Chemoradiotherapy versus radiotherapy in high risk salivary gland cancer.

OBJECTIVE: The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables. METHODS: Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model. RESULTS: A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36-4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17-3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT. CONCLUSION: Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.

Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6-9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

Proceedings of the Think Tank for Osteosarcoma Medical Advisory Board.

A "Think Tank for Osteosarcoma" medical advisory board meeting was held in Santa Monica, CA, USA on February 2-3, 2024. The goal was to develop a strategic approach to prevent recurrence of osteosarcoma. Osteosarcoma metabolism and the genomic instability of osteosarcoma, immunotherapy for osteosarcoma, CAR-T cell therapy, DeltaRex-G tumor-targeted gene therapy, repurposed drugs, alternative medicines, and personalized medicine were discussed. Only DeltaRex-G was voted on. The conclusions were the following: No intervention has been demonstrated to improve survival in a clinical trial. Additionally, the consensus (10/12 in favor) was that DeltaRex-G without immunotherapy may be administered for up to one year. Phase 2/3 randomized studies of DeltaRex-G should be performed to determine whether the incidence of recurrence could be reduced in high-risk individuals. Furthermore, a personalized approach using drugs with minimal toxicity could be attempted with the acknowledgement that there are no efficacy data to base this on. Repurposed drugs and alternative therapies should be tested in mouse models of osteosarcoma. Moreover, unmodified IL-2 primed Gamma Delta (NK) cell therapy may be used to prevent recurrence. Lastly, rapid development of CAR-T cell therapy is recommended, and an institute dedicated to the study of osteosarcoma is needed.

Successful Treatment of Refractory or Relapsed Hepatoblastoma With Autologous Hematopoietic Stem Cell Transplantation in Children.

BACKGROUND: The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma. METHODS: We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen. RESULTS: We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy. CONCLUSION: This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.

Management of internal iliac and obturator lymph nodes in mid-low rectal cancer.

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.

Mild hyperthermia with magnetic resonance- guided high intensity focused ultrasound combined with salvage chemoradiation for recurrent rectal cancer.

INTRODUCTION: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU). METHODS: All patients were deemed ineligible for salvage surgery and were evaluated in a multidisciplinary fashion with a surgical oncologist, radiation oncologist and medical oncologist. Radiation was delivered to a dose of 30.6 Gy in 1.8 Gy per fraction with concurrent capecitabine. MR-HIFU was delivered on days 1, 8 and 15 of concurrent chemoradiation. Our primary objective was feasibility and toxicity. RESULTS: Six patients (total 11 screened) were treated with concurrent chemoradiation and mild hyperthermia with MR-HIFU. Tumor size varied between 3.1-16.6 cm. Patients spent an average of 228 min in the MRI suite and sonication with the external transducer lasted an average of 35 min. There were no complications on the day of the MR-HIFU procedure and all acute toxicities (no grade >/=3 toxicities) resolved after completion of treatment. There were no late grade >/=3 toxicities. CONCLUSION: Mild hyperthermia with MR-HIFU, in combination with concurrent chemoradiation for appropriately selected patients, is safe for localized pelvic recurrences from rectal cancer. The potential for MR-HIFU to be applied in the recurrent setting in rectal cancer treatment requires further technical development and prospective evaluation.

Laser Interstitial Thermotherapy (LITT) in Recurrent Glioblastoma: What Window of Opportunity for This Treatment?

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.

[Advances in immunotherapy for pulmonary sarcomatoid carcinoma].

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.

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.

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.

The outcome of relapsed childhood acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantations: A single-center experience.

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.

Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Clinical features and outcomes of young patients with low-grade non-rhabdomyosarcoma soft tissue sarcomas treated with a risk-based strategy: A report from Children's Oncology Group study ARST0332.

