Parallel sequencing of a 50 genes panel in metastatic colorectal cancer (MCRC) patients (pts) treated with intensive first-line FIr-B/FOx triplet chemotherapy plus bevacizumab (BEV): Preliminary data and clinical outcome.

644 Background: RAS/BRAF genotype guide MCRC treatment. First line triplet chemotherapy/BEV significantly improved PFS and OS. OS was significantly worse in KRAS c.35G > A and BRAF mutant (mt). Most CRC (86%) harbored mt genes, prevalently TP53, RAS, BRAF, PIK3CA. Methods: MCRC samples of 67 pts treated with FIr-B/FOx (77% overall) were analyzed through a 50 genes panel (PGM/Colon Lung Cancer) by ION Torrent: 57 (85%) primary, 10 (15%) metastatic samples; 59 (88%) pre-, 8 (12%) post-treatment. Molecular diagnostic criteria: > 50% coverage; > 1% mutant allelic fraction. Clinical outcomes were evaluated and compared by log-rank. Results: All wild-type (wt) and mt MCRC were 6 (8.9%) and 61 (91.1%), respectively; median mt genes 3 (1-12). Mt genes, 35 (%): KRAS 44 (65.6%), TP53 38 (56.7%), APC 26 (38.8%), KIT 23 (34.3%), PDGFRA 19 (28.3%), PIK3CA 18 (26.8%), EGFR and NRAS 15 (22.3%), SMAD4 10 (14.9%), FBXW7 and MET 7 (10.4%), GNAS and PTEN 6 (8.9%), BRAF and NOTCH1 5 (7.4%), ATM, PTPN11 and SMARCB1 4 (5.9%), HRAS, KDR, JAK3 and VHL 3 (4.4%), ERBB2, FGFR2, FGFR3, IDH1 and STK11 2 (2.9%), ABL1, AKT1, CDKN2A, FGFR1, FLT3, HNF1A, RB1, RET 1 (1.4%). BRAF mutations: c.1756G > A, 1796C > T, 1405G > A, 1406G > C. Median follow-up 21 months (m), overall PFS 13, OS 27m: KRAS exon 2 ( KRAS2) wt/mt, PFS 14/12m, OS 28/21m, respectively, not significantly different; c.35G > A KRAS mt showed trendly worse OS 14m; BRAF mt significantly worse PFS (8 vs 14m, p .026) and OS (11 vs 28m, p .002); RAS2-4/ BRAF15 wt/mt, PFS 18/13m (p .954), OS 28/22m (p .956). TP53 wt/mt, PFS 14/12m, OS 28/23m. All wt, PFS 24, OS 44m, not significantly different vs ≥ 1 mt gene. Conclusions: Multigenic analysis of MCRC patients treated with FIr-B/FOx shows worse clinical outcome conferred by uncommon BRAF mutations.

Abstracts of Meeting Papers

Vol.36 p. 954: In abstract 0014, the concentration of total plasma homocysteine (TH) should be in mmol/L. Vol.37 p. 933: In abstract 0114, line 7, the actual value for Patient 2 should be 2700 U/L. p. 1187: In Table 1, the column heading for the right-most column should be "Rel. std. dev. of mean, %." p. 1290: In Table 1, the name of the steroid is dehydrochloromethyltestosterone. p. 1667: In the right-hand column, line 13, the correct name of the manufacturer of the antigen-based assay is Innogenetics. p. 1977: The captions for Figures 1 and 2 are correct, but the chromatograms should be interchanged. p. 2017: In the first sentence in the Letter that begins on this page, the incorrect editorially inserted word "gut" should be omitted. p.2138: In Table 1, footnote α should indicate that the results for Guadeloupe and for Martinique are significantly different from the previous data (P 0.001, chisquare test) but are not significantly different from each other; results in references 2-6 also are not significantly different from one another.

A Bisṭāmī-legend

Brockelmann, G.A.L. Erster Supplementband, p. 353, mentions a Kitāb Masā'il al-ruhbān, ascribed to the famous Ṣūfī Abū Yazīd al-Bisṭāmī, of which a copy is preserved in the Āṭafīya Library in Hyderabad. (Two other copies of the same work, one in Hyderabad and one at Istanbul, are recorded ibid. Nachträge, p. 954.) Through the kindness of Dr. Stapleton I have obtained a copy of the Hyderabad manuscript (described in vol. i, p. 388, of the Āṣafīya catalogue), and this transcript is now deposited in the India Office Library, under the serial number 4585.