Terms Of Overall Survival Research Articles

Survival Effect of Surgery in Patients with Stage IIIB/N2 Non-small Cell Lung Cancer: A Comparative Study with Definitive Chemoradiotherapy.

We compared the survival outcomes of surgery within multimodality treatment regimens with the outcomes of definitive chemoradiation treatments in patients diagnosed with clinical (c) IIIB/N2 non-small cell lung cancer (NSCLC). We investigated whether surgery within multimodality treatment provides a survival advantage at this stage. Data from 79 patients with cIIIB/N2 between 2009 and 2016 were analyzed retrospectively. While the surgery was performed after neoadjuvant therapy in 51 cases (IIIB/Surgery Group), definitive chemotherapy ± radiotherapy was applied in 28 cases (IIIB/Definitive Group). In cIIIB/N2 cases, the 5-year overall survival (OS) was 27.4%, with a median OS of 24.6 months. The 5-year OS of the IIIB/ Surgery Group was 27.3% (median survival 22.5 months), while it was 28.6% (median survival 29.1 months) in the IIIB/Definitive Group (P = .387, HR = 0.798, 95% CI, 0.485-1.313). Although there was a survival advantage in the group with a pathological complete response (PCR) after surgery (n = 14) compared to the group that did not (n = 37), the observed difference was not statistically significant. (5-year OS; 42.9% vs. 18.5%, P = .104). Additionally, there was no statistically significant difference between the survival of PCR patients and the IIIB/Definitive Group in terms of OS (P = .488). Surgery performed within multimodality treatment regimens in selected cIIIB/N2 cases did not provide a survival advantage over definitive chemoradiation treatments.

The Optimal Busulfan Dose of Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation in Younger Patients with Acute Myeloid Leukemia

Background: In allogeneic hematopoietic cell transplantation (HCT) for younger patients with acute myeloid leukemia (AML), myeloablative conditioning (MAC) regimens have been considered as standard conditioning. MAC can reduce the risk of relapse, but increase non-relapse mortality, including organ toxicity and severe graft versus host disease. Therefore, the optimal busulfan dose in conditioning regimens has not been established in younger patients with AML. Thus, we aimed to investigate post-HCT outcomes according to the busulfan dose of conditioning regimens in younger patients with AML. Methods: We retrospectively analyzed long-term outcomes according to the busulfan dose (2 days vs. 3 days vs. 4 days) in 686 adult patients (age <55 years) with AML who had undergone HCT between 2000 and 2020 at the Asan Medical Center, Seoul, Korea. The clinical data was collected from the Asan Medical Center HCT registry. Patients with AML who had undergone a second or third HCT were excluded from this study. Results: The median age was 41 (range 15-54). The 5-year overall survival (OS) and event-free survival (EFS) rate was 52.2% and 46.4%, respectively. The 3 days of busulfan (Bu3) (n=88) showed significantly higher OS than 4 days of busulfan (Bu4) (n=229) and 2 days of busulfan (Bu2) (n=369) (2-year OS; 76.1% vs. 65.1% and 56.3%, respectively; P<0.001). The EFS rate of Bu3 and Bu4 was significantly higher than that of Bu2 (2-year EFS; 60.2% and 59.8% vs. 46.9%, respectively; P<0.001). Among the three groups, there was no significant difference in GRFS (P=0.952). The cumulative incidence of relapse was significantly lower in Bu4 (26.2% at 2 years) than in Bu2 (40.4%) and Bu3 (36.4%) (P<0.001). However, the NRM was significantly higher in Bu4 (13.9% at 2 years) and Bu2 (12.7%) than in Bu3 (3.4%) (P=0.005). In HCT at complete remission (CR) status, Bu3 showed significantly better OS than Bu4 and Bu2 (P=0.039), whereas there was no significant difference in EFS according to the busulfan dose (P=0.121). In patients with refractory disease, however, the higher dose of busulfan (Bu3 or Bu4) did not show survival advantages in terms of OS (P=0.153) and EFS (P=0.829) over Bu2. Regarding donor types, Bu3 showed significantly better OS than Bu2 in HCT from matched sibling donors (MSD) (P=0.030) and haploidentical family donors (HFD) (P<0.001). However, in HCT from unrelated donors (URD), the Bu2 group showed the best GRFS, and OS in Bu2 or Bu3 was significantly longer than in Bu4 (P=0.028). Conclusion: For younger patients with AML, Bu3 would be the optimal conditioning intensity in HCT from MSD or HFD at CR status. In URD, Bu2 or Bu3 would be appropriate. In refractory disease, increasing busulfan dose intensity could not improve post-HCT outcomes.

Synthetic Control Arm from Clinical Trials and Real-World Data from Lysa Group for Untreated Diffuse Large B Cell Lymphoma Patients Aged over 80 Years: A Bona Fide Strategy for Innovative Clinical Trials

