ABOUT THE AUTHORS
The ADT Book is the product of the ADT Working Group which is made up of clinicians and researchers from medical and academic institutions across Canada. Our goal is to investigate and facilitate ways to help prostate cancer patients manage the side effects of androgen deprivation therapy (ADT). These medications (such as Lupron®, Xtandi®, Nubeqa®) help control prostate cancer growth by reducing testosterone in the body. However, the depletion of testosterone has a number of side effects that impact the lives of both patients and their loved ones. To deal with these problems, we produced Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their loved ones. The book contains extensive information on ADT, introduces the side effects patients may experience while on ADT, and provides strategies to help them and their loved ones deal with those side effects in order to maintain good health and quality of life.
LEAD AUTHORS
Richard Wassersug, PhD
A research scientist, who received his PhD in evolutionary biology from the University of Chicago. He then spent most of his career studying the biology of amphibians and teaching anatomy in the medical school at Dalhousie University in Halifax, Nova Scotia. At the age of 52 Richard was diagnosed with prostate cancer and has since received multiple treatments for the disease. After beginning androgen deprivation therapy, he redirected his research to study the psychology of androgen deprivation in various populations. Richard is now an Honorary Professor in the Department of Cellular and Physiological Sciences at the University of British Columbia. He is also an Adjunct Professor in the Australia Research Centre in Sex, Health and Society in Melbourne, Australia.
Lauren Walker, PhD
A clinical psychologist and a Research Assistant Professor in the Department of Oncology at the University of Calgary and the Tom Baker Cancer Centre. She completed her doctorate research evaluating an educational initiative for preparing prostate cancer patients (and their partners) to manage the side effects of ADT. She works clinically with couples helping them adapt to the sexual implications of cancer treatments. She is an active researcher, who has contributed several key articles to the scientific literature on the psychosocial adaptation to ADT. Recently she received the Rising Star in Prostate Cancer Research Award from Prostate Cancer Canada/Movember.
John Robinson, PhD
A clinical psychologist and a member of the Genital Urinary Program at the Tom Baker Cancer Centre in Calgary, Alberta since 1986. He concurrently provides clinical service and develops new ways to ease the psychological burden of cancer on not just patients but also their loved ones. He has appointments in both Oncology and Clinical Psychology at the University of Calgary where he teaches and carries on an active research program.
The ADT book also has additional contributions from:
Kristen L. Currie, MA, CCRP; Kirsten C. Kukula, BSc, MD; Linette Lawlor-Savage, PhD; Andrew Matthew, PhD, C Psych; Deborah McLeod, RN, PhD; Daniel Santa Mina, CEP PhD; Carly Sears, BA; Hannah Stremick; Cheri Van Patten, RD, MSc; and Eric Wibowo, PhD
Relevant Publications from the Authors
2024
Shah, F.I., MacLeod, F. & Walker, L.M. Patient Reported Sexual Adaptation Following Prostate Cancer Treatment: An Analysis of Related Variables and Sexual Outcomes Associated with Sexual Adaptation Styles. Arch Sex Behav (2024). https://doi.org/10.1007/s10508-024-02855-z
2023
Walker, L. M., & Santos-Iglesias, P. (2023). Sexual satisfaction in prostate cancer: a multi-group comparison study of treated patients, patients under active surveillance, patients with negative biopsy, and controls. Journal of cancer survivorship : research and practice, 10.1007/s11764-023-01420-2. Advance online publication. https://doi.org/10.1007/s11764-023-01420-2
Mainwaring, J. M., Lee, T. K., Wassersug, R. J., & Wibowo, E. (2023). Scales for Assessing Male Sexual Function are not Entirely Applicable to Gay and Bisexual Men with Prostate Cancer. Urologic Clinics.
