title: Rapid and objective CT scan prognostic scoring identifies metastatic patients with long-term clinical benefit on anti-PD-1/-L1 therapy.
abstract: Drugs targeting programmed death receptor-1 (PD-1) and its ligand PD-L1 have shown activity in multiple malignancies. Considering their novel mechanism of action, whether traditional prognostic scores also apply to patients treated with these drugs is unknown. We investigated whether a baseline 3-point (pt) computed tomography (CT) scan (PS3-CT) score and a 7-pt prognostic (PS7) score allowed identifying long-term survivors on anti-PD-1/-L1 therapy.
  
  
  
  We reviewed 251 consecutive patients enrolled in phase I trials evaluating anti-PD-1/-L1 agents between 26th December 2011 and 7th September 2015. PS3-CT was calculated using high tumour burden (TB1D-RECIST > 9 cm), low skeletal muscle index (SMI < 53 cm(2) m(-2)) and non-pulmonary visceral metastases (NPVM) (1 pt each). PS7 was calculated by adding lower performance status, decreased serum albumin, increased serum lactate dehydrogenase and more than two distant metastases (1 pt each). Effect on overall survival (OS) of each parameter was tested using Kaplan-Meier and multivariable Cox analyses.
  
  
  
  PS3-CT was a significant independent predictor of OS (hazard ratio [HR] = 1.39 [95% confidence interval {CI} = 1.07-1.81], p = 0.01) when compared to the Royal Marsden Hospital, Barbot and American Joint Committee on Cancer scores. High TB (n = 78), low SMI (n = 55) and NPVM (n = 146) were associated with poorer survival (p < 0.01). High TB and low SMI were independent predictors of OS (respective HR of death: 2.00 [95% CI = 1.38-2.88], p < 0.01 and 1.75 [95% CI = 1.15-2.66], p < 0.01). PS7 was a significant predictor of OS (HR = 1.40 [95% CI = 1.25-1.56], p < 0.01).
  
  
  
  Objective and rapid-risk scoring based on three CT scan parameters allows identifying patients with prolonged OS on anti-PD-1/-L1 therapy, independently from conventional clinical-biological prognostic scores.
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France; Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, F-94805, France. Electronic address: laurent.dercle@gustaveroussy.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dercle
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Ammari
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Champiat
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferté
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France.
authors.forename: Lokmane
authors.initials: L
authors.lastname: Taihi
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France.
authors.forename: Romain-David
authors.initials: RD
authors.lastname: Seban
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Aspeslagh
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Mahjoubi
authors.affiliation: Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Department of Medical Oncology, Villejuif, F-94805, France.
authors.forename: Nyam
authors.initials: N
authors.lastname: Kamsu-Kom
authors.affiliation: Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Department of Medical Oncology, Villejuif, F-94805, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.affiliation: Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, F-94805, France; Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France; Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, F-94805, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.affiliation: Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France; Gustave Roussy, Université Paris-Saclay, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Villejuif, F-94805, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France; Gustave Roussy, Université Paris-Saclay, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Villejuif, F-94805, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009378:Neoplasms, Multiple Primary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D066066:Response Evaluation Criteria in Solid Tumors; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen
keywords: CT scan; Immunotherapy; PD-1; PD-L1; Prognostic score