BACKGROUND: In retrospective analyses, the Pediatric Oncology Group [POG) and the Federation National des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade predict outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), but prospective data on grading, clinical features, and outcomes of low-grade NRSTS are limited. METHODS: We analyzed patients less than 30 years of age enrolled on Children's Oncology Group (COG) study ARST0332 (NCT00346164) with POG grade 1 or 2 NRSTS. Low-risk patients were treated with surgery alone. Intermediate-/high-risk patients received ifosfamide/doxorubicin and radiotherapy, with definitive resection either before or after 12 weeks of chemoradiotherapy. RESULTS: Estimated 5-year event-free and overall survival were 90% and 100% low risk (n = 80), 55% and 78% intermediate risk (n = 15), and 25% and 25% high risk (n = 4). In low-risk patients, only local recurrence was seen in 10%; none with margins greater than 1 mm recurred locally. Sixteen of 17 intermediate-/high-risk patients who completed neoadjuvant chemoradiotherapy underwent gross total tumor resection, 80% with negative margins. Intermediate-/high-risk group events included one local and seven metastatic recurrences. Had the FNCLCC grading system been used to direct treatment, 29% of low-risk (surgery alone) patients would have received radiotherapy ± chemotherapy. CONCLUSIONS: Most low-risk patients with completely resected POG low-grade NRSTS are successfully treated with surgery alone, and surgical margins greater than 1 mm may be sufficient to prevent local recurrence. Patients with intermediate- and high-risk low-grade NRSTS have outcomes similar to patients with high-grade histology, and require more effective therapies. Use of the current FNCLCC grading system may result in overtreatment of low-risk NRSTS curable with surgery alone.

Nonoperative management protocol for locally advanced rectal cancer.

AIM: The standard treatment for low rectal cancer is preoperative chemoradiotherapy followed by surgery with low anterior resection with diverting ileostomy or abdominoperineal resection, both of which have significant long-term effects on bowel and sexual function. Due to the high morbidity of surgery, there has been increasing interest in nonoperative management for low rectal cancer. The aim of this work is to conduct a pan-Canadian Phase II trial assessing the safety of nonoperative management for low rectal cancer. METHOD: Patients with Stage II or III low rectal cancer completing chemoradiotherapy according to standard of care at participating centres will be assessed for complete clinical response 8-14 weeks following completion of chemoradiotherapy. Subjects achieving a clinical complete response will undergo active surveillance including endoscopy, imaging and bloodwork at regular intervals for 24 months. The primary outcome will be the rate of local regrowth 2 years after chemoradiotherapy. Nonoperative management will be considered safe (i.e. as effective as surgery to achieve local control) if the rate of local regrowth is ≤30% and surgical salvage is possible for all local regrowths. Secondary outcomes will include disease-free and overall survival. CONCLUSION: The results will be highly clinically relevant, as it is expected that nonoperative management will be safe and lead to widespread adoption of nonoperative management in Canada. This change in practice has the potential to decrease the number of patients requiring surgery and the costs associated with surgery and long-term surgical morbidity.

Dutch national guidelines for locally recurrent rectal cancer.

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.

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed/refractory large B-cell lymphoma: findings from a German monocentric study.

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.

Translational insights into the genetics and immunobiology of relapsed/refractory follicular lymphoma.

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.

Prolonged remission with ibrutinib maintenance therapy following radiation in a patient with relapsed primary CNS lymphoma.

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.

Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy.

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.

Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry.

ABSTRACT: Optimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHLs) is unknown. In this population-based study, outcomes in R/R peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-positive (ALK+) and ALK-negative (ALK-) anaplastic large cell lymphoma (ALCL) were evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL, and ALK- ALCL (≥18 years) diagnosed in 2014 to 2019 were identified using the Netherlands Cancer Registry. End points were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% received salvage chemotherapy, 20% received brentuximab vedotin (BV), and 36% received other treatment. In third-line treatment, BV was most commonly used (38%). ORR after second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. The risk of second relapse was negatively affected by early relapse (<12 months after diagnosis), whereas BV reduced this risk compared with salvage chemotherapy. Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for patients with R/R T-NHL treated with BV compared with patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for patients with R/R T-NHL is challenged.

Role of radiation in chimeric antigen receptor T-cell therapy for patients with relapsed/refractory non-Hodgkin lymphoma: Current studies and future prospects.

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.