Introduction Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy among older patients (pts), and about 25% of new diagnoses involve population aged > 80y.o. Most clinical trials (CTs) exclude the very older (Kanapuru et al, 2017). Rituximab + miniCHOP is considered gold-standard for untreated DLBCL aged >80 y.o with an overall survival (OS) of ~60% at 2y and improving outcomes for this frail population is challenging. Synthetic control arms (SCA) may engender more innovative randomized trials, by allowing indirect comparisons with enhanced statistical confidence and by sparing a part of the control population. We present SCA built from CTs and real-world (RW) data, and their applications to a randomized phase 3 protocol in this clinical setting. Methods We used 3 CTs, with >80 y.o pts treated by anti-CD20+miniCHOP. Two phase 2 CTs for sourcing of SCA patients, LNH03-7B and LNH09-7B, which assessed efficacy of 6 anti-CD20+miniCHOP, preceded in the latter trial by pre-phase treatment, reducing early non-disease related mortality (Peyrade F. et al, 2011 and 2017). SENIOR trial was a phase III randomized trial comparing 6 R-miniCHOP to R-miniCHOP+Lenalidomide, showing no differences in terms of OS (HR= 0.996, 95% CI= 0.66-1.51) (Oberic L. et al, 2022). We further used prospective REALYSA cohort (Ghesquières et al, 2021) with enrolled pts with at least 18 months follow-up and treated by R-miniCHOP as RW pool. We excluded non-compliant diagnoses, as well as early deaths within 3 first months of follow-up from CTs, to avoid the bias for absence of pre-phase from LNH03-7B trial. First step was to build SCA matched with internal SENIOR control arm to check reproducibility of pts outcomes. Then, SENIOR experimental arm was used as the matching source for SCA constructions. Propensity scores (PS) were estimated for each pt using relevant baseline covariates as described in Figure 1. If data was missing, CTs pts were excluded. For RW pts, multiple imputations method was used. Pts between groups were matched using stabilized inverse probability of treatment weighting (IPTW) method, the probability of treatment being assessed by PS, after removing pts with extreme PS from analyses. We subsequently performed sensitivity analyses using 1 : 1 PS matching (PSM). Standardized mean differences (SMD) were calculated for each covariate to assess matching efficacy. The endpoint was OS. Results Control SCAs matched to SENIOR internal control arm have no significant different OS with an HR of 0.81 (95%CI= 0.51-1.27, p = 0.397) using CTs data and an HR of 1.00 (95% CI= 0.62-1.61, p = 0.998) using RW data, with stabilized IPTW. PS set is the baseline population after applying exclusion criteria and including only pts for whom PS could be assessed. For SCA-CT, PS set was composed of 91 pts from experimental SENIOR arm and 169 from LNH03-7B and LNH09-7B. Thirty one pts were excluded for early death, mostly not disease-related. IPTW and PSM methods were both efficient with all SMD <0.10. With SCA-CT, OS curves comparison with stabilized IPTW was very close to SENIOR results: HR of 0.98 (95%CI= 0.643-1.492, p=0.93) (Figure 2). For SCA-RW, PS set included 104 pts from SENIOR experimental arm and 93 from REALYSA database. All SMD were below 0.10 with IPTW and all but one were below 0.15 with PSM. Regarding the outcome analysis, censorship was chosen at 24 months of follow-up as too few patients were still at risk. OS was not significantly different with an HR of 0.84 (95%CI=0.51-1.39, p= 0.551) with stabilized IPTW. Sensitivity analyses with PSM, for SCA-CT and SCA-RW are consistent with results after IPTW, but exclusion process for matching led to a loss of power (84 pts in each arm for SCA-CT and 71 pts in each arm for SCA-RW) Discussion We demonstrated that well matched SCAs built from historical CTs data can achieve a high level of confidence to replicate randomized phase III results in DLBCL pts >80 y.o. We replicated with a SCA the internal control arm with similar OS comparisons (HR= 0.996 (95% CI= 0.66-1.51) for SENIOR, HR= 0.98 (95% CI = 0.643-1.492) for SCA-CT). Matching procedures with RWD patients were also efficient, and SCA-RW OS behaved the same way as SCA-CT and internal control arm of SENIOR trial. The loss of power due to the pool shrinkage for matching procedures could be limited by mixing 50%/50% pts from internal control arm and historical CTs pts. These complementary data will be presented during the meeting.

Neoadjuvant chemotherapy prior to radical hysterectomy in locally advanced cervical cancer: a systematic review and meta-analysis

ObjectiveThe objective of this systematic review was to evaluate the effect of different types of neoadjuvant chemotherapy regimens, in terms of optimal pathological response and oncological outcomes, in patients with...

Systemic Chemotherapy with or without Hepatic Arterial Infusion Chemotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Oligometastasis: A Propensity Score–Matched Analysis

PurposeTo compare the effectiveness of hepatic arterial infusion chemotherapy (HAIC) plus systemic chemotherapy (SYS) with that of SYS alone in patients with intrahepatic cholangiocarcinoma (ICC) with extrahepatic oligometastasis in terms of overall survival (OS) and mortality related to liver failure. Materials and MethodsConsecutive patients diagnosed with ICC with extrahepatic oligometastasis who received either HAIC plus SYS or SYS alone between January 2019 and January 2021 were included in this retrospective cohort study. Propensity score matching (PSM) analysis was performed to address potential confounding factors. OS, progression-free survival (PFS), and intrahepatic progression–free survival (IPFS) were analyzed. The occurrence of death due to liver failure was also assessed. ResultsThe study included a total of 179 patients, with 96 receiving SYS alone and 83 receiving HAIC plus SYS. After PSM, 83 pairs were included for further analysis. The median OS and IPFS were significantly longer in the HAIC plus SYS group compared to the SYS alone group (OS: 15.8 months vs 12.7 months; P = .023; IPFS: 9.7 vs 6.1 months; P < .001). No difference was found in PFS between the 2 groups. The HAIC plus SYS group had a significantly lower rate of mortality due to liver failure compared to the SYS alone group (42% vs 72%; P = .002). ConclusionsHAIC plus SYS is a promising treatment approach for patients with ICC and extrahepatic oligometastasis with improved OS, IPFS, and freedom from liver failure mortality compared with SYS alone.

Evaluation of the effectiveness of a nationwide precision medicine program for patients with advanced non-small cell lung cancer in Germany: a historical cohort analysis

The national Network Genomic Medicine (nNGM) Lung Cancer provides comprehensive and high-quality multiplex molecular diagnostics and standardized personalized treatment recommendation for patients with advanced non-small cell lung cancer (aNSCLC) in Germany. The primary aim of this study was to investigate the effectiveness of the nNGM precision medicine program in terms of overall survival (OS) using real-world data (RWD). A historical nationwide cohort analysis of patients with aNSCLC and initial diagnosis between 04/2019 and 06/2020 was conducted to compare treatment and OS of patients with and without nNGM-participation. Patients participating within the nNGM (nNGM group) were selected based on a prospective nNGM database. The electronic health records (EHR) of the prospective nNGM database were case-specifically linked to claims data (AOK, German health insurance). The control group was selected from claims data of patients receiving usual care without nNGM-participation (non-nNGM group). The minimum follow-up period was six months. Overall, n=509 patients in the nNGM group and n=7213 patients in the non-nNGM group met the inclusion criteria. Patients participating in the nNGM had a significantly improved OS compared to the non-nNGM group (median OS: 10.5 months vs. 8.7 months, p=0.008, HR=0.84, 95% CI: 0.74-0.95). The 1-year survival rates were 46.8% (nNGM) and 41.3% (non-nNGM). The use of approved tyrosine kinase inhibitors (TKI) in the first-line setting was significantly higher in the nNGM group than in the non-nNGM group (nNGM: 8.4% (43/509) vs. non-nNGM: 5.1% (366/7213), p=0.001). Overall, patients receiving first-line TKI treatment had significantly higher 1-year OS rates than patients treated with PD-1/PD-L1 inhibitors and/or chemotherapy (67.2% vs. 40.2%, p<0.001). This is the first study to demonstrate a significant survival benefit and higher utilization of targeted therapies for aNSCLC patients participating within nNGM. Our data indicate that precision medicine programs can enhance collaborative personalized lung cancer care and promote the implementation of treatment innovations and the latest scientific knowledge into clinical routine care. The study was funded by the AOK Federal Association Germany.

