Blood tests to predict one- to two-year survival of patients with difficult cancers.
Authors: De Jager Robert L. , Bruckner Howard , Bassali Fred , Dusowitz Elisheva , Book AJ , Distenfeld Shoshana , Hirschfeld Azriel 
Published: June 2021

e16158

Background: A sequence of drug combinations produces > 1 median (M) -strong 2-year (yr) survival (S) (Bruckner et al AACR 14 Antica Res (ACR) 16, 18 SIGO 19). Trials included high-risk patients (pts). Each initial series has 5-yr Ss, after pts were referred for hospice care. Prognostic ALAN blood tests (Ts) have been validated for stage IV (Adv) Cholangiocarcinoma (CCA) (Salati et al EuJCa18). Other Ts predict unexpected favorable (F) S of pts with gastric ca, PS 2-3. Bruckner et al JAMA, 82); but, there is little known about Ts for resistant (R) Ca. Methods: Planned Kaplan-Meier intent to treat analysis to find Ts that: expand eligibility (El) for therapy; identify biomarkers that predict therapy can prolong S and identify new hypotheses for therapy. El pts have:R to test drugs, Pancreatic (PC), Intrahepatic bile duct, CCA, Colon, CRC and new (N) APC. All series: -/+ high risk, -/+ aged, PS 0-2. El: Helsinki criteria- consent, recovered from severe (gr3) toxicity; able to reach office, -/+ help, and S > 6 wks. Inel: CNS involved, IV needed, F clinical factors predict 1 yr MST. Ts include A.L.A.N. scores, (AS) (Salati ibid) and other blood Ts (ACR ibid, Lavin et al CTR 82) Therapy GFLIO in mg/M2: gemcitabine 500, leucovorin 180, fluorouracil 1200, 24 hr infusion. Irinotecan 80 D2 Oxaliplatin 40. Then for progression (pg), add docetaxel 20-25, except CRC mitomycin C 4-6; next pg add cetuximab, except APC or KRAS-M, weekly, and next pg replace cetuximab with bevacizumab 10mg/kg ibid ACR 16. Results: At all ages, overall (O) S is > 1 yr for RCRC, and NAPC and sets with any 1 F or UnF T other than < 3.1 Albumin (Alb) or < 2.1 lymph/monocyte ratio (LMR) b For CCA, 17R/16N, OMS > 2 yrs 66% of pts and ≥ 2 yrs for all test sets except UnF, 26% of pts, MS 17 mos, with low Alb. For CRC: 50R OMS is 16.5 mos; 42% S 2 yrs, Fav Ts: MS > ̃ 2yrs, 39-82% of pts have FTs; Neutrophil Lymphocyte Ratio (NLR); < 3.1, 61% S 2 yrs, p < .02; Lymphs > 1.5, 53% S 2 yrs, p < .02; AS 0; 59% S 2 yrs, p < .06; Platelets < 300,000, 54% S 2 yrs, p < .06; Alb: ≥ 3.5, 48% S 2 yrs, p < .11. For N-APC: 53 pts, OS is 14.5 mos and > 12 mos in sets with any 1 UnF T other than Alb or LMR. FTs: MST 16.4-18 mos. 34-77% of pts have FTs; Alb ≥ 3.5, 34% S 2 yrs, p < 0.001; WBC < 10, 29% S 2 yrs, p < .06; AS 0-2, 35% S 2 yrs, p 2.7E-7. For R-PC: 53 pts, OS is 12 mos for 44% of pts, FTs: MST 13.6-17 mos, 21-70% of pts have FTs: Alb ≥ 3.5 30% S 2 yrs, p .0004; AS: 0, 41% S 2 yrs, p .0006; NLR < 3, 37% S 2 yrs, p < .02. GFLIO’s < 5% gr3 induction toxicity, is reversible, with no hospitalization, neutropenic fever or gr3 neuropathy. Conclusions: Robust Ts identify many difficult pts with median > 1 and testable prospective > 2 yr rates of S. Ts warrant development: validation with GFLIO and other therapy and other cancers; to improve Ts, models for eligibility and geriatric criteria; to identify false -/+ trials; and personalize trials to correct UnF Ts. FTs, with GFLIO, can change prognosis and practice for > 50% of pts now advised “against” any therapy due to a clinical estimate of “less than 6 -10 mos to live.” Clinical trial information: NCT01905150.