Prognostic Factor For PFS Research Articles

Clinical features and outcomes of patients with follicular lymphoma grade 3A: A real-world study in single center.

e19058 Background: Follicular lymphoma (FL) was classified into three grades based on the number of centroblasts (FL1-2, FL3A, and FL3B). Guidelines suggest that FL1-2 should be treated according to the treatment recommendations for classical FL. FL3B is usually treated as diffuse large B-cell lymphoma (DLBCL).There is no consensus yet on the management of FL3A. In order to explore the relationship between clinical features and outcomes of FL3A, we conducted this study. Methods: We conducted a retrospective study of newly diagnosed FL patients who were admitted to our hospital from January 2013 to December 2022. The data were collected from the hospital electronic medical record system, including but not limited to: demographic characteristics, pathological information, clinical features at diagnosis, treatment, and efficacy evaluation. The survival curve was calculated through Kaplan-Meier method and compared with Log Rank test.The prognostic factors of PFS was compared by COX regression analysis. Results: There were 253 FL3A patients admitted, accounting for 27.55% of all FL patients. After screening, a total of 223 FL3A patients were included in this study. Among 223 patients, the male to female ratio was close to 1:1; The median age is 57 years old. At diagnosed, 33 patients in early stage and 190 in advanced stage. Among advanced patients, 144 had no treatment indications according to the GELF criteria. 86.1% (192/223) of patients received systemic treatment, with the majority of rituximab contained regimens. The overall response rate (ORR) was 96%, and 62.9% of patients who responded to chemotherapy received maintenance therapy with CD20 monoclonal antibody. A median follow-up of 41 months, with an estimated 5-year OS of 91.3% and 5-year PFS of 73%. The PFS of advanced FL patients treated with RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was significantly longer than that of non-RCHOP regimen patients (P<0.05). The PFS of patients receiving maintenance treatment was better than that of those not (P<0.05). Conduct prognostic analysis on advanced FL3A patients. Univariate analysis showed that treatment plan selection, maintenance of treatment, PET scan of FDG metabolic maximum uptake value (SUVmax), Ki-67, lactate dehydrogenase (LDH), white blood cell count (WBC), IgA, IgM, all significantly affected PFS; Multivariate analysis shows SUVmax ≥ 15 and platelet count<100 × 109/L and LDH>210U/L are all correlated with poor PFS. Conclusions: This study found that FL3A accounts for 27.55% of all FLs, with a median age of 57 years old and mostly in the advanced stage. FL3A has a long survival period, with a 5-year PFS of 73%. COX regression analysis showed that SUVmax, platelet count, and LDH were all associated with PFS in advanced FL3A patients.Those may explore new clinical prognosis prediction models.

Cerebellum/liver index on baseline 18F-FDG PET/CT to improve prognostication in post-transplant lymphoproliferative disorders: a multicenter retrospective study

BackgroundBesides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses.ResultsA total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0–4.0) and 2.4 (1.3–4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 (p = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS.ConclusionCLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.

Real-World Safety and Outcome of First-Line Pembrolizumab Monotherapy for Metastatic NSCLC with PDL-1 Expression ≥ 50%: A National Italian Multicentric Cohort ("PEMBROREAL" Study).

Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan-Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Clinical Features and Prognostic Factors of Cervical Clear Cell Adenocarcinoma: A Retrospective Analysis of 74 Cases from a Tertiary Hospital.

The retrospective study aimed to analyze the clinical characteristics, primary treatment, and prognosis of cervical clear cell adenocarcinoma in a tertiary referral center. The medical data of cervical clear cell adenocarcinoma patients treated in our institution between 1993 and 2020 were reviewed. Their clinical characteristics and information on treatment and follow-up were collected. Seventy-four cases were included. Six early-stage patients successfully preserved their fertility. Forty-five patients underwent a radical hysterectomy. Patients with pathological risk factors all received adjuvant treatment including chemotherapy, radiotherapy, and chemoradiation. Fifteen patients without risk factors underwent surveillance and five patients received adjuvant chemotherapy for poorly differentiated disease. Twenty cases had radiation for primary treatment. Six of them underwent surgery after chemoradiotherapy, and five had pathological residual disease, including three who had pathological risk factors. The median follow-up interval was 36 months, with a 3-year OS and PFS rate of 82.4% and 81.4%, respectively. No recurrence or death was observed in patients with fertility-sparing treatment. FIGO stage was prognostic factors of PFS (P = .001) and OS(P = .006) and lymph node status was that of PFS (P = .023). FIGO stage and lymph node status were prognostic factors for survival. Fertility-sparing treatment is a safe option for young patients in early stage. Early-stage patients without risk factors may benefit from postoperative surveillance. Occult tumor after chemoradiotherapy is common, and surgical resection is recommended when operable residual disease is detected.

