Favorable Progression-free Survival Research Articles

Different Role of PET‐CT Evaluation in Newly Diagnosed Follicular Lymphoma Upon Rituximab‐Based Chemotherapy and Chemo‐Free Immunotherapy

ABSTRACTNewly diagnosed follicular lymphoma (FL) patients usually received first‐line rituximab‐based immunochemotherapy (R‐chemo). Recently, rituximab plus lenalidomide (R2) emerged as an alternative chemo‐free immunotherapy. We performed a comparative analysis of positron emission tomography/computed tomography (PET/CT) in FL undergoing R‐chemo or R2. With data of sequential PET/CT at the baseline, interim, and end‐of‐induction, treatment responses and survival outcomes were analyzed using Deauville scores at the interim and end‐of‐induction. Additionally, correlations between interim Deauville scores and baseline PET/CT parameters were explored. Conclusively, we revealed that Deauville 1–3 at the interim and end‐of‐induction showed lower disease progression within 24 months (POD24) and superior progression‐free survival (PFS) in R‐chemo and R2 cohorts. Also, patients with interim Deauville 1–3 exhibited reduced POD24 and favorable PFS as compared to those with interim Deauville 4–5/end‐of‐induction Deauville 1–3. Furthermore, total lesion glycolysis of baseline PET‐CT surpassed standardized uptake value and total metabolic tumor volume in predicting interim Deauville 1–3, with different optimal cutoffs of 2600 and 600 mL in the R‐chemo and R2 cohort. These findings underscored the potential of PET‐CT‐adapted strategies to achieve durable remission in FL undergoing rituximab‐based immunochemotherapy or immunotherapy.

The clinicopathological and molecular features of primary high-grade neuroendocrine tumour in the breast.

Nottingham grade for breast cancers, rather than gastro-entero-pancreatic (GEP) grade for neuroendocrine tumours (NETs), is currently applied to primary breast NETs, which need further clarification. High-grade NETs in breast also remain poorly recognised. Among 595 breast carcinomas with diffuse synaptophysin (Syn) or chromogranin A (CgA) immunostaining (≥ 90%), 197 eligible cases were selected, including 69 NETs, 123 invasive breast carcinomas of no special type (IBC-NSTs) and five neuroendocrine carcinomas (NECs). The prognostic significance of these two grading systems in breast NETs was assessed. Furthermore, the clinicopathological features were compared in Nottingham G3 cases among three entities. Targeted sequencing and immunostaining (INSM1/p53/Rb/p16) were also performed in all Nottingham G3 NETs, NECs and 10 Nottingham G3 IBC-NSTs. All Nottingham G3 NETs (9 of 69, 13.0%) fell into GEP G3 cases (20 of 69,29.0%). Nottingham grade provided better prognostic discrimination between G1/G2 and G3 NETs than GEP grade. Among Nottingham G3 cases, there was a trend towards reduced progression-free survival (PFS) in NETs compared with IBC-NSTs (P = 0.057), and the former were more often immunoreactive for INSM1 (44.4 versus 0%, P = 0.033). Nottingham G3 NETs were all of luminal-like phenotype (P < 0.001) and exhibited less aberrant p53 patterns (11.1 versus 80.0%, P = 0.023) as well as more favourable PFS (P = 0.012) and disease-specific survival (P = 0.002) than NECs. Rb loss (4of 5, 80%), p16 overexpression (5 of 5, 100%) and RB1 mutation (2 of 5, 40%) were observed exclusively in NECs. Based on expression data, epithelial-mesenchymal transition and KRAS signalling pathways were significantly up-regulated in Nottingham G3 NETs (P < 0.05). Nottingham grade, rather than GEP grade, holds important prognostic significance in primary breast NETs. Nottingham G3 NETs represent a small proportion of breast NETs, and may demonstrate distinct clinicopathological and molecular features from other high-grade breast carcinomas with diffuse neuroendocrine markers expression.

Dynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-Cell Lymphoma.

Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immune suppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. Here, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, tisagenlecleucel 24.7%). Following infusion, patients remain persistently immunosuppressed, with 48.1% having CD4+ T cell counts <200/µL and median CD3-19+ B cell counts remaining zero through 1 year after CAR-T. IR differences exist by product, with fastest CD4+ T cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7-45RA- effector memory subset. Natural killer cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR: 0.647; 95% CI: 0.476-0.880) and overall survival (HR: 0.637; 95% CI: 0.441-0.920) and inversely correlated with inflammatory markers measured at time of infusion.

Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer

Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs. To evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC. This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024. Patients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment. The primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy. Among 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; P < .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; P = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, HLA-A11+ HLA-B62- haplotype, wild-type KMT2D and COL4A4, or sequence variations in CTNNA2 or SCN4A correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively). In this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC. ClinicalTrials.gov Identifier: NCT04012606.

PATH-21. SINGEL CELL TRANSCRIPTOMICS OF SPINAL EPENDYMOMA SUBTYPES IDENTIFIES INTRATUMORAL HETEROGENEITY

Abstract Spinal ependymomas comprise glial neoplasms that are classified by histological and molecular features. Two of the respective types, myxopapillary ependymomas (MPE) and spinal ependymomas (SP-EPN) are largely understudied. For each of these, our group identified clinically relevant subtypes with poorer (MPE-A; SP-EPN-A) and more favorable progression-free survival (MPE-B; SP-EPN-B) employing global methylation and transcriptomic profiling. As cellular origin and pathogenesis of these tumors are largely unknown, therapeutic options for patients with unfavorable subtypes are unavailable. We performed single cell transcriptomic sequencing of 12 formalin-fixed and paraffin-embedded spinal ependymomas including all MPE and SP-EPN subtypes and obtained a median of 10,091 cells per tumor after quality control. Uniform Manifold Approximation and Projection (UMAP) analysis revealed intertumoral heterogeneity as most samples formed separate clusters with tumors of the same subtype located in proximity. The expression of literature-defined neoplastic consensus cell states was examined for each cell of the data set and revealed intratumoral heterogeneity. Tumors expressed predominantly two programs, being a ciliated (ependymal-like) cell state (61% of all neoplastic cells) and the astrocytic state (31 % of all neoplastic cells). Interestingly, third and fourth most abundant states (mesenchymal and hypoxia) were almost exclusively expressed in MPE-A and SP-EPN-A. Furthermore, distinct clones of chromosomal copy number variations were identified across all tumors. These clones can be distinguished in UMAP representation of MPE single cell transcriptomes and to a lesser extend in SP-EPN. Next, we sought to characterize the resemblance of integrated tumor subtypes to normal spinal cord cell populations and observed a high similarity to human spinal cord ependymal cells. All spinal ependymoma subtypes display intratumoral heterogeneity with respect to the transcriptomic cell state resemblance of the neoplastic cells. Together with the transcriptomic similarity to ependymal and astrocytic cells, our data suggest the tumor origin within the astro-ependymal lineage.

INNV-09. DISTANT PARENCHYMAL RECURRENCE DURING LONG-TERM USE OF TTFIELDS TREATMENT FOR GLIOBLASTOMA

Abstract BACKGROUND Tumor treating fields (TTFields) treatment has been an important option for the treatment of glioblastoma. The introduction of novel treatment options may lead to distinct recurrence patterns compared to those observed with conventional therapies; however, the specific recurrence pattern during TTFields treatment has not been elucidated. METHODS AND RESULTS Here, we analyzed 39 cases of glioblastoma treated with TTFields. Although a usage rate of more than 75% is recommended, among 39 cases, 18 discontinued TTFields treatment owing to requests by patients with lower usage rates. In these discontinued cases, patients exhibiting sensory aphasia were more frequently included compared to those who continued TTFields (44.4%, p&amp;lt;0.001). Among 21 cases involving patients who continued TTFields, tumor recurrence was observed in 15 of those cases. Five out of 15 cases (33.3%) exhibited recurrence in distant parenchyma from the primary lesion. A higher usage rate and relatively longer use of TTFields were observed in these five cases, along with more favorable progression-free survival than those in the other 10 cases (p=0.019, p=0.040, and p=0.024, respectively). In one case, recurrent tumors with lower-grade glioma histology but molecular markers characteristic for glioblastoma, IDH-wildtype were identified. This tumor arose in an area that received a lower local minimum power density of TTFields compared to the primary lesion, following long-term TTFields therapy CONCLUSIONS Long-term use of TTFields might be correlated with a high frequency of distant parenchymal recurrence in cases with favorable response.

Survival outcomes of patients with gastric cancer treated with first-line nivolumab plus chemotherapy based on claudin 18.2 expression.

