Era Of Immunotherapy Research Articles

Efficacy of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma in immunotherapy era clinical practice

AbstractAimSince the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression‐free survival (PFS) in Dur/Tre treatment cases.MethodsEnrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74 years; male patients, 152; Child–Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C, 59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated.ResultsThe median observation period was 7.2 months (interquartile range, 3.2–10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p = 0.028) (median PFS: without vs. with = 5.6 vs. 2.7 months, p < 0.001). Although immune‐mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p = 0.523 and p = 0.038, respectively).ConclusionHistory of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

P195 Upfront cytoreductive nephrectomy for synchronous metastatic renal cell carcinoma in the era of immunotherapy

P195 Upfront cytoreductive nephrectomy for synchronous metastatic renal cell carcinoma in the era of immunotherapy

Current Radiotherapy Management of Extensive-Stage Small-Cell Lung Cancer in the Immunotherapy Era: An Italian National Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients.

The Optimal Radiotherapy Strategy for Patients With Small Cell Lung Cancer and Brain Metastasis: A Retrospective Analysis.

Extensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era. ES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis. A total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases. Our study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.

End-of-life management of multiple myeloma patients in the era of CD38 and immunotherapy

BackgroundIn spite of spectacular advances in the treatment of multiple myeloma, a majority of patients will die from this disease or related complications. While a great amount of focus has been dedicated to the development of novel therapies, little attention has been paid to latter stages of patient follow-up.Patients and methodsIn order to describe patient management during this critical period as well as the immediate causes and circumstances of death, we have analyzed a single center series of 100 patients diagnosed with myeloma who died between 2016 and 2021.ResultsPatients received a median of 3 lines of treatment, including 2 during their last year of life. Sixty per cent of patients had received daratumumab. Fifty patients had obtained complete remission or very good partial response at some time during the course of disease but 75 were refractory to the last treatment line. Eighteen patients died while their disease was stable or in remission while 77 had confirmed progressive disease at time of death. Thirty six patients had uncontrolled sepsis, 49 were in renal failure and 24 had hypercalcemia at the time of death. Seventy three patients presented with lymphopenia. Disease progression was documented in a majority of MM patients at the time of death and was associated with disease-related complications in a significant number of patients.ConclusionDisease progression remains the main cause of death in patients with multiple myeloma.

Follicular lymphoma research: an open dialogue for a collaborative roadmap.

Follicular lymphoma (FL) is the second most common type of lymphoma (20% of all non-Hodgkin lymphomas), derived from germinal centre (GC) B cells, and is characterised by its significant clinical, prognostic and biological heterogeneity, leading to complexity in management. Despite significant biological investigation and indisputable clinical progress since the advent of the immunotherapy era more than 20 years ago, much remains to be done to understand and cure this lymphoma. Today, FL is metaphorically a giant puzzle on the table with patches of sky, landscape and foliage clearly appearing. However, many of the remaining pieces are held by various stakeholders (e.g. clinicians, pathologists, researchers, drug developers) without global agreement on what the gaps are, or any clear blueprint on how to solve the puzzle of understanding the heterogeneity of this disease and create curative and tailored therapies. With the advent of new investigation and drug technologies, together with recent advances in our capacity to manage big data, the time seems ripe for a change of scale. More than ever, this will require collaboration between and within all stakeholders to overcome the current bottlenecks in the field. As for every investigator, we acknowledge that this first draft is necessarily biased, incomplete and some FL expert readers might recognise some remaining gaps not addressed. We hope they will reply to make this effort a collaborative one to assemble all the pieces in the most ideal fashion. As such, this review intends to be a first step and an interactive platform to a collaborative roadmap towards better understanding and care of FL.

Survival Improvement of StageIV Non-small Cell Lung Cancer in the Immunotherapy Era: A Retrospective Cohort Study in a US Population.