Cytoreduction Plus Hyperthermic Intraperitoneal Chemotherapy in Primary and Recurrent Ovarian Cancer: A Single-Center Cohort Study

Epithelial ovarian cancer (EOC) is the most frequent cause of death among women with gynecologic malignant tumors. Primary debulking surgery (PDS) with maximal surgical effort to reach completeness of cytoreduction, followed by chemotherapy, has become the standard of care; moreover, some experiences have shown that a comprehensive treatment approach of surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) could improve the prognosis of ovarian cancer. We carried out a retrospective analysis of all consecutive sixty-six patients diagnosed with primary advanced or recurrent ovarian cancer who underwent debulking surgery plus HIPEC in a single center between September 2005 and October 2020. For 33 patients with primary EOC, with a median follow-up period of 70 months, the median overall survival was 56 months (range: 48.1–96.9); and the median disease-free survival (DFS) was 13 months (range: 19.9–53.7). In the recurrent population, the median follow-up period was 78 months, the median overall survival (OS) was 82 months (range: 48.1–96.9), and the median DFS was 17 months (range: 19.7–53.0). In our study, we have found that CRS plus HIPEC is feasible, with very low rates of major complications and good results in terms of overall survival.

The Impact of Sentinel Lymph Node Biopsy on Female Patients With T3-4c Breast Cancer and 1-2 Positive Lymph Nodes: A Population-Based Cohort Study

PurposeThis study aimed to evaluate the efficacy of sentinel lymph node biopsy (SLNB) in patients diagnosed with cT3-4c breast cancer with no more than 2 positive sentinel lymph nodes. MethodsUsing data from the Surveillance, Epidemiology, and End Results (SEER) database, this retrospective study identified patients diagnosed with T3-4c breast cancer between 2010 and 2015. These patients were then categorized into 2 groups: the SLNB group, which underwent examination of 1-5 regional lymph nodes and the axillary lymph node dissection (ALND) group, which underwent examination of ≥10 regional lymph nodes. Propensity score matching analysis was used to assess the efficacy of SLNB in cT3-4c patients. ResultsA total of 1139 patients were included in the analysis, with 423 and 716 patients in the SLNB and ALND groups, respectively. The 10-year overall survival (OS) and breast cancer-specific survival (BCSS) rates in the SLNB group were 66.1% and 76.3%, respectively, compared with 66.0% and 73.8%, respectively. Statistical analysis revealed no significant differences between the 2 groups in terms of OS (HR = 1.00, 95% CI = 0.80-1.25, P = .997) and BCSS (HR = 1.08, 95% CI = 0.83-1.41, P = .551). Even after 1:1 propensity score matching, there were no significant differences in OS (HR = 0.87, 95% CI = 0.65-1.16, P = .341) and BCSS (HR = 0.82, 95% CI = 0.59-1.16, P = .266) between the 2 groups. ConclusionThis study demonstrates that SLNB does not adversely affect the survival of cT3-4c breast cancer patients with 1-2 sentinel lymph node metastases.

Tumor microenvironment heterogeneity in bladder cancer identifies biologically distinct subtypes predicting prognosis and anti-PD-L1 responses

Bladder cancer (BCa) is heterogeneous in the tumour microenvironment (TME). However, the role of the TME in BCa in modulating the response to immunotherapy has not been fully explored. We therefore analysed fractions of immune cells using CIBERSORTx and clustered BCa into subtypes. We also analyzed weighted correlation networks to generate immunotherapy-related hub genes that we used to construct a prediction model using multivariate Cox and LASSO regression analyses. We found that BCa comprised three subtypes (C1‒C3). The prognosis of the patients was the most favourable and the response rate to anti-programmed death ligand 1 (PD-L1) was the highest in C1 among the three subtypes. Immune cells, including CD8+, CD4+ memory activated, and follicular helper T cells, activated NK cells, and M1 macrophages infiltrated the C1 subtype. The C2 subtype was enriched in M0 macrophages and activated mast cells, and the C3 subtype was enriched in B and resting immune cells. Mechanistically, the enhanced immunogenicity of subtypes C1 and C2 correlated positively with a higher response rate, whereas the dysregulated ECM-related pathways in the C2 subtype and glycolytic and fatty acid metabolic pathways in the C3 subtype impaired the responses of patients to anti-PD-L1 therapy. We also constructed a TME-related signature based on 18 genes that performed well in terms of overall survival. In conclusion, we determined prognoses and anti-PD-L1 responses by analysing TME heterogeneity in BCa.

CTNI-39. REGOMA-OS: A LARGE ITALIAN MULTICENTER, PROSPECTIVE, OBSERVATIONAL STUDY ANALYZING REGORAFENIB EFFICACY AND SAFETY IN RECURRENT GLIOBLASTOMA PATIENTS

Abstract BACKGROUND in the randomized phase 2 REGOMA trial, regorafenib (REG) showed promising activity in recurrent glioblastoma (GBM) patients (PTS); subsequently, in Italy the National Health System has permitted the reimbursement of the REG as second-line therapy. We performed a large multicenter, prospective and observational study to confirm REGOMA data in a real-world setting. Materials and METHODS major inclusion criteria were: histologically confirmed diagnosis of GBM according to WHO 2016 and relapse after Stupp treatment, good performance status (ECOG PS 0-1), good liver function. REG was administered at standard dose of 160mg/die for 3 weeks on/1 week off. Brain MRI was performed within 14 days before starting REG and every 8-12 weeks, subsequently. Primary endpoint was overall survival. RANO criteria were used for response evaluation, CTACAE v. 5 for adverse events. RESULTS from Sept 2020 to Oct 2022, 192 recurrent GBM PTS were enrolled from 29 Cancer Centres in Italy: median age was 58ys (IQR 52.8-67.0), 68% male, ECOG PS was 0 in 85 (44%), 115 PTS (60%) undertook steroids at baseline. MGMT was methylated in 43%, IDHwt in 92%. Median follow-up was 16.6 months (IQR 12.6-19.6). Median OS was 8.2ms (95% CI 6.5-9.6), 12ms-OS 34.7% (95%CI 27.2-42.4); median PFS was 2.6ms (95%CI 2.3-2.9), 6ms-PFS 14.3%. Radiological response was PR and SD in 12 (8%) and 25 (16%) PTS. 77 (44%) PTS received third-line therapy. The median of REG cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 adverse events (AE) were reported in 53 (28%) PTS; reduction/delay and permanent discontinuation due to AE in 36% and 8% of PTS. No death was considered as treatment-related AE. CONCLUSIONS compared to the REGOMA trial, this large Italian multicenter, prospective and observational trial confirmed the results in terms of overall survival with a good toxicity profile of REG in recurrent GBM PTS.