Claudin 18.2 has emerged as a viable therapeutic target in gastric cancer; however, its clinical relevance in the context of immune checkpoint inhibitor-based chemotherapy is not known. This study aimed to investigate the efficacy of nivolumab plus chemotherapy according to claudin 18.2 expression in patients with gastric cancer. This single-center study included patients with advanced gastric cancer who were treated with first-line nivolumab plus chemotherapy (n = 204) or chemotherapy alone (n = 183) whose claudin 18.2 immunohistochemistry results were available. Claudin 18.2 positivity (moderate-to-strong expression in ≥ 75% by the 43-14A clone) was analyzed in terms of efficacy outcomes. Among patients treated with nivolumab plus chemotherapy, 96 (47.1%) were assessed to have claudin 18.2-positive tumors. Between patients with claudin 18.2-positive and -negative tumors, objective response rate with nivolumab plus chemotherapy was comparable. Progression-free survival (PFS) and overall survival (OS) with nivolumab plus chemotherapy were comparable between those with claudin 18.2-positive and -negative tumors. For both subgroups with PD-L1 combined positive score ≥ 5 and < 5, PFS and OS with nivolumab plus chemotherapy were also comparable between patients with claudin 18.2-positive and -negative tumors. A consistent trend of favorable PFS and OS was observed with nivolumab plus chemotherapy compared to that of chemotherapy alone in both claudin 18.2-positive and -negative subgroups. The efficacy of nivolumab plus chemotherapy did not vary according to claudin 18.2 positivity. The clinical benefit of nivolumab plus chemotherapy over chemotherapy was consistently observed in claudin 18.2-positive and -negative gastric cancer cases.

NGS MRD Negativity on Day 28 after Brexu Cel in Adults with R/R ALL Is Associated with Favorable Progression Free Survival

NGS MRD Negativity on Day 28 after Brexu Cel in Adults with R/R ALL Is Associated with Favorable Progression Free Survival

PCV ALONE IN GRADE 2 AND GRADE 3 OLIGODENDROGLIOMA – LONG-TERM RESULTS FROM A UK TERTIARY CARE CENTRE

Abstract AIMS Oligodendroglioma is a subgroup of gliomas which affects young adults and has a favourable overall survival (OS) ranging between 31.5 to 56.6.% at 10 years. Standard management of these tumours is maximal safe resection followed by adjuvant radiotherapy and systemic chemotherapy with Procarbazine, Lomustine and Vincristine (PCV), or surveillance where appropriate. PCV alone is an option that helps defer or avoid radiotherapy and its neurocognitive side effects in a selected group of patients. Our retrospective study analyses outcomes with PCV alone in Oligodendroglioma. METHOD We screened patient records between 1999 to 2021 and identified 31 patients who had a histological diagnosis of grade 2/3 oligodendroglioma (with confirmation of 1p19qcodeletion on molecular testing) and received PCV alone after surgery (biopsy/ tumour resection). RESULTS Out of 31 patients, twenty-six patients were grade 2 and five patients were grade 3 oligodendroglioma. Median age was 44 years and male: female was 15:16. Median follow up was 9.5 years. Twenty-five patients (80%) presented with seizures. 80% of patients had tumour resection &amp; twenty four patients received 5 or more cycles of PCV alone as first-line oncological treatment. There was no significant difference in outcomes for grade2/3 tumours. Eighteen patients (58%) had local tumour relapse. Fourteen patients (45%) underwent salvage radiotherapy. Median time to radiotherapy was 7 years. Median OS was 19.4 years and median progression free survival (PFS) was 13.3 years. 9 deaths were reported. CONCLUSION PCV chemotherapy alone is an effective adjuvant treatment option for selected patients with oligodendroglioma, with a favourable PFS and OS shown in our series. Its use may allow deferral of radiotherapy and avoidance of associated neurocognitive side effects which can have a detrimental effect of quality of life for these young patients.

Impact of low-dose regorafenib on survival outcomes in patients with metastatic colorectal cancer: A retrospective study from a tertiary care center in South India

