Trend For Worse Overall Survival Research Articles

Dissecting the Significance of Acid Phosphatase 1 Gene Alterations in Prostate Cancer.

The acid phosphatase 1 (ACP1) gene encodes low-molecular-weight protein tyrosine phosphatase, which is overexpressed in prostate cancer (PC) and a potential therapeutic target. We analyzed ACP1 expression in primary/metastatic PC and its association with molecular profiles and clinical outcomes. NextGen sequencing of DNA (592-gene/whole-exome sequencing)/RNA(whole-transcriptome sequencing) was performed for 5,028 specimens. ACP1-High/ACP1-Low expression was defined as quartile (Q4/1) of RNA transcripts per million (TPM). DNA mutational profiles were analyzed for ACP1-quartile-stratified samples. Gene set enrichment analysis was used for Hallmark collection of pathways. PD-L1+(≥2+, ≥5%; SP142) was tested by immunohistochemistry. Tumor microenvironment's (TME) immune cell fractions were estimated by RNA deconvolution/quanTIseq. Overall survival (OS) was assessed from initial diagnosis/treatment initiation to death/last follow-up. We included 3,058 (60.8%) samples from the prostate, 634 (12.6%) from lymph node metastases (LNMs), and 1,307 (26.0%) from distant metastases (DMs). ACP1 expression was higher in LNM/DM than prostate (49.8/47.9 v 44.1 TPM; P < .0001). TP53 mutations were enriched in ACP1-Q4 (37.9%[Q4] v 27.0%[Q1]; P < .001) among prostate samples. Pathways associated with cell cycle regulation and oxidative phosphorylation were enriched in ACP1-Q4, whereas epithelial-mesenchymal transition and tumor necrosis factor-alpha signaling via nuclear factor kappa-light-chain-enhancer of activated B-cell pathways were enriched in ACP1-Q1. Neuroendocrine and androgen receptor signaling was increased in ACP1-Q4. M2 macrophages and natural killer cell fractions were increased, whereas T cells and M1 macrophages were decreased in ACP1-Q4. While OS differences between ACP1-Q1/Q4 were not statistically significant, there was a trend for worse OS among ACP1-Q4 prostate samples (Q4 v Q1: hazard ratio [HR], 1.19 [95% CI, 0.99 to 1.42]; P = .06) and DM (HR, 1.12 [95% CI, 0.93 to 1.36]; P = .22) but not LNM (HR, 0.98 [95% CI, 0.74 to 1.29]; P = .87). ACP1-High tumors exhibit a distinct molecular profile and cold TME, highlighting ACP1's potential role in PC pathogenesis and novel therapeutic targeting.

Abstract 7650: An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC)

Abstract Introduction: Sarcopenia, progressive and generalized loss of skeletal muscle mass, is difficult and labor intensive to directly measure as it requires manual segmentations by radiologists from computed tomography (CT) scans. Sarcopenia has been shown to be a prognostic factor in some metastatic cancers. We evaluated the impact of sarcopenia derived via an automated segmentation algorithm on outcomes in the Phase 3 NSCLC clinical trial, CheckMate 227 (NCT02477826) Methods: The sarcopenia score assessment involves automated selection of the L3 vertebra level slice from abdominal or chest, abdomen, and pelvis (CAP) CT scans, followed by automated segmentation of the muscle area from that slice. Sarcopenia scores were derived from previously established definitions of sarcopenia, with values below 41 cm2/m2 for female patients (regardless of BMI) and below 43 cm2/m2 or 53 cm2/m2 for male (based on BMI &amp;lt; 25 kg/m2 or ≥ 25 kg/m2). Among the 967 patients with evaluable scans, sarcopenia at baseline was identified in 68.39% (n=329/481) patients receiving nivolumab (NIVO) with ipilimumab (IPI) and 70.2% (n=341/486) receiving chemotherapy (Chemo). Results: There was a trend of worse overall survival (OS) in patients with baseline sarcopenia across both treatment arms (minimum follow up 49.4 months). In patients with baseline sarcopenia vs ITT, median OS was 16.5 mo vs. 21.8 mo (p= 0.219) within the NIVO + IPI arm and 12.9 mo vs.15.0 mo (p= 0.273) within the Chemo arm respectively. Any increase in muscle mass from baseline to week 12 was associated with better OS for patients treated with NIVO+IPI (n=98) with sarcopenia at baseline compared to those without an increase in muscle mass (median OS 45.3 mo vs.19.5 mo, p= 0.012). This was not seen in those who received Chemo (n=87). Weight and muscle mass were moderately correlated at baseline (r=0.60). Conclusions: We found that in CheckMate 227, baseline sarcopenia is associated with numerically worse OS, regardless of treatment, leading to potential use as a negative prognostic biomarker. Patients with NSCLC receiving immunotherapy might benefit from changes in muscle mass being monitored during treatment. Validation of these findings in other studies and other tumor types is warranted. Citation Format: Wiem Safta, Rafael Santana-Davila, David Paulucci, William J. Geese, Diederik J. Grootendorst. An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC) [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 7650.