TMIC-10. TGF-Β2 DRIVEN SURVIVAL IN DMG AND GBM

Abstract OT-101 is being developed as immunotherapy for a broad range of cancers. Cancers overexpress TGF-β, which suppresses host innate immune response to the cancers. Treatment with OT-101 lifts the TGF-β cloaking effect and allows innate or therapeutic immunity to attack and eliminate the cancers. OT-101 completed phase 2 for pancreatic cancer and melanoma and phase 2 in glioblastoma with robust efficacy and safety. Here we are presenting data and clinical trial design for OT-101 in DMG (Diffuse Midline Glioma). ADME studies were performed on OT-101 demonstrating perfusion of the brain including the midline by either intracerebral or intraventricular administration. The studies allowed us to bridge intraventricular administration to corpus of CED administered OT-101. Safety studies were performed in two species supporting the safety of OT-101 intraventricular administration. Expression analyses of pediatric brainstem cases of the TCGA database yielded highly significant survival benefit across all four quartiles of TGF-β2 expression. This was not observed for either TGF-β1 and less so for TGF-β3. Expression analyses of all gliomas treated with radiation yielded highly significant survival benefit across all four quartiles of TGF-β2 expression. This was not observed for either TGF-β1 nor TGF-β3. In adult gliomas, OT-101 is noninferior to the most active drugs (TMZ, BCNU, or PCV) in both chemo naïve and chemo-resistant patients. In terms of overall survival when compared to standard chemotherapy (TMZ, BCNU, or PCV) in both G004 and G005 as both the hazard ratio, which was 0.9168, and the 90% upper limit of the confidence interval, which was 1.2245, were both less than the initial non-inferiority bound of 1.25. Together the data support the development of OT-101 for DMG. The phase 2 clinical trial design is being presented for OT-101 in DMG administered using Ommaya reservoir following radiation in newly diagnosed DMG

Machine Learning Quantification of Intraepithelial Tumor-Infiltrating Lymphocytes as a Significant Prognostic Factor in High-Grade Serous Ovarian Carcinomas.

The prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) has been demonstrated in various neoplasms. The few publications that have addressed this topic in high-grade serous ovarian carcinoma (HGSOC) have approached TIL quantification from a semiquantitative standpoint. Clinical correlation studies, therefore, need to be conducted based on more accurate TIL quantification. We created a machine learning system based on H&E-stained sections using 76 molecularly and clinically well-characterized advanced HGSOC. This system enabled immune cell classification. These immune parameters were subsequently correlated with overall survival (OS) and progression-free survival (PFI). An intense colonization of the tumor cords by TILs was associated with a better prognosis. Moreover, the multivariate analysis showed that the intraephitelial (ie) TILs concentration was an independent and favorable prognostic factor both for OS (p = 0.02) and PFI (p = 0.001). A synergistic effect between complete surgical cytoreduction and high levels of ieTILs was evidenced, both in terms of OS (p = 0.0005) and PFI (p = 0.0008). We consider that digital analysis with machine learning provided a more accurate TIL quantification in HGSOC. It has been demonstrated that ieTILs quantification in H&E-stained slides is an independent prognostic parameter. It is possible that intraepithelial TIL quantification could help identify candidate patients for immunotherapy.

Circulating Tumor Cells Prediction in Hormone Receptor Positive HER2-Negative Advanced Breast Cancer: A Retrospective Analysis of the MONARCH 2 Trial.

The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials. Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage IVindolent (pStage IVindolent, <5 predicted CTCs). Prognosis was tested in terms of progression-free-survival (PFS) and overall survival (OS) through Cox regression. Patients classified as predicted pStage IVaggressive and predicted pStage Stage IVindolent were, respectively, 183 (28%) and 461 (72%). After multivariable Cox regression, predicted CTCs were confirmed as independently associated with prognosis in terms of OS, together with ECOG performance status, liver involvement, bone-only disease, and treatment arm. Patients in the pStage Stage IVindolent subgroup treated with abemaciclib experienced the best prognosis both in terms of PFS and OS. The treatment effect of abemaciclib on OS was then explored through subgroup analysis, showing a consistent benefit across all subgroups. This study is the first analysis of CTCs modeling for stage IV disease stratification. These results show the need to expand biomarker profiling in combination with CTCs stratification for improved biomarker-driven drug development.

Results of an Italian Retrospective Clinical Experience on Mediastinal Gray Zone Lymphoma