ABSTRACT Background: Metastatic colorectal cancer (mCRC) poses a significant health challenge, with limited treatment options and poor survival outcomes. Regorafenib, an oral multikinase inhibitor, is effective for patients with mCRC who have progressed after multiple chemotherapy lines. This study evaluates the impact of low-dose regorafenib on survival outcomes in patients at a tertiary care center in South India. Objectives: The primary objective was to determine overall survival outcomes associated with regorafenib in South Indian patients with prior colorectal cancer (CRC) treatment. Secondary objectives included assessing progression-free survival (PFS), safety profiles, and prognostic factors linked to regorafenib use. Materials and Methods: We analyzed patients treated with regorafenib from January 2015 to December 2023 in the Department of Medical Oncology at Amrita Institute of Medical Sciences, Kochi. Patient characteristics, including age, sex, primary tumor location, and metastatic sites, were recorded. PFS and overall survival (OS) were assessed, alongside treatment responses as per Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 criteria and adverse events (AEs) leading to treatment discontinuation. Results: We enrolled 81 patients, predominantly males (66.7%), with a mean age of 59.8 years. Distant metastasis at presentation occurred in 84% (n = 68) of patients. The median PFS was 9.2 months (95% CI, 8.05-10.35), while the mean OS was 39.2 months (95% CI, 33.3-45.1). The overall response rate was 13.5%, and AEs leading to discontinuation were noted in 16% (n = 13) of patients. Conclusion: Low-dose regorafenib demonstrated effectiveness, with favorable PFS and OS outcomes. Age and gender were identified as significant prognostic factors.

Prognostic factors of early recurrence after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offer the potential for long-term survival in peritoneal carcinomatosis, outcomes following CRS/HIPEC vary significantly. To identify the clinical factors associated with progression-free survival (PFS) after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal, ovarian, and gastric cancers. We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival (OS) in patients recruited between 2015 and 2020. Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS. Of the 80 enrolled patients, 39 had an unfavorable PFS (< 1 year) and 41 had a favorable PFS (≥ 1 year). Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0 (CC-0) or length of CRS ≤ 6 h had a favorable PFS [odds ratio (OR) = 0.141, P = 0.004; and OR = 0.361, P = 0.027, respectively]. In multiple logistic regression, achieving CC-0 was the strongest prognostic factor for a favorable PFS (OR = 0.131, P = 0.005). A peritoneal cancer index score > 12 was associated with a lower rate of achieving CC-0 (P = 0.027). The favorable PFS group had a significantly longer OS (median 81.7 mo vs 17.0 mo, P < 0.001). Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival. This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.

SOX17 expression in tumor endothelial cells in colorectal cancer and its association with favorable outcomes in patients

The high mortality rate of colorectal cancer (CRC) highlights the need for new treatment strategies; however, the venous invasion mechanisms in tumor endothelial cells within CRC remain unexplored. Therefore, we investigated the clinicopathological features of SRY-box transcription factor 17 (SOX17) in CRC. Immunohistochemical staining was performed on 55 CRC tissue specimens using a SOX17-specific antibody, followed by Kaplan–Meier and Cox proportional hazards regression analyses. SOX17 immunoreactivity was detected in the endothelial cells of tumor-penetrating vessels in 35/55 CRC samples. Kaplan–Meier analysis indicated that patients with SOX17 immunoreactivity had favorable overall and progression-free survival (log-rank test, P = 0.03 and 0.02, respectively). Notably, tumor endothelial SOX17 immunoreactivity was associated with a favorable prognosis in patients with stage III or IV disease (OS, P = 0.0089; PFS, P = 0.0065). Cox proportional hazard regression analysis indicated that SOX17 immunoreactivity is an independent factor for predicting favorable overall and progression-free survival in CRC (P = 0.02 and 0.01, respectively). The present findings suggest that SOX17 expression in tumor endothelial cells is a potential indicator of favorable prognosis in patients with CRC.

Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.

BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3β-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

Characteristics and outcomes of salvage surgery after immune checkpoint inhibitor therapy for initially unresectable non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) improved the long-term survival outcomes in patients with advanced non-small cell lung cancer (NSCLC), whereas the role of salvage surgery after ICIs was unknown. The object of this study was to investigate characteristics and outcomes of patients who underwent salvage surgery after ICIs. Retrospective chart review was performed on the basis of our multi-institutional database in search of consecutive patients who underwent salvage surgery after ICIs for initially unresectable NSCLC between 2016 and 2022. Patient characteristics, intraoperative findings, perioperative outcomes, histopathological findings, progression-free survival (PFS), and overall survival (OS) were investigated. Fifteen patients with a median age of 71 years were included in the study. The surgical approach was open thoracotomy in 5 and robotic or thoracoscopic surgery in 10 patients. Resection was performed for primary lesions in 8 and metastatic lesions in 7 patients. Postoperative complication was noted in 1 patient with grade 1 phrenic nerve palsy. The median PFS was 47.9 months, and the median OS was not reached. Three-year PFS was 0% in those with metastatic lesions and 87.5% in those with primary lesions (P=0.12). Salvage surgery after ICIs may be associated with low perioperative morbidity and acceptable long-term outcomes in selected patients. Salvage resection of primary lesions may be associated with more favorable PFS than of metastatic lesions.

