The role of response as predictor of improved outcome in advanced pancreatic cancer (APC) patients (pts) treated with first-line Gemcitabine plus Nab-paclitaxel (GemNab).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16758-e16758
Author(s):  
Maria Bensi ◽  
Brunella Di Stefano ◽  
Cinzia Bagalà ◽  
Alexia Spring ◽  
Marta Chiaravalli ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Small Population ◽  
Uncinate Process ◽  
Tumor Shrinkage ◽  
First Line ◽  
Homogeneous Population ◽  
The Impact ◽  
Improved Outcome

e16758 Background: GemNab is one of the first-line standard treatment (tx) of APC. To date, no predictive factors, both clinical and molecular, of benefit from this regimen exist. Two retrospective studies showed that early tumor shrinkage (ETS) can predict an improved outcome in APC pts receiving a first-line tx with FOLFIRINOX or GemNab. However, data regarding GemNab, limited to a small population of only 57 pts, seem to not confirm the association of ETS with a better outcome. Hence, we retrospectively analysed an homogeneous population of APC treated with first-line GemNab at our Institution, investigating the impact of several clinical factors, including response and ETS. Methods: APC pts receiving a first-line tx with GemNab were included in the analysis. The association of RECIST response and ETS with PFS and OS was evaluated. The following variables were collected: gender; age ( > vs ≤ 55 years and ≥ vs < 70 years ); baseline ECOG PS; Ca 19.9 baseline level (≥ vs < 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); locally A vs metastatic (m) PC; synchronous vs metachronous; number of m sites (1 vs > 1); m sites (liver, peritoneum, lung, nodes); number of tx lines (1 vs > 1). Univariate and multivariate analyses for PFS and OS were performed. Results: A total of 184 APC pts receiving first-line GemNab at our Institution from February 2014 to May 2019 were included in the analysis. RR and ETS were assessed in 174 and 168 pts, respectively. RR was 30%, disease control rate (DCR) 63% and ETS was 24%. Responders had a significant better PFS (12.5 vs 5.7 months, p < 0.0001) and OS (25.1 vs 12.1 months, p < 0.0001). ETS was significantly associated with improved PFS (12.3 vs 6.2 months, p < 0.0001) and OS (24.0 vs 12.8 months, p < 0.0001). At the multivariate analysis a significant association with survival parameters was confirmed for RECIST response, but not for ETS. At the multivariate analysis, also metachronous disease and number of tx lines > 1 were independently associated with better OS. Conclusions: Despite its retrospective nature, this is one of the largest series of APC pts treated with first-line GemNab investigating the role of RECIST response and ETS in predicting outcome. On the basis of our results, RECIST response may be considered a positive prognostic factor, whereas ETS does not. In conclusion, achieving tumor shrinkage, not necessarily early, significantly delays PC progression and prolongs survival in pts treated with first-line GemNab.

The impact of 2nd-line treatment (tx) after 1st-line Gemcitabine plus Nab-paclitaxel (GemNab) in advanced pancreatic cancer (APC) patients (pts).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16759-e16759
Author(s):  
Brunella Di Stefano ◽  
Maria Bensi ◽  
Cinzia Bagalà ◽  
Alexia Spring ◽  
Marta Chiaravalli ◽  
...  
Keyword(s):  
Baseline Level ◽  
Advanced Pancreatic Cancer ◽  
Uncinate Process ◽  
Phase Iii ◽  
Combination Regimen ◽  
Homogeneous Population ◽  
Significant Survival ◽  
Ca 19.9 ◽  
Ecog Ps ◽  
The Impact

e16759 Background: Three main phase III randomized studies investigated the role of 2nd-line tx in APC pts. The PANCREOX study failed to demonstrate a survival advantage of mFOLFOX vs 5FU/LV. Conversely, the CONKO-003 and NAPOLI-1 trials, demonstrated a significant survival improvement from the combination regimen OFF and 5FU+Nal-IRI, respectively, in comparison to 5FU/LV alone. Recently, final OS analysis from NAPOLI-1 demonstrated an association of specific characteristics (ECOG PS, age, Ca 19.9 baseline level, neutrophil-to-lymphocyte ratio and no liver metastases (m)) with OS > 1 year. The main limit of all these studies was due to the period they were carried out: no pts received 1st-line GemNab. Hence, we retrospectively analysed an homogeneous population of APC treated with 1st-line GemNab at our Institution, investigating the impact of 2nd-line tx. Methods: APC pts receiving a 2nd-line tx after 1st-line GemNab were included in the analysis. The following variables were collected: gender; age ( > vs ≤ 55 years and ≥ vs < 70 years ); baseline ECOG PS (0-1 vs 2-3); Ca 19.9 baseline level (≥ vs < 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); number of m sites (1 vs > 1); m sites (liver, peritoneum, lung, nodes); RECIST response and ETS during 1-line GemNab. Univariate and multivariate analyses for PFS and OS were performed. Results: Out of 167 APC pts progressed to 1st-line GemNab, 93 (56%) pts received a 2nd-line tx, specifically 58 pts received an oxa-based regimen, 11 FOLFIRINOX, 8 FOLFIRI and 16 pts received other tx. Median 2nd-line PFS and OS were 3.3 and 5.6 months, respectively. Out of 87 pts evaluable for response, 7 pts achieved a partial response and 27 a stable disease, with a RR and a disease control rate (DCR) of 8% and 39%, respectively. Pts with baseline ECOG PS 0-1 had a significant better outcome in comparison to pts with PS 3-4 (PFS 4.2 vs 1.2 months, p < 0.0001; OS 7.2 vs 2.6 months, p = 0.0001). This significant association with survival parameters and ECOG PS was confirmed at the multivariate analysis. Conclusions: Despite the limited number of pts evaluated and the restrospective nature of our analysis, our results are in line with previous evidences, confirming the importance of a 2nd-line combination tx, when feasible, as well in an homogeneous population of APC pts treated with 1st-line GemNab. On the basis of our results, ECOG PS may be considered a prognostic factor and the choice of 2nd-line tx should be guided in primis by the baseline general conditions of APC pts.

Prognostic role of neutrophil-to-lymphocyte ratio (NLR) dynamics during first-line FOLFOXIRI in advanced pancreatic cancer (aPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15754-e15754
Author(s):  
Irene Pecora ◽  
Gianna Musettini ◽  
Silvia Catanese ◽  
Caterina Vivaldi ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
Poor Prognostic Factor

e15754 Background: Elevated pre-treatment NLR is a well-known poor prognostic factor in several tumours, including aPC. However, the role of NLR changes during first-line chemotherapy is less investigated. Methods: We retrospectively evaluated aPC patients (pts) treated with FOLFOXIRI (infusional 5-fluorouracil, oxaliplatin, irinotecan). NLR was calculated before the first (NLR-0) and the fourth (NLR-3) cycle, high NLR being defined as > 4. We evaluated the correlation between NLR change and overall survival (OS), progression-free survival (PFS), response rate (RR) and disease-control-rate (DCR). Survival curves were estimated using the Kaplan-Meier method. Log-rank and chi-square tests were applied. Multivariate analysis was performed by Cox proportional hazards model. Results: Ninety-four pts were evaluable. Median age was 62 years; at diagnosis, 38 (40.4%) pts had unresectable stage III and 56 (59.6%) had stage IV disease. In the overall population, median PFS (mPFS) and OS (mOS) were 8.0 and 12.9 months, respectively. NLR-0 was significantly associated with poor prognosis: among the 12 pts with NLR-0 > 4 mOS was 5.1 months compared with 13.5 months for the 82 pts with NLR-0 ≤4 (p < 0.001). As regards NLR dynamics, NLR-3 remained high or was increased (H/I) in 5 pts (5.3%) while was stably low or decreased (L/D) in 89 pts (94.7%). mOS was 5.1 months (95%CI 0.4-9.8) in H/I and 13.5 months (95%CI 10.9-16.1) in L/D (p < 0.001) pts. The same association was found for PFS, with 4.7 (95%CI 2.1-7.3) vs 8.3 months (95%CI 6.2-10.4, p = 0.004), respectively, but not for RR and DCR. At multivariate analysis, NLR change was confirmed as independent predictor of OS (HR 6.854, 95%CI 2.109-22.269, p = 0.001) and, when added to performance status, liver metastases and NLR-0, allowed a better risk stratification in good (no negative factors), intermediate (1-2 factors) and poor (3-4 factors) risk groups, with mOS of 18.0, 10.0 and 5.1 months, respectively (p = 0.012). Conclusions: Not only NLR-0, but also changes after 3 cycles of first-line FOLFOXIRI could predict OS in aPC pts. Early variations in NLR might be a cheap, reproducible and useful factor to predict prognosis and to better refine treatment strategy.

The Role of Transplantation in Diffuse Large B-Cell Lymphoma: The Impact of Rituximab Plus Chemotherapy in First-line and Relapsed Settings

2010 ◽  
Vol 6 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Celso Arrais Rodrigues ◽  
Poliana Alves Patah ◽  
Yana A. S. Novis ◽  
Chitra Hosing ◽  
Marcos de Lima
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

scholarly journals Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 939 ◽  
Author(s):  
Caterina Vivaldi ◽  
Lorenzo Fornaro ◽  
Carla Cappelli ◽  
Irene Pecora ◽  
Silvia Catanese ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Tumor Shrinkage ◽  
First Line ◽  
Free Survival ◽  
Depth Of Response ◽  
Early Tumor Shrinkage ◽  
Early Tumor

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

A New Cytokine-Based Stratification Is Highly Predictive of Survivals in AML Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1412-1412
Author(s):  
Pierre Peterlin ◽  
Joelle Gaschet ◽  
Thierry Guillaume ◽  
Alice Garnier ◽  
Marion Eveillard ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Risk Stratification ◽  
Univariate Analysis ◽  
Standard Of Care ◽  
Healthy Controls ◽  
First Line ◽  
Serum Samples ◽  
Gm Csf ◽  
Significant Difference ◽  
The Impact

Introduction: Recently, a significant impact of the kinetics of Fms-like tyrosine kinase 3 ligand concentration (FLc) during induction (day[D]1 to D22) has been reported on survivals in first-line acute myeloid leukemia (AML) patients (pts) (Peterlin et al, 2019). Three different FLc profiles were disclosed i) sustained increase of FLc (FLI group, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, intermediate-risk) and iii) stagnation of low levels (&lt;1000 pg/mL, FLL group, high-risk). An update of this prospective monocentric study (www.ClinicalTrials.gov NCT02693899) is presented here evaluating also retrospectively the impact on outcomes of 6 other cytokine level profiles during induction. Methods: Between 05/2016 and 01/2018, 62 AML pts at diagnosis (median age 59 yo [29-71], &lt;60 yo n=33) eligible for first intensive induction were included and provided informed consent. They received standard of care first-line chemotherapy. Serum samples collected on D1, 8, 15 & 22 of induction were frozen-stored until performing ELISA for FL, TNFa, SCF, IL-1b, IL-6, IL-10, GM-CSF. Normal values were assessed in 5 healthy controls. Pts outcomes considered were relapse/leukemia-free (LFS) and overall (OS) survivals. Results: FLI, FLD and FLL profiles were observed for 26, 22 and 14 pts respectively. A total of 372 samples were assayed for the 6 other cytokines. Median concentrations at D1, D8, D15, D22 for these 6 cytokines were as follows, considering the whole cohort (and healthy donors): TNFa: 0.53, 0, 0, 0 (0); SCF: 5.91, 0, 0, 0 (3); IL-1b : 0, 0, 0, 0 (0); IL-6: 4.85, 16.28, 10.11, 7.1 (0), IL-10: 0, 0, 0, 0 (0) and GM-CSF:1.63, 1.8, 0.67, 1.34 (9.98). Median IL-6 and GM-CSF levels, compared to healthy controls, were respectively higher and lower during induction. No significant difference was observed in terms of median cytokine concentrations at any time when comparing the three FL sub-groups or FLI vs FLD pts. With a median follow-up of 28 months (range: 17-37), FLI and FLD pts show now similar 2-y LFS (62.9% vs 59%, p=0.63) and OS (69.2% vs 63.6%, p=0.70). FLL pts have a significantly higher rate of relapse (85,7% vs FLI 19,2% vs FLD 32%, p=0,0001). Comparing FLL vs FLI+FLD pts disclosed significantly different LFS (7.1% vs 61.1%, p&lt;0.001) but not OS (36.7% vs 66.6%, p=0.11). In univariate analysis, 2y LFS and OS were not affected by the concentration (&lt; or &gt; median) of the 7 cytokines studied except for LFS and GM-CSFc at D8 (p=0,04) and D15 (p=0,08), for LFS and FLc at D1 (p=0.06), D8 (p=0,03), D15 (p=0,04) and D22 (p=0,03) and for OS and GM-CSF at D15 (p=0.08). A significant association between LFS was observed with ELN 2017 risk stratification (2-y LFS: favorable: 68,1% vs intermediate: 48,1% vs unfavorable: 30,7%, p=0.03) but not OS (2 y: 77% vs 55,5% vs 46,1%, p=0.09). Multivariate analysis showed that no factor was independently associated with OS while LFS remained significantly associated with the FLc profile (FLL vs others, HR: 5.79. 95%CI: 2.48-13.53, p&lt;0.0001) and GM-CSF at D15 (HR: 0.45; 95%CI: 0.20-0.98, p=0.04) but not with ELN 2017 risk stratification (p=0.06). Cytokine levels were then assessed to try to better discriminate FLI and FLD pts. A significant higher IL-6 level at D22 was found in relapsed or deceased FLI/FLD pts (median:15,34 vs 5,42 pg/mL, p=0,04). FLI/FLD pts with low IL-6 at D22 (&lt; median, 15.5 pg/mL, n=35 vs n=14 with high level) had significant better 2y LFS and OS (74,2% vs 38,4%, p=0,005 and 77,1% vs 38,4%, p=0,009, respectively). A new prognostic risk-stratification could thus be proposed, i.e. FLI/FLD with IL-6 &lt;15.5 pg/mL (favorable), FLI/FLD with IL-6 &gt;15.5 pg/mL (intermediate) and FLL (unfavorable). This new classification was considered for a second multivariate analysis, showing that it is the strongest factor associated with OS (p=0.006, ELN p=0.03, FL profile p=0.04) and LFS (p&lt;0.0001, ELN p=0.005, GM-CSFc D15 p=0.03) (figure 1). Conclusion: This study confirms stagnation of low FLc during AML induction as a strong poor prognosis factor. Moreover, IL-6 levels at D22 further discriminate FLI/FLD pts. Thus, a new cytokine-based risk-stratification integrating FL kinetics and IL-6 levels during induction may help to better predict outcomes in first-line AML patients. These results need to be validated on a larger cohort of AML patients while anti-IL-6 therapy should be tested in combination with standard 3+7 chemotherapy. Figure 1 Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy; Astellas: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria.

The predictive role of CA 19–9 kinetics for time-to-progression (TTP) and overall survival (OS) in patients receiving palliative first-line chemotherapy for advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15637-e15637
Author(s):  
M. Haas ◽  
S. Boeck ◽  
P. Stieber ◽  
R. P. Laubender ◽  
H. Buchner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
First Line ◽  
Predictive Role ◽  
Pre Treatment ◽  
Line Chemotherapy

e15637 Background: Previous studies showed contradictory results for a predictive role of CA 19–9 kinetics during chemotherapy in patients (pts) with pancreatic cancer (PC). Methods: We performed a retrospective, multicenter study in order to evaluate the role of CA 19–9 as a biomarker for TTP and OS in PC. Main inclusion criteria: histological confirmed diagnosis of PC, treatment with first-line chemotherapy for advanced disease, pre-treatment CA 19–9 level of > 5.2 U/ml. As CA 19–9 measurements were conducted in different laboratories using different commercial assays, we defined a subgroup of pts where CA 19–9 was assessed exclusively by the Elecsys assay (Roche Diagnostics). For the analysis of CA 19–9 kinetics, at least one follow-up measurement between day 20 and 64 during first-line chemotherapy had to be available. Pts were divided into two subgroups of CA 19–9 responders and non-responders by cut-offs of a 25% and 50% decline, respectively. OS and TTP were estimated with the Kaplan-Meier-Method, differences between the subgroups were analyzed by using the log-rank test. Results: One hundred and eighty-six pts were included, 83 of them were tested with the Elecsys method. Median age was 63 years, 90 % of the pts were treated within prospective clinical trials. Median pre-treatment CA 19–9 was 1076 U/ml (range 5.7–100,000 U/ml), the median bilirubin was 0.6 mg/dl. Median OS and TTP were 9.8 months (mo) and 5.4 mo, respectively. In univariate analysis, pts with a CA 19–9 decline of at least 25% during chemotherapy lived significantly longer (11.9 mo vs. 8.2 mo, p=0.003) and had a significantly prolonged TTP (5.8 mo vs. 4.4 mo, p=0.018) than those with a lower decline or even CA 19–9 increase. Data for the Elecsys-measurements were comparable (OS: 13.4 mo vs. 8.6 mo, p=0.004; TTP: 7.0 mo vs. 2.6 mo, p=0.003). None of the analyses demanding a CA 19–9 drop of at least 50% reached the level of statistical significance. Conclusion: An early CA 19–9 decline of 25% during first-line chemotherapy may predict OS and TTP in pts with advanced PC. Innovative statistical methods are required to improve our understanding of the utility of CA 19–9 as a predictive biomarker in PC. [Table: see text]

Clinical outcomes of pancreas cancer patients with peritoneal spread: Results from the chord consortium.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19268-e19268
Author(s):  
Mehrnoosh Pauls ◽  
Abdulaziz AlJassim AlShareef ◽  
Winson Y. Cheung ◽  
Rachel Anne Goodwin ◽  
Brandon M. Meyers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Advanced Pancreatic Cancer ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
The Impact ◽  
Line Chemotherapy

e19268 Background: Prior studies have demonstrated that clonal cells that give rise to pancreatic peritoneal metastases (PM) are geographically and genetically distinct from clonal cells, giving rise to lung and liver metastases. The objective of this study was to assess if there is a distinct difference in prognosis and therapeutic response among patients with pancreatic cancer with (PM compared to the lung/liver. Methods: Using a retrospective cohort design, medical records from adult patients diagnosed with metastatic adenocarcinoma of the pancreas at five Canadian academic cancer centers (2014 - 2019) were reviewed. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and first line chemotherapy were collected. Cox proportional hazards model (MVA) was used to examine the association between peritoneal involvement and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 patients were included. Metastatic sites included peritoneum (n = 170, 14.6%), lung (n = 145, 12.5%) and liver (n = 563, 48.5%). Patients with PM received first-line FOLFIRINOX (FFX, n = 31), Gemcitabine + nab-paclitaxel (G/N, n = 20), Gemcitabine (G, n = 18), and no treatment (n = 97). In univariate analyses, worse ECOG PS was associated with PM (p = 0.002). The majority of patients died (89%), with a median overall survival (OS) of 3 vs 7 months for patients with PM and those without PM (p < 0.001), respectively. The median OS in patient whom receive first-line chemotherapy was 7 months in FFX group (95% CI 1.66-12.33), 6 months in G/N (95% CI 4.54-7.45) and 2 months in G group (95% CI 1.42-2.57). Patients had significantly better OS when treated with FFX or G/N compared to G alone (p = 0.002). Time to treatment failure was significantly shorter among patient treated with G alone compare to patients treated with FFX and G/N (P < 0.005). Conclusions: In the setting of combination chemotherapy for advanced pancreatic cancer, patients with PM continue to have a poor prognosis. This may be due to the impact of PM on PS and the inability to administer palliative chemotherapy. For eligible patients, FFX or G/N results in a higher OS than G monotherapy.

scholarly journals Genetic recombination of poliovirus facilitates subversion of host barriers to infection

2018 ◽  
Author(s):  
Ashley Acevedo ◽  
Andrew Woodman ◽  
Jamie J. Arnold ◽  
Ming Te Yeh ◽  
David Evans ◽  
...  
Keyword(s):  
Virus Replication ◽  
Genetic Recombination ◽  
Rna Virus ◽  
Small Population ◽  
Viral Fitness ◽  
Primary Role ◽  
Rna Recombination ◽  
Viral Mutant ◽  
The Impact

AbstractThe contribution of RNA recombination to viral fitness and pathogenesis is poorly defined. Here, we isolate a recombination-deficient, poliovirus variant and find that, while recombination is detrimental to virus replication in tissue culture, recombination is important for pathogenesis in infected animals. Notably, recombination-defective virus exhibits severe attenuation following intravenous inoculation that is associated with a significant reduction in population size during intra-host spread. Because the impact of high mutational loads manifests most strongly at small population sizes, our data suggest that the repair of mutagenized genomes is an essential function of recombination and that this function may drive the long-term maintenance of recombination in viral species despite its associated fitness costs.Significance StatementRNA recombination is a widespread but poorly understood feature of RNA virus replication. For poliovirus, recombination is involved in the emergence of neurovirulent circulating vaccine-derived poliovirus, which has hampered global poliovirus eradication efforts. This emergence illustrates the power of recombination to drive major adaptive change; however, it remains unclear if these adaptive events represent the primary role of recombination in virus survival. Here, we identify a viral mutant with a reduced rate of recombination and find that recombination also plays a central role in the spread of virus within animal hosts. These results highlight a novel approach for improving the safety of live attenuated vaccines and further our understanding of the role of recombination in virus pathogenesis and evolution.

Sign in / Sign up

Export Citation Format

Share Document