Genetic Markers and Front Line FCR/BR Vs. Rve, Gve and Give Treatment - Outcome Results from the CLL13/GAIA Trial

BACKGROUND: Genomic aberrations, IGHV mutation status and recurrent mutations in genes such as TP53 are established prognostic factors in CLL in the context of chemoimmunotherapy (CIT). For time limited treatment with venetoclax in combination with Rituximab (RVe), Obinutuzumab (GVe) and Obinutuzumab and Ibrutinib (GIVe) the role of these factors is less-well established. METHODS: The phase 3 GAIA/CLL13 trial compared 3 different time-limited venetoclax-based combinations against CIT in fit, treatment-naïve patients with CLL without del(17p) or TP53 mutations detected via Sanger sequencing. Patients were randomized to receive CIT (FCR for patients ≤65y; BR for patients >65y), RVe, GVe or GIVe. Co-primary endpoints were PFS and MRD in peripheral blood at month 15 via 4-colour flow. Genomic aberrations were assessed at enrolment by FISH, IGHV by sequencing with a threshold of 98% homology and mutations via amplicon-based targeted NGS for TP53, NOTCH1, SF3B1, MYD88, KRAS, NRAS, BRAF, EGR2, NFKBIE, RPS15, XPO1 and BIRC3 in 913 of 926 patients (98.6%) of the full trial cohort. RESULTS: The incidences of genomic aberrations based on the hierarchical model were del(11q) 17.5%, +12 16.2%, mono-allelic del(13q) 44.6% and normal karyotype 21.7%. IGHV was unmutated (U-IGHV) in 55.9% and mutated (M-IGHV) in 41.0% of patients (ITT). Subset#2 accounted for 50 patients equally distributed among U-IGHV and M-IGHV. The incidence of gene mutations was SF3B1 22.6%, NOTCH1 20.5% (exon 34 and 3'UTR), NFKBIE 13.6%, BIRC3 11.8%, BRAF/KRAS together 9.6%, XPO1 7.9%, EGR2 5.6%, RPS15 5.5% and MYD88 4.2%. Minor mutations with a variant allele fraction (VAF) of 1.5% to 10% were frequent in BIRC3 and NFKBIE (59.6% and 56.0% of all variants, respectively), while minor mutations in TP53 not previously detected by Sanger sequencing were rare (2.0%). Undetectable MRD (uMRD) was not associated with any genetic subgroup in the pooled analysis of GVe/RVe/GIVe. Single arm analysis revealed NOTCH1 mutation associated with lower rate of uMRD with GVe (74.4% vs 88.6%, p=0.02) and higher uMRD rate in +12 cases with RVe (73.5% vs. 52.2% in del(13q), p=0.03). With CIT a significantly lower uMRD rate was found in U-IGHV (42.0% vs. 66.3% in M-IGHV, p<0.01) and del(11q) (39.0% vs. 58.4% in del(13q), p=0.04) while mutated MYD88 associated with a higher uMRD rate (92.3% vs 50.2%, p=0.02). At a median follow-up of 38.8 months, there were 188 PFS events in the ITT population. For CIT U-IGHV (HR 4.47, p<0.01), del(11q) (HR 2.68, p<0.01) and mutated NOTCH1 with VAF>10% (HR 2.01, p=0.01) associated significantly with shorter PFS in univariate analysis. In the combined analysis for RVe/GVe/GIVe U-IGHV (HR 2.29, p<0.01), mutations in NOTCH1 (HR 1.76, p<0.01) and BRAF/RAS (HR 2.45, p<0.01) were associated with significantly shorter PFS and del(13q) (HR 0.67, p=0.03) with longer PFS. A separate analysis for each venetoclax arm identified mutated NOTCH1 (GVe: HR 2.2 p=0.04 and GIVe: HR 2.2, p=0.05), BIRC3 (GIVe: HR 3.6 p<0.01), BRAF/KRAS/NRAS (RVe: HR 3.6, p<0.01 and GIVe: HR 3.7, p<0.01) NFKBIE (GVe: HR 3.0, p<0.01), del(13q) (GVe: HR 0.4, p=0.01) and U-IGHV (GVe: HR 2.6, p=0.03 and GIVe: HR 2.7, p=0.03) as prognostic factors for PFS. Subset 2 was not associated with shorter PFS, also not among M-IGHV patients. In multivariable analysis including all clinical, laboratory and genetic markers significantly associated with PFS, treatment with GVe and GIVe were independent favorable factors (HR 0.42 and 0.33, respectively, both p<0.01) and U-IGHV (HR 2.43, p<0.01), and mutated NOTCH1 (HR 1.46, p=0.03) were confirmed as independent prognostic factors. In a separate multivariable analysis only for CIT, del(11q) (HR 1.89, p=0.03), U-IGHV (HR 3.08, p<0.01), and mutated NOTCH1 >10% VAF (HR 2.12, p=0.01) were verified as independent adverse genetic risk factors. For the combined RVe/GVe/GIVe group, mutated BRAF/RAS (HR 1.87, p=0.01), U-IGHV (HR 1.85, p<0.01), and mutated NOTCH1 (HR 1.54, p=0.04) were confirmed as independent adverse prognostic factors. CONCLUSIONS: Early results from CLL13/GAIA show association of gene mutations with lower rate for uMRD and shorter PFS after CIT or venetoclax-based therapy. IGHV and NOTCH1 mutation retain their prognostic role with both treatment types. Mutations in the RAF/RAS pathway (9.6% overall) were associated with shorter PFS with venetoclax-based therapy, while with CIT an impact on outcome is not apparent at present. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