Integrative analysis of the immunological significances of guanylate binding protein family genes in microsatellite stability colorectal cancer

BackgroundMicrosatellite stability (MSS) colorectal cancer (CRC) has poor sensitivity to immunotherapy and its underlying mechanisms are still unclear. Guanylate binding proteins (GBPs) are a family of GTPase involving innate immune responses by providing defense against invading microbes and pathogens. However, the immunological significances of GBPs in MSS CRC remain unknown. MethodsWe utilized bioinformatic tools to comprehensively analysis the expression pattern, clinical relevance, prognostic value, biological function, and immunoregulation effect of distinct GBP members in MSS CRC. ResultsThe expression of all seven GBPs in MSS samples are remarkably decreased compared to microsatellite instability-high (MSI-H) samples. Among them, GBP1/2/4/5 are obviously correlated with distant metastasis status. High expression of GBP1/4/5/6 was remarkably related to favorable overall survival (OS) and progression-free survival (PFS) in CRC patients with MSS tumor. Subsequent enrichment analysis revealed that Interferon-gamma (IFN-γ) and NOD-like receptor signaling are the most relevant functions. Besides, the expression patterns of GBPs are remarkably associated with several tumor infiltrated immune cells (e.g. regulatory T cells, CD4+ T cells, and macrophages) and diverse immunoregulatory molecules (e.g. immune checkpoint biomarkers (ICBs) and major histocompatibility complex (MHC) molecules). Moreover, high GBP1/2/4/5 expression predicted better immunotherapy responsiveness in immunotherapy cohorts. ConclusionThese findings might provide novel insights for the identification of therapeutic targets and potential prognostic biomarkers of GBP family in CRC with MSS samples.

Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis.

A previous network meta-analysis (NMA) compared the efficacy of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC). The phase III INSPIRE study of iruplinalkib was published recently. The present study aimed to add the results related to iruplinalkib to the NMA. A systematic literature search was performed in PubMed, Embase, Cochrane Library, Google, and Baidu. Randomized controlled trials (RCTs) reporting the independent review committee-assessed progression-free survival (PFS), objective response rate (ORR), or disease control rate (DCR) results of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC were eligible for inclusion in the NMA. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Bayesian fixed-effect models were used for the direct and indirect pairwise comparisons. This study was registered with PROSPERO (CRD42024555299). Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. In terms of the overall risks of bias, all of the studies had "some concerns". All the next-generation ALK inhibitors were statistically superior to crizotinib in terms of PFS. Iruplinalkib had the best surface under the cumulative ranking curve (74.0%), followed by brigatinib (69.1%) and ensartinib (63.7%). Most of the pairwise comparisons did not reveal significant differences in the ORR and DCR. In terms of both the ORR and DCR, alectinib ranked first, followed by lorlatinib. Next-generation ALK inhibitors had better efficacy than crizotinib in the treatment of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC. Iruplinalkib may have more favorable PFS benefit than other ALK inhibitors for Asians.

Utility of Assessing Early Tumor Shrinkage as an Efficacy Predictor in Patients with Non-Surgically Indicated or Recurrent Esophageal Cancer Treated with Nivolumab plus Ipilimumab.

Nivolumab plus ipilimumab combination therapy has been administered as a first-line treatment in Japan since 2022 for patients with unresectable progressive or recurrent esophageal cancer. The efficacy and safety of this immune checkpoint inhibitor (ICI) doublet therapy are now being evaluated, and it is necessary to identify populations that benefit from this treatment at an early phase after initiation. For patients not showing early benefit, changing as soon as possible to other therapeutic strategies could improve their survival outcomes. Therefore, we attempted to identify decision-making factors such as early tumor shrinkage (ETS) based on treatment experience with ICI doublet therapy. The study included 19 patients who received nivolumab plus ipilimumab for non-surgically indicated or recurrent esophageal cancer between July 2022 and November 2023. Tumors were assessed approximately every 2 months after treatment initiation. The effects of ETS, depth of response (DpR), and clinicopathologic features, including immune-related adverse events (irAEs), on progression-free and overall survival were evaluated using Kaplan-Meier plots and Cox proportional hazard models. The mean duration of ICI doublet administration was 5.89 months (range, 1-16 months). At first evaluation, patients who exhibited no tumor progression &gt;20% indicated possible response to ICI doublet therapy, and patients whose tumors shrank even minimally exhibited favorable progression-free survival. Higher DpR at any cut-off line exhibited better progression-free survival than those with lower DpR. Fifteen patients experienced irAEs, with 13 of these patients experiencing irAEs within 3 months of treatment initiation. irAEs were associated with the efficacy of ICI doublet therapy, but efficacy could not be predicted based on early irAE experience. ETS-high, DpR-high, and irAEs might be associated with favorable responses to nivolumab plus ipilimumab. As a predictor of efficacy at an early phase, ETS &gt;0% could be a deciding factor for continuing ICI doublet therapy.

