On Overall Survival In Univariate Analysis Research Articles

Association of HPV genotype and phylogenic clade with oropharyngeal cancer outcomes.

6058 Background: Human papillomavirus (HPV) is a causative agent of oropharyngeal squamous cell carcinoma (HPVOPC). There are multiple different HPV genotypes based on variations in the nucleotide sequence of the L1 capsid, with HPV16 being most common in HPVOPC (85%). HPV genotypes can be further classified into phylogenic clades, including alpha-9 (A9) and alpha-7 (A7). HPVOPC is associated with a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for de-escalation studies in HPVOPC. Methods: A retrospective cohort study was conducted at a large multicenter health system. Patients diagnosed with non-metastatic HPVOPC or unknown primary from 2012-2021 and treated with curative intent were included. Low-risk HPV types (6, 11, etc) and local recurrences were excluded. HPV molecular typing was prospectively performed according to institutional protocol. Cox regressions were used to measure the effect of HPV genotype (16 versus non-16) on overall survival (OS) and event-free survival (EFS). Gender, smoking status, alcohol use, ECOG performance status, T stage, N stage, and subsite (oropharynx versus known primary) were covariates. A secondary survival analysis according to high-risk HPV clade (A9 versus A7) was also performed. Results: The total cohort included 520 patients, the majority of whom were HPV16 (86.9%, n = 452), A9 clade (97.1%, n = 505), oropharynx primary (94.8%, n = 493), male (86.9%, n = 452), white (72.5%, n = 377), non-Hispanic (74.2%, n = 386), non-active smokers (88.3%, n = 459), ECOG 0 (75.6%, n = 393), and N2 stage (65.2%, n = 339). The most common non-16 HPV genotypes were 18 (n = 7), 33 (n = 21), and 35 (n = 29). HPV genotype was not associated with OS (HR = 1.64, 95% CI 0.85-3.16, p= 0.14) or EFS (HR = 1.15, 95% CI 0.64-2.07, p= 0.65). A7 clade was associated with a worse OS compared to A9 in the univariate analysis (HR = 3.43, 95% CI 1.07-10.97, p= 0.04), but not in the multivariate analysis (HR = 1.67, 95% CI 0.45-6.17, p = 0.44). Finally, HPV clade was not associated with EFS (HR = 1.38, 95% CI 0.34-5.60, p= 0.66). Conclusions: While HPV genotype was not associated with survival differences in patients with HPVOPC, HPV A7 clade only predicted worse OS in univariate analysis. Although the total cohort size was large, this analysis was limited by small numbers of subjects with non-16 HPV genotypes and non-A9 clade, which is reflective of the predominance of HPV16 in HPVOPC. Thus, a pooled multicenter collaboration is needed to further address this question. Moreover, future studies should investigate whether outcomes may be related to intratypic HPV16 variants that affect oncoprotein function and/or immunogenicity. Detection of a subgroup of HPVOPC with possible inferior outcomes has important implications for studying treatment de-escalation in HPVOPC.

RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases

BackgroundGenetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT).Patients and MethodsRetrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004–2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan–Meier curves were used to determine overall survival.ResultsOne hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4–184.9 months) and median OS was 38.7 months (95% CI 32.4–44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402–16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995–2.843, p = 0.052).ConclusionsRAS mutation status should not in isolation be used to select patients for CRS/HIPEC.

Surgical outcome and molecular pattern characterization of recurrent glioblastoma multiforme: A single-center retrospective series

ObjectiveDespite recent advances in diagnosis and treatment of the disease, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. While the value of molecular pattern profiles at first diagnosis has been demonstrated, only few studies have examined these biomarkers at the time of recurrence. The aim of this study was to explore the impact of extent of resection at repeated craniotomy on overall survival (OS) of patients with recurrent GBM. In addition, we investigated the molecular pattern profiles at first and second surgery to evaluate possible temporal evolution of these patterns and to assess the effect of these modifications on OS. MethodsWe conducted a retrospective cohort study of 63 patients (mean age 59.2 years) surgically treated at least two times for recurrent GBM between 2006 and 2020. ResultsMedian OS and progression-free survival (PFS) were 22 months (range 2–168 months) and 10 months (range 1–96 months), respectively. The OS following gross-total resection (GTR) at recurrence for patients with initial GTR (GTR/GTR) was significantly increased (42.6 months) compared with sub-total resection (STR) at reoperation after initial GTR (GTR/STR) (19 months) and with GTR at reoperation after initial STR (STR/GTR) (17 months) (p = 0.0004). Overall surgical morbidity resulted 12.7% and 11.1% at first and at second surgery, respectively. Changes in genetic profiles between first and second surgery of 1p/19q co-deletion, MGMT promoter methylation and p53 mutations occurred in 5.6%, 1.9% and 9.3% of cases, respectively. MGMT promoter methylation appeared to affect OS in univariate analysis at first (p = 0.038) and second surgery (p = 0.107), whereas p53 mutation appeared to affect OS only at second surgery (p = 0.01). In a multivariate analysis female sex (HR = 0.322, 95% CI 0.147–0.705; p = 0.005), PFS (HR = 0.959, 95% CI 0.934–0.986; p = 0.003), GTR at first and second surgery (HR = 0.195, 95% CI 0.091–0.419; p < 0.0001) and adjuvant chemotherapy at recurrence (HR = 0.407, 95% CI 0.206–0.809; p = 0.01) were associated with longer OS. ConclusionsThis study confirmed the role of extent of resection (EOR) at first and at recurrence as a significant predictor of outcome in patients with recurrent GBM. In addition, this study highlighted the concept of a dynamic evolution of GBM genome after initial surgical resection, supporting the need of further studies to investigate the clinical and therapeutic implications of the changes in genetic profiles after initial surgery.

Long-term Outcomes for Extraskeletal Myxoid Chondrosarcoma: A SEER Database Analysis.

Extraskeletal myxoid chondrosarcoma (EMCS) is a rare tumor that typically has an indolent course but high rate of recurrence. We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess factors associated with metastasis, treatment, and survival. We queried the SEER 1973-2016 database for patients with myxoid chondrosarcoma (ICD-O-3: 9231/3). Kaplan-Meier analyses and Cox proportional hazard models assessed effects on overall survival (OS) of demographics and clinical characteristics. Logistic regression assessed associations between tumor location and distant disease. Primary analysis was a complete case analysis; multiple imputation (MI) was used in a sensitivity analysis. Locoregional disease (LRD) was found in 373 (85%) of patients. In univariate analysis with LRD, surgery correlated with superior OS [HR = 0.27; 95% confidence interval (CI), 0.16-0.47]; chemotherapy and radiotherapy associated with inferior OS (HR = 1.90; 95% CI, 1.11-3.27 and HR = 1.45; 95% CI, 1.03-2.06, respectively). No treatment modality associated with OS in the adjusted, complete case model. In the adjusted sensitivity analysis, surgery associated with superior outcomes (HR = 0.36; 95% CI, 0.19-0.69). There was no OS difference by primary tumor site. 10-year OS with distant disease was 10% (95% CI, 2%-25%). Surgery in LRD associated with improved OS in univariate analysis and adjusted models correcting for missing data. There was no OS benefit with chemotherapy or radiotherapy. This represents the largest report of EMCS with long-term follow-up. Despite the reputedly indolent nature of EMCS, outcomes with metastatic disease are poor. We provide OS benchmarks and guidance for stratification in future prospective trials.

The effect of locality of residence (LOR) and socioeconomic status (SES) on mortality in patients with squamous cell carcinoma of the head and neck (HNSCC): 20-year experience at the UPMC Hillman Cancer Center.

e19043 Background: As cancer centers expand, evaluation of potential disparities in outcomes amongst the catchment area is critically important. We examined the effect of LOR and SES on overall survival (OS) in HNSCC patients treated at HCC, which spans 29 counties in western Pennsylvania with diverse socioeconomic profiles across urban and rural localities. Methods: Retrospective review included patients with primary HNSCC (excluding M1 and recurrent disease) treated at HCC 1997-2018. Using Rural-Urban Commuting Area codes, LOR was classified as urban/suburban or rural according to ZIP code. SES was defined by medium income level (low, moderate (Mod), middle (Mid), Upper) via Federal Financial Institutions Examination Council geocoded census tract data. Kaplan-Meier methods and Cox regression models were used to evaluate OS. Results: 3512 patients were identified. Median age was 61, 72.7% male, 93.2% White, 18% HPV +, 75.5% urban/suburban, and by SES: 4% Low, 21% Mod, 46% Mid, and 19% Upper. Primary site included 35.2% oral cavity, 28.4% oropharynx, 28.1% larynx, 8.3% other, stage was majority III/IVa (61%), 66% had surgery and 54% received multimodality treatment (tx). While median OS differed significantly by race (Black: 5.8 vs. White: 7.3 years, p = 0.0457) and SES (Low: 4.1 vs. Mod: 5.3 vs. Mid: 7.3 vs. Upper: 9.1 years, p &lt; 0.0001), there was no difference by LOR (rural: 7.7 vs. urban/suburban: 7.2 years, p = 0.99). Multivariable Cox Regression showed lower SES was associated with a higher risk of death [(Low vs. Upper, HR: 1.416, 95% CI: 1.023-1.959) (Mod vs. Upper, HR:1.443, 95% CI: 1.214 – 1.716), p = 0.0004], adjusting for LOR and factors associated with OS in univariate analysis (age, smoking status, primary site, staging, tx, HPV status, race, and enrollment on clinical trial). The effect of LOR, race, and enrollment on clinical trial were not significant in multivariate analysis. Conclusions: SES was independently associated with OS in HNSCC patients treated at HCC, while LOR was not associated with OS. The lack of difference by LOR may be partially explained by HCC’s efforts to increase access to care throughout the catchment area by establishing community sites. However, a focus on improving outcomes for lower SES HNSCC patients is needed.

Does the Interval Between Hysterectomy and Start of Adjuvant Radiation Treatment Influence Survival in Women With Endometrial Carcinoma?: A National Cancer Database analysis.

The objective of this study was to analyze the impact of the time interval (TI) between hysterectomy and initiation of adjuvant radiation treatment (ART) on overall survival (OS) among women with early stage endometrial carcinoma (EC) using the National Cancer Database (NCDB). The NCDB was queried for women with the International Federation of Gynecology and Obstetrics (FIGO) stage I to II EC who underwent hysterectomy followed by ART. We examined the prognostic impact of TI on OS using the cutoff ≤8 or >8 weeks to initiate radiation treatment (RT). Two groups of patients were created. Kaplan-Meier curves were created for OS analysis. Predictors of OS were identified. A total 16,520 women were identified. The median follow-up time for the entire cohort was 59.1 months. Median age was 63 years, and 82% were FIGO stage I. Pelvic external beam RT alone was used in 9569 (58%) and vaginal brachytherapy alone in 4265 women (26%). In total, 10,040 women (61%) received RT ≤8 weeks. Delay in initiating RT >8 weeks was associated with shorter 5-year OS (P=0.048). Independent predictors of shorter OS includes older age, African American race, higher comorbidity burden, higher tumor grade, the presence of lymphovascular invasion and stage II tumors. Although TI in initiating RT was a significant predictor for OS in univariate analysis, its independent significance of OS was lost on multivariate analysis (P=0.28). Our study suggests that TI between hysterectomy and initiation of ART was not an independent predictor of OS in women with early stage EC.

The impact of thyroid hormones on patients with hepatocellular carcinoma.

Background & aimsHypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients.MethodsOf 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated.ResultsThyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9–15.7 months) vs. 7.3 months (5.4–9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5–13.6 months) vs. 3.3 months (2.2–4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3–3.3); p = 0.002) in multivariate analysis.ConclusionsTSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

Adjuvant chemotherapy in resectable synovial sarcoma.

The role of adjuvant chemotherapy (AC) for synovial sarcoma (SS) is controversial. Using a large national dataset we evaluate the impact of AC on overall survival (OS) following curative-intent resection of SS. Patients with stage I-III SS 2004-2012 undergoing resection were identified in the National Cancer Data Base. Clinicopathologic factors associated with OS were identified using Cox proportional-hazard modeling, adjusting for factors associated with receipt of AC. Among 544 patients, 131 received AC. Median age of the cohort was 42 years; 269 were female. AC was not associated with OS in univariate analysis in the overall cohort. After stratification by stage, AC was associated with prolonged OS in univariate analysis in stage III patients only (P = 0.028), which remained significant in multivariable analysis (P = 0.033). Other factors associated with OS in stage III patients were age >55 years, (P = 0.001), positive margins (P = 0.037), biphasic histology (P = 0.013), and adjuvant radiation (P < 0.001). The association between AC and OS remained significant after adjustment for factors predictive of receipt of AC. In this national cohort, AC was associated with prolonged OS for SS for stage III patients but not in lower stages. Less restricted use of this therapy may be warranted in this population.

The impact of dose modification or termination of S-1 as adjuvant therapy on survival of locally advanced gastric cancer underwent curative gastrectomy.

193 Background: Adjuvant S-1 therapy for pStage II/III gastric cancer (GC) patients (pts) after curative resection is standard treatment in Japan, however, prognosis of pStage III is still poor. There are few reports investigating the association of treatment exposure with survival. Therefore, we investigated the impact of dose modification or termination of S-1 as adjuvant therapy on overall survival (OS). Methods: The data of locally advanced GC pts who underwent gastrectomy with D2 lymph-node dissection in Shizuoka Cancer Center between Jan 2007 and Aug 2013 were retrospectively collected. Inclusion criteria were as follows: age 20 to 80 years; ECOG PS 0 or 1; histologically proven adenocarcinoma; pStage III under TNM 7th edition; R0 resection; initiation of S-1 within 56 days after surgery. S-1 was administered for 4 weeks followed by a 2 weeks rest. We defined completion of planned S-1 therapy as continuation of S-1 one year after surgery. Results: One hundred and six pts satisfied inclusion criteria. Pts’ characteristics were as follows: median age, 67 years (range, 38-78); male/female, 77/29 pts; ECOG PS 0/1, 72/34 pts; primary tumor location EGJ/U/M/L, 1/27/45/33 pts; and pStage IIIA/IIIB/IIIC, 25/41/40 pts. Fifty-five pts (51%) needed dose modification (dose reduction and/or schedule alteration). Eighty-two pts (77%) achieved completion of planned S-1 therapy. Five year OS rate was 59.9%. Among potential prognostic factors for OS in univariate analysis (age, PS, pStage, completion of planned S-1 therapy, dose modification), completion of planned S-1 therapy (HR 0.26; 95% CI 0.13-0.51; p &lt; 0.001) and PS 0 (HR 0.52; 95% CI 0.27-0.99; p = 0.048) were good prognostic factors and dose modification was not prognostic factor (HR 1.06; 95% CI 0.53-2.12; p = 0.876) for OS. Conclusions: This study suggested that completion of planned adjuvant S-1 therapy and PS 0 were good prognostic factors for OS and appropriate dose modification might not worsen their prognosis.

Prognostic value of neutrophil to lymphocyte ratio for gastric cancer.

Although the prognostic value of the neutrophil to lymphocyte ratio (NLR) in gastric cancer (GC) patients has been investigated by many studies, the results are heterogeneous. The objective of this systematic review is to ascertain the prognostic value of NLR in GC patients. PubMed and Embase were retrieved to identify potential studies published before 8 June, 2014. Newcastle-Ottawa Scale (NOS) for cohort study was used to assess the quality of all eligible studies. Of the 20 studies included in this systematic review, 17 studies investigated the effect of NLR on overall survival (OS), 11 studies reported that NLR negatively affected OS in their multivariante analysis, and 16 studies reported that NLR negatively affected OS in univariate analysis. Three studies investigated the effect of NLR on progression-free survival (PFS), reporting that increased NLR was associated with worse PFS. Four studies investigated the effect of NLR on disease-free survival (DFS), two of which reported that increased NLR was associated with worse DFS. Two studies investigated the effect of NLR on disease special survival (DSS), but neither observed any significant association between NLR and DSS. The major design deficiencies of the studies available were retrospective data collection, inadequacy of follow-up cohorts, and unavailability of the method used for outcome assessment. Based on the above findings, we conclude that NLR may be a useful prognostic index (PI) for GC. In addition, future studies with prospective design, long-term follow-up and fully adjusted confounding factors are needed to rigorously assess the prognostic value of NLR for GC.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Prognostic quality of the Union Internationale Contre le Cancer/American Joint Committee on Cancer TNM classification, 7th edition, for cancer of the maxillary sinus

Carcinomas of the maxillary sinus are classified according to the Union Internationale Contre le Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification. The purpose of this study was to assess the prognostic significance of the UICC/AJCC TNM classification seventh edition, which was introduced in 2010. One hundred thirteen patients with malignant tumors of the maxillary sinus were included in this study. The prognostic impact of the TNM classification and the UICC/AJCC seventh edition's stage grouping were analyzed in univariate and multivariate analysis. The UICC/AJCC stage grouping, the T classification, and the N classification had a significant impact on overall survival (OS) in univariate analysis (p < .05). No significant differences were observed between the groups T4a and T4b (p = .109). In multivariate analysis, the UICC/AJCC stage grouping (p = .031), the N classification (p = .014), and age (p < .001) had a significant impact on OS. Although UICC/AJCC stage grouping and the N classification provided a significant prediction of OS in univariate and multivariate analysis, T classification only influenced OS in univariate analysis.

A Novel Prognostic Staging System for Light Chain Amyloidosis (AL) Incorporating Markers of Plasma Cell Burden and Organ Involvement.

Abstract 2797Poster Board II-773 Background:Primary systemic amyloidosis (AL) is characterized by deposition of light chain derived amyloid fibrils in multiple organs leading to varying degree of dysfunction. Cardiac involvement is a common feature of AL, and when significant is highly predictive of poor outcome. The currently used prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro B-type Natriuretic peptide (NT-ProBNP) and is effective at predicting outcome in patients with AL. However, this is driven primarily by the degree of cardiac involvement and does not take into account the degree of plasma cell burden and its impact on the disease course. It is possible that some of the heterogeneity in outcome can be explained by the plasma cell characteristics rather than the degree of the end organ damage. Methods:We examined the baseline clinical and laboratory data from 2119 patients with AL who were seen at our institution with in 90 days of their diagnosis. The data were collected from a prospectively maintained data base, and additional testing was done for free light chain levels (FLC) on stored sera from patients seen before the routine introduction of FLC testing. Cox proportional hazards analysis was performed to estimate the prognostic values of different variables. Results:We first examined the impact of plasma cell clone related characteristics namely, difference between involved and uninvolved FLC (FLC-Diff), bone marrow plasma cell (BMPC) %, plasma cell labeling index (PCLI), beta 2 microglobulin (B2M), and presence of circulating plasma cells, on overall survival (OS) from diagnosis. All variables were dichotomized into high and low based on their median value (FLC-diff: 20 mg/dL, BMPC: 10%, PCLI as a continuous variable, B2M: 3 mg/dL and circulating cells: absent or present). While all were found to be prognostic for OS in univariate analysis; in a multivariate analysis incorporating a stepwise selection only B2M and FLC-diff were significant. We then used these two variables along with the cTnT and NT-ProBNP that are used in the current model to develop a staging system. The median values for all four variables were used for developing the scores. Patients were assigned a score of 1 for presence of each characteristic (FLC difference > 20 mg/dL, troponin-T > 0.02, NT-ProBNP > 1000, and B2M > 3) or 0 if the value was at or below the cutoff. The scores were added to obtain a composite prognostic score that grouped the 370 patients (who had all the variables available for analysis) into 5 groups with very different OS (4.4, 9.3, 24.4, 43, and not reached for stages 4, 3, 2, 1, and 0 respectively; Figure A). However, since the NT-ProBNP did not have independent impact on survival in a multivariable model incorporating all the four variables, we also examined a system that only included FLC-diff, cTnT and B2M. This system again allowed grouping of patients (n=450 with all three variables available) into four distinct groups with divergent outcome with OS of 4.6, 10.5, 36.8, and not reached for stages 3, 2, 1, and 0 respectively; (Figure B). Conclusion:Incorporation of plasma cell related measurements into the existing staging system using cardiac biomarkers allows better risk stratification of patients with AL amyloidosis. The system using FLC, B2M and troponin has the advantage of easily available laboratory values and can be widely adopted. Addition of NT-ProBNP into the system allows better refinement of the intermediate risk groups. This system will allow upfront risk stratification and development of risk-adapted therapies for patients with AL. [Display omitted] Disclosures:Gertz:Genzyme: Research Funding.