Introduction and methods: Mediastinal gray zone lymphoma (GZL) emerged as a rare and challenging entity due to its high rate of pathological reclassification and heterogeneous clinical management. The bio-GZL2020 study was designed to centralize histological samples and clinical data of patients (pts) diagnosed with GZL between 2006 and 2020 in 16 Italian hematological centers. We here report the preliminary clinical results of this retrospective analysis. Results: Overall, we collected samples and clinical data of 68 pts with GZL. According to the 2022 WHO and ICC classifications we excluded nine pts for lacking mediastinal involvement, hence 59 pts were analyzed. Pts were mostly stage I-II (62.7%); 57.6% had a mediastinal bulky disease. The site of diagnostic biopsy was the mediastinum in 29 pts. Additional clinical characteristics at baseline are reported in Table 1. One patient died before the start of treatment and was excluded from survival analysis. First line chemotherapy (CHT) consisted in DA-EPOCH in 31 pts, CHOP-like regimens in 17 pts, ABVD in six pts, MACOP-B in three pts and DHAP in only one case. Eight pts did not receive rituximab with CHT (six ABVD pts, two CHOP-like pts). Dose escalation in R-DA-EPOCH was performed in 75% of pts, with 18 pts (64.3%) attaining level 3 or higher. Four advanced stage, high-risk pts received central nervous system prophylaxis. Twenty-two pts performed an interim PET-scan during first line therapy; data on Deauville score was available in 19 cases, with 9 pts obtaining a score 1-3. Restaging after first line CHT showed 37 pts in complete remission (CR; 63.8%), nine pts in partial remission (PR; 15.5%), five pts in stable disease (SD; 8.6%) and seven pts in progressive disease (PD; 12.1%). Thirty-one pts (53.4%) received a consolidative treatment (26 pts radiotherapy (RT) only, seven pts autologous transplant (ASCT) only, two pts both RT and ASCT). Restaging after first line consolidation showed 43 CR (74.1%), four PR (6.9%), two SD (5.2%) and eight PD (13.8%). Nineteen pts underwent a second line CHT, 16 of them with a platinum-based regimen; brentuximab vedotin, BeGEV and HyperCVAD were used in one patient each. Second line consolidation ASCT was performed in seven pts, while one received an allogeneic transplant. Of the 17 restaged pts after second line CHT seven were in CR, 10 were not responsive (four SD, six PD). Considering all salvage lines five pts received a checkpoint inhibitor, nine underwent brentuximab vedotin treatment. Overall survival (OS) was 86.9% at 5 years and 71.3% at 10 years; beta2-microglobulin (available only in 32 pts) and the response after first line therapy were associated to a statistically significant difference in OS in univariate analysis. Progression-free survival (PFS) was 61.9% at 5 and 10 years. The use of rituximab, the Deauville score 1-3 at interim PET during induction, and the response after first line therapy were associated to a statistically significant difference in PFS in univariate analysis. ABVD was associated to poorer results in terms of OS and PFS although no significant difference was observed. No statistically significant difference in term of PFS was observed between pts treated with intensified regimens (DA-EPOCH, MACOP-B, DHAP) and other treatments in first line. Excluding pts directly shifted to salvage therapy, consolidative RT after first line CHT showed no statistically significance in term of both OS and PFS. Conclusions: To our knowledge our study represents the largest retrospective data collection on GZL among hematological Italian centers. This preliminary analysis did not show a clear advantage of intensive therapies such as DA-EPOCH or MACOPB, while the positive prognostic role of rituximab was confirmed in PFS. The prognostic role of interim PET-CT scan seems interesting and should be evaluated in subsequent trials. Further refinement of the reported results is expected in relation of an ongoing central pathological review by a panel of expert hematopathologists.

Bispecific T-Cell Engagers for B-Cell NON-Hodgkin Lymphoma Patients before Allogeneic Stem Cell Transplantation. a Study on Behalf Od Geth-TC

Background: Bispecific T-cell engagers antibodies (BiTEs) have shown promising efficacy across B-cell non-Hodgkin lymphoma (BCL) subtypes. If a response is observed, consolidation with allogeneic hematopoietic cell transplantation (alloHCT) could be reasonably pursued for high risk patients. To date, no data are available regarding BiTEs exposure prior to an alloHCT. Our aim was to describe patient characteristics, response, survival outcomes and treatment-related toxicities of patients treated with anti CD20-CD3 BiTE before alloHCT. Methods: We performed a multicentric, retrospective study including adult patients (&amp;gt;18 years old) who received an alloHCT as consolidative therapy following anti-CD20-CD3 BiTE treatment for relapsed/refractory (R/R) BCL between February 2018 and March 2023. The primary endpoint was non-relapse mortality (NRM). Secondary endpoints were overall survival (OS), progression-free survival (PFS), relapse/progression of disease (Rl/POD), cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), and hematological recovery. Probabilities of OS and PFS were calculated using Kaplan-Meier estimator method, and NRM, RI/POD, GVHD and hematological recovery as cumulative incidences. Results: A total number of 29 patients were included in the analysis. Patient's characteristics are described in Table 1. Median age was 57 (range 22-67) and 62.1% of patients were males. Twenty-four (82.8%) patients had stage III-IV at diagnosis and 21 (72.4%) were primary refractory. Nine (31%) patients had received an autologous transplant and 10 (34.5%), anti-CD19 CART prior to BiTE. Median number of lines at alloHCT were 4 (range 3-11). Median time from diagnosis to alloHCT was 39 (range 9 -208) months. Epcoritamab (n=16) was administered in monotherapy. Glofitamab (n= 13) was given in either monotherapy (n=2) or combination with either atezolizumab (n=2), polatuzumab (n=3) or englumafusp (n=6). The median number of BiTE's administered doses was 10 (range 4-20). The median time between BiTE's last dose and alloHCT was 44 (range 13 - 203) days. Median follow-up among survivors was 21.9 months (range 3.3 - 52.6 months). At 18-months, OS, PFS, NRM and RI/POD were 66% (95% confidence interval [CI]: 45-81%), 62% (95% CI: 40-78%), 33% (95% CI: 15-53%), and 4% (95% CI: 0-12%), respectively. Causes of death were 1 relapse and 9 transplant toxicities (7=infections, 1=cGVHD, 1=cerebrovascular disease). Fifty-five percent of toxicity-related deaths were observed during the first 3 months from transplant. The cumulative incidence of neutrophil and platelet engraftment at day +30 was 90% (95% CI, 78-100%) and 68% (95% CI, 50-86%), respectively. The cumulative incidence of all grade and grade II-IV aGVHD at day +100 was 31% (95% CI: 13-49%) and 22% (95% CI: 7-37%), respectively. The cumulative incidence of all grade cGVHD at 18 months was 16% (95% CI: 2-30%), with only 1 patient presenting with moderate cGVHD. On univariate analysis, no prognostic factors were found in terms of OS, PFS, RI/POD and NRM. A comparison with a contemporary cohort of alloHCT recipients for BCL (N=101) from the Grupo Español de Trasplante y Terapia Celular (GETH-TC) who were not exposed to BiTE was performed ( figure 1). Propensity score matching using most significant patient, disease and alloHCT characteristics was performed to reduce cohort's heterogeneity ( Table 1). In the final 1:1 matched population (n=58; 29 patients treated with BiTE prior alloHCT and 29 patients who did not receive BiTE prior alloHCT), no differences in terms of OS, PFS, RI/POD and NRM at 18 months were observed (66% [95% CI, 45-81%] vs 48% [95% CI, 29-65%] [p=0.18]; 62% [95% CI, 40-78%] vs 45% [95% CI, 27-62%] [p=0.17]; 33% [95% CI, 14-52%] vs 41% [95% CI, 22-60%] [p=0.35] and 4% [95% CI, 0-10%] vs 10% [95% CI, 0-20%] [p=0.24]. Conclusions: We describe for the first time the results of BiTE exposure before alloHCT in terms of safety and efficacy. AlloHCT as consolidation therapy is feasible and does not seem to be detrimental for transplant outcomes in patients with R/R BCL with expected toxicity and surprisingly low relapse rate.