Impact of Large Cells and Ki-67% on Outcomes in Patients with Newly Diagnosed Marginal Zone Lymphoma - Results from a Multicenter Cohort Study

Introduction Marginal zone lymphoma (MZL) is an indolent B-cell lymphoma primarily composed of small/medium cells with low proliferation. However, there are cases where large B-cells (LC) are increased on the biopsy or Ki-67 expression is higher. The significance of LC content and Ki-67 in MZL is uncertain compared to other lymphomas (e.g., follicular or mantle cell). Previous studies evaluating prognostic indices in MZL or the risk of histologic transformation (HT) to diffuse large B-cell lymphoma did not assess these factors. Clinicians and patients often have concerns about the meaning and implications of increased LC or Ki-67 expression. We analyzed a large dataset of US MZL patients to evaluate the impact of LC and Ki-67 on outcomes. Methods This retrospective, multicenter study involved adults with MZL treated at 10 US medical centers on or after 1/1/2010. We included patients with splenic (SMZL), nodal (NMZL), and extranodal MZL (EMZL) of the mucosa-associated lymphatic tissue (MALT). Cases with information on LC or Ki-67+ cell percentages determined by immunohistochemistry on the diagnostic biopsy were included. Patients with HT at or within 60 days after MZL diagnosis were excluded. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS) and cumulative incidence of HT. We assessed PFS and OS from diagnosis and the start of first-line treatment for patients receiving systemic therapy. Cox models were adjusted for age, sex, performance status, MZL subtype, stage, hemoglobin, albumin, and lactate dehydrogenase (LDH), and used multiple imputation for missing data. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) are reported. Results The study included 783 MZL patients (median age: 63 years; 53% women; 60% EMZL, 20% NMZL, 20% SMZL). Of these, 91 (12%) had LC reported in the biopsy, and 44 (6%) had &amp;gt;10% LC content ( Fig. 1A). Ki-67 staining was performed on biopsies from 438 MZL patients. Of those, 235 (54%) had low Ki-67 expression (≤10%), and 98 (22%) had Ki-67 &amp;gt;20%, which we determined to be the best prognostic cutoff for high Ki-67 in MZL. Ki-67 &amp;gt;20% correlated with increased LDH (34% versus 20%, P=.017), but not with other clinical parameters or with the use of first-line RCHOP chemotherapy ( P=.07). The Ki-67 &amp;gt;20% group had significantly worse PFS (aHR=1.69, 95%CI=1.12-2.55, Fig. 1B) with a trend for worse OS from diagnosis (aHR=2.00; 95%CI = 0.97-4.15). These associations were statistically significant for survival outcomes measured from the start of first-line systemic therapy: both PFS (aHR = 1.84, 95%CI = 1.15-2.94) and OS (aHR = 2.71, 95%CI = 1.11-6.60). There were no significant differences in PFS or OS within the Ki-67 &amp;gt;20% group based on first-line therapy (R-CHOP vs. BR/RCVP). The cumulative incidence of HT was significantly higher in the high Ki-67 group (5-year risk, 9.8% versus 3.8%, p=0.013). LC presence was associated with higher Ki-67 but not other clinical characteristics. Patients with LC-containing MZL received R-CHOP as first-line chemotherapy (18%) more frequently than those without LC (5%; P=.004). Presence of LC was linked to shorter PFS from diagnosis (aHR = 1.56, 95%CI = 1.08-2.26), but not OS (aHR = 1.07; 95%CI = 0.53-2.18). Presence of LC did not affect PFS or OS from the start of first-line systemic therapy (n=523). Among patients with LC, there was no significant difference in PFS or OS according to the type of first-line therapy (R-CHOP vs. BR/RCVP). The cumulative incidence of HT (31 events, 5-year risk 3.7% [95%CI, 2.4-5.3%]), was higher in the group with LC (5-year risk 9.4% versus 2.9%, P=0.04). Comparing patients with &amp;gt;10% LC to others yielded similar associations without statistical significance for any endpoint (possibly due to few patients with &amp;gt;10% LC). Discussion In this large retrospective cohort of newly diagnosed MZL patients, Ki-67 staining &amp;gt;20% was an independent prognostic factor for worse PFS and OS. LC content in the tumor was not significantly associated with most outcomes. Anthracycline-based chemotherapy did not impact PFS or OS in the presence of high Ki-67 or LC. These findings, along with the increased risk of HT, suggest that MZL with Ki-67 &amp;gt;20% may represent a higher-risk subset to prioritize for experimental approaches. Patients with LC or high Ki-67 at diagnosis should undergo a repeat biopsy at relapse to assess for HT.

Outcomes of Acute Myeloid Leukemia Patients Suffering from an Additional Active Malignancy Treated with Venetoclax and Azacitidine: A Single Center Experience