Evolving consolidation patterns and outcomes for a large cohort of patients with primary CNS lymphoma

AbstractConsolidation for primary central nervous system lymphoma (PCNSL) after induction chemoimmunotherapy include whole-brain radiotherapy (WBRT; ≤24 Gy reduced-dose [RD], >24 Gy standard-dose) and cytarabine, nonmyeloablative chemotherapy (NMC), or autologous hematopoietic cell transplantation (AHCT). Comparative outcomes are lacking. Outcomes from 1983-2020 were stratified by decade and Memorial Sloan Kettering Cancer Center recursive partitioning analysis (RPA) class. Clinicodemographic associations were analyzed by multinomial logistic regression. Progression-free survival (PFS) and overall survival (OS) were analyzed by proportional hazards. Of 559 patients, 385 (69%) were consolidated. Median follow-up and OS were 7.4 and 5.7 years, respectively. WBRT use declined (61% (1990s) vs 12% (2010s)), whereas AHCT (4% (1990s) vs 32% (2010s)) and NMC (27% (1990s) vs 52% (2010s)) rose. Compared with RPA 1, RPA 2 was more likely to receive NMC. Those with partial response to induction were less likely to receive AHCT (odds ratio, 0.36; P = .02). Among 351 with complete response to consolidation, only receipt of rituximab, methotrexate, procarbazine, and vincristine induction was associated with improved PFS (hazard ratio, 0.5; P = .006). Among RPA 1, median PFS and OS were not reached for AHCT or RD-WBRT, vs 2.5 and 13.0 years, respectively, after NMC. Among RPA class 3, median PFS and OS after RD-WBRT were 4.6 and 10 years, vs 1.7 and 4.4 years after NMC. No significant adjusted survival differences were seen across consolidation strategies. NMC is increasingly used in lieu of RD-WBRT despite a trend toward less favorable PFS. RD-WBRT can be considered in patients ineligible for AHCT.

DCE-CT parameters as new functional imaging biomarkers at baseline and during immune checkpoint inhibitor therapy in patients with lung cancer – a feasibility study

BackgroundWith the development of immune checkpoint inhibitors for the treatment of non-small cell lung cancer, the need for new functional imaging techniques and early response assessments has increased to account for new response patterns and the high cost of treatment. The present study was designed to assess the prognostic impact of dynamic contrast-enhanced computed tomography (DCE-CT) on survival outcomes in non-small cell lung cancer patients treated with immune checkpoint inhibitors.MethodsThirty-three patients with inoperable non-small-cell lung cancer treated with immune checkpoint inhibitors were prospectively enrolled for DCE-CT as part of their follow-up. A single target lesion at baseline and subsequent follow-up examinations were enclosed in the DCE-CT. Blood volume deconvolution (BVdecon), blood flow deconvolution (BFdecon), blood flow maximum slope (BFMax slope) and permeability were assessed using overall survival (OS) and progression-free survival (PFS) as endpoints in Kaplan Meier and Cox regression analyses.ResultsHigh baseline Blood Volume (BVdecon) (> 12.97 ml × 100 g−1) was associated with a favorable OS (26.7 vs 7.9 months; p = 0.050) and PFS (14.6 vs 2.5 months; p = 0.050). At early follow-up on day seven a higher relative increase in BFdecon (> 24.50% for OS and > 12.04% for PFS) was associated with an unfavorable OS (8.7 months vs 23.1 months; p < 0.025) and PFS (2.5 vs 13.7 months; p < 0.018). The relative change in BFdecon (categorical) on day seven was a predictor of OS (HR 0.26, CI95: 0.06 to 0.93 p = 0.039) and PFS (HR 0.27, CI95: 0.09 to 0.85 p = 0.026).ConclusionDCE-CT-identified parameters may serve as potential prognostic biomarkers at baseline and during early treatment in patients with NSCLC treated with immune checkpoint inhibitor therapy.