First-line PD-1 inhibitors immunotherapy and chemotherapy combined with or without radiotherapy for patients with advanced non-small cell lung cancer.

2606 Background: Immunochemotherapy has become a standard first-line regimen for advanced non-small-cell lung cancer (NSCLC). Several studies showed the synergistic effects of immunotherapy and radiotherapy on local and abscopal tumour control. But the data of first-line immunochemotherapy combined with radiotherapy for the advanced NSCLC is still scarce. Methods: Patients with advanced NSCLC receiving first-line PD-1 inhibitors immunotherapy plus chemotherapy in a single center were retrospectively analyzed in this study. They were divided into two groups according to whether they had received radiotherapy. The efficacy and safety of first-line immunochemotherapy combined with radiotherapy (ICRT group) and immunochemotherapy alone (ICT group) were investigated. Results: A total of 135 patients were included; 65 patients received PD-1 inhibitors plus chemotherapy and radiotherapy, while other 70 patients were treated with immunochemotherapy alone. The median interval time between radiotherapy and PD-1 inhibitors immunotherapy was 5 days (range, 0-96 days). The overall response rate (ORR) was 50.8% in the ICRT group and 40.0% in the ICT group, respectively. Patients in the ICRT group achieved significant longer progression-free survival (PFS, median 16.5 vs 10.4 months, P= 0.043) and overall survival (OS, median not reached vs 21.0 months, P= 0.030) compared with those in the ICT group. The addition of radiotherapy was the only prognostic factor for PFS (HR = 0.617, 95%CI: 0.385-0.989, P= 0.045) and OS (HR = 0.512, 95%CI: 0.277-0.947, P= 0.033) by univariate Cox regression analysis. Patients were well tolerated and the overall incidence of adverse events was similar between the ICRT group and ICT group. One patient in ICRT group stopped immunotherapy because of severe immune-associated pneumonia. 3.1% of grade 3-4 radiation-related adverse events were observed. Conclusions: Adding radiotherapy to first-line PD-1 inhibitors immunotherapy and chemotherapy improved outcomes of patients with advanced NSCLC and showed acceptable toxicity. Additional prospective studies exploring the first-line combination of immunochemotherapy and radiotherapy are warranted.

Prognostic and Predictive Factors in Elderly Patients With Glioblastoma: A Single-Center Retrospective Study.

Glioblastoma (GBM) is the most common primary malignant intracranial tumor and the median age at diagnosis is 65 years. However, elderly patients are usually excluded from clinical studies and age is considered as an independent negative prognostic factor for patients with GBM. Therefore, the best treatment method for GBM in elderly patients has remained controversial. Elderly GBM patients (≥ 60 years old) treated between January 2015 and December 2019 were enrolled in this study. Medical records were reviewed retrospectively, and clinicopathological characteristics, treatments, and outcomes were analyzed. A total of 68 patients were included, with a median age of 65.5 years (range: 60–79). The median preoperative Karnofsky performance scale (KPS) score was 90 (range 40–100) and median postoperative KPS score was 80 (range 0–90). Univariate analysis results showed that age, gender, comorbidities, preoperative KPS < 90 and MGMT promoter methylation were not significantly associated with PFS and OS. On the other hand, total resection, postoperative KPS ≥ 80, Ki67 > 25%, and Stupp-protocol treatment were significantly associated with prolonged PFS and OS. Moreover, multivariate analysis found that postoperative KPS ≥ 80, total resection, and Stupp-protocol treatment were prognostic factors for PFS and OS. The findings of this study have suggested that, on the premise of protecting function as much as possible, the more aggressive treatment regimens may prolong survival for elderly patients with GBM. However, further studies, particularly prospective randomized clinical trials, should be conducted to provide more definitive data on the appropriate management of elderly patients, especially for patients with MGMT promoter methylation.