Introduction: Venetoclax (ven) and azacitidine (aza) has become the standard of care for the treatment of patients (pts) with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy on the basis of the phase III VIALE-A trial, which showed prolonged overall survival with ven-aza vs. placebo-aza. Pts with active additional malignancies (AM) at the time of AML diagnosis are often unfit for intensive chemotherapy but are excluded from clinical trials, including VIALE-A. We aim to compare the characteristics and outcomes of AML patients with AM vs without AM (non-AM), all treated in a real world setting. Methods: A retrospective analysis including all AML pts diagnosed between Jan 2019 and Apr 2023 and treated with ven-aza in Tel Aviv Sourasky Medical Center. We defined active malignancy as any malignancy additional to AML that was diagnosed within 2 years prior to or concomitantly with the diagnosis of AML, or receiving active treatment at the time of the diagnosis of AML. We excluded prior MDS, MPN and basal cell or localized squamous cell carcinomas of the skin. We defined patients eligible for registration trial (RTE) as pts meeting the inclusion criteria for the VIALE-A trial. We compared categorical and continuous variables as appropriate, and examined survival outcomes by a Kaplan Meier and Log-Rank test. Event free survival (EFS) was defined as time until treatment failure (2 courses of ven-aza without achievement of response), relapse, or death. Results: We analyzed 113 pts diagnosed with AML and treated with ven-aza. 17 patients had an additional AM; 11 solid and 6 hematological, at the time of AML diagnosis. Six pts had more than one additional malignancy. Six patients had newly diagnosed AM, 6 had AM in remission and were treated with maintenance therapy at the time of AML diagnosis, and 5 had an active relapsed / progressive AM. Five patients received treatment for AM concomitantly or alternating with ven-aza, including surgery, letrozole, olaparib, arabiterone acetate, pazopanib, and trabectedin. We compared the baseline characteristics and outcomes of AML pts with AM to AML pts treated with ven-aza who did not have AM (96 pts, non-AM) and pts who met inclusion criteria for the registration VIALE-A trial (57 pts, RTE). Pts with AM were younger than non-AM pts or RTE pts (11.8% over the age of 75 vs. 67% and 68%; respectively, p&amp;lt;0.001), and had a slightly higher baseline creatinine level than RTE pts (median=1.1 range 0.6-1.4 mg/dL vs. median=0.9 range 0.5-1.3 mg/dL; p=0.01). ECOG functional status, ELN risk category, and baseline cell counts were similar between all groups. Treatment with ven-aza was initiated within a median of 6 days from diagnosis in AM pts (range 1-20). 58.2% of AM pts achieved CR/CRi vs. 57% of non-AM pts and 68% of RTE pts (p=0.9 and p=0.46, respectively). The 30 day mortality rate for AM pts was 17.6% vs 7.3% for non-AM pts (p=0.17) and 3.5% for RTE pts (p=0.07). Causes of early mortality among AM patients were non-responsive/progressive AML (2 pts) and sepsis (1 pt). Overall, 13 of 17 AM pts died, 7 from progressive AML, 3 from progressive additional malignancy and 3 from treatment complications. Six of the AM pts underwent allogeneic stem cell transplant (35%) vs. 14 non-AM pts (14.5%, p=0.07) and 11 RTE pts (19.2%, p=0.19). Median length of follow-up was 23.8 months (95% CI, 12.9-34.7). Overall survival (OS) EFS, and relapse free survival (RFS) were similar between AM and non-AM pts. (Figure 1A). ECOG score other than 0 (p=0.009, HR=2.2 95% CI 1.2-4.1) and secondary AML type (p=0.049, HR=1.8, 95% CI 1.001-3.124) but not AM (p=0.354, HR=1.42, 95% CI 0.67-3.03) were associated with reduced overall survival in a multivariate analysis which included age, sex and ELN risk category. A trend for worse survival outcomes in AM vs. RTE pts was noted (HR=1.82, CI 0.95-3.46 p = 0.068) (Figure 1B). EFS and RFS were similar between AM and RTE pts. Conclusions: Among pts diagnosed with AML and an additional active malignancy, treatment with ven-aza in the real world setting resulted in similar response and survival rates as in patients without active malignancies, but with a trend for worse overall survival and higher early mortality than pts who meet the eligibility criteria of the VIALE-A trial. 21.8% of AM pts were alive at 24 months. These results imply that treatment for AML for pts with active malignancy with ven-aza is feasible, and should not be withheld from these pts.

Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer.

Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. Additionally, no data exists regarding treatment of lateral nodes in the setting of short course radiation and nonoperative intent. We evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. This was a retrospective study. This study was conducted at a large, tertiary referral center. Patients treated with radiation and consolidation chemotherapy were included. All primary tumors were biopsy confirmed and disease-staged with pelvic magnetic resonance imaging. Primary tumors were biopsy proven and staged with pelvic magnetic resonance imaging. A subset of lateral pelvic lymph nodes patients received simultaneous integrated boost to 35 Gy in 5 fractions. Then, chemotherapy was administered with the majority receiving mFOLFOX (modified folinic acid, fluorouracil, and oxaliplatin). Clinical partial response required total mesorectal excision. Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. Between January 2017 - January 2022, 155 patients were treated with short course and chemotherapy with 121 included in final analysis. Forty-nine percent underwent nonoperative management. Median follow-up was 36 months and median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease (p < 0.001) with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. Limitations included retrospective nature and lack of lateral nodes pathology; however, thorough radiographic review was performed. Lateral node positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course and in those receiving nonoperative intent.

Association Between Obesity and Poor Prognosis in Patients Receiving Anlotinib for Advanced Non-Small Cell Lung Cancer.

Background: Anlotinib is a novel anti-angiogenesis drug. In non-small cell lung cancer (NSCLC), high body mass index (BMI) was not associated with worse survival in patients treated with bevacizumab compared with those with normal or low BMI. However, it remains unknown whether such an association still exists in NSCLC patients receiving anlotinib therapy. Hence, we conducted this study to investigate whether BMI is associated with clinical outcomes in patients treated with anlotinib for advanced NSCLC. Methods: Data of 554 patients from the ALTER-0302 and the ALTER-0303 trials were analyzed in this study. The patients were classified into non-obesity (BMI <28 kg/m2) and obesity (BMI ≥28 kg/m2) subgroups. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). OS was defined as the interval between the first drug administration and death. PFS was defined as the time span from the date of initiating the treatment to the first documented progression or death from any cause, whichever occurred first. ORR included complete response (CR) and partial response (PR). Results: There were 354 patients (63.9%) who received anlotinib in this study. Restricted cubic spline model showed a U-shaped relation between BMI and the risk of death in the anlotinib group. In a multivariable Cox regression model, a trend of worse overall survival was observed in obese patients who received anlotinib compared with placebo (HR, 2.33; 95% CI, 0.77–7.06; p = 0.136). The interaction between BMI stratification and treatment was significant for OS (P for interaction = 0.038). Conclusion: Our results revealed a U-shaped relationship between BMI and risk of death in patients receiving anlotinib for advanced NSCLC. More importantly, obesity (BMI ≥28 kg/m2) might be a potential predictor of use of anlotinib in advanced NSCLC.

TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML

AbstractA subset of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) show complex karyotype (CK), and these cases include a relatively high proportion of cases of therapy-related myeloid neoplasms and TP53 mutations. We aimed to evaluate the clinicopathologic features of outcome of 299 AML and MDS patients with CK collected from multiple academic institutions. Mutations were present in 287 patients (96%), and the most common mutation detected was in TP53 gene (247, 83%). A higher frequency of TP53 mutations was present in therapy-related cases (P = .008), with a trend for worse overall survival (OS) in therapy-related patients as compared with de novo disease (P = .08) and within the therapy-related group; the presence of TP53 mutation strongly predicted for worse outcome (P = .0017). However, there was no difference in survival between CK patients based on categorization of AML vs MDS (P = .96) or presence of absence of circulating blasts ≥1% (P = .52). TP53-mutated patients presented with older age (P = .06) and lower hemoglobin levels (P = .004) and marrow blast counts (P = .02) compared with those with CK lacking TP53 mutation. Multivariable analysis identified presence of multihit TP53 mutation as strongest predictor of worse outcome, whereas neither a diagnosis of AML vs MDS nor therapy-relatedness independently influenced OS. Our findings suggest that among patients with MDS and AML, the presence of TP53 mutation (in particular multihit TP53 mutation) in the context of CK identifies a homogeneously aggressive disease, irrespective of the blast count at presentation or therapy-relatedness. The current classification of these cases into different disease categories artificially separates a single biologic disease entity.

Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma ≤2 cm in size: A retrospective cohort study

Lung cancer patients can have advanced-stages at diagnosis, even the tumor size is ≤2cm. We aimed to study the relationship between image characteristics, clinical, and patholoigcal results. We retrospectively enrolled patients with lung adenocarcinoma at Taichung Veterans General Hospital and Chang Gung Memorial Hospital from 2007 to 2015, who were diagnosed with treatment naïve primary tumor lesions at sizes less than 2cm, as measured by computed tomography (CT) scans. The patient was analyzed for lymph node (LN) and distant metastasis evaluation, with clinicopathological characteristics, including tumor-disappearance ratio (TDR) (tumor diameter at the mediastinal/lung window) over chest CT scans, pathological diagnosis, disease-free survival (DFS), and overall survival (OS). Totally 280 patients were surveyed initially and showed significantly increase of clinical LN involvement and distant metastasis when TDR ≤75% compared with >75% (21.6% vs 0% for LN involvement; 27.1% vs 0% for distant metastasis; both p<0.001). We included 199 patients having surgical treatment and follow-up for the survival analysis. With a TDR ≤75%, significantly worse DFS (HR, 19.23; 95% CI, 2.60-142.01; p=0.004) and a trend of worse OS (HR, 4.97; 95% CI, 0.61-40.61; p=0.134) were noted by Kaplan-Meier method. TDR ≤75% revealed more advanced pathological stage, and more tumors containing micropapillary or solid subtypes when diagnosed adenocarcinoma. For lung cancer patients with primary tumor ≤2cm, TDR ≤75% was related to more advanced stages, the presence of micropapillary or solid components of adenocarcinoma subtypes, worse DFS, and a trend of worse OS.

Plasma insulin-like growth factor binding protein 1 in pulmonary arterial hypertension

Background Beside the pulmonary vasoconstriction observed in pulmonary arterial hypertension (PAH), severe proliferative and antiapoptotic cellular phenotypes result in vascular remodelling. Many recent findings indicate similarities between PAH and tumour pathology. For instance, insulin-like growth factor (IGF)-1 signalling, which is known to promote tumour development, is implicated in PAH. Higher circulating IGF binding protein (IGFBP)-1 levels are associated with worse survival in PAH. The present study aimed to investigate the relationship between plasma levels of various tumour-related biomarkers and PAH. Methods: IGFBP-1, -2 and -7, along with other tumour-related biomarkers, were measured in plasma from 48 treatment-naïve PAH patients and 16 healthy controls, using proximity extension assays. Among the PAH patients, 33 were also studied at an early treatment follow-up. Results: Plasma IGFBP-1 (p < .003), IGFBP-2 (p < .001), IGFBP-7 (p < .008), vimentin (p < .001), carbonic anhydrase 9 (p < .001), S100A11 (p < .001), human epididymis protein 4 (p < .001) and folate receptor-α (p < .004) were elevated in PAH, compared to controls. IGFBP-1 exhibited the most interesting correlations to clinical parameters and was selected for further analyses. IGFBP-1 correlated specifically to N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.44, p < .002), mean right atrial pressure (r = 0.41, p < .004), venous oxygen saturation (r = –0.43, p < .003), cardiac index (r = –0.32, p < .03) and 6-minute walking distance (r = –0.29, p < .05). Plasma IGFBP-1 also correlated to risk scores based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) PAH guidelines (r = 0.43, p < .003) and the REVEAL model (r = 0.46, p < .001). PAH patients with supra-median baseline IGFBP-1 levels showed a trend for worse overall survival than those with infra-median levels (p = .087). IGFBP-1 was unaltered between baseline and an early treatment follow-up. However, IGFBP-1 changes, between baseline and follow-up, correlated to changes in NT-proBNP (r = 0.48, p < .006). Conclusion: Plasma IGFBP-1 levels at PAH diagnosis show moderate association to NT-proBNP and hemodynamics as well as with ESC/ERS and REVEAL risk scores.

Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors

BackgroundIn the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant.MethodsUsing FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors.ResultsIn the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups.ConclusionsOur findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.

The impact of inflammatory biomarkers, BMI, and sarcopenia on survival in advanced hepatocellular carcinoma treated with immunotherapy.

553 Background: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of inflammatory biomarkers, BMI and sarcopenia on survival in advanced hepatocellular carcinoma (HCC) patients treated with immunotherapy. Methods: We performed a retrospective review of advanced HCC patients treated with immunotherapy-based therapies at Winship Cancer Institute between 2015 and 2019. Baseline computed tomography and magnetic resonance imaging scans were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m)2. Gender-specific sarcopenia was defined by median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall Survival (OS) was set as primary outcome and Cox proportional hazard model was performed. Results: 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% ECOG PS 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9%. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 vs. 14.3 months in sarcopenic vs. non-sarcopenic patients (p=0.054). Median OS was 5 and 17.5 months in patients with BMI &lt;25 and BMI ≥25 respectively (p=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil to lymphocyte ratio (NLR) ≥ 5.15 vs. NLR &lt; 5.15 (p&lt;0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (HR: 4.17, 1.52-11.39, p=0.005). Gender specific sarcopenia showed a trend of worse OS (HR: 1.71, 0.73-4.00, p=0.215) but was not statistically significant. BMI&lt;25 was associated with worse OS (HR: 2.73, 1.15-6.53, p=0.023). In the association with PFS, neither baseline BMI nor gender specific sarcopenia showed statistical significance. Conclusions: Baseline BMI and NLR may predict OS after immunotherapy treatment. After controlling for baseline Child Pugh Score and NLR, gender specific sarcopenia was not associated with OS significantly.

Prognostic Significance of IKZF1, PAX5, and CDKN2A Deletions in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated with Hyper-CVAD/MA with Dasatinib or Ponatinib

Prognostic Significance of IKZF1, PAX5, and CDKN2A Deletions in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated with Hyper-CVAD/MA with Dasatinib or Ponatinib

S115 IMPACT OF MESURABLE RESIDUAL DISEASE POSITIVITY ON OUTCOMES FOLLOWING UNMBILICAL CORD BLOOD TRANSPLANTATION: A STUDY FROM THE ACUTE LEUKEMIA WORKING PARTY OF THE EBMT AND EUROCORD

Background:Cord blood transplantation (CBT) has been associated with good transplantation outcomes in acute leukemia patients with mesurable residual disease (MRD) at transplantation (Milano et al., N Engl J Med 375 :944–953, 2016).Aims:In the current retrospective analysis we assessed the impact of MRD positivity on CBT outcomes.Methods:Inclusion criteria were adult patients with acute myeloid (AML) or lymphoblastic (ALL) leukemia, undergoing CBT as first allogeneic hematopoietic cell transplantation from 2002–2017, first or second complete remission (CR) at transplantation, and available MRD status at the time of transplantation.Results:Data from 506 patients were included in the survey. Among them, 317 patients had AML and 189 ALL (including 102 patients with Phi‐pos ALL). Patients received either a single unit (n = 227) or a double CBT (n = 279). MRD positivity was reported in 169 patients (33%) while the remaining 337 patients were MRD negative at CBT. MRD was more frequently detected in ALL than in AML patients (P = 0.02), in patients given single CBT than in those receiving double CBT (P = 0.02), and in those given in vivo T‐cell depletion of the graft (P = 0.006). At 2 years, relapse incidence was 18% in patients with MRD negativity versus 33% in those with MRD positivity at transplantation (P &lt; 0.001). Two‐year leukemia‐free survival (LFS) and overall survival (OS) were 57% and 60%, respectively, in MRD negative patients, versus 38% (P &lt; 0.001) and 48% (P = 0.004), respectively, in those with MRD positivity. There was no statistical interaction between the impact of MRD positivity and disease type (AML versus ALL) nor disease status at transplantation (first versus second CR). In multivariate analyses, MRD positivity was associated with a higher risk of relapse (HR = 1.8, P = 0.003), comparable non‐relapse mortality (P = 0.44), worse LFS (HR = 1.4, P = 0.008) and a trend for worse OS (HR = 1.3, P = 0.065). Other factors associated with relapse incidence included reduced‐intensity conditionng (RIC) (HR = 1.8, P = 0.01) and in vivo T cell depletion (HR = 2.2, P &lt; 0.001). Other factors associated with worse LFS included CR2 at transplantation (HR = 1.3, P = 0.04) as well as in vivo T cell depletion (HR = 1.9, P &lt; 0.001)Summary/Conclusion:In acute leukemia patients undergoing CBT achieving MRD negativity at time of transplantation is associated with a lower risk of relapse translated into better LFS. Novel strategies are in need for those leukemic patients with positive MRD pre‐CBT aiming at achieving MRD negativity and thus improving transplantation results.

Genomic alterations and survival in young patients aged under 40 years with completely resected non-small cell lung cancer.

Young patients are rarely diagnosed with non-small cell lung cancer (NSCLC), and little is known about its predisposing genomic alterations and survival. This retrospective study was conducted to evaluate the genomic alterations, treatment and prognosis of young patients under 40 years old from a cohort of 640 lung adenocarcinoma and squamous carcinoma cases from Zhejiang Cancer Hospital. All patients were examined for EGFR, KRAS, NRAS, PIK3CA, BRAF and HER2 mutations and ALK, ROS1 and RET fusion genes. In total, 54 patients were aged under 40 years. The frequencies of genomic alterations in younger (≤40 years) and older (>40 years) patients were 68.5% and 54.8%, respectively (P=0.05). Younger patients harbored a higher frequency of fusion genes (22.2% vs. 4.1%, P<0.001) but not gene mutations (46.3% vs. 45.6%, P=0.92). There was a general trend toward shorter recurrence-free survival (RFS) (35.2 vs. 43.8 months, P=0.050), while no overall survival (OS) difference existed between younger and older patients (50.2 vs. 51.4 months, P=0.112). Younger patients with NSCLC had a higher frequency of gene fusions than older patients and had a trend of worse OS.

Abstract P2-08-01: Factors predicting relapse in early breast cancer patients with a pathological complete response after neoadjuvant therapy – Results of a pooled analysis based on the GBG meta-database

Abstract Background Even though patients with a pCR following neoadjuvant chemotherapy have an excellent prognosis still some of these patients will eventually relapse. A better identification of pts with an increased risk of relapse despite a pCR would be helpful to select these patients for additional post-neoadjuvant treatment strategies. Thus, the rationale of this retrospective analysis was to identify factors predicting relapse despite a pCR. Methods This pooled retrospective analysis based on the GBG meta-database includes the neoadjuvant trials GeparTrio, GeparQuattro, GeparQuinto, GeparSixto and GeparSepto. In these trials 2188 (27%) of 7933 pts had a pCR according to ypT0/ypTis ypN0 Definition and were included. The primary endpoint was disease-free survival (DFS), secondary endpoints were distant DFS (DDFS) and overall survival (OS). A multivariate Cox proportional hazards model was used to report hazard ratios with 95% confidence interval (CI). The two-sided significance level was set to α=0.05. Endpoints were analysed for all pts and in subgroups defined by intrinsic subtypes. The potential risk factors intrinsic subtype (HER2 negative/hormone receptor (HR) positive, triple negative, HER2 positive/HR positive, HER2 positive/HR negative), histological tumor type (lobular vs other), grade (G1/G2 vs G3), KI67 (≤20% vs higher), initial cT and cN stadium (cT1 vs cT2 vs cT3/4; cN0 vs cN+), age (≤40 vs 41-59 vs ≥60), BMI (&amp;lt; 25 vs 25-29 vs ≥ 30), planned number of cycles of chemotherapy (≤6 vs &amp;gt; 6), menopausal status (pre- vs postmenopausal) and clinical response after 2-4 cycles (SD vs PR vs CR vs PD) were included as covariates in multivariate Cox regression models as well as study identification. Results From 2188 evaluable patients DFS, DDFS and OS events were observed in 290/197/130 pts respectively; the median follow-up over all studies was 59 months. In multivariate analysis including study and all potential risk factors DFS was significantly different with regard to the initial cN status (cN+ vs cN0, hazard ratio (HR) 1.70; 95% CI [1.2, 2.4], p=0.002). Of borderline significance was histological type (non-lobular vs lobular, HR 0.52 95% CI [0.3, 1.1]; p=0.076) and initial tumor stage (cT3/4 vs cT1, HR 1.61 95% CI [1.0, 2.7]; p=0.064). In terms of DDFS significant differences were seen for the initial cN status (cN+ vs cN0, HR 2.34; 95% CI [1.5, 3.6], p&amp;lt;0.001) and initial tumor stage (cT3/4 vs cT1, HR 1.83 95% CI [1.0, 3.3]; p=0.044); histological type was again close to significance (non-lobular vs lobular, HR 0.46 95% CI [0.2, 1.1]; p=0.067). Multivariate analysis showed significantly worse OS with initial cT3/4 tumors (cT3/4 vs cT1, HR 2.48 95%CI [1.1, 5.7]; p=0.030), and the lobular type (non-lobular vs lobular, HR 0.35 95% CI [0.1, 0.9]; p=0.026) and a trend for worse OS in pts with cN+ (cN+ vs cN0, HR 1.67 95% CI [1.0, 2.9]; p=0.067). Conclusions Initial tumor load before start of neoadjuvant chemotherapy (tumor stage and nodal status) and lobular subtype were predictors of long term outcome after a pCR following neoadjuvant chemotherapy. Intrinsic subtype, KI67, grade and planned number of cycles were not predictive for a relapse. Citation Format: Huober J, Schneeweiss A, Blohmer J-U, Denkert C, Tesch H, Hanusch CA, Salat C, Rhiem K, Rezai M, Solbach C, Fasching PA, Jackisch C, Mehta K, Nekljudova V, Seither F, von Minckwitz G, Loibl S, Untch M. Factors predicting relapse in early breast cancer patients with a pathological complete response after neoadjuvant therapy – Results of a pooled analysis based on the GBG meta-database [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-01.

Systematic Review of Non-Conventional Dosing of Oral Anticancer Therapies in Malignant Haematology

IntroductionSurvival outcomes for patients with lymphoid, myeloid and plasma cell malignancies, have improved with the use of oral small molecule inhibitory agents. Oral anti-cancer therapies are often administered continuously and can have significant side-effects, which can adversely impact adherence, quality of life (QoL) and survival outcomes. In order to improve tolerability, non-standard dosing strategies are increasingly adopted in clinical practice; although, with limited guidance. A systematic review was conducted to identify evidence of, and outcomes from, non-conventional dosing of oral anti-cancer therapy in malignant haematology.MethodsA comprehensive search of all oral anti-cancer therapy listed in the British National Formulary for use to treat haematological malignancies was undertaken using the following databases: MEDLINE®, EMBASE®, and Cochrane Library©, and Cumulative Index to Nursing and Allied Health Literature (CINAHL©). The search was expanded using prospective citation chaining in the Web of Science and retrospective snowballing of reference lists of included studies to ensure a sensitive, comprehensive search. Studies were selected based on predefined inclusion/exclusion criteria, and were critically appraised. Extracted data were tabulated to summarise key findings, which were analysed by type of non-dosing strategy: dose interruption; dose reduction; and other dosing strategies.ResultsEleven studies were included and reviewed: two late phase clinical trials, four cohort studies, and five case reports. Findings from each included study (aim, design, treatment schdeule, reported efficacy/toxicty/QoL outcomes) are presented in the accompanying Table 1. These studies evaluated non-standard dosing of dasatinib, imatinib, lenalidomide and thalidomide. Four studies were conducted in Italy, four in the US, and one in Brazil, South Korea and UK. Dose reductions were the most commonly reported strategy (five studies). Two studies reported dose interruptions and four reported other dosing strategies. The quality of the studies ranged from moderate to high (e.g. clinical trials) to moderate to low (e.g. case reports).Russo et al (2015) conducted a single arm, open-label trial, in which the use of one month on/one month off schedule of imatinib was investigated in 96 CML patients aged ≥65 years. Although this trial did not report toxicity or QoL outcomes, there were no transformations (progressions) of CML to an accelerated or blast phase of disease using this alternative schedule. Therefore, results do not draw definitive conclusions that intermittent treatment can be offered to optimal and stable responders. However, they indicate a role for alternative treatment schedules tailored to individual patients, particularly those experiencing significant toxicities.Mangiacavalli et al (2012) investigated efficacy and adverse effects of a one-week interruption of thalidomide following daily administration for three weeks, compared to continuous therapy. Limited patient numbers (13 vs. 10) prevented this trial from obtaining definitive data regarding efficacy, but there was a trend for worse overall survival (OS, p< 0.001) and progression free survival (PFS, p=0.02) in the intermittent arm compared to the continuous one, with no difference in peripheral neuropathy.Dose reduction was reported in two imatinib retrospective cohort studies and three case reports (2 dasatinib, 1 imatinib). Results were inconclusive, primarily due to limitations in the design of the studies, small sample sizes and lack of detail in reporting toxicities and QoL outcomes. Lenalidomide was investigated in two small prospective cohort studies using alternate-day dosing in myelodysplastic syndrome and multiple myeloma. Toxicity outcomes were only reported in the myeloma study and QoL outcomes were reported in neither study.ConclusionsThis review identified limited evidence to support non-standard dosing strategies in malignant haematology. Imatinib dose interruption in optimally responsive CML patients warrants further investigation in large-scale, prospective, ideally blinded trials. DisclosuresDjebbari:Pfizer: Other: conference registration; Takeda: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding.

Abstract P3-04-03: Identification, clinical characteristics and treatment outcomes of somatic human epidermal growth factor receptor 2 (ERBB2) mutations in metastatic breast cancer patients

Abstract Background The human epidermal growth factor receptor 2 (ERBB2) can be altered by somatic mutations (with/without ERRB2 amplification) that likely drive tumorigenesis. Here, we present the first study that thoroughly investigates the behavior of patients with ERBB2 mutated tumors in a large unselected cohort of metastatic breast cancer (MBC) patients. Patients and Methods We included retrospectively all MBC patients with sufficient tumor material available, independent of hormone receptor or ERBB2 amplification status, diagnosed between 2000 and 2015 at the Multidisciplinary Breast Center of University Hospitals Leuven. Genomic DNA extracted from primary breast tumors was subjected to deep targeted re-sequencing using an assay covering 5 exons (exons 8, 17, 19, 20 and 21) known to accumulate ERBB2 hotspot mutations. Clinical characteristics, treatment response and outcomes (excluding bilateral BC) were compared between patients with and without ERBB2 mutations. Results We established and validated a research use only next-generation sequencing assay across five exons of ERBB2. Somatic ERBB2 mutations with an allelic frequency of ≥5% in at least one independent analysis, were observed in 1.8% (13/721) of MBC patients. MBC patients with ERBB2 mutant primary tumors appear to have similar patient and tumor characteristics (TNM stage, grade, and receptor and HER2 status) compared to non-mutant patients and ERBB2 mutations occur in all molecular subtypes (7 ER+/HER2-, 4 HER2+, 2 triple negative). However, we see a small trend towards enrichment in the invasive lobular carcinomas (ILC) in the ERBB2 mutant patients vs. the non-mutant patients (4/13 (31%) vs. 97/695 (14%), p=0.086). ER+ patients with an ERBB2 mutant tumor who received first line aromatase inhibitor (AI) (n=3) had a worse median time to progression (TTP) compared to non-mutant patients (n=156) (TTP 103 vs. 311 days, p=0.04), AI use in any line had also a worse TTP (n=8 vs. 376; TTP 74 vs. 213 days, p=0.006). TTP was not significantly different for other standard therapies, but numbers were small. Median distant disease free survival (DDFS) defined as time from primary diagnosis to first metastasis, was slightly shorter for ERBB2 mutant tumors (n=9 vs 514; DDFS 1.4 vs. 2.9 years, p=0.066). However, in ER+/HER2- ERBB2 mutant tumors, median DDFS was significantly shorter in non-mutant patients (n=5 vs. 328; DDFS 0.8 vs. 4.0 years, p=0.02). Median overall survival (OS) after diagnosis of MBC was numerically lower for mutant patients in all subtypes vs. non-mutant patients (n=11 vs. 669; OS 1.1 vs. 2.3 years, p=0.457), and in ER+/HER2- disease (n=6 vs. 431; OS 1.0 vs. 2.9 years, p=0.07). Conclusion In our large MBC cohort, patients with ERBB2 mutant tumors appear to have similar tumor and patient characteristics as ERBB2 non-mutant tumors. ERBB2 mutations do not seem to occur more or less often in specific breast cancer subtypes except for a slight increase for ILC. In ER+/HER2- MBC, patients with ERBB2 mutant tumors appear to be adversely prognostic; having a shorter DDFS after early breast cancer treatment, and in metastatic disease, they respond worse on AI and have a trend for worse OS compared to non-mutant cases. Citation Format: Jongen L, Floris G, Lambrechts D, Laenen A, Neven P, Mann G, Cutler Jr. RE, Lalani AS, Wildiers H. Identification, clinical characteristics and treatment outcomes of somatic human epidermal growth factor receptor 2 (ERBB2) mutations in metastatic breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-04-03.

Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas

BackgroundCancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. MethodsWe queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan–Meier analysis. ResultsOf the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39%) experienced distant recurrence, and four (17%) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95% confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression. ConclusionsInstitutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

Frequencies of actionable mutations and survival in variants of invasive adenocarcinoma of lung

Background: The objective of the present study was to explore the common actionable mutations and survival in variants of invasive adenocarcinoma (VIA) of lung. Methods: A total of 1,120 lung adenocarcinoma patients with pathologically confirmed VIA and completely resected stage I–IIIA were enrolled from 2010 to 2013. For comparison, we evaluated the gene status and survival of 380 non-VIA lung adenocarcinoma patients. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2 and fusions of ALK, ROS1 and RET. Survival curves were plotted with Kaplan-Meier method. Results: Thirty-one patients were selected, including invasive mucinous adenocarcinoma (n=15), enteric adenocarcinoma (n=9), colloid adenocarcinoma (n=4) and fetal adenocarcinoma (n=3). The overall frequency of gene abnormality was 48.4% (15/31) in VIA. The gene abnormalities were as follows: KRAS mutation (n=5), ALK rearrangement (n=4), PIK3CA mutation (n=2), EGFR mutation (n=2), HER2 mutation (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS, BRAF or RET were observed. The frequency of gene abnormality was lower in VIA than non-VIA patients (48.4% vs. 74.7%, P=0.0015). No difference in recurrence-free survival (RFS) was found between VIA and non-VIA patients (38.0 vs. 47.0 months, P=0.524). There was a trend of worse overall survival (OS) in VIA than non-VIA patients (48.0 vs. 57.0 months, P=0.052). Conclusions: As a rare type of lung adenocarcinoma, VIA has a lower frequency of common gene abnormality. Invasive mucinous adenocarcinoma is the most frequent subtype and KRAS represents a predominant actionable mutation in VIA patients. There is a trend of worse survival in VIA than non-VIA patients.

Is Mean Radiation Dose to the Subventricular Zone a Prognostic Indicator?

It has been postulated that the capability of glioblastoma (GBM) to withstand multi-modality treatment is driven by a niche of mutated neural progenitor cells (NPCs) called cancer stem cells (CSCs) residing in the subventricular zone (SVZ). Previous studies suggest that increased radiation dose to the SVZ is associated with improved outcomes while others have not found this association and underline the importance of NPC preservation during radiation therapy (RT). Given this conflicting data, we examined the relationship between dose to the SVZ and treatment outcomes in GBM patients treated with surgery followed by RT- Temozolomide (TMZ). Patients with GBM who completed a course of RT-TMZ at single institution between 2010 and 2016 were included. All patients were >18 years old, underwent surgery followed by intensity modulated radiation therapy (IMRT) to 60 Gy in 30 fractions with concomitant TMZ, and had a minimum of 6 month follow-up. Time to tumor recurrence was defined as the date that tumor progression on Magnetic Resonance Imaging (MRI) was documented by both the neuro-radiologist and treating neuro-oncologist. Dates of patients’ deaths were obtained from medical records and the Social Security Death Index. SVZ contours were delineated on the fused computed tomography simulation and post-surgical MRI T1-weighted images and defined as the lateral wall of the lateral ventricles using a 5-mm brush. Mean doses were calculated for ipsilateral, contralateral and bilateral SVZ regions. Log Rank tests, cox regression and backward stepwise model selection were employed for data analyses. 109 patients (median age 62 years) were identified. 45.9% underwent gross total resection, 43.1% subtotal resection, and 11% biopsy. At diagnosis, 18.3% of patients were RPA Class III, 47% RPA Class IV, 16% Class V. 66.1% of patients had tumor in contact with the SVZ. The median ipsilateral, contralateral, and bilateral mean doses were 57.8 Gy, 37.5 Gy, and 47.1 Gy, respectively. At a median follow up of 14.4 months, the 1 and 2-year progression-free survival (PFS) and overall survival (OS) rates were 27.5%, 6.4%, 67.0% and 21.1%, respectively. There was a trend of worse OS with higher mean ipsilateral SVZ dose in patients who received >57.8 Gy (14.5 vs 19.4 months, p=0.06). Lack of SVZ involvement at diagnosis was associated with an OS benefit on univariate analysis (16.8 vs 13.8 months, p=0.03). On multivariate analysis, lower RPA class and greater extent of resection were associated with improved PFS. Younger age, higher performance status, greater extent of resection, and MGMT methylation were associated with improved OS. This study suggests a trend towards worse OS with higher mean ipsilateral SVZ doses and significantly worse OS with SVZ involvement. Additionally, our study continues to underline the importance of RPA class, age, performance status, resection type and MGMT status as the most important prognostic indicators of survival outcomes.