , Breast Neoplasms/therapy , Quality of Life , Research Design , Delphi Technique , Endpoint Determination , Neoplasm Recurrence, Local/therapy , Outcome Assessment, Health Care/methods , Systematic Reviews as Topic
12.
Pediatr Blood Cancer ; 71(7): e31026, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38679864

ABSTRACT

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.


Subject(s)
Bone Neoplasms , Lung Neoplasms , Sarcoma, Ewing , Humans , Sarcoma, Ewing/mortality , Sarcoma, Ewing/therapy , Sarcoma, Ewing/pathology , Female , Male , Child , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lung Neoplasms/secondary , Retrospective Studies , Adolescent , Bone Neoplasms/mortality , Bone Neoplasms/therapy , Bone Neoplasms/secondary , Bone Neoplasms/pathology , Child, Preschool , Survival Rate , Prognosis , Follow-Up Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Young Adult , Remission Induction , Infant , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Induction Chemotherapy
13.
Curr Oncol Rep ; 26(5): 496-503, 2024 05.
Article in English | MEDLINE | ID: mdl-38602581

ABSTRACT

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.


Subject(s)
Neoplasm Recurrence, Local , Urinary Bladder Neoplasms , Humans , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/secondary , Neoplasm Metastasis , Immunotherapy , Combined Modality Therapy , Urologic Neoplasms/pathology , Urologic Neoplasms/therapy , Prognosis
14.
J Neurooncol ; 168(1): 13-25, 2024 May.
Article in English | MEDLINE | ID: mdl-38587609

ABSTRACT

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.


Subject(s)
Acromegaly , Humans , Acromegaly/therapy , Combined Modality Therapy , Neoplasm Recurrence, Local/therapy
15.
Pediatr Blood Cancer ; 71(7): e31038, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38679840

ABSTRACT

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.


Subject(s)
Neoplasm Recurrence, Local , Sarcoma, Synovial , Humans , Sarcoma, Synovial/therapy , Sarcoma, Synovial/mortality , Sarcoma, Synovial/pathology , Retrospective Studies , Male , Female , Child , Adolescent , Child, Preschool , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Prognosis , Europe , Survival Rate , Combined Modality Therapy , Follow-Up Studies , Young Adult , Adult , Infant
16.
J Immunother Cancer ; 12(4)2024 04 16.
Article in English | MEDLINE | ID: mdl-38631712

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Humans , Leukocytes, Mononuclear , Neoplasm Recurrence, Local/therapy , Transplantation, Autologous , Lymphoma, Large B-Cell, Diffuse/therapy , Treatment Outcome , T-Lymphocytes
17.
Best Pract Res Clin Gastroenterol ; 68: 101885, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38522883

ABSTRACT

Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Neoplasm Recurrence, Local/therapy , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/surgery , Chemoradiotherapy , Treatment Outcome , Retrospective Studies
18.
J Cancer Res Ther ; 20(1): 79-84, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38554302

ABSTRACT

BACKGROUND: Ewing's sarcoma (EWS) is an aggressive small round cell tumor, affecting bone and soft tissues and is mostly seen in childhood and second decade of life. EWS accounts for 10-12% of bone tumors in more than 15 years age group and is even rarer after 40 years of age. MATERIALS AND METHODS: This retrospective analysis was conducted among patients aged more than 15 years with histologically proven EWS. RESULTS: Among 240 cases of EWS treated at our center during 2001-2010, 130 (54%) were more than 15 years of age. The median age was 20 years with a male: female ratio of 2.4:1. Ninety percent had skeletal EWS, 10% had extra skeletal EWS, and 37% patients were metastatic at presentation. Eighty-two received curative treatment with chemotherapy (vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide (VAC/IE)) along with local treatment, radiotherapy (RT) in 61, surgery alone in seven, and RT plus surgery in 14. Two- and 5-year overall survival (OS) was 43.3% and 25.5%, respectively, for the entire series. The OS for the non-metastatic group was 63.2% at 2 years and 36.5% at 5 years, and the progression free survival was 53.7% at 2 years and 37.8% at 5 years. High lactate dehydrogenase was found to be a significant poor prognostic factor (P = 0.001). Median OS for localized central EWS was 49.2 months and that for peripheral EWS was 24 months. Patients more than 20 years of age with non-metastatic disease had better OS compared to those with 15-20 years of age. CONCLUSION: Treatment of EWS requires a multidisciplinary approach with radical surgery and/or radiation to control local disease and multiagent chemotherapy to control systemic disease. Long-term follow-up is essential because of disease relapse and treatment-related complications.


Subject(s)
Bone Neoplasms , Sarcoma, Ewing , Adult , Humans , Male , Adolescent , Female , Young Adult , Sarcoma, Ewing/epidemiology , Sarcoma, Ewing/therapy , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/drug therapy , Bone Neoplasms/therapy , Bone Neoplasms/drug therapy , Cyclophosphamide , Ifosfamide , Doxorubicin/therapeutic use , Vincristine
19.
World J Gastroenterol ; 30(8): 806-810, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38516235

ABSTRACT

Approximately 50%-70% of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation. As a result, many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival. The therapy recommended by national guidelines can differ, and guidelines do not specify when to initiate adjuvant therapy or how long to continue it. These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient. These questions need to be addressed by clinicians and researchers.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/surgery , Liver Neoplasms/drug therapy , Chemotherapy, Adjuvant/adverse effects , Combined Modality Therapy , Hepatectomy/adverse effects , Neoplasm Recurrence, Local/therapy
20.
N Engl J Med ; 390(14): 1290-1298, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38477966

ABSTRACT

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cell-engaging antibody molecule (TEAM). Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants. (Funded by Gateway for Cancer Research and others; INCIPIENT ClinicalTrials.gov number, NCT05660369.).


Subject(s)
ErbB Receptors , Glioblastoma , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , Humans , CD8-Positive T-Lymphocytes/metabolism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Glioblastoma/therapy , Glioblastoma/pathology , Immunotherapy, Adoptive/adverse effects , Neoplasm Recurrence, Local/therapy , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/therapeutic use , Receptors, Chimeric Antigen/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...