Comparison of clinical behavior between mucinous ovarian carcinoma with infiltrative and expansile invasion and high-grade serous ovarian carcinoma: a retrospective analysis

BackgroundThe aim of this study was to evaluate the clinicopathological factors and prognosis of mucinous carcinoma (MC) with infiltrative invasion, MC with expansile invasion, and high-grade serous carcinoma (HGSC).MethodsCases of MC and HGSC between 1984 and 2019 were identified. The clinicopathological factors and prognosis of MC with infiltrative invasion or expansile invasion and HGSC were retrospectively compared. Although our present study included cases in our previous studies, we extended observational period when analysis was performed. Accordingly, our study added increased cases and survival analysis was newly conducted.ResultsAfter pathological review, 27 cases of MC with infiltrative invasion, 25 cases of MC with expansile invasion, and 219 cases of HGSC were included. MC had a better prognosis in terms of progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than HGSC for all International Federation of Gynecology and Obstetrics (FIGO) stages; however, multivariate analysis did not show statistical differences in PFS and OS. There were no statistically significant differences in PFS and OS for all FIGO stages between MC with infiltrative invasion and HGSC. However, in cases with FIGO stages II to IV, MC with infiltrative invasion had worse PFS (p < 0.01) and OS (p < 0.01) than HGSC. In univariate analysis, MC with infiltrative invasion was a worse prognostic factor for PFS (hazard ratio [HR] 2.83, p < 0.01) and OS (HR 3.83, p < 0.01) than HGSC. Compared with HGSC, MC with expansile invasion had better PFS (p < 0.01) and OS (p < 0.01). Multivariate analysis demonstrated that MC with expansile invasion was a better prognostic factor for PFS (HR 0.17, p < 0.01) and OS (HR 0.18, p = 0.03) than HGSC.ConclusionsCompared to the prognosis of HGSC, that of MC was different according to the invasive pattern and FIGO stage. Therefore, future study may be needed to consider this association.

Improving outcomes in limited-stage de novo CD5+ DLBCL: systemic approaches with consolidative radiation

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis after frontline immunochemotherapy. This retrospective study investigated the effect of consolidative radiation after systemic treatment in newly diagnosed stage I–II de novo CD5+ DLBCL. In this study, 22 patients received consolidative radiotherapy (RT) after immunochemotherapy (chemotherapy + RT group) and 28 patients received chemotherapy alone. Patients who received chemotherapy alone had a significantly shorter PFS and OS than those who received consolidative radiotherapy. The five-year PFS rates for the chemotherapy + RT and chemotherapy alone groups were 75.1% and 40.5%, respectively. The five-year OS rates for the chemotherapy + RT and chemotherapy alone groups were 84.2% and 50.1%, respectively. Even after receiving consolidation radiotherapy, 2/22 (9.1%) patients experienced CNS relapse. Age >60 years and lack of radiotherapy were independent prognostic factors for PFS and OS. Ki-67 (≥80%) was an independent prognostic factor for poor OS. Consolidative radiotherapy might be a good option for stage I-II CD5+ DLBCL, but further investigation is needed.

Combined prognostic value of the SUVmax derived from FDG-PET and the lymphocyte-monocyte ratio in patients with stage IIIB-IV non-small cell lung cancer receiving chemotherapy

BackgroundWe evaluated the prognostic potential of tumor 18F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy.MethodsA total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response.ResultsPatients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001).ConclusionsPre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.

High IL-6 expression in the tumor microenvironment is associated with poor prognosis of patients with extranodal natural / killer T-cell lymphoma (ENKTL)

ABSTRACT Objectives: Extranodal natural/killer T-cell lymphoma (ENKTL) is a rare subtype of T cell non-Hodgkin’s lymphoma. Current clinical prognostic models for ENKTL still have their limitations. Validated prognostic models for ENKTL have not yet been established. Methods: Tumor microenvironment IL-6 was measured by immunohistochemistry in 78 ENKTL patients. Results: Patients with negative IL-6 expression in the tumor microenvironment have a longer PFS (56.0 months vs. 25.6 months, p < 0.001) and OS (96.0 months vs. 43.3 months, p < 0.001). In the multivariate analysis, tumor microenvironment IL-6 [p = 0.048, HR = 1.76(1.00–3.08)] and extranodal involvement [p = 0.001, HR = 2.69(1.50–4.82)] were independent prognostic factors for PFS. Tumor microenvironment IL-6 [p = 0.033, HR = 2.69 (1.08–6.67)], Ann Arbor stage [p = 0.002, HR = 2.77 (1.47–5.23)] and B symptom [p = 0.027, HR = 2.02 (1.08–3.78)] were independent prognostic factors for OS. Expert opinion: A high IL-6 expression was related to poor survival, which may be a valuable biomarker for prognostic evaluation at baseline in ENKTL. These results showed that anti-IL-6R may be a potential targeted therapy for the treatment of advanced or relapsed ENKTL.

