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 ProgramsSister Institution Network (N= 26)

SINF

National Breast Cancer Foundation: $300,000

Joint Publications

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, 2011.

2. 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, 2012.

3. 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, 2012.

4. 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

1985 200019691930

~80%

~50%

~35%

0%

NPC: Stage at Diagnosis

Anne Lee (PYNEH-Hong Kong) 1994-2005: 1185 patients

Nasopharyngeal Carcinoma 5-Year Disease Specific Survival Rate

Source: Anne Lee, Pamela Youde Nethersole Eastern Hospital, Hong Kong

1985 200019691930

~80%

~50%

~35%

0%

Cobalt

LINAC

Chemotherapy& IMRT

Standard Therapy for Locally Advanced NPC IMRT+ CDDP CDDP+FU x3

P= 0.005

Al-Sarraf et al., JCO, 1998Validation: Wee et al., JCO, 2005

7060504030201000

10

20

30

40

50

60

70

80

90

100

N= 87 Median FU=30 months

Months

Per

cen

t

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

Series N Stage FU(Mos)

LC DM-Free

BucciIJROBP, 2004 (US)

118 50%T3-4 30 96%

(4-Y)72%(4-Y)

KamIJROBP, 2004 (HK)

63 51%T3-4 29 92%

(3-Y)79%(3-Y)

WoldrenIJROBP, 2005 (Canada)

74 50%T3-4 35 91%

(3-Y)78%(3-Y)

LeeJCO, 2005 (RTOG)

68 58%T2-4 30 93%

(2-Y)85%(2-Y)

Nasopharyngeal CarcinomaImpact 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

>500 copies

>500 copies

REGISTER

NPC Trial Concept

T≥2 or N+

WHO I-III

CDDP + 5FU x3

IMRT (70 Gy)

+ CDDP

(40 mg/m2

X7) Taxane+ Gem

EBV>0 R

REBV= 0

Observe

IMRT Credentialing & QAEBV Assay Harmonization

Phase III: 770

Phase IIR: 156

Credentialing & QA: IMRT H&N Phantom

Primary PTV4 cm diameter4 TLD

Secondary PTV2 cm diameter2 TLD

Organ at risk1 cm diameter2 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 QT1, Zhang Q2, Cao HB1, Cheng AJ3, Pinsky BA1, Hong RL4, Chang JT3, Wang CW4, Kuo-Chien Tsao KC3, Lo YMD6, Lee N5,

Ang KK7, Chan ATC6, Chan AKC6

1Stanford University, 2RTOG Statistical Center, 3Chang-Gung University,4National Taiwan University Hospital, 5Memorial Sloan Kettering Cancer Center,

6The Chinese University of Hong Kong, 7M.D. Anderson Cancer Center