Immune checkpoint inhibitors (ICIs) greatly improved outcomes of stageIV non-small cell lung cancer (NSCLC) in randomized clinical trials. Limited data exists regarding the survival improvement of ICI use at the population level. Clinical data of patients with pathologically confirmed stageIV NSCLC diagnosed in 2013 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were compared before and after ICI use to assess the survival improvement in the immunotherapy era in the real world. A total of 19,433 patients with stageIV NSCLC were included. Being female, age < 60years, of American Indian and Asian or Pacific Islander race, married, non-squamous histology, without bone, brain, or liver metastases, and receiving chemotherapy were significantly associated with better prognosis in multivariable analyses. Propensity score matching (PSM) based on associated factors resulted in 8743 patients each in the non-immunotherapy and immunotherapy groups (1:1 ratio). After PSM, both overall survival (OS) (p < 0.001) and cancer-specific survival (CSS) (p < 0.001) were significantly improved in the immunotherapy group. The median OS (mOS) was 6.0months in the non-immunotherapy group and 8.0months in the immunotherapy group. The 1-, 2-, and 3-year OS rate was 29.0%, 14.2%, and 8.5% in the non-immunotherapy group, and 37.8%, 23.5%, and 16.7% in the immunotherapy group, respectively. Patients who were male, under 60years old, married, white, had adenocarcinoma, had no bone or liver metastases, and received chemotherapy or radiation therapy were more likely to benefit from immunotherapy. Survival outcomes of patients with stageIV NSCLC were significantly improved in the immunotherapy era. Population-level benefits of survival varied among subgroups, and not all the increase in OS meant a clinically meaningful benefit.

Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era.

Treatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider. Newly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017-December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan-Meier analysis. Outcomes were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021). Among 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0-1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7-29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5-7.6), 5.2 (95% CI: 4.6-7.6), and 2.3 (95% CI: 2.1-3.0) months, respectively; for the subgroup of patients with ECOG PS 0-1, rwToT was 9.4 (95% CI: 5.0-20.8), 7.1 (95% CI: 5.0-10.1), and 2.9 (95% CI: 2.2-4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9-17.9), 14.8 (95% CI: 10.5-19.4), and 9.1 (95% CI: 7.1-11.5) months; for the subgroup of patients with ECOG PS 0-1, median rwOS was 25.1 [95% CI: 14.9-not reached (NR)], 17.6 (95% CI: 14.3-NR), and 11.3 (95% CI: 9.2-21.3) months, respectively. For ECOG PS 0-1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9-NR) and NR for PDM and PDC, respectively. For ECOG PS 0-1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1-NR) and 11.2 (95% CI: 9.1-21.3) months for PDC and PBC, respectively. Our real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

P2.11A.09 Survival Outcomes of Lung Adenocarcinoma with Intestinal Differentiation in the Era of Immunotherapy

P2.11A.09 Survival Outcomes of Lung Adenocarcinoma with Intestinal Differentiation in the Era of Immunotherapy

Perioperative immunotherapy for non-small cell lung cancer: consensus and controversy (2024 edition)

Lung cancer is the malignant tumour with the highest morbidity and mortality rate in China, among which non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80% to 85%. Radial surgery is the standard treatment for early-stage NSCLC, but postoperative recurrence is an inevitable problem in clinical practice. Adding perioperative chemotherapy to surgery can only increase the 5-year overall survival rate by about 5%. There is an urgent need for better systemic treatments. In recent years, immunotherapeutic drugs, represented by PD-1/PD-L1 monoclonal antibodies, have brought breakthroughs from subsequent-line treatment to front-line treatment for NSCLC. Several Phase III studies on perioperative immunotherapy have shown that adding immunotherapy during the neoadjuvant and adjuvant treatment can significantly improve survival outcomes for patients, leading to the development of a new standard treatment for resectable NSCLC. In January 2024, the first PD-1 monoclonal antibodies (Toripalimab) were approved for perioperative treatment of NSCLC in China, starting a new era of perioperative immunotherapy. At present, there is still a lack of unified consensus on the application of perioperative immunotherapy at all levels of medical institutions. In order to privide diagnostic and treatment guidance for clinicians, promote the standardization of clinical practice for immunotherapy in resectable NSCLC, and clarify the controversial opinions regarding perioperative immunotherapy, Lung Cancer Expert Committee of the Chinese Anti-Cancer Association, Chinese Thoracic Oncology Group, Lung Cancer Expert Committee of the Chinese Medical Association Oncology Society jointly published this Consensus and Controversy to provide a guidance for the standardized management of perioperative immunotherapy for NSCLC.

The promise of immunotherapeutic strategies to advance cancer treatment in pet dogs.