Age-Based Validation of the Advanced-Stage Hodgkin Lymphoma International Prognostic Index (A-HIPI) in a Real-World Danish Study: Suboptimal Performance in Older Patients

Purpose: Improved predictive tools are desired in classic Hodgkin lymphoma (cHL) to improve prognostication and to better risk stratify patients (pts) for clinical trials. In younger pts who tolerate intensive therapies, focus has been on limiting late treatment toxicity through risk-adapted, PET-guided treatment strategy. In older pts, acute treatment toxicities are limiting factors for optimal disease control. Due to these fundamental differences, predictive tools may perform differently in younger and older pts. In particular, tools developed in younger pts may be suboptimal in older populations and vice versa. The primary objective of this study was to assess the performance of the A-HIPI (development was limited to 18-65 years of age) against the international prognostic score (IPS) for modelling overall survival (OS) and progression-free survival (PFS) in younger and older pts with cHL. Methods: This study utilized data from the population-based, nationwide Danish National Lymphoma registry. Pts with advanced-stage cHL (Ann Arbor stage III-IV or IIB with extra nodal disease) were included and categorized by age in two groups: ages ≤65 years vs. &amp;gt;65 years. In the primary analysis, all pts regardless of therapy were included. A sensitivity analysis restricting to pts starting on BEACOPP or ABVD was performed (Only ABVD in the &amp;gt;65 cohort). Concordance index (C-index) and calibration were used to assess model performance and generalizability. Calibration was visualized using calibration plots and quantified by calibration in the large (CITL) and calibration slope (CS) at 5-years post diagnosis. Results: A total of 893 advanced-stage HL pts fulfilled the inclusion criteria (634 in the ≤65 cohort and 259 in the &amp;gt;65 cohort). The 5-year OS and PFS in the &amp;gt;65-year cohort were 44% (Confidence intervals (CI); 37-51%) and 35% (CI; 30-42%), respectively. Fifty-six pts in the &amp;gt;65 cohort were classified as low-intermediate-risk (IPS; 1-2), 128 intermediate-risk (IPS; 3-4), and 75 high-risk (IPS; 5-7). For the ≤65 cohort, the 5-year OS and PFS was 88% (CI; 85-90%) and 76% (CI; 73-80%), respectively. Twenty-three pts were classified as low-risk (IPS; 0), 244 low-intermediate-risk, 286 intermediate-risk, and 81 high-risk. The A-HIPI had a C-index of 0.74 and 0.63 for OS and PFS, respectively in the ≤65 years cohort vs. 0.65 and 0.64 for OS and PFS, respectively, in the &amp;gt;65 cohort. The IPS had a C-index in the ≤65 cohort of 0.66 and 0.60 for OS and PFS, respectively, vs. 0.58 and 0.59 for OS and PFS, respectively, in the &amp;gt;65 cohort (i.e., the IPS performed better in the ≤65 cohort in terms of OS and PFS but was inferior to the A-HIPI). When restricting to pts treated with ABVD or BEACOPP, the A-HIPI C-index in the &amp;gt;65 cohort (116 pts) were reduced to 0.55 for OS and 0.54 for PFS. For the ≤65 cohort (595 pts), the A-HIPI C-index was stable at 0.75 and 0.62 for OS and PFS, respectively. In terms of A-HIPI calibration in the &amp;gt;65 cohort, CITL and CS were -0.78 and 0.39 for OS vs. -0.98 and 0.80 for PFS. In the ≤65 cohort, CITL and CS were -0.06 and 0.99 for OS vs. 0.21 and 1.18 for PFS. Visual inspection of the calibration plot (Figure 1) for the &amp;gt;65 cohort showed that the A-HIPI underestimated the observed proportion for both OS and PFS (i.e., the observed events were higher than the predicted). Calibration plot for the ≤65 cohort (Figure 2) indicated that the A-HIPI accurately modelled the observed proportion for both OS and PFS (i.e., the predicted probability was consistent with the observed proportion). Conclusion: The newly developed A-HIPI was validated in a large population-based cohort of Danish pts with advanced-stage cHL. Performance of the A-HIPI was high in the ≤65 cohort and superior to the IPS for OS prediction. Calibration of A-HIPI was excellent in pts ages ≤65 years. However, A-HIPI performed significantly worse among pts &amp;gt;65 years and attained poor performance in pts receiving ABVD or BEACOPP, which is not surprising since patients older than 65 were not included in the development. This study emphasizes the importance of further efforts to develop or update models that apply specifically in older individuals. The inclusion of additional variables reflecting comorbidities and pts fitness into a prognostic model may be necessary to effectively deliver accurate prognoses and risk assessments for the older pt.

Primary and Secondary Plasma Cell Leukemia Risk Stratification By Circulating Plasma Cells