2022
Walker, L. M. (2022). Sexual recovery interventions following prostate cancer treatment. Nature Reviews. Urology, 19(6), 329–330. https://doi.org/10.1038/s41585-022-00582-5
Fu, F., Duthie, C. J., Wibowo, E., Wassersug, R. J., & Walker, L. M. (2022). Openness to Using an External Penile Prosthesis for Maintaining Sexual Intimacy by Individuals with Erectile Dysfunction: A Cross-Sectional Study. Sexual medicine, 10(5), 100559. https://doi.org/10.1016/j.esxm.2022.100559
Lee, T. K., Wibowo, E., Dowsett, G. W., Nelson, C. J., Oliffe, J. L., Mitteldorf, D., Wong, S. T. S., & Wassersug, R. J. (2022). Development of a Sexual Quality of Life Questionnaire for Men-Who-Have-Sex-With-Men With Prostate Cancer. Sexual medicine, 10(2), 100480. https://doi.org/10.1016/j.esxm.2021.100480
Fox, I. N., & Wassersug, R. (2022). Case studies on psychosocial factors that help make exercise programmes for prostate cancer patients self-sustaining. BMJ Supportive & Palliative care, bmjspcare-2021-003370. Advance online publication. https://doi.org/10.1136/bmjspcare-2021-003370
Galvin, K. T., Garland, S. N., & Wibowo, E. (2022). The relationship between sleep hygiene, mood, and insomnia symptoms in men with prostate cancer. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 10.1007/s00520-021-06680-1. Advance online publication. https://link.springer.com/epdf/10.1007/s00520-021-06680-1?sharing_token=z5ALnVToHGVX0buSj04I-fe4RwlQNchNByi7wbcMAY6i6KBjSPxLgp2B0zWDszsEa-ejteUMaABqzJNyILOuaznEwLyLCmqWybn18BlPrEU-TzguXmIn4qHxtpxyMG--ix-fk6TbwBANv6cWafWa8RZNSqyY45H-qLOV04dcH3A%3D
Matthew, A. G., Trachtenberg, L. J., Yang, Z. G., Robinson, J., Petrella, A., McLeod, D., Walker, L., Wassersug, R., Elliott, S., Ellis, J., Jamnicky, L., Fleshner, N., Finelli, A., Singal, R., Brock, G., Jarvi, K., Bender, J., & Elterman, D. (2022). An online Sexual Health and Rehabilitation eClinic (TrueNTH SHAReClinic) for prostate cancer patients: a feasibility study. Supportive Care in Cancer, 30(2), 1253–1260. https://doi.org/10.1007/s00520-021-06510-4
Muermann, M. M., & Wassersug, R. J. (2022). Prostate Cancer From a Sex and Gender Perspective: A Review. Sexual Medicine Reviews, 10(1), 142–154. https://doi.org/10.1016/j.sxmr.2021.03.001
2021
Walker L. M. (2021). Psychosocial contributors to patients' and partners' postprostate cancer sexual recovery: 10 evidence-based and practical considerations. International Journal of Impotence Research, 33(4), 464–472. https://doi.org/10.1038/s41443-020-00369-5
Wibowo, E., Wong, S., Wassersug, R. J., & Johnson, T. W. (2021). Sexual Function After Voluntary Castration. Archives of Sexual Behavior, 50(8), 3889–3899. https://doi.org/10.1007/s10508-021-02094-6
Walker, L. M., Sears, C. S., & Santos-Iglesias, P. (2021). Hard Times: Prostate Cancer Patients' Experiences with Erectile Aids. The Journal of Sexual Medicine, 18(10), 1775–1787. https://doi.org/10.1016/j.jsxm.2021.07.012
Mainwaring, J. M., Walker, L. M., Robinson, J. W., Wassersug, R. J., & Wibowo, E. (2021). The Psychosocial Consequences of Prostate Cancer Treatments on Body Image, Sexuality, and Relationships. Frontiers in Psychology, 12, 765315. https://www.frontiersin.org/articles/10.3389/fpsyg.2021.765315/full