In this article, which is part of the Currents in One Health series, principles of immunotherapeutics are discussed and their clinical exploration in dogs reviewed with emphasis on their translatability for improving treatment of commonly diagnosed cancers. With increasing longevity and sustained quality of life in pet dogs through dietary, environmental awareness, and preventative medical practices, the geriatric pet population has continued to steadily grow and, consequently, so have age-related pathologies. Not surprisingly, cancer is the most common cause of mortality in elderly dogs, accounting for 1 in 4 deaths in dogs > 10 years of age. Importantly, some cancer types that arise spontaneously in pet dogs are similar to cancers afflicting people. The shared clinical and biological behaviors of certain cancers observed in pet dogs and people underscore the opportunity to leverage comparative oncology studies, which can accelerate the validation and clinical implementation of innovative therapies that can benefit pet dogs and ultimately guide these strategies toward clinical practice in people too. In the era of immunotherapy, the inclusion of pet dogs that develop cancers under an intact immune system affords a unique and high-value opportunity to study the evolving nature of cancers shaped by immunosurveillance pressures. Complementing these discovery efforts and through a comparative oncology approach, the exploration and clinical validation of novel immunotherapeutic strategies in pet dogs can be foundational for defining the safety and immune-activating potential of new anticancer immune approaches that hold promise to transform cancer treatment in both pets and people alike.

A Four-Gene Autophagy-Related Prognostic Model Signature and Its Association With Immune Phenotype in Lung Squamous Cell Carcinoma.

In the era of immunotherapy, there is a critical need for effective biomarkers to improve outcome prediction and guide treatment decisions for patients with lung squamous cell carcinoma (LUSC). We hypothesized that the immune contexture of LUSC may be influenced by tumor intrinsic events, such as autophagy. We aimed to develop an autophagy-related risk signature and assess its predictive value for immune phenotype. Expression profiles of autophagy-related genes (ARGs) in LUSC samples were obtained from the TCGA and GEO databases. Survival analyses were conducted to identify survival-related ARGs and construct a risk signature using the Random Forest algorithm. Four ARGs (CFLAR, RGS19, PINK1, and CTSD) with the most significant prognostic value were selected to construct the risk signature. Patients in the high-risk group exhibited worse prognosis than those in the low-risk group (p < 0.0001 in TCGA; p < 0.01 in GEO) and the risk score was identified as an independent prognostic factor. We observed that the high-risk group displayed an immune-suppressive status and showed higher levels of infiltrating regulatory T cells and macrophages, which are associated with poorer outcomes. Additionally, the risk score exhibited a significantly positive correlation with the expression of PD-1 and CTLA4, as well as the estimate score and immune score. This study provided an effective autophagy-related prognostic signature, which could also predict the immune phenotype.

EP.13B.04 The Value of Radiotherapy Based on the Failure of Extensive-Stage Small Cell Lung Cancerin the Era of Immunotherapy

EP.13B.04 The Value of Radiotherapy Based on the Failure of Extensive-Stage Small Cell Lung Cancerin the Era of Immunotherapy

Novel protein-based prognostic signature linked to immunotherapeutic efficiency in ovarian cancer

BackgroundPersonalized medicine remains an unmet need in ovarian cancer due to its heterogeneous nature and complex immune microenvironments, which has gained increasing attention in the era of immunotherapy. A key obstacle is the lack of reliable biomarkers to identify patients who would benefit significantly from the therapy. While conventional clinicopathological factors have exhibited limited efficacy as prognostic indicators in ovarian cancer, multi-omics profiling presents a promising avenue for comprehending the interplay between the tumor and immune components. Here we aimed to leverage the individual proteomic and transcriptomic profiles of ovarian cancer patients to develop an effective protein-based signature capable of prognostication and distinguishing responses to immunotherapy.MethodsThe workflow was demonstrated based on the Reverse Phase Protein Array (RPPA) and RNA-sequencing profiles of ovarian cancer patients from The Cancer Genome Atlas (TCGA). The algorithm began by clustering patients using immune-related gene sets, which allowed us to identify immune-related proteins of interest. Next, a multi-stage process involving LASSO and Cox regression was employed to distill a prognostic signature encompassing five immune-related proteins. Based on the signature, we subsequently calculated the risk score for each patient and evaluated its prognostic performance by comparing this model with conventional clinicopathological characteristics.ResultsWe developed and validated a protein-based prognostic signature in a cohort of 377 ovarian cancer patients. The risk signature outperformed conventional clinicopathological factors, such as age, grade, stage, microsatellite instability (MSI), and homologous recombination deficiency (HRD) status, in terms of prognoses. Patients in the high-risk group had significantly unfavorable overall survival (p < 0.001). Moreover, our signature effectively stratified patients into subgroups with distinct immune landscapes. The high-risk group exhibited higher levels of CD8 T-cell infiltration and a potentially greater proportion of immunotherapy responders. The co-activation of the TGF-β pathway and cancer-associated fibroblasts could impair the ability of cytotoxic T cells to eliminate cancer cells, leading to poor outcomes in the high-risk group.ConclusionsThe protein-based signature not only aids in evaluating the prognosis but also provides valuable insights into the tumor immune microenvironments in ovarian cancer. Together our findings highlight the importance of a thorough understanding of the immunosuppressive tumor microenvironment in ovarian cancer to guide the development of more effective immunotherapies.