Interim PET/CT result is the sole prognostic factor of survival in patients with advanced-stage diffuse large B-cell lymphoma: a subset analysis of a prospective trial

This study aimed to evaluate the prognostic value of interim positron emission tomography (iPET) in diffuse large B-cell lymphoma (DLBCL). Among 53 enrolled patients, 39 had iPET-negative (iPET−) and 14 had iPET-positive (iPET+) scans. The objective response rate was 94.3%. The 3-year progression-free survival was 65.7% and the 3-year overall survival was 79.9%. The iPET− patients had significantly higher 3-year PFS rate (78.1% vs. 34.3%) and improved OS (87.1% vs. 62.3%) than iPET+ patients. In the univariate analysis, iPET− was the sole independent prognostic factor for PFS. In conclusion, PET/CT has a good prognostic value in patients with advanced-stage DLBCL. Trial registration: ClinicalTrials.gov, NCT 01804127. Registered on March 5th, 2013, https://www.clinicaltrials.gov/ct2/show/NCT01804127?term=01804127&rank=1 .

Bone Marrow Microenvironment Immune Cells Measured By Flow Cytometry Can Predict Survival and Identify a Subgroup in Risk of Early Relapse in Diffuse Large B Cell Lymphoma Patients

INTRODUCTION: Several studies have disclosed the predictive role of tumor microenvironment (ME) in diffuse large B cell lymphoma (DLBCL). However, there is limited data regarding the prognostic impact of immune cells (IC) in the bone marrow (BM) of DLBCL patients (pts). Regulatory molecules secreted from primary tumor sites may induce a pro-tumorigenic ME within BM, resulting in an impaired systemic immune response that could promote lymphoma survival. AIMS: -To determine the prognostic impact on survival and risk of early relapse (ER) of the % of T lymphocytes (TL), monocytes (Mo), neutrophils, NK cells and polyclonal B lymphocytes (BL) measured by flow cytometry (FC) in pre-treatment BM aspirates of DLBCL pts. METHODS: We selected pts with DLBCL and available BM aspiration FC data at the time of diagnosis who received treatment at our institution between 2012 and 2019. Clinical information was collected from medical records. FC analysis was performed with 8-color FC panels according to international Euroflow protocols. % of TL, Mo, neutrophils, NK cells and polyclonal BL by FC were compared to the normal values determined by Matarraz et al. (Cytometry part B, 2010). All parameters were analyzed as ordinal variables in 3 categories: low, normal and high. Odds ratio for ER (relapse within a year) was calculated using logistic regression. The survival analysis was estimated with Kaplan-Meier method. The comparison between variables was performed through log-rank test and multivariate analysis with Cox regression. RESULTS: A total of 119 pts were included in this retrospective study. Pts characteristics are summarized in Table 1. All pts were treated with immunochemotherapy regimens. Median PFS and OS were not reached, 75th percentile of 12.7 and 27.8 months (m), respectively; with a median follow up time of 30.7 m (range: 3.4-60). ER was documented in 25 pts. Regarding BM IC, pts with normal TL, polyclonal BL and Mo % were significantly associated with superior PFS and OS (figure 1A and table 2). No correlation between BM NK cells or neutrophils levels and outcome was observed. Moreover, BM IC levels did not statistically differ in involved vs not involved BM. In our cohort, the R-IPI was able to discriminate outcomes in poor and good-very good (G-VG) risk (median OS of 48 m vs. not reached, p &amp;lt;0.001; and median PFS of 34.8 m vs. not reached, p: 0.001, respectively). Histopathologic involved BM also predicted inferior survival (median OS of 48.3 vs not reached, p:0.037; and median PFS of 16.9 m vs not reached, p:0.028). R-IPI, BM involvement and BM IC were included in a multivariate analysis. G-VG R-IPI and low BM TL % remained independent prognostic factor of PFS on multivariate analysis with HR of 0.43 (95% CI 0.21-0.89, p: 0.023), and 3.77 (95% CI 1.8-7.92, p &amp;lt;0.001) respectively (Table 3). The odds of ER was 4 times higher in pts with low BM TL % (95% CI 1.47-10.84, p: 0.006) and 2.8 times higher in pts with low polyclonal BL (95% CI 1.07-7.58, p: 0.036). On the contrary, G-VG R-IPI showed a protective effect with an odds ratio for ER of 0.22 (95% CI 0.08-0.61, p: 0.003). On multivariate analysis both the low BM TL % [OR 5.18 (95% CI 1.45-18.53, p: 0.011)] and the R-IPI subgroup [OR 0.21 in G-VG R-IPI (95% CI 0.06-0.71, p: 0.012)] were predictive of ER. Pts with poor R-IPI were subsequently stratified according to BM TL categories. Pts with low and high TL % had a median PFS of only 9.4 vs 17 m respectively. However, it was unexpectedly not reached in the normal TL subgroup, p: 0.005 (Figure 1B). There was also a trend towards inferior OS in pts with low and high TL (median of 23.1 and 27.8 m respectively vs not reached for the normal subgroup, p: 0.09). CONCLUSIONS: Normal BM % of TL, BL and Mo in DLBCL pts measured by FC was associated with better outcomes in our cohort irrespective of BM involvement. Furthermore, concomitant low BM TL% and poor R-IPI identified a subgroup of pts with extremely poor results. These two variables presented at diagnosis might be used as prognostic factors of early relapse in DLBCL. In the future, therapies that could target the crosstalk between lymphoma cells and the BM ME might represent an encouraging strategy to improve outcomes in DLBCL. Disclosures No relevant conflicts of interest to declare.

