Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy.
OBJECTIVE
The Cancer Imaging Program of the National Cancer Institute convened a workshop to assess the current status of hypoxia imaging, to assess what is known about the biology of hypoxia as it relates to cancer and cancer therapy, and to define clinical scenarios in which in vivo hypoxia imaging could prove valuable.


RESULTS
Hypoxia, or low oxygenation, has emerged as an important factor in tumor biology and response to cancer treatment. It has been correlated with angiogenesis, tumor aggressiveness, local recurrence, and metastasis, and it appears to be a prognostic factor for several cancers, including those of the cervix, head and neck, prostate, pancreas, and brain. The relationship between tumor oxygenation and response to radiation therapy has been well established, but hypoxia also affects and is affected by some chemotherapeutic agents. Although hypoxia is an important aspect of tumor physiology and response to treatment, the lack of simple and efficient methods to measure and image oxygenation hampers further understanding and limits their prognostic usefulness. There is no gold standard for measuring hypoxia; Eppendorf measurement of pO(2) has been used, but this method is invasive. Recent studies have focused on molecular markers of hypoxia, such as hypoxia inducible factor 1 (HIF-1) and carbonic anhydrase isozyme IX (CA-IX), and on developing noninvasive imaging techniques.


CONCLUSIONS
This workshop yielded recommendations on using hypoxia measurement to identify patients who would respond best to radiation therapy, which would improve treatment planning. This represents a narrow focus, as hypoxia measurement might also prove useful in drug development and in increasing our understanding of tumor biology.
Tatum
James L
JL
National Cancer Institute, Executive Plaza North, Room 6000, 6130 Executive Boulevard, Rockville, MD 20852-7440, USA. tatumj@mail.nih.gov
Kelloff
Gary J
GJ
Gillies
Robert J
RJ
Arbeit
Jeffrey M
JM
Brown
J Martin
JM
Chao
K S Clifford
KS
Chapman
J Donald
JD
Eckelman
William C
WC
Fyles
Anthony W
AW
Giaccia
Amato J
AJ
Hill
Richard P
RP
Koch
Cameron J
CJ
Krishna
Murali Cherukuri
MC
Krohn
Kenneth A
KA
Lewis
Jason S
JS
Mason
Ralph P
RP
Melillo
Giovanni
G
Padhani
Anwar R
AR
Powis
Garth
G
Rajendran
Joseph G
JG
Reba
Richard
R
Robinson
Simon P
SP
Semenza
Gregg L
GL
Swartz
Harold M
HM
Vaupel
Peter
P
Yang
David
D
Croft
Barbara
B
Hoffman
John
J
Liu
Guoying
G
Stone
Helen
H
Sullivan
Daniel
D
D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009316:National Institutes of Health (U.S.); D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D011379:Prognosis; D011859:Radiography; D015203:Reproducibility of Results; D014481:United States
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051793:Hypoxia-Inducible Factor 1; D007527:Isoenzymes; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D010100:Oxygen