Healthcare resource utilization and associated cost in patients with metastatic non-small cell lung cancer treated in the immunotherapy era.

Treatment approach for metastatic non-small cell lung cancer (mNSCLC) has revolutionized in the recent decade with the introduction of immunotherapy and targeted medications in first-line (1L) therapy. We present real-world data on clinical outcomes and direct healthcare resource utilization (HCRU) and cost in a 2.7-million-member Israeli health provider. Newly diagnosed mNSCLC patients between January 2017 and December 2020 were categorized by 1L treatment: platinum-based chemotherapy, targeted therapy, or immunotherapy. HCRU and costs were calculated based on the Ministry of Health Prices and were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021). A total of 886 patients were included in the study: 40.6% female, median age 68 years (IQR 61-74), 24.3% never smokers, 80.6% with adenocarcinoma, and 54% with a 0-1 performance status. The median follow-up was 27.12 months (95% CI, 24.7-29.6) and the median duration of first-line (1L) treatment was 2.3 months for platinum-based chemotherapy (n = 177), 12.3 months for targeted therapy (n = 255), and 4.8 months for immunotherapy (n = 463). The median overall survival was 9.09, 27.68, and 12.46 months, respectively. Total 1L costs were driven by radiotherapy for platinum-based chemotherapy and medication for targeted therapy or immunotherapy. Total costs for deceased patients over the entire follow-up were €121 155, €129 458, and €110 716, respectively. The treatment of mNSCLC carries a high economic burden, primarily driven by first-line therapy, especially with targeted and immune therapies. Further studies are needed to evaluate the impact of innovative treatments on the disease management costs of mNSCLC.

Evaluating the reduction of elective radiotherapy fields for de novo metastatic nasopharyngeal carcinoma in the immunotherapy era.

This study evaluates the outcomes of omitting the high- and low-risk clinical tumor volume (CTV1 and CTV2) radiation in de novo metastatic nasopharyngeal carcinoma (dnm-NPC) patients in the immunotherapy era. We retrospectively analyzed 45 consecutive dnm-NPC patients receiving chemotherapy and immunotherapy combined with radiotherapy (CIR) from October 9, 2018 to June 1, 2022. Irradiation was only delivered to the primary tumor and retropharyngeal nodes (GTVnx+rn) and gross cervical lymph nodes (GTVnd). The median follow-up was 45 (range, 15-67) months. There was no recurrence in the omitted elective regions. The 36-month LRRFS, PFS, and OS were 95.4%, 44.6%, and 90.8%, respectively. The main grade 3/4 hematologic toxicities were neutropenia (42.2%), anemia (20.0%), and thrombocytopenia (13.3%). The incidence of acute grade 3/4 dermatitis, mucositis, and xerostomia were 4.4%, 8.9%, and 4.4%, respectively. Omitting CTV1 and CTV2 was well-tolerated and provided favorable clinical outcomes in the era of immunotherapy.

Characteristics, efficacy, and prognosis analysis of newly diagnosed marginal zone lymphoma.