Plasma cell leukemia (PCL) is a rare plasma cell dyscrasia associated with poor outcomes. PCL can present de novo as primary PCL (pPCL) or from preceding multiple myeloma as secondary PCL (sPCL). The International Myeloma Working Group (IMWG) in 2021 updated the diagnostic criteria for pPCL using circulating plasma cells (CPC) to ≥5% instead of ≥20% as both carry similar survival. In this single center retrospective analysis, we compared clinical features and overall survival (OS) for 104 patients: with pPCL ≥5% CPC ( N = 35), sPCL 5-19% CPC (sPCL-A) ( N = 11), sPCL ≥20% CPC (sPCL-B) ( N = 38), and spillover group 1-4% CPC regardless of newly diagnosed or secondary status ( N = 20). Mean ages were 57 - 59 years old for all groups (range: 25 - 84) with no difference in age between groups ( p = 0.90). There was a slight predominance of females (54.8%) over males and blacks (53.9%) over non-blacks. More patients with pPCL were black (65.7%) compared to sPCL and spillover groups, although this difference was not statistically significant ( p = 0.35). pPCL patients presented with the highest mean WBC at diagnosis (23.4 x10 9/L) compared to sPCL-A (5.5 x10 9/L), sPCL-B (12.2 x10 9/L), and spillover (7.2 x10 9/L) groups ( p &amp;lt;0.001). Patients in all groups were anemic (hemoglobin 7.8 - 9.3 g/dL), thrombocytopenic (platelets 60.2 - 101.2 x 10 9/L), and had abnormal renal function (creatinine 1.4 - 2.7 mg/dL), elevated LDH (918.7 - 1515.5 units/L, highest in sPCL-A), and elevated uric acid levels (5.9 - 8.2 mg/dL). sPCL patients and spillover group had more lytic lesions on skeletal survey ( p = 0.009) and positron emission tomography (PET) ( p = 0.02) compared to patients with pPCL. sPCL-A patients had higher incidences of lymphadenopathy ( N = 5/11, 62.5%, p = 0.02) and central nervous system invasion ( N = 4/11, 36.4%, p = 0.02) compared to other groups. There was no difference in incidence of extramedullary disease ( p = 0.29) between groups. Over 90% of patients with PCL had high-risk cytogenetics with 63% carrying a complex karyotype. Hypodiploidy was seen more often in patients with pPCL and sPCL-B compared to sPCL-A and spillover ( p = 0.005). There was no difference between groups in incidence of deletion 17p ( p = 0.53). All patients benefited in terms of OS from daratumumab (HR 0.44, 95% CI 0.25 - 0.76; p = 0.004), IMiDs (HR 0.13, 95% CI 0.08 - 0.23; p &amp;lt;0.001), PIs (HR 0.43, 95% CI 0.25 - 0.75; p = 0.003), chemotherapy (HR 0.56, 95% CI 0.32 - 0.98; p = 0.04), and autologous hematopoietic stem cell transplantation (HR 0.33, 95% CI 0.16 - 0.71; p = 0.004). DVT-PACE type regimens (dexamethasone-bortezomib-thalidomide-cisplatin-doxorubicin-cyclophosphamide-etoposide) are used for pPCL and may be less effective in sPCL and spillover patients who have been heavily pretreated. We noted no benefit in OS for all patients including pPCL, sPCL-A, sPCL-B, and spillover groups who received DVT-PACE (HR 0.97, 95% CI 0.62 - 1.50, p = 0.88). The lack of OS benefit in pPCL patients receiving DVT-PACE persisted on multivariate analysis when adjusting for PCL group alone (HR 0.79, 95% CI 0.50 -1.26; p = 0.33) and PCL group, age, platelet count, and presence of high-risk cytogenetics (HR 1.11, 95% CI 0.63 - 1.94; p = 0.72). After median follow-up of 6.70 months, median OS was 7.14 months for the entire cohort with 92.3% ( N = 96) deceased. On univariate analysis, male sex, age &amp;gt;58 years old, high-risk cytogenetics, LDH &amp;gt;604 units/L, creatinine &amp;gt;1.40 mg/dL, hemoglobin &amp;lt;8.3 g/dL, platelets &amp;lt;53.5 x10 9/L, lytic lesions on skeletal survey and on PET, extramedullary disease on PET, and plasmacytoma were associated with inferior median OS (Table 1). pPCL had higher median OS (13.1 months) compared to sPCL-A (3.1 months, p = 0.03) and sPCL-B (3.5 months, p = 0.003) (Figure 1). There was no statistically significant difference in median OS between pPCL (13.1 months) and spillover patients (10 months) ( p = 0.48) as well as sPCL-A (3.1 months) and sPCL-B (3.5 months) ( p = 0.80). Although the spillover group was associated with a trend towards better OS compared to sPCL-A and sPCL-B groups, this was not statistically significant, which may be due to low N which is a limitation of the study. Further research is required to better understand the clinical features, treatment responses, and outcomes of pPCL, sPCL, and spillover group (1-4% CPC).

Matching-Adjusted Indirect Comparison (MAIC) of Brexucabtagene Autoleucel (Brexu-cel) and Pirtobrutinib in Patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor (cBTKi)

Introduction: Patients with MCL often require multiple lines of therapy and exhibit a generally unfavorable prognosis, particularly following failure of cBTKi therapy. Therapies such as chimeric antigen receptor (CAR) T-cell therapies and non-covalent BTKi therapies have shown promise in improving outcomes. Brexu-cel (formerly known as KTE-X19) is the only CAR T-cell therapy approved in the US for R/R MCL based on results from a phase 2 multicenter, single-arm trial (ZUMA-2; NCT02601313) in patients with R/R MCL who had 1-5 prior therapies, including a BTKi. Pirtobrutinib, a highly selective, non-covalent BTKi, was recently approved in the US for treatment of R/R MCL after at least two lines of systemic therapy including a BTKi, based on ongoing results from a multicenter phase 1/2 study (BRUIN; NCT03740529). In the absence of a direct head-to-head trial comparing brexu-cel and pirtobrutinib, we performed an unanchored MAIC to estimate the relative treatment effects of these therapies in the post-BTKi setting for R/R MCL. Methods: Individual patient-level data were available for ZUMA-2 (N=68; 35.8 months median follow-up as of July 24, 2021 data cut-off) whereas study-level data were available for BRUIN (N=90 in the BTKi pre-treated cohort; 23.5 months median follow-up as of July 29, 2022 data cut-off). Longer-term overall survival (OS) data for ZUMA-2 from the July 23, 2022 data cut-off (46.1 months median follow-up) were available and used. Logistic propensity score models were used to weight the brexu-cel infused population from ZUMA-2 to match the aggregate baseline characteristics of the BTKi pre-treated cohort in BRUIN. These baseline characteristics represented clinically relevant prognostic factors which were pre-specified based on input from clinical experts and data availability. The base-case model incorporated the top five most pertinent factors, which were reported in at least 50% of patients in both trials: blastoid morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplantation. A sensitivity analysis additionally incorporated TP53 mutation (missing in &amp;gt;50% of patients in ZUMA-2 and BRUIN) and Ki-67 proliferation index (missing in &amp;gt;50% of patients in BRUIN). Several prognostic factors (response to prior BTKi therapy, response to last therapy, and duration on prior BTKi therapy) could not be considered due to not being reported for BRUIN. The effective sample size was calculated as a measure of the degree of precision after weighting, reflecting the extent of overlap in the distribution of covariates between the trial populations. Relative treatment effects were expressed as odds ratios or hazard ratios with 95% confidence intervals. Outcomes included objective response (ORR), complete response (CR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: In the base-case MAIC, a significant difference in the odds of ORR and CR in favor of brexu-cel versus pirtobrutinib was observed (Table 1). Similarly, brexu-cel demonstrated a significant improvement in PFS (Table 2). OS and DOR point estimates were in favor of brexu-cel when compared to pirtobrutinib, although not statistically significant. These findings were consistent with unadjusted naïve analyses as well as the sensitivity analyses including adjustment for TP53 mutation and Ki-67 proliferation index. Conclusions: While acknowledging the inherent limitations of an unanchored indirect comparison, our findings suggest that brexu-cel offers clinically and statistically significant efficacy benefits in terms of ORR, CR, and PFS compared to pirtobrutinib in patients with R/R MCL after prior cBTKi therapy. Both treatments were not statistically different in terms of OS and DOR although the estimated hazard ratios indicated a favorable trend for brexu-cel; however, given the relatively shorter follow-up and the high degree of censoring in BRUIN, an updated analysis incorporating longer follow-up data with more events from BRUIN could provide more reliable results. Although efforts were made to ensure a robust approach to the selection of prognostic factors for inclusion in the model, the possibility of some residual confounding variables cannot be completely ruled out. Nevertheless, these results provide valuable insights that may help inform treatment decisions for this population.

Patient-Reported Outcome Measures Associated with Overall Survival and Acute Care Use in Patients with Newly Diagnosed Myelodysplastic Syndrome, Acute Myelogenous Leukemia, or Acute Lymphoblastic Leukemia

Background: There is limited data on the real-world application of patient-reported outcomes (PROs) and their clinical utility in patients with acute leukemias or myelodysplastic syndrome (MDS). While the associations of PROs with clinical outcomes, such as overall survival (OS) and acute care utilization have been established in patients with solid tumors (Basch E et al. JAMA, 2017.318(2):197-198), these same associations are not well known in patients with hematologic malignancies. Objectives: We assessed the characteristics of baseline PRO measurements in patients with newly diagnosed acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) and examined their associations with OS as well as time to acute care use (TAC). Methods: This retrospective cohort study was conducted on patients with newly diagnosed AML, ALL or MDS between 11/2018-02/2022 who were receiving care at our institution and completed a baseline PRO survey within 30 days of therapy initiation. The PRO survey consisted of a 14-question assessment from the National Cancer Institute's PRO Version of The Common Terminology Criteria for Adverse Events. Each of the symptom domains of the survey are measured on a 1-5 Likert scale. OS was defined as time from therapy initiation to the time of death. TAC was defined as time from therapy initiation to first unplanned acute care visit (emergency room visit or unplanned admission). OS curves were estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional-hazards regression modeling was used to compare the hazards of death and acute care use between groups. Results: 56 patients were included with a median age of 63 years (range 26-79). The cohort consisted of more males, non-Hispanic Whites, and patients that received intensive initial therapy (Table 1). Fatigue was the most frequently reported symptom (n=49, 87.5%, mean score of 2.90/5 (SD 1.30), with a majority reporting mild or no symptoms (score &amp;lt; 4, n=33, 58.9%) and 28.6% (n=16) reporting more severe symptoms (scores &amp;gt; or = 4). Similarly, most patients in this cohort reported mild or no symptoms in terms of anorexia, anxiety, or sadness (Table 1). In terms of OS, univariate models for the presence of fatigue, anorexia, anxiety, or sadness was not associated with significantly higher hazard of death. On multivariate analyses adjusting for age, sex, and treatment intensity, every point increase in reported fatigue severity was associated with a 41% increased hazard of death (HR 1.41,95% CI: 1.03-1.93). When stratified by fatigue severity (&amp;gt; or = 4 severe vs &amp;lt; or = 3 mild/no symptoms), patients reported severe fatigue had an 145% increased hazard of death compared to those reported mild/no fatigue (HR 2.45 (95% CI: 1.07-5.61) (Figure 1). Multivariate analyses for anorexia, anxiety, and sadness were not associated with significant differences after adjusting for the above covariates, respectively. Fourteen (25.0%) and 24 (42.9%) patients in this cohort had at least one unplanned acute care visit within 30 and 90 days from initiation of therapy, respectively. The median TAC for this cohort was 4.15 months (range 0.60-27.20 months). Univariate regression modeling revealed no differences for any of the PROs examined in this study. Similarly, no differences were observed in multivariate analyses for each of the PROs after adjusting for age, sex, and therapy intensity. Conclusions: Fatigue was the most severe and frequently reported baseline symptom among patients with newly diagnosed acute leukemia or MDS. Patients reporting increased fatigue were found to have a higher hazard of death compared to those who did not after adjusting for age, sex, and treatment intensity. The characteristics and PROs examined in this study were not associated with TAC or predictive of acute care use at different time points from therapy initiation. Future work is needed to understand how PRO data can be used to identify higher-risk patients prior to treatment initiation.

METASTASES-01 OUTCOME OF BRAIN METASTASES TREATED WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY (GKSR): COHORT RETROSPECTIVE STUDY ON 205 CASES

Abstract BACKGROUND Brain metastases (BMs) are the most common expansive intracranial lesions in adults. Approximately 50% of patients diagnosed with new brain metastases have more than one brain metastasis at the time of diagnosis. OBJECTIVE We report our experience of brain metastases treated with GKSR and evaluate the outcome. METHODS Patients treated by Gamma Knife stereotactic radiosurgery (GKSR) in our institution between 2008 and 2021 for BM were recorded retrospectively. RESULTS A total of 205 patients (56.6% females) were included, with a median age of 59 (25-83) years old. Breast (n=85, 42.5%) and lung (n=76, 38%) were the common original locations for the primary tumors (Table 1). There were 103 patients (50.3%) with single BM and 102 patients (49.7%) with multiple BM⩾2. The median number of multiple BM treated was 4 (2-43). The overall mean survival time was 6.00(95% CI, 5.07-6.93) months for all BM. The median percentage of tumor control after radiosurgery treatment was 65% (20-99) over the median follow-up time of 6.00(3-84) months. In the overall population, the 1-year OS rate was 37.55%, the 2-year OS rate was 25.12%, and the 5-year OS was 18.51%. The mean survival time among patients with BM was higher in those with multiple BM than those with single BM ([10 (95%CI 6.67-13.33) months vs 5(4.21-5.70) months, P (0.03)]). Retreatment, tumor stability (control), and progression influence the overall survival of BM, whether single or multiple (P&amp;lt;0.001). CONCLUSION Stereotaxic Radiosurgery provides good results in terms of Overall survival and better Quality of Life for BM, whether single or multiple. Stability and retreatment influenced the overall survival of BM.