Prognostic gene expression signature for high-grade serous ovarian cancer
Por:
Millstein, J, Budden, T, Goode, EL, Anglesio, MS, Talhouk, A, Intermaggio, MP, Leong, HS, Chen, S, Elatre, W, Gilks, B, Nazeran, T, Volchek, M, Bentley, RC, Wang, C, Chiu, DS, Kommoss, S, Leung, SCY, Senz, J, Lum, A, Chow, V, Sudderuddin, H, Mackenzie, R, George, J, Fereday, S, Hendley, J, Traficante, N, Steed, H, Koziak, JM, Kobel, M, McNeish, IA, Goranova, T, Ennis, D, Macintyre, G, De Silva, DS, Cajal, TRY, Garcia-Donas, J, Polo, SH, Rodriguez, GC, Cushing-Haugen, KL, Harris, HR, Greene, CS, Zelaya, RA, Behrens, S, Fortner, RT, Sinn, P, Herpel, E, Lester, J, Lubinski, J, Oszurek, O, Toloczko, A, Cybulski, C, Menkiszak, J, Pearce, CL, Pike, MC, Tseng, C, Alsop, J, Rhenius, V, Song, H, Jimenez-Linan, M, Piskorz, AM, Gentry-Maharaj, A, Karpinskyj, C, Widschwendter, M, Singh, N, Kennedy, CJ, Sharma, R, Harnett, PR, Gao, B, Johnatty, SE, Sayer, R, Boros, J, Winham, SJ, Keeney, GL, Kaufmann, SH, Larson, MC, Luk, H, Hernandez, BY, Thompson, PJ, Wilkens, LR, Carney, ME, Trabert, B, Lissowska, J, Brinton, L, Sherman, ME, Bodelon, C, Hinsley, S, Lewsley, LA, Glasspool, R, Banerjee, SN, Stronach, EA, Haluska, P, Ray-Coquard, I, Mahner, S, Winterhoff, B, Slamon, D, Levine, DA, Kelemen, LE, Benitez, J, Chang-Claude, J, Gronwald, J, Wu, AH, Menon, U, Goodman, MT, Schildkraut, JM, Wentzensen, N, Brown, R, Berchuck, A, Chenevix-Trench, G, DeFazio, A, Gayther, SA, Garcia, MJ, Henderson, MJ, Rossing, MA, Beeghly-Fadiel, A, Fasching, PA, Orsulic, S, Karlan, BY, Konecny, GE, Huntsman, DG, Bowtell, DD, Brenton, JD, Doherty, JA, Pharoah, PDP, Ramus, SJ
Publicada:
1 sep 2020
Resumen:
Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is similar to 4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.
Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.
Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.
Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.
Filiaciones:
Millstein, J:
Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90007 USA
Budden, T:
Univ NSW Sydney, Fac Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
Univ Manchester, CRUK Manchester Inst, Manchester, Lancs, England
Goode, EL:
Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, NY USA
Anglesio, MS:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada
Talhouk, A:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada
Intermaggio, MP:
Univ NSW Sydney, Fac Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
Leong, HS:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Chen, S:
Cedars Sinai Med Ctr, Ctr Canc Prevent & Translat Genom, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA
Elatre, W:
Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90007 USA
Gilks, B:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
Nazeran, T:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Volchek, M:
Royal Womens Hosp, Anat Pathol, Parkville, Vic, Australia
Bentley, RC:
Duke Univ Hosp, Dept Pathol, Durham, NC USA
Wang, C:
Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, NY USA
Chiu, DS:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Kommoss, S:
Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Leung, SCY:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Senz, J:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
Lum, A:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Chow, V:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Sudderuddin, H:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Mackenzie, R:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
George, J:
Jackson Lab Genom Med, Farmington, CT USA
Fereday, S:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Hendley, J:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Traficante, N:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Steed, H:
Royal Alexandra Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Edmonton, AB, Canada
Koziak, JM:
Alberta Hlth Serv Canc Care, Calgary, AB, Canada
Kobel, M:
Univ Calgary, Foothills Med Ctr, Dept Pathol & Lab Med, Calgary, AB, Canada
McNeish, IA:
Imperial Coll London, Div Canc, Dept Surg & Canc, London, England
Imperial Coll London, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England
Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland
Goranova, T:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
Ennis, D:
Imperial Coll London, Div Canc, Dept Surg & Canc, London, England
Imperial Coll London, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England
Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland
Macintyre, G:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
De Silva, DS:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain
Garcia-Donas, J:
HM Hosp D Ctr Integral Oncol HM Clara Campal, Madrid, Spain
Polo, SH:
Hosp Univ Funcac Alcorcon, Med Oncol Serv, Alcorcon, Spain
Rodriguez, GC:
Univ Chicago, NorthShore Univ HealthSyst, Div Gynecol Oncol, Evanston, IL USA
Cushing-Haugen, KL:
Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA
Harris, HR:
Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA
Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
Greene, CS:
Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA
Zelaya, RA:
GeiselSch Med Dartmouth, Dept Genet, Hanover, NH USA
Behrens, S:
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Vic, Australia
Fortner, RT:
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Vic, Australia
Sinn, P:
Univ Hosp Heidelberg, Inst Pathol, Dept Pathol, Heidelberg, Germany
Herpel, E:
Univ Hosp Heidelberg, Inst Pathol, Dept Pathol, Heidelberg, Germany
Univ Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany
German Canc Res Ctr, Heidelberg, Germany
Lester, J:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA
Lubinski, J:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Oszurek, O:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Toloczko, A:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Cybulski, C:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Menkiszak, J:
Pomeranian Med Univ, Dept Gynecol Surg & Gynecol Oncol Adults & Adoles, Szczecin, Poland
Pearce, CL:
Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA
Univ Southern Calif, Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA
Pike, MC:
Univ Southern Calif, Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA
Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA
Tseng, C:
Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA
Alsop, J:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Rhenius, V:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Song, H:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Jimenez-Linan, M:
Addenbrookes Hosp NHS Trust, Dept Pathol, Cambridge, England
Piskorz, AM:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
Gentry-Maharaj, A:
UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit UCL, London, England
Karpinskyj, C:
UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit UCL, London, England
Widschwendter, M:
UCL, Inst Womens Hlth, Dept Womens Canc, London, England
Singh, N:
Barts Hlth Natl Hlth Serv Trust, Dept Pathol, London, England
Kennedy, CJ:
Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Sharma, R:
Univ Sydney, Westmead Hosp, Pathol West ICPMR Westmead, Sydney, NSW, Australia
Univ Western Sydney, Westmead Hosp, Sydney, NSW, Australia
Harnett, PR:
Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia
Westmead Hosp, Crown Princess Mary Canc Ctr Westmead, Sydney West Canc Network, Sydney, NSW, Australia
Gao, B:
Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia
Westmead Hosp, Crown Princess Mary Canc Ctr Westmead, Sydney West Canc Network, Sydney, NSW, Australia
Johnatty, SE:
QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia
Sayer, R:
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Boros, J:
Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Winham, SJ:
Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, NY USA
Keeney, GL:
Mayo Clin, Div Anat Pathol, Dept Lab Med & Pathol, Rochester, NY USA
Kaufmann, SH:
Mayo Clin, Dept Oncol, Rochester, NY USA
Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, NY USA
Larson, MC:
Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, NY USA
Luk, H:
Univ Hawaii, Canc Epidemiol Program, Canc Ctr, Honolulu, HI 96822 USA
Hernandez, BY:
Univ Hawaii, Canc Epidemiol Program, Canc Ctr, Honolulu, HI 96822 USA
Thompson, PJ:
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Genet Program, Los Angeles, CA 90048 USA
Wilkens, LR:
Univ Hawaii, Canc Epidemiol Program, Canc Ctr, Honolulu, HI 96822 USA
Carney, ME:
Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA
Trabert, B:
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
Lissowska, J:
M Sklodowska Curie Natl Res Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland
Brinton, L:
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
Sherman, ME:
Mayo Clin, Coll Med, Dept Hlth Sci Res, Jacksonville, FL 32224 USA
Bodelon, C:
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
Hinsley, S:
Univ Glasgow, Inst Canc Sci, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland
Lewsley, LA:
Univ Glasgow, Inst Canc Sci, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland
Glasspool, R:
Beatson West Scotland Canc Ctr, Dept Med Oncol, Glasgow, Lanark, Scotland
Univ Glasgow, Glasgow, Lanark, Scotland
Banerjee, SN:
Royal Marsden NHS Fdn Trust, London, England
Inst Canc Res, London, England
Stronach, EA:
Imperial Coll London, Div Canc, Dept Surg & Canc, London, England
Imperial Coll London, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England
Haluska, P:
Mayo Clin, Dept Oncol, Rochester, NY USA
Ray-Coquard, I:
Ctr Leon Berard, Lyon, France
Univ Claude Bernard Lyon 1, Lyon, France
Mahner, S:
Ludwig Maximilians Univ Munchen, Dept Obstet & Gynecol, Univ Hosp, Munich, Germany
Winterhoff, B:
Univ Minnesota, Dept Obstet Gynecol & Womens Hlth, Minneapolis, MN USA
Slamon, D:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA
Levine, DA:
Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, 1275 York Ave, New York, NY 10021 USA
NYU Langone Med Ctr, Laura & Isaac Pearlmutter Canc Ctr, Gynecol Oncol, New York, NY USA
Kelemen, LE:
Med Univ South Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA
Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA
Benitez, J:
Ctr Invest Red Enfermedades Raras CIBERER, Madrid, Spain
Spanish Natl CancerRes Ctr CNIO, Human Canc Genet Programme, Madrid, Spain
Chang-Claude, J:
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Vic, Australia
Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg UCCH, Canc Epidemiol Grp, Hamburg, Germany
Gronwald, J:
Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
Wu, AH:
Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA
Menon, U:
UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit UCL, London, England
Goodman, MT:
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Genet Program, Los Angeles, CA 90048 USA
Schildkraut, JM:
Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA
Wentzensen, N:
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
Brown, R:
Imperial Coll London, Div Canc, Dept Surg & Canc, London, England
Imperial Coll London, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England
Berchuck, A:
Duke Univ Hosp, Dept Gynecol Oncol, Durham, NC USA
Chenevix-Trench, G:
QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia
DeFazio, A:
Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Gayther, SA:
Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA
Cedars Sinai Med Ctr, Cedars Sinai Genom Core, Los Angeles, CA 90048 USA
Garcia, MJ:
Spanish Natl CancerRes Ctr CNIO, Human Canc Genet Programme, Madrid, Spain
Biomed Network Rare Dis CIBERER, Madrid, Spain
Henderson, MJ:
Univ NSW Sydney, Lowy Canc Res Ctr, Childrens Canc Inst, Sydney, NSW, Australia
Rossing, MA:
Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA
Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
Beeghly-Fadiel, A:
Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Dept Med,Sch Med,Div Epidemiol, Nashville, TN USA
Fasching, PA:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA
Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr ER EMN, Dept Gynecol & Obstet, Erlangen, Germany
Orsulic, S:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA
Karlan, BY:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA
Konecny, GE:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA
Huntsman, DG:
Univ British Columbia, Vancouver Gen Hosp, BC Canc, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada
BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada
Bowtell, DD:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Brenton, JD:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
Doherty, JA:
Univ Utah, Dept Populat Hlth Sci, Huntsman Canc Inst, Salt Lake City, UT USA
Pharoah, PDP:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England
Ramus, SJ:
Univ NSW Sydney, Fac Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
Univ NSW Sydney, Lowy Canc Res Ctr, Adult Canc Program, Sydney, NSW, Australia
Green Published, Green Accepted, hybrid, Green Submitted
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