Usha Patel1,2, Sadhana Kannan2,3, Swapnil U Rane2,4, Neha Mittal2,5, Poonam Gera2,6, Asawari Patil2,4, Subhakankha Manna1, Vishwayani Shejwal1, Vanita Noronha2,7, Amit Joshi2,7, Vijay M Patil2,7, Kumar Prabhash2,7, Manoj B Mahimkar8,9. 1. Mahimkar Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India. 2. Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, India. 3. Biostatistician, Clinical Research Secretariat, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India. 4. Department of Pathology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India. 5. Department of Pathology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. 6. Biorepository, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India. 7. Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. 8. Mahimkar Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India. mmahimkar@actrec.gov.in. 9. Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, India. mmahimkar@actrec.gov.in.
Abstract
BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are needed to identify the patients most likely to benefit from these therapies. Here, we present predictive and prognostic associations of different cancer stem cell markers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Pretreatment tumour tissues of 404 HPV-negative LA-HNSCCs patients, a subset of-phase 3-randomised study comparing cisplatin-radiation(CRT) and nimotuzumab plus cisplatin-radiation(NCRT) were examined. The expression levels of CD44, CD44v6, CD98hc, ALDH1A1, SOX2 and OCT4A were evaluated using immunohistochemistry. Progression-free survival(PFS), loco-regional control(LRC),- and overall survival(OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: NCRT showed significantly improved OS with low membrane expression of CD44 compared to CRT [HR (95% CI) = 0.63 (0.46-0.88)]. Patients with low CD44v6 also showed better outcomes with NCRT [LRC: HR (95% CI) = 0.25 (0.10-0.62); OS: HR (95% CI) = 0.38 (0.19-0.74)]. No similar benefit with NCRT observed in patients with high CD44 or CD44v6 expression. Bootstrap resampling confirmed the predictive effect of CD44 (Interaction P = 0.015) and CD44v6 (Interaction P = 0.041) for OS. Multivariable Cox analysis revealed an independent negative prognostic role of CD98hc membrane expression for LRC [HR (95% CI) = 0.63(0.39-1.0)] and OS[HR (95% CI) = 0.62 (0.40-0.95)]. CONCLUSIONS: CD44 and CD44v6 are potential predictive biomarkers for NCRT response. CD98hc emerged as an independent negative prognostic biomarker. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).
BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are needed to identify the patients most likely to benefit from these therapies. Here, we present predictive and prognostic associations of different cancer stem cell markers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Pretreatment tumour tissues of 404 HPV-negative LA-HNSCCs patients, a subset of-phase 3-randomised study comparing cisplatin-radiation(CRT) and nimotuzumab plus cisplatin-radiation(NCRT) were examined. The expression levels of CD44, CD44v6, CD98hc, ALDH1A1, SOX2 and OCT4A were evaluated using immunohistochemistry. Progression-free survival(PFS), loco-regional control(LRC),- and overall survival(OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: NCRT showed significantly improved OS with low membrane expression of CD44 compared to CRT [HR (95% CI) = 0.63 (0.46-0.88)]. Patients with low CD44v6 also showed better outcomes with NCRT [LRC: HR (95% CI) = 0.25 (0.10-0.62); OS: HR (95% CI) = 0.38 (0.19-0.74)]. No similar benefit with NCRT observed in patients with high CD44 or CD44v6 expression. Bootstrap resampling confirmed the predictive effect of CD44 (Interaction P = 0.015) and CD44v6 (Interaction P = 0.041) for OS. Multivariable Cox analysis revealed an independent negative prognostic role of CD98hc membrane expression for LRC [HR (95% CI) = 0.63(0.39-1.0)] and OS[HR (95% CI) = 0.62 (0.40-0.95)]. CONCLUSIONS: CD44 and CD44v6 are potential predictive biomarkers for NCRT response. CD98hc emerged as an independent negative prognostic biomarker. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).
Authors: Maura L Gillison; Andy M Trotti; Jonathan Harris; Avraham Eisbruch; Paul M Harari; David J Adelstein; Richard C K Jordan; Weiqiang Zhao; Erich M Sturgis; Barbara Burtness; John A Ridge; Jolie Ringash; James Galvin; Min Yao; Shlomo A Koyfman; Dukagjin M Blakaj; Mohammed A Razaq; A Dimitrios Colevas; Jonathan J Beitler; Christopher U Jones; Neal E Dunlap; Samantha A Seaward; Sharon Spencer; Thomas J Galloway; Jack Phan; James J Dignam; Quynh Thu Le Journal: Lancet Date: 2018-11-15 Impact factor: 79.321
Authors: Hisham Mehanna; Max Robinson; Andrew Hartley; Anthony Kong; Bernadette Foran; Tessa Fulton-Lieuw; Matthew Dalby; Pankaj Mistry; Mehmet Sen; Lorcan O'Toole; Hoda Al Booz; Karen Dyker; Rafael Moleron; Stephen Whitaker; Sinead Brennan; Audrey Cook; Matthew Griffin; Eleanor Aynsley; Martin Rolles; Emma De Winton; Andrew Chan; Devraj Srinivasan; Ioanna Nixon; Joanne Grumett; C René Leemans; Jan Buter; Julia Henderson; Kevin Harrington; Christopher McConkey; Alastair Gray; Janet Dunn Journal: Lancet Date: 2018-11-15 Impact factor: 79.321