PO-1025: Prognostic factors for PFS and OS in radically treated patients with oligometastatic NSCLC

PO-1025: Prognostic factors for PFS and OS in radically treated patients with oligometastatic NSCLC

Supratentorial pediatric cortical ependymomas: a comprehensive retrospective study.

Pediatric cortical ependymomas (CEs) are rare; the clinical features and optimal treatment remain ill-defined. We aimed to clarify the clinical characteristics and outcome of pediatric CEs based on institutional series and literature review. Thirteen children with CEs from our department were included in the present study. Furthermore, a search of English language peer-reviewed articles yielded 43 patients with CEs. The clinical data, treatment, and outcome were retrospectively reviewed and statistically analyzed. Our institutional series consisted of nine males and four females. The literature review yielded 56 pediatric CE cases (including ours) for further analysis. Of these 56 cases, frontal lobe (n = 19, 41.3%) was the most common location and most of the tumors were located in the right hemisphere (n = 27, 58.7%). Seizures (n = 23, 41.1%) were the most frequent preoperative symptoms. Thirty patients (n = 30, 53.6%) were WHO grade II. Five continuous patients in our series screened for C11orf95-RELA fusion and all the patients (100%) were RELA fusion positive. Fourteen (26.4%) patients experienced tumor recurrence and 4 (7.5%) patients died during the follow-up. Multivariate survival analysis depicted extent of surgery resection was the only prognostic factor for PFS and patient with gross total resection (P = 0.037, HR 3.682, 95% CI 1.082-13.79) had longer PFS. Furthermore, Log-rank testing for Kaplan-Meier survival analysis showed the extent of surgery resection (P = 0.007) was the only prognostic factor for OS. Pediatric CEs are rare, commonly seen in frontal lobe and right hemisphere. Seizures are the most common symptoms. They may have higher rate of RELA fusions, but favorable outcome. A low incidence of anaplastic histology has been depicted. Gross total resection is significantly associated with longer PFS and OS. Careful follow-up is necessary because the tumors may progress.

Retrospective analysis of clinical characteristics and prognostic factors of neuroendocrine carcinoma of the gynecologic tract: A preliminary report of ten years follow-up.

e18001 Background: To investigate the clinical characteristics and prognostic factors of neuroendocrine carcinoma of the gynecologic tract (NECGT). Methods: Patients with NECGT diagnosed during 2010 to 2019 were enrolled in this retrospective study. Clinical parameters were calculated, including age, childbearing history, initial symptoms, blood indexs, International Federation of Gynaecology and Obstetrics (FIGO) stages, treatment modalities and survival data. The cut-off values of parameters were screened by receiver-operating characteristic (ROC) curves and their significance was assessed by multivariate logistic regression. Results: We indentified forty five NECGT patients available with the median follow-up time of 5.5 months (9.7±1.98 months). 42 cases (93.3%) originated from cervix uteri, 2 cases (4.4%) from vagina and 1 case (2.2%) from fallopian tube. Irregular vaginal bleeding was the most frequent symptom at the first visit accounting for 75.6%. FIGO stages I to IV distributions were 16 (35.6%), 15 (33.3%), 6 (13.3%), and 8 patients (17.8%). Squamous carcinoma (16.7%) and adenocarcinoma (11.9%) were the common mixed pathological types. 66.7% patients underwent radical surgery, almost all of which received 4-6 cycles adjuvant chemotherapy and half followed by radiation therapy. While data analysis showed that adjuvant radiotherapy could not bring additional survival benefits (p = 0.523). The median PFS of enrolled patients was 14 months (1-78months). Pelvic recurrence (66.7%) and lymphatic metastasis (52.6%) were the main failure patterns. In multivariate analysis, leukocyte count (HR = 0.068, 95%CI: 0.007-0.673, p = 0.021), neutrophil-to-leukocyte ratio (HR = 0.151, 95%CI: 0.024-0.95, p = 0.044), lactic dehydrogenase (LDH) (HR = 6.632, 95%CI: 1.31-33.569, p = 0.022) and carbohydrate antigen-ca 125 (CA-125) (HR = 7.173, 95%CI: 1.25-41.06, p = 0.027) were the independent prognostic factors of PFS. In addition, age at natural menopause (ANM) later than 51.5years (p = 0.009) and an optimal maximum diameter &gt; 62.1mm (p = 0.002) were closely related with poor survival. Conclusions: NECGT is a rare malignant tumor of female genital system. Surgery combined with chemotherapy is the essential treatment, addition of adjuvant radiotherapy did not improve survival. More high-quality clinical trials are needed to provide powerful evidence.

