GAP - Overall Goal Facilitates and administers MD Anderson's Sister Institution Network (the largest network of cancer centers) working collaboratively on education, research, patient care aimeing at lessening the world's cancer burden

MDACC Global Academic Programs Sister Institution Network (N= 26)

SINF National Breast Cancer Foundation: $300,000

Joint Publications

1.Yang W, Xia Y, Ji H, Zheng Y, Liang J, Huang W, Gou X, Aldape K, Lu Z. Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature, 480(7375):118–22, Dietrich S, Glimm H, Andrulis M, Kalle von C, Ho AD, Zenz T. BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med, 366(21):2038–40, Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Alfred Yung WK, Lu Z. PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis. Cell, 150(4):685–96, Zhang M, Maiti S, Bernatchez C, Huls H, Rabinovich B, Champlin RE, Vence LM, Hwu P, Radvanyi L, Cooper LJ. A New Approach to Simultaneously Quantify Both TCR - and -Chain Diversity after Adoptive Immunotherapy. Clin Cancer Res, 18(17):4733–42, 2012.

Nasopharyngeal Carcinoma MDACC RTOG CUHK CGU, NTU

Nasopharyngeal Carcinoma 5-Year Disease Specific Survival Rate Source: Anne Lee, Pamela Youde Nethersole Eastern Hospital, Hong Kong ~80% ~50% ~35% 0%

NPC: Stage at Diagnosis Anne Lee (PYNEH-Hong Kong) : 1185 patients

Nasopharyngeal Carcinoma 5-Year Disease Specific Survival Rate Source: Anne Lee, Pamela Youde Nethersole Eastern Hospital, Hong Kong ~80% ~50% ~35% 0% Cobalt LINAC Chemotherapy & IMRT

Standard Therapy for Locally Advanced NPC IMRT+ CDDP  CDDP+FU x3 P= Al-Sarraf et al., JCO, 1998 Validation: Wee et al., JCO, N= 87 Median FU=30 months Months Percent 5-Y nodal control: 97% 5-Y primary tumor control: 94% 5-Y metastasis-free: 66% Lee et al., IJROBP, 2002 Intergroup Trial

IMRT + Chemotherapy for NPC SeriesNStage FU (Mos) LCDM-Free Bucci IJROBP, 2004 (US) % T % (4-Y) 72% (4-Y) Kam IJROBP, 2004 (HK) 63 51% T % (3-Y) 79% (3-Y) Woldren IJROBP, 2005 (Canada) 74 50% T % (3-Y) 78% (3-Y) Lee JCO, 2005 (RTOG) 68 58% T % (2-Y) 85% (2-Y)

Nasopharyngeal Carcinoma Impact of Post-Rx EBV Titer on Outcome Chan et al., JNCI 94: 1614, 2002 (Chinese University of Hong Kong) Validation: Lin et al., NEJM, 2004 (Taiwan); Le et al., CCR, 2004 (US) <500 copies >500 copies

REGISTERREGISTER NPC Trial Concept T≥2 or N+ WHO I-III CDDP + 5FU x3 IMRT (70 Gy) + CDDP (40 mg/m 2 X7) Taxane + Gem EBV>0 R R EBV= 0 Observe IMRT Credentialing & QA EBV Assay Harmonization Phase III: 770 Phase IIR: 156

Credentialing & QA: IMRT H&N Phantom  Primary PTV 4 cm diameter 4 TLD  Secondary PTV 2 cm diameter 2 TLD  Organ at risk 1 cm diameter 2 TLD  Axial and sagittal radiochromic films 1º PTV treated to 6.6 Gy 2º PTV treated to 5.4 Gy OAR limited to < 4.5 Gy Secondary PTV Primary PTV Organ at Risk Designed in collaboration with RTOG; Molineu et al, IJROBP, October 2005 MDACC (P01 funded)

Results of Two Centers

EBV Assay An International Collaboration to Harmonize the Quantitative Plasma Epstein-Barr Virus (EBV) DNA Assay for Future Biomarker-Guided Trials in Nasopharyngeal Carcinoma Le QT 1, Zhang Q 2, Cao HB 1, Cheng AJ 3, Pinsky BA 1, Hong RL 4, Chang JT 3, Wang CW 4, Kuo-Chien Tsao KC 3, Lo YMD 6, Lee N 5, Ang KK 7, Chan ATC 6, Chan AKC 6 1 Stanford University, 2 RTOG Statistical Center, 3 Chang-Gung University, 4 National Taiwan University Hospital, 5 Memorial Sloan Kettering Cancer Center, 6 The Chinese University of Hong Kong, 7 M.D. Anderson Cancer Center