To retrospectively analyze the characteristics of newly diagnosed marginal zone lymphoma (MZL) patients, evaluate the efficacy of different treatment regimens, and explore prognostic factors in the era of immunotherapy. We reviewed the clinical data of newly diagnosed MZL patients treated at the Department of Hematology, The First Hospital of Jilin University, from October 2013 to October 2023. Survival differences between groups were analyzed using the log-rank test, and prognostic factors were identified. A total of 265 newly diagnosed MZL patients were included, with a median age of 59 years (range 22-90). The most common pathological type was mucosa-associated lymphoid tissue (MALT) lymphoma, accounting for 66.0% of cases. Among the 147 MZL patients included in the efficacy analysis, the median follow-up was 43.4 months. Both the median progression-free survival (PFS) and overall survival (OS) were not reached. The 5-year PFS and OS rates were 76.0% and 86.6%, respectively. Patients who achieved complete response (CR) after induction therapy had significantly better PFS (P=0.0045), OS (P<0.001), and time to next treatment (TTNT) (P=0.0045) compared to those who did not achieve CR. A subgroup analysis was conducted on 51 MZL patients with high tumor burden who received ≥4 cycles of treatment. It was found that the CR rate (CRR) in patients receiving obinutuzumab (G) ± chemotherapy was significantly higher than in those receiving rituximab (R) ± chemotherapy (93.8% vs. 48.6%, P=0.002). Multivariate analysis revealed that disease progression or death within 24 months of initial treatment (POD24) was an independent risk factor affecting OS (P<0.001). Patients who experienced POD24 had a median survival of only 19.7 months, with a 3-year OS rate of just 37.6%, whereas those without POD24 had a 3-year OS rate of 97.3%. MZL is predominantly seen in middle-aged and elderly patients and is a specific indolent B-cell lymphoma, with MALT lymphoma being the most common subtype. Achieving CR after induction therapy significantly prolongs survival in MZL patients. Compared to R ± chemotherapy, G ± chemotherapy achieves a higher CRR in high tumor burden MZL patients. In the era of immunotherapy, POD24 is an independent prognostic factor for MZL.

DNA Nanostructures: Advancing Cancer Immunotherapy

AbstractCancer immunotherapy is a groundbreaking medical revolution and a paradigm shift from traditional cancer treatments, harnessing the power of the immune system to target and destroy cancer cells. In recent years, DNA nanostructures have emerged as prominent players in cancer immunotherapy, exhibiting immense potential due to their controllable structure, surface addressability, and biocompatibility. This review provides an overview of the various applications of DNA nanostructures, including scaffolded DNA, DNA hydrogels, tetrahedral DNA nanostructures, DNA origami, spherical nucleic acids, and other DNA‐based nanostructures in cancer immunotherapy. These applications explore their roles in vaccine development, immune checkpoint blockade therapies, adoptive cellular therapies, and immune‐combination therapies. Through rational design and optimization, DNA nanostructures significantly bolster the immunogenicity of the tumor microenvironment by facilitating antigen presentation, T‐cell activation, tumor infiltration, and precise immune‐mediated tumor killing. The integration of DNA nanostructures with cancer therapies ushers in a new era of cancer immunotherapy, offering renewed hope and strength in the battle against this formidable foe of human health.

18F]FDG PET/CT Integration in Evaluating Immunotherapy for Lung Cancer: A Clinician's Practical Approach.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment paradigm of lung cancer, resulting in notable enhancements in patient survival. Nevertheless, evaluating treatment response in patients undergoing immunotherapy poses distinct challenges due to unconventional response patterns like pseudoprogressive disease (PPD), dissociated response (DR), and hyperprogressive disease (HPD). Conventional response criteria such as the RECIST 1.1 may not adequately address these complexities. To tackle this issue, novel response criteria such as the iRECIST and imRECIST have been proposed, enabling a more comprehensive assessment of treatment response by incorporating additional scans and considering the best overall response even after radiologic progressive disease evaluation. Additionally, [18F]FDG PET/CT imaging has emerged as a valuable modality for evaluating treatment response, with various metabolic response criteria such as the PERCIMT, imPERCIST, and iPERCIST developed to overcome the limitations of traditional criteria, particularly in detecting pseudoprogression. A multidisciplinary approach involving oncologists, radiologists, and nuclear medicine specialists is crucial for effectively navigating these complexities and enhancing patient outcomes in the era of immunotherapy for lung cancer. In this review, we delineate the key components of these guidelines, summarizing essential aspects for radiologists and nuclear medicine physicians. Furthermore, we provide insights into how imaging can guide the management of individual lung cancer patients in real-world multidisciplinary settings.

Philadelphia-like B-cell acute lymphoblastic Leukaemia: Disease features and outcomes in the era of immunotherapy.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL.