Analysis Of Survival Outcomes Research Articles

The Prognostic Impact of Plasma Cell Chromosome 17 Abnormality Percentage Cut-offs on Patient Outcomes in Multiple Myeloma

Abstract Abnormalities in chromosome 17 encompassing the TP53 locus [deletion of the small arm {del (17p)} and monosomy 17] as identified by fluorescent in-situ hybridization (FISH), are a well-established adverse prognostic factor in multiple myeloma (MM). Previous research suggested that higher percentages of these chromosome 17 abnormalities correlate with worse prognoses, proposing various cutoff points to assess this relationship, ranging between 50-60%. Of note, these studies employed extensive plasma cell enrichment protocols and often included only cases with high plasma cell percentages (70-90%). Our study aims to investigate the relationship between the percentage of plasma cells with chromosome 17 abnormalities and patient outcomes at the time of acquisition of the abnormality, scrutinizing various cut-off points for prognostic significance. We retrospectively reviewed 339 MM patients at our institution, including newly diagnosed and relapsed cases, examining chromosome 17 abnormality levels identified by FISH on bone marrow specimens. After CD138 magnetic bead enrichment, 50 nuclei were scored for these abnormalities and the percentage calculated. It is important to note that the precise percentage of plasma cells in the sample was not quantified. We analyzed survival outcomes across different percentage cut-off points (20%, 40%, 50%, 55%, 60%, and 80%) using Kaplan Meier analysis and log-rank tests. Significant differences in median survival were noted at the 40% and 50% cut-offs. Patients with >40% chromosome 17 abnormalities showed a median survival of 17.5 months compared to 25.8 months for those with ≤40% (p<0.05), an absolute difference of 8.3 months. Similarly, the >50% group had a median survival of 19.4 months versus 24.3 months in the ≤50% group (p<0.05), with an absolute difference of 4.9 months. However, these differences, while statistically significant, may not be clinically substantial. Furthermore, a 55% cut-off did not yield a significant survival difference (23.5 months vs. 19.8 months for ≤55% and >55% groups, p>0.05) in our cohort. Our findings confirm some prognostic value of chromosome 17 abnormality levels in MM but suggest that the absolute differences in median survival at certain cut-offs, based on the test as performed in our laboratory, might not be clinically impactful. This may be due to differences in the proportion of non-plasma cells within the samples being scored, resulting in ambiguity when interpreting FISH results. Future research should aim to improve the consistency of plasma cell enrichment, develop approaches to score only plasma cells, establish risk-specific cut-offs, and explore the relationship between chromosome 17 abnormality levels, treatment response, and overall significance. The study raises important questions about the necessity of stratifying patients based on chromosome 17 abnormality levels versus simply detecting their presence for prognostic assessment.

Analysis of 2-Year Survival Outcomes of Japanese Older Populations on Hemodiafiltration: A Propensity Score-Matched Study Based on Insurance Claims Data

Despite the lack of evidence that suggests hemodiafiltration (HDF) offers a better survival outcome than standard hemodialysis (HD), the number of patients initiating HDF in Japan continues to rise. This study examined the temporal change in the number of HDF incidents, evaluated factors associated with all-cause mortality, and compared the mortality risk and survival time of patients on HDF with patients receiving standard HD in three sets of 2-year cohorts. The primary analyses included the insurance claims data of 460 HDF patients and propensity score-matched 903 standard HD patients who initiated dialysis therapy between 1 April 2012 and 31 March 2018. Patient follow-up was censored at the time of death or the end of the 2-year study period. The number of patients who initiated HDF and the proportion of all-cause mortality cases were evaluated. Additionally, the survival outcomes between propensity score-matched HDF and standard HD patient groups were compared throughout cohorts. The number of HDF patients increased throughout cohorts, but the proportions of mortality cases across cohorts slowly decreased. Adjusting for all study covariates, we observed that HDF patients had a lower mortality risk and longer survival time than patients on standard HD. This study supports the notion that HDF lowers all-cause mortality compared with standard HD in an incident dialysis population in Fukuoka Prefecture, Japan.

Early versus late response to PD-1-based immunotherapy in metastatic melanoma

BackgroundImmune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort. MethodsPatients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR). ResultsOf 522 patients, 8.2 % were EarlyR (n = 43), 19.0 % were LateR (n = 99), 37.0 % had a SD (n = 193) and 35.8 % were NonR (n = 187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95 %-CI=1.14–3.46, p = 0.015), and normal serum CRP (RR=1.59, 95 %-CI=0.93–2.70, p = 0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95 % CI 19.1; NR) and 47.8 months (95 %-CI 36.9; NR) for EarlyR, NR (95 %-CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95 %-CI 1.9; 2.1) and 6.1 months (95 %-CI 4.6; 8.8) for NonR patients. ConclusionLess than 10 % of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.

Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure

EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant subsequent treatment. For this study, we aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) among advanced EGFR-mutant NSCLC patients receiving platinum-pemetrexed after progression on EGFR-TKIs. Our analysis specifically focuses on 1st-line treatments limited to 1st- or 2nd-generation EGFR-TKIs, while not restricting later-line treatments involving osimertinib prior to chemotherapy. From 2012 to 2017, 363 patients who received first-line treatment with first- or second-generation EGFR-TKIs, including gefitinib, erlotinib, and afatinib were enrolled. Some patients received different EGFR-TKIs, including osimertinib, as later-line treatment before platinum-pemetrexed. Median OS from the initiation of platinum-pemetrexed was 22.0 months and median PFS with platinum-pemetrexed was 6.2 months. In the multivariate Cox model, we identified three independent prognostic factors for better OS: postoperative recurrence (HR: 0.34, p=0.004), first-line EGFR-TKI PFS ≥12 months (HR: 0.54, p=0.002), and osimertinib treatment after platinum-pemetrexed (HR: 0.56, p=0.005) while BMI <18.5 indicated poor prognosis (HR:1.76, p=0.049). No statistically significant independent prognostic factors for PFS were found. Receiving osimertinib before platinum-pemetrexed treatment did not impact PFS with platinum-pemetrexed treatment (HR: 1.11, p=0.64). Postoperative recurrence, first-line EGFR-TKI PFS ≥12 months and osimertinib treatment after platinum-pemetrexed predicted better OS, while BMI <18.5 predicted worse OS. Osimertinib treatment before platinum-pemetrexed treatment did not affect the efficacy of platinum-pemetrexed.

Surgical resection of glioblastoma in the very elderly: An analysis of survival outcomes using the surveillance, epidemiology, and end results database

ObjectivePatients with glioblastoma (GBM) often undergo surgery to prolong survival. However, the use of surgery, and more specifically achieving gross total resection (GTR), in patients >80 years old has yet to be fully assessed. Using the Surveillance, Epidemiology, and End Results (SEER) database, we aim to assess the efficacy of surgical resection, radiotherapy (RT) and chemotherapy (CT) on overall survival (OS) in very elderly GBM patients compared to elderly counterparts (age 65–79 years). MethodsThe SEER database was queried for all patients >65 years old with GBM (2000–2020). Patients not undergoing surgery or biopsy were excluded. Patients were stratified by age, and demographic relationships were assessed with chi-squared testing for categorical variables. Bivariable models were created using Kaplan-Meier survival estimates. All significant variables from bivariable analysis were included on multivariable Cox survival regression models to determine independent associations between clinical variables and OS. ResultsA total of 27,090 operative GBM patients were identified; 1868 patients (15.92 %) were very elderly and 10,092 patients (84.38 %) were elderly. Very elderly patients were less likely to undergo GTR (28 % vs 35 %, p<0.001), RT (59 % vs 78 %, p<0.001) and CT (40 % vs 66 %, p<0.001). In multivariable Cox regression analysis, very elderly patients who achieved GTR (HR=.696, p<0.001), received RT (HR=0.583, p<0.001) and underwent CT (HR=0.4197, p<0.001) had significantly improved OS compared to very elderly patients that did not undergo these treatment options. ConclusionCurrently, very elderly GBM patients undergo lower rates of aggressive surgery, RT and CT. However, very elderly patients that undergo surgery, RT and CT may have a survival advantage. These treatments should be considered as potential options for this patient population.

Proton therapy for intracranial meningioma: a single-institution retrospective analysis of efficacy, survival and toxicity outcomes.

To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.

MASH: MEDIATION ANALYSIS OF SURVIVAL OUTCOME AND HIGH-DIMENSIONAL OMICS MEDIATORS WITH APPLICATION TO COMPLEX DISEASES.

Environmental exposures such as cigarette smoking influence health outcomes through intermediate molecular phenotypes, such as the methylome, transcriptome, and metabolome. Mediation analysis is a useful tool for investigating the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposures and health outcomes. However, little work has been done on mediation analysis when the mediators are high-dimensional and the outcome is a survival endpoint, and none of it has provided a robust measure of total mediation effect. To this end, we propose an estimation procedure for Mediation Analysis of Survival outcome and High-dimensional omics mediators (MASH) based on sure independence screening for putative mediator variable selection and a second-moment-based measure of total mediation effect for survival data analogous to the measure in a linear model. Extensive simulations showed good performance of MASH in estimating the total mediation effect and identifying true mediators. By applying MASH to the metabolomics data of 1919 subjects in the Framingham Heart Study, we identified five metabolites as mediators of the effect of cigarette smoking on coronary heart disease risk (total mediation effect, 51.1%) and two metabolites as mediators between smoking and risk of cancer (total mediation effect, 50.7%). Application of MASH to a diffuse large B-cell lymphoma genomics data set identified copy-number variations for eight genes as mediators between the baseline International Prognostic Index score and overall survival.

Survival outcomes post radical gastrectomy and D2 lymphadenectomy: Real-world evidence from a tertiary care cancer center.

e16075 Background: Radical gastrectomy and D2 lymphadenectomy (RGD2) are pivotal therapeutic strategies in gastric cancer that enable more accurate staging and offer the potential for a cure. Perioperative systemic therapy compared to surgery alone can improve survival in resectable gastric cancer. In the present analysis we analyzed survival outcomes in patients undergoing RGD2. Methods: This retrospective analysis included a consecutive series of patients who had undergone RGD2 at our hospital between Jan'17 to Dec'22. The primary objective was event free survival (EFS) with "Event" defined as a local/distant recurrence, death from any cause and being "lost to follow-up(LTFU)" for &gt; 18 months since the last followup. Secondary objectives include overall survival (OS), pathological complete response (pCR), safety and tolerability of NACT and ACT. For the study protocol, "completion of planned chemotherapy" (CPCT) is defined as 6 - 8 cycles of FLOT/CAPEOX or 5 - 6 cycles of EOX/DOX/CIS5FU delivered as per the treating physician’s discretion as neoadjuvant (NACT) or adjuvant (ACT) chemotherapy. Results: A total of 207 patients had undergone RGD2 in the study period. The mean age of the cohort is 57.3 yrs (range 28 to 87). At the data cut-off time (14th Oct'23) and at the median follow-up period of 45.8 mths, 120 events had occurred (72 disease recurrence, 29 dead and 19 LTFU) and the median EFS for the entire cohort was 28.0 mths (CI 20.1 - 36.0). In the univariate analysis, EFS was significantly improved in those who had received NACT, ACT, attained CPCT, early pathological stage, absence of LVI or PNI, and negative surgical margins (P &lt; 0.05). In Cox-regression analyses, factors that remained significant for improved EFS were CPCT(HR 0.53, CI 0.33 – 0.83, p 0.007), absence of PNI(HR 0.55, CI 0.34 - 0.90, p 0.016), early pathological stage (HR 0.51, CI 0.29 – 0.88, p 0.016), and margin-negative status(HR 0.38, CI 0.18 – 0.81, p 0.013). For the OS analyses, patients lost to follow-up at the data cut-off time (25/207) were excluded. At a median follow-up of 43.9 mths, mOS for the analyzed cohort was 38.8 mths (CI 28.3 - 49.27). Factors for improved mOS in univariate analyses were CPCT, early pathological stage, negative LVI, PNI, margin, and well-differentiated histology (P &lt; 0.05). In Cox-regression analyses, factors significant for improved OS were negative margin(HR 0.42, CI 0.19 – 0.91, p 0.028), CPCT (HR 0.54 CI 0.32 – 0.93, p 0.026), and early pathological stage (HR 0.30 CI 0.16 – 0.58, p 0.000). For those who received NACT, pCR was 12.1% (20.5% for FLOT). Grade 3 &amp; 4 toxicities, and significant weight loss were noted similarly among those receiving NACT (19.6% &amp; 46.7%) and ACT (17.6% &amp; 49%). Conclusions: There is improved survival in those completing the planned systemic therapy and histological markers of involved margins, PNI and advanced pathological stage negatively impact the survival post RGD2.

Treatment outcomes of brain metastasis from primary renal cell carcinoma in United States: A National Cancer Database analysis.

4561 Background: The advent of stereotactic radiosurgery (SRS) in treatment of brain metastasis (BM) has improved both clinical outcomes and survival in patients with BM. Recent studies suggest that immunotherapy presents a promising potential in the treatment of patients with BM. However, data regarding the effectiveness of combining SRS with immunotherapy for BM in metastatic renal cell carcinoma (RCC) remain largely unknown. We aim to delineate the impact of various treatment therapies including combination therapy for treatment of RCCBM. Methods: We queried the National Cancer Database (NCDB) to include patients with BM from mRCC from 2004 to 2020. We divided the patients into groups based on the treatment they received. Resultantly, 5 different treatment groups i.e., WRBT± immunotherapy, SRS± immunotherapy and immunotherapy alone were identified. We excluded patients with unknown treatment status. We analyzed survival outcomes using the Kaplan-Meier analysis and compared the effect of treatment modalities on survival with the log-rank test. Results: The NCDB yielded 6,446 patients diagnosed with BM from mRCC. In eligible cases, the median age was 63 years (range: 19-90+ years), 69.2% were male, 86.8% were White, 7.9% were Black, 41.9% had Medicare as primary payor, 27.7% had annual income &gt;$74,063, 79.3% belonged from metropolitan areas, 39.6% were treated at academic/research program, 68.3% had Charlson-Deyo score of 0, 44.6% had an unknown grade of the primary RCC. 1,705 (43.44%) patients who were given WBRT had a median overall survival (OS) of 5.65 months, 427 (10.88%) patients were treated with SRT + immunotherapy had an OS of 19.0 months, 987 (25.15%) patients who underwent SRT only had an OS of 9.7 months, 431 (10.98%) patients who received immunotherapy only showed an OS of 12.9 months, and 375 (9.55%) patients who underwent WBRT + immunotherapy had an OS of 12.78 months (log-rank p &lt;0.001). Conclusions: This national database analysis reveals that the combination of SRS with immunotherapy significantly increases the OS in RCCBM compared to immunotherapy, WBRT, or combination of WRBT and immunotherapy. Further prospective studies are warranted to confirm these findings. [Table: see text]

Survival outcomes after autologous stem cell transplantation in T follicular helper type lymphoma.

7073 Background: T follicular helper (TfH)-type lymphoma is the most common subtype of peripheral T-cell lymphoma (PTCL). TfH lymphoma consists of angioimmunoblastic T-cell lymphoma (AITL), PTCL-TfH and Follicular T cell lymphoma. Most patients receive first-line treatment with anthracycline-based chemotherapy regimens with a potential role for consolidation with autologous stem cell transplantation (ASCT). In this study we analyzed survival outcomes in TfH lymphoma. Methods: This is an IRB approved retrospective analysis of patients with TfH lymphoma followed between 1997–2023 at the MD Anderson Cancer Center. Demographics, treatment history, response and survival outcomes were collected and analyzed. Next-generation sequencing (NGS) data was collected from a panel of 162 cancer-related genes. Survival analysis was performed with Kaplan Meier curves and comparisons were made with log-rank tests. Results: Of the 218 patients with TfH lymphoma for whom information was known about prior history of ASCT, 84 (39%) underwent ASCT (Table). At the time of diagnosis, the majority of patients had advanced stage disease (92% with stage III or IV) and elevated LDH (89%). NGS testing was available from 31 patients and the genes with recurrent somatic mutations identified were TET2 (65% patients), DNMT3A (29%), RHOA (13%), IDH2 (10%), PLCG1 (10%), TP53 (10%), ATM (6%), CCR7 (6%), JAK3 (6%) and STAT3 (6%). The three most common first-line treatments were CHOP (37%) followed by CHOEP (14%) and combination of brentuximab with either CHP or CHEP (13%). Patients who received ASCT were significantly younger (Table). The median overall survival (OS) for the cohort was 40.3 months with median progression-free survival (PFS) after first treatment of 12.5 months. Patients who received ASCT had a significantly higher overall survival (log-rank test p-value &lt; 0.01) compared to those who did not receive ASCT. Conclusions: This retrospective analysis of a large single institution cohort of patients with TfH lymphoma found significantly improved OS in those who underwent ASCT compared to those who did not. Given the sizeable proportion of patients who are transplant-ineligible due to age or comorbidities, there is a need for newer consolidation approaches for TfH lymphoma. [Table: see text]

Comparative efficacy of six programmed cell death protein-1 inhibitors in first-line treatment for advanced non-small cell lung cancer: A retrospective cohort study.

e14702 Background: All six programmed cell death-1 (PD-1) inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) have been used as first-line therapy in Chinese patients with advanced non-small cell lung cancer (NSCLC), but the comparative efficacy of these different drugs remains unclear. Methods: Retrospective collection of patient data from the First, Third, and Fifth Medical Centers of the Chinese PLA General Hospital who received PD-1 inhibitors (monotherapy or combination therapy) from June 2015 to April 2023. Analysis of patient clinical characteristics, treatment response, and survival outcomes was conducted, with the primary endpoints being overall survival (OS) and progression-free survival (PFS). Secondary endpoints include objective response rate (ORR) and disease control rate (DCR). Results: 913 patients were included and divided into 6 groups: nivolumab (123, 13.5%), pembrolizumab (421, 46.1%), sintilimab (239, 26.1%), tislelizumab (64, 7.0%), toripalimab (39, 4.3%), and camrelizumab (27, 3.0%). Median PFS was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and median OS was 33.7, 36.1, 32.5, not reached, 30.9, and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. PFS and OS did not differ among the different PD-1 inhibitor groups (all P&gt;0.05). There were differences in ORR among the different PD-1 inhibitors (P&lt;0.05), but no differences in DCR (P&gt;0.05). Conclusions: Nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab exhibit similar efficacy in first-line treatment for patients with advanced NSCLC.

A single-center retrospective analysis of allergies and survival outcomes in pancreatic adenocarcinoma.

e16299 Background: Survival from pancreatic adenocarcinoma (PDAC) remains poor, with a 5 year survival of 12.5%. A prior 2010 epidemiological study done at Memorial Sloan Kettering Cancer Center (MSKCC) found an association between self-reported allergies and improved survival in PDAC patients. In this retrospective study, we analyzed self-reported allergies and outcomes in both resected and unresected PDAC patients. Methods: Data including allergy status and clinical information were collected from an ongoing PDAC registry study at MSKCC. 1389 eligible PDAC patients were approached and 917 were enrolled between April 2004 and November 2017. 874 patients were included in our overall survival (OS) analysis using Kaplan-Meier methods. 43 patients were excluded due insufficient data or loss to follow up. Cox proportional hazards models were used to adjust for covariates. Results: Of the 874 patients analyzed, mean age at diagnosis was 63.5 years (standard deviation: 11.4), 52% were male, and race was 87% white, 6% black, 4% Asian, and 3% other race. 32.3% had surgery and 85% received chemotherapy. Median overall survival (OS) was 32.8 vs. 27.7 months [Hazard Ratio (HR) 0.95, p = 0.73] and 12.5 vs. 11.2 months [HR 1.04, p = 0.66] in for PDAC patients with allergies compared to those without in the resected and unresected cohorts, respectively. Advanced stage was associated with worse outcomes in both groups. Chemotherapy was significantly associated with improved survival only in the unresected group (HR 0.48, 95% CI 0.30-0.78, p = 0.030). Other established PDAC risk factors were also analyzed. Smoking history, diabetes, and family history were not associated with survival. Only obesity was significantly associated with worse outcomes in the unresected group (HR 1.3, 95% CI 1.01-1.67, p = 0.04). Conclusions: Contrary to previous findings, self-reported allergies were not significantly associated with improved survival in PDAC. In atopic patients, T helper type 2 cells are upregulated with allergen exposure and produce more IgE. Tumor-specific IgE has shown protective benefits in preclinical models but can be downregulated in the tumor microenvironment in PDAC. Further studies are needed to explore the relationship between allergies and PDAC and understand potential aspects of the immune system that can be harnessed to improve outcomes. One study limitation was that allergies were self-reported and not confirmed with allergy testing. We were also able to redemonstrate worse outcomes with more advanced stages and the benefit of chemo in the advanced setting. Further studies are needed to explore the mechanisms behind obesity and PDAC. [Table: see text]

Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery followed by adjuvant docetaxel and S-1 for patients with large type 3 or type 4 gastric cancer: Short-term outcomes of the phase II OGSG1902 trial.

4031 Background: Patients with large type 3 (≥8 cm) or type 4 gastric cancer (GC) face a dismal prognosis, necessitating the development of multidisciplinary treatment, including neoadjuvant chemotherapy. We present the short-term results from the OGSG1902 (jRCTs051190060) trial, where resectable large type 3 or type 4 GC patients were treated with neoadjuvant docetaxel (DTX)/oxaliplatin (L-OHP)/S-1 (DOS) plus surgery and adjuvant DTX/S-1 (DS) therapy. Methods: Untreated large type 3 or type 4 GC patients without distant metastasis other than positive peritoneal lavage cytology (CY), aged 20-80 years, and with ECOG PS 0-1, were enrolled. Patients received three cycles of DTX (40 mg/m2, day1) + L-OHP (100 mg/m2, day1) + S-1 (80 mg/m2, day1-14) every 3 weeks, followed by gastrectomy with D2 lymph node dissection and 1-year DS therapy. The primary end point was the 3-year progression-free survival (PFS) rate. The secondary end points included PFS time, overall survival time, pathological response rate, response rate according to RECIST version 1.1, neoadjuvant chemotherapy completion rate, R0 resection rate, protocol completion rate, CY negative conversion rate, adverse event occurrence rate, and nutritional evaluation. Results: Forty-eight patients (pts) were enrolled from 2019 to 2022. The neoadjuvant chemotherapy completion rate was 91.7%, pathological response rate (≥Grade 1b) was 66.7%, response rate according to RECIST version1.1 for 10 pts with measurable lesions was 50.0%, CY negative conversion rate for nine CY positive pts was 88.9%, R0 resection rate was 89.6%, and the protocol completion rate was 45.8%. Adverse events (≥CTCAE Grade 3) during neoadjuvant DOS included neutropenia in 18 pts (38%), febrile neutropenia in one pt (2%), nausea in five pts (10%), diarrhea in six pts (13%), and anorexia in 18 pts (38%). Gastrectomy was performed in 47 pts [total/distal gastrectomy: 32(68%)/15(32%)]. Major postoperative complication (≥Clavien-Dindo Grade IIIa) was observed in one pt (2%), including pleural infection. Adverse events (≥CTCAE Grade 3) in 39 patients receiving adjuvant DS therapy included neutropenia in 16 pts (41%), anemia in five pts (13%), nausea in one pt (3%), diarrhea in two pts (5%), anorexia in nine pts (23%), fatigue in three pts (8%), and febrile neutropenia in four pts (10%). No treatment-related deaths were observed. Conclusions: Neoadjuvant DOS therapy for large type 3 or type 4 GC demonstrates promising efficacy with high histological response and acceptable adverse events. Future analysis of survival outcomes is planned. Clinical trial information: jRCTs051190060 .

The efficacy and safety of trastuzumab biosimilar HLX02 compared with reference trastuzumab plus pertuzumab in combination with chemotherapy as the first-line treatment for HER2 positive metastatic breast cancer: A real-world study in China.

e13016 Background: Dual-targeted anti-HER2 therapy with trastuzumab (H) and pertuzumab (P) significantly improves outcomes in HER2-positive breast cancer and has become the first-line standard treatment for patients with advanced HER2-positive breast cancer in China in 2019 based on the results of the CLEOPATRA and PUFFIN study. HLX02 (Zercepac) was the first trastuzumab biosimilar manufactured in China. Here, we present the first real-world comparison of HLX02 versus reference trastuzumab (RTZ) and pertuzumab with chemotherapy as the first-line treatment for HER2-positive metastatic China.Between January 2019 and August 2023, 121 patients with HER2-positive MBC patients were enrolled at Beijing Cancer Hospital in China. These patients received HLX02 or RTZ in combination with pertuzumab and various chemotherapies as first-line treatment. We retrospectively analyzed survival outcomes, efficacy, and adverse events. Methods: Between January 2019 and August 2023, 121 patients with HER2-positive MBC patients were enrolled at Beijing Cancer Hospital in China. These patients received HLX02 or RTZ in combination with pertuzumab and various chemotherapies as first-line treatment. We retrospectively analyzed survival outcomes, efficacy, and adverse events. Results: Both groups, 68 received RTZ and 53 received HLX02, showed similar characteristics of age, disease status (de novo or recurrent), metastatic sites (visceral or non-visceral), and treatment history. A total of 118 (97.5%) received trastuzumab plus pertuzumab combined with chemotherapy as the first-line palliative therapy, with a median number of 6 cycles in each group. Taxanes were the most commonly used chemotherapy regimen in both groups (91.2 vs. 92.5%), including nab-paclitaxel (44.1 vs. 45.3%), docetaxel (41.2 vs. 17.0%), paclitaxel (5.9 vs. 30.2%). With a median follow-up of 15.0 months (range 1.0 - 58.0), the results showed no significant difference in PFS between the RTZ and HLX02 arms (median PFS: 22.0 vs. 19.0 months, p=0.900). Additionally, the efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), and safety profiles did not show significant differences between the two groups. Among 121 patients, 20 patients (16.5%) experienced CNS progression. For these patients, the median time from the first-line therapy to the CNS progression was 15.0 months (95% CI 12.8 - 17.2). Conclusions: The real-world data suggest similar efficacy and safety of HLX02 and RTZ plus pertuzumab with different chemotherapy regimens as the first-line treatment for patients with HER2-positive advanced breast cancer patients in China. Overall, the PFS was consistent with the CLEOPATRA trial in both groups, and there was no new safety signal.

Mutation patterns and prognostic implications in acute myeloid leukemia with chromosomal 7 deletions.

6547 Background: Chromosomal 7 deletions (del7/7q) are the most common adverse cytogenetic event in acute myeloid leukemia and are associated with high rate of relapse. We analyzed gene mutation profiles in del7/7q AML patients who relapsed after initial remission to identify molecular patterns associated with clinical outcomes. Methods: Out of 351 newly diagnosed AML patients with del7/7q, 115 (32%) achieved complete remission after first-line treatment between 2012-2023. Of the 115 patients, 77 (67%) patients relapsed during the study follow-up. Kaplan-Meier and Cox regression were used to analyze survival outcomes. Next-generation sequencing was performed on a targeted panel of 81 genes for 59 patients who relapsed on bone marrow samples at diagnosis and relapse for paired analysis. Results: The median age of the 115 patients at diagnosis was 74 (41-93). Thirty-four patients (30%) received intensive treatment. With 30.8-month median follow-up, the median overall survival (OS) was 10.4 months, with improved survival in patients without TP53 mutation (13.04 vs. 8.6 months, p=0.005) or complex karyotype (12.4 vs. 8.6 months, p=0.03). The median duration of response for the 77 patients who relapsed was 5 months (2-7). Allo-HSCT significantly improved median OS (not reached vs. 8.5 months, P=6e-06), and was identified as the key variable impacting survival in multivariate analysis. TP53 was the most commonly mutated gene at diagnosis (67%) and relapse (71%). Mutations in CBLC and KDM6A were cleared after induction therapy, while BCOR and BCORL1 were commonly acquired at relapse (Table). At diagnosis, a lower co-mutation burden was observed in TP53 mutant patients as compared with wild type (average 1.84 vs. 3.65 respectively, p=0.0001). Patients with mutated TP53 and coexisting mutations in GATA2, NF1, BCORL1, or RUNX1 at diagnosis had shorter relapse free survival (RFS, 2 vs. 5 months, p=0.01) and OS (7.2 vs. 10.4 months, p=0.01) compared to patients with solely mutated TP53 (HR 2.2; 95% CI 1.2-4; P = 0.004). Allo-HSCT significantly improved the OS in patients with mutated TP53 (13 vs. 8 months, p=0.01). Conclusions: Mutated TP53 clones persist from diagnosis to relapse in patients with del7/7q AML. In patients with mutated TP53, co-occurring mutations in GATA2, NF1, BCORL1or RUNX1 at diagnosis were linked to a shorter RFS and indicate a particularly high-risk subgroup that require proceeding to allo-HSCT in CR1 without delay. [Table: see text]

Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Survival Outcomes in Stage IV Gastric Cancer Patients with Krukenberg Tumors: A Systematic Review and Meta Analysis.

Stage IV gastric cancer patients with Krukenberg tumors typically exhibit poor survival outcomes, often less than 2years. The management of this tumor subgroup remains non-standardized, and the impact of oophorectomy on survival remains uncertain. In this study, we systematically analyzed survival outcomes among gastric cancer patients with ovarian metastases who underwent standard chemotherapy, surgical resection of ovarian metastases, or combined chemotherapy and surgery. We conducted a systematic reviewand meta-analysis of randomized controlled trials and observational studies retrieved from MEDLINE (PubMed), Embase, and the Cochrane Library until January 25, 2024,applying the Boolean logic. Participants included individuals with pathologically and radiologically confirmed ovarian metastasis or clinically symptomatic cases with imaging evidence. Statistical analyses were performed using R (v.4.3.2., Vienna). The study was registered with PROSPERO(ID-CRD42023488373). A total of 1502 patients from 17 retrospective studies were pooled for analysis of overall survival (OS) outcomes. The OS in the standard chemotherapy cohort, as determined by the random effects model, was 6.708months (95% CI 3.867 to 9.548; P<0.0001), with non-significant heterogeneity (I2 = 5.5%). In the surgical resection cohort, OS was 12.786months (95% CI 6.9 to 18.671; P<0.0001), with low heterogeneity (I2 = 0%). In the combined chemotherapy and surgical resection cohort, OS was 16.228months (95% CI 12.254 to 20.202), with insignificant heterogeneity (I2 = 0%). This meta-analysis offerskey insights into survival outcomes associated with different therapeutic modalities in gastric cancer with Krukenberg metastases. It provides valuable evidence for clinical decision-making and future research directions. While the combined approach of chemotherapy and surgery demonstrates the highest effect size for OS, careful consideration of patient-centric approaches is essential in the oncological care landscape.

Consolidation therapy with autologous stem cell transplantation after remission of induction chemotherapy prolongs the survival of patients with peripheral T-cell lymphoma.

There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL. A total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival. With a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (p<0.003 for OS, p=0.015 for PFS). Subgroup analysis found that patients with high risks benefited more from ASCT. Combination with hemophagocytic lymphohistiocytosis (HLH) (p<0.001), clinical stage more than III (p=0.014), IPI score above 3 (p=0.049), and bone marrow involvement (p=0.010) were the independent prognostic factors significantly associated with worse OS and PFS. Additionally, pegylated liposomal doxorubicin (PLD)-containing chemotherapy regimen could bring a higher overall response rate (ORR) and prolong the survival of patients with PTCL who underwent ASCT. ASCT may improve the long-term survival of patients with PTCL as consolidation therapy after achieving complete or partial remission of induction treatment, particularly for those with high risks. The chemotherapy regimen containing pegylated liposomal doxorubicin may induce deeper remission than traditional doxorubicin in PTCL. It is crucial to identify the specific groups most likely to benefit from upfront ASCT.

Prediction analysis of TBI 24-h survival outcome based on machine learning

BackgroundTraumatic brain injury (TBI) is the major reason for the death of young people and is well known for its high mortality and morbidity. This paper aim to predict the 24h survival of patients with TBI. MethodsA total of 1224 samples were involved in this analysis, and the clinical indicators involved included age, gender, blood pressure, MGAP and other fields, among which the target variable was “outcome”, which was a binary variable. The methods mainly involved in this paper include data visualization analysis, single factor analysis, feature engineering analysis, random forest model (RF), K-Nearst Neighbors (KNN) model, and so on. Logistic regression model (LR) and deep neural network model (DNN). We will oversample the training set using the SMOTE method because of the very unbalanced labeling of the sample itself. ResultsAlthough the accuracy of all models is very high, the recall rate is relatively low. The DNN model with the best performance only reaches 0.17, and the corresponding AUC is 0.80. After resampling, we find that the recall rate of positive samples of all models has increased a lot, but the AUC of some models has decreased. Finally, the optimal model is LR, whose positive sample recall rate is 0.67 and AUC is 0.82. ConclusionThrough resampling, we obtained that the best model is the RF model, whose recall rate and AUC are the best, and the AUC level is about 0.87, indicating that the accuracy performance of the model is still good.

Abstract 813: Primary cutaneous gamma-delta T-Cell lymphoma in the United States: A nationwide analysis of demographics and survival outcomes among the Hispanic population

Abstract BACKGROUND: Primary Cutaneous Gamma-Delta T-Cell Lymphoma (PCGDTCL) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that, despite comprising &amp;lt;1% of cutaneous lymphomas, has gained recognition in recent years as an entity separate from other rare CTCLs. (LeukemiaPMID 35732829) A 5 year survival of 11% demonstrates a low response to current available therapies. (BloodPMID 30635287, Clin Hematol Int.PMID 35950208) Due to lack of consistency in behavior between CTCLs, there exists a need for studies of demographic, clinical, and survival disparities, including between Hispanics (HI) vs. non-Hispanics (NH). METHODS: Data were analyzed on PCGDTCL patients in the United States reported to the National Cancer Database (NCDB) between 2004-2019. Demographic and treatment characteristics were compared between ethnic groups. Kaplan-Meier and Cox regression analyses were used to compare OS between populations. Multivariate analysis and propensity score matching was performed with adjustment for age, stage, co-morbidity score, and insurance status, type of facility and great circle distance. RESULTS: Among 132 PCGDTCL patients studied (5% HI, 92% NH), the HI group was younger at diagnosis than NH (49.5y vs. 60y) (p=0.384); The majority of HI (50%) was diagnosed between 2010-2012 vs 2017-2019 for NH (45%) (p=0.673). Most of HI and NH were white (67% vs 79%). Private insurance was the most prevalent type in HI (67%) vs government sponsored for NH (49%). The most non-Insured group was NH (3%) vs HI (0%). The most prevalent bracket for Census Median Income (2008-2012) was $63,000+ for both HI (50%) and NH (31%). 17% HI vs 13%. NH had median income &amp;lt;$38,000. For Charlson-Deyo Score (comorbidities score), HI had 0% =/&amp;gt; 2 score, vs NH 6%. NCI-designated comprehensive cancer centers were the most prevalent type of facility providing care for HI (100%) and NH (56%) Survival probability (OS) at 2, 5 and 10y (HI vs NH) were (80% vs 48%), (80% vs 44%), and (80% vs 26%), respectively. Median survival time (MS) was not reached for HI vs 1.9 years for NH. Overall survival (OS) difference favored HI (p=0.13) On multivariate analysis, there was no independent variable associated with better or worse OS. Interestingly, the propensity matched analysis demonstrated significant MS difference between HI vs NH (median not reached vs. 1.35 years). CONCLUSION: There was no significant difference in OS between groups; however, the weighed MS favored the HI cohort, likely in part due to the difference in numbers between cohorts. The drastically low survival in all demographics is consistent with prior studies. These results demonstrate an unmet need for more comprehensive studies with the potential inclusion of correlatives looking at intrinsic biologic characteristics that may offer insight into druggable targets, aiming for improvement in survival outcomes for this rare lymphoma. Citation Format: Katherine Thiel, Rosa White, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque. Primary cutaneous gamma-delta T-Cell lymphoma in the United States: A nationwide analysis of demographics and survival outcomes among the Hispanic population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 813.