Is there a role for conventional-dose chemotherapy in relapsed germ cell tumors?

404 Background: Patients with germ cell tumors (GCT) that relapse after first-line platinum-based chemotherapy can still be successfully rescued with second-line regimens. High-dose chemotherapy has shown favorable outcomes, and is a preferred option in most instances. Herein, we argued if conventional-dose chemotherapy (CDCT) could also be an alternative in selected patients. Methods: We performed a retrospective observational study, analyzing medical data of 57 GCT male patients treated with salvage chemotherapy after relapse to first-line platinum-based treatment from 2000 to 2015 at the Brazilian National Cancer Institute. Results: The median age was 28 years (range 15 to 49). 26 patients (46%) were Afro-Brazilian, 45 (79%) were non-seminoma, and 53 (93%) had primary testis tumors. 14 patients (25%) had bone, liver or brain metastasis at relapse, and in 35 (61%) the progression-free interval (PFI) after first-line was &lt; 3months. The International Prognostic Factors Study Group (IPFSG) risk classification at relapse for very-low/low, intermediate and high/very-high risk were 8 (14%), 25 (44%), 24 (42%), respectively. After a median follow-up of 8 years, the 2-year PFS was 30% (95% IC, 20 % to 45 %) and the 2-year overall survival (OS) was 34% (95% IC, 23% to 49%). PFI &lt; 3m after first-line (HR 2,38; p&lt;0,005) and AFP &gt; 1000 at relapse (HR 2,38, p&lt;0,023) were negative prognostic factors for PFS and OS. The 2-year PFS and OS for IPFSG risk classification very-low/low, intermediate and high/very-high risk were 75% and 73%, 28% and 32%, 18% and 24%, respectively. Conclusions: In patients with relapsed GCT and very-low/low risk disease by the IPFSG classification, CDCT may be a reasonable option, achieving long-term survival rates. However, CDCT was associated with poor outcome in intermediate and high/very-high risk groups. Further studies should be conducted to assess the best treatment in this subset, since even in second-line, many of patients are still potentially curable.

Prognostic significance of rate of tumor marker (TM) decline during high-dose chemotherapy (HDCT) for relapsed germ cell tumors (rGCT).

403 Background: Rate of serum TM decline is prognostic in patients (pts) with GCT receiving first-line chemotherapy. We investigated the prognostic value of TM decline in rGCT treated with HDCT+peripheral-blood stem-cell transplant (PBSCT). Methods: 462 consecutive pts with rGCT treated with HDCT+PBSCT at Indiana University between 1/2004-1/2019. All pts were planned for 2 consecutive HDCT courses with carboplatin+etoposide per protocol (N Engl J Med 2007;357:340-8). Pts with elevated AFP and/or hCG were included (N=347). Slope and half-life (T1/2) were calculated for weekly AFP+hCG during HDCT starting with peak value at days 1-7 to avoid interference from lysis. T1/2 AFP≤7 days and hCG≤3 days were categorized satisfactory (SAT). Progression-free (PFS) and overall survival (OS) were compared for SAT vs unsatisfactory (UNSAT) using log-rank test and analyzed using Kaplan-Meier. Uni- and multivariable analysis using Cox regression model was performed. Results: 347 pts had elevated TM: 312 had non-seminoma and 35 had seminoma. Median age was 31 (range, 17-58). Primary site: testis (292), mediastinum (26), retroperitoneum/other (29). Metastatic sites included retroperitoneum (277), lung (233), liver (83), brain (77), and bone (21). At initiation of HDCT, 77 pts had elevated AFP, 222 elevated hCG, and 48 elevated both AFP+hCG. Median AFP 9 (1-21,347) and hCG 113 (1-178,140). 314 pts (91%) completed 2 planned cycles of HDCT. Overall, 46/347 pts had SAT decline (13 for AFP; 30 for hCG; 3 for both). Pts with SAT TM decline had superior outcomes compared to UNSAT: 2-yr PFS 69% vs 45% (p=0.006) and 2-yr OS 75% vs 51% (p=0.006). When evaluating each TM separately, SAT decline in hCG had superior outcomes vs UNSAT: 2-yr PFS 74% vs 47% (p=0.002). There was statistically non-significant difference for AFP: 2-yr PFS 48% vs 42% (p=0.65). In univariable analysis, UNSAT decline of hCG, but not AFP, was an adverse prognostic factor for PFS: HR=2.51 (95% CI, 1.40-4.51); p=0.002. Multivariable analysis will be presented. Conclusions: SAT rate of TM decline, particularly in hCG, predicts superior outcomes in rGCT undergoing HDCT+PBSCT. Pts with UNSAT TM decline are at higher risk for relapse and death.

Preoperative serum artemin (ARTN) as a predictive biomarker of recurrence following curative resection for hepatocellular carcinoma (HCC).

571 Background: Tumor-induced generation of splenic erythroblast- like cells (Ter-cells) has been shown to promote tumor progression. These Ter-cells produce the glial-line derived neurotropic factor, ARTN. We investigated the association of pre-operative serum ARTN and the risk of recurrence in HCC patients (pts) undergoing curative resection. Methods: Blood samples were collected prior to surgery as part of an institutional molecular epidemiologic study. Serum ARTN concentration was measured using an enzyme-linked immunosorbent assay (ELISA). Demographics, pathological variables known to be associated with outcomes and clinical outcomes were collected. Uni- and multi-variate analysis were conducted. The optimal cutpoint method was used to define high and low ARTN concentrations. Cox models (hazard ratios, HR) were used to compare progression-free (PFS, primary endpoint), and overall survival (OS) of pts with high vs low serum ARTN. Results: Pre-operative blood samples were available for 58 pts. Median age was 63 years (range: 25-85 years); 74% were male and 50% were Asian. Etiology of liver disease was hepatitis B (43%) and hepatitis C (22%); 43% of tumors were ≤5cm, and vascular invasion was seen in 62%. A baseline alpha-fetoprotein (AFP) of &gt; 100 mcg/L was observed in 36% pts. Median follow-up was 18.9 months. Median ARTN concentration was 0.322 ng/mL. The optimal ARTN concentration cut-off was 0.206 ng/mL. Median PFS for pts with high ( &gt; 0.206 ng/mL) vs low (≤0.206 ng/mL) ARTN was 15.7 vs 55 months (p = 0.04) respectively. Three year PFS was 34% vs 55%, and three year OS 54% vs 91% for high vs low groups. Univariate analysis found that high ARTN concentration (HR 2.44, p = 0.05) and multifocal tumors were associated with a worse PFS. In a multivariate analysis adjusted for AFP &gt; 100mcg/L, vascular invasion, hepatitis status and multifocal tumors, high ARTN remained a negative prognostic factor for PFS, aHR 3.32 (95% CI: 1.22-9.05, p = 0.02). Conclusions: A high pre-surgery serum ARTN is associated with earlier recurrence in HCC pts undergoing curative resection. ARTN should be further studied in HCC to determine its value as a prognostic marker.

The failure patterns and related factors of nasopharyngeal carcinoma treated by intensity modulated radiation therapy in Xiangxi area

Objective To analyze the failure patterns and related factors of intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) in Xiangxi. Methods 107 patients with nasopharyngeal carcinoma without distant metastasis were selected from December 2012 to June 2015 in the first affiliated hospital of Jishou University. Locoreginal recurrence-fee survival rate (LRFS), distant metastasis-free survival rate (DMFS) and progression-free survival (FPS) rate were collected. The survival rate was analyzed by Kaplan-Meier method, univariate analysis was analyzed by Logrank method, and multivariate analysis was analyzed by Cox regression. Results Tumor progression occurred in 40 cases of 107 patients with nasopharyngeal carcinoma. Among them, 14 cases(13.1%) had local recurrence and 33 cases (30.8%) had distant metastasis. Univariate analysis showed that there was significant difference in LRFS between different ages and T staging (P<0.05). There was significant difference in DMFS and PFS between different gender, ages, diabete history, smoking history, T staging, N stage, clinical stage and treatment mode (P<0.05). Multivariate analysis showed that age and T staging were independent prognostic factors for LRFS. Age, T staging and N staging were independent prognostic factors for DMFS. Age, diabetes, T staging, and N staging were independent prognostic factors for PFS (P<0.05). Conclusions Distant metastasis is still the main model of treatment failure of NPC. Age, T staging and N staging before treatment are the significant prognostic factors. Key words: Nasopharyngeal neoplasms; Radiotherapy, intensity-modulated; Prognosis; Factor analysis, statistical