Garland, S. N., Savard, J., Eisel, S. L., Wassersug, R. J., Rockwood, N. J., Thoms, J., Jim, H., & Gonzalez, B. D. (2021). A 2-year prospective analysis of insomnia as a mediator of the relationship between androgen deprivation therapy and perceived cognitive function in men with prostate cancer. Cancer, 127(24), 4656–4664. https://doi.org/10.1002/cncr.33850
Duthie, C. J., Graham, K., Rapsey, C. M., & Wibowo, E. (2021). Factors associated with various strategies for maintaining sexual activity after prostate cancer treatment. International journal of impotence research, 10.1038/s41443-021-00466-z. Advance online publication. https://doi.org/10.1038/s41443-021-00466-z
Tulk, J., Rash, J. A., Thoms, J., Wassersug, R., Gonzalez, B., & Garland, S. N. (2021). Androgen deprivation therapy and radiation for prostate cancer-cognitive impairment, sleep, symptom burden: a prospective study. BMJ Supportive & Palliative Care, bmjspcare-2021-003098. Advance online publication. https://doi.org/10.1136/bmjspcare-2021-003098
Palmer-Hague, J. L., Wong, S., Wassersug, R. J., Kingstone, A., & Wibowo, E. (2021). Hormones and visual attention to sexual stimuli in older men: an exploratory investigation. The Aging Male : The Official Journal of the International Society for the Study of the Aging Male, 24(1), 106–118. https://doi.org/10.1080/13685538.2021.1960964
Shah, S. I. A., Wilson, H. C. P., Abel, P. D., Wassersug, R. J., Trebicky, V., Fialova, J. T., Allen, C., Adomat, H. H., Bell, R. H., Tomlinson Guns, E. S., & Roberts, S. C. (2021). Gonadal suppression alters axillary steroid secretions in men, but does that affect olfactory social signalling? Journal of Men’s Health, 17(3), 69-76. https://oss.jomh.org/jomh/article/20210630-328/pdf/JOMH2021022501.pdf
Muermann, M. M., & Wassersug, R. J. (2021). Prostate Cancer From a Sex and Gender Perspective: A Review. Sexual Medicine Reviews, S2050-0521(21)00010-X. Advance online publication. https://www.sciencedirect.com/science/article/abs/pii/S205005212100010X?casa_token=Oj8FFI_gsd8AAAAA:BcyA_SJ3ZQeaZClIJKFEXsUxc6KnRNLwIdWRaKHAPUGsQrK_cNRbGQkDtcpu3nZhHEmNTqoPbQ
Wassersug, R.J. & Fox, I.N. (2021). The molecule that makes prostate cancer easy to find shows why it will be so difficult to cure. Journal of Men’s Health, 17(2), 1-3. https://jomh.org/articles/10.31083/jomh.2021.014
Mangar, S., Mondal, S., Edwards, S., Ahmed, H.U., Wassersug, R.J., Falconer, A., Iles, R., & Dimitriou, D. (2021). Evaluating the prevalence and nature of sleep disturbances in prostate cancer patients receiving androgen deprivation therapy using a combination of actigraphy and sleep questionnaires. Journal of Clinical Oncology, 39(15, suppl, e17046-e17046). doi: 10.1200/JCO.2021.39.15_suppl.e17046. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.e17046
Galvin, K. T., Garland, S. N., & Wibowo, E. (2021). The Association between Insomnia and Orgasmic Difficulty for Prostate Cancer Patients - Implication to Sex Therapy. Journal of Sex & Marital Therapy, 47(2), 174–185. https://doi.org/10.1080/0092623X.2020.1848947
Delpachitra, S., Campbell, A., & Wibowo, E. (2021). The influence of education level on sleep-related outcomes and sleep management strategies in prostate cancer patients. Journal of Men’s Health. Advance Online Publication. JOMH2021012903.pdf
Wassersug R. Editorial Comment. J Urol. 2021 Aug 12:101097JU000000000000194602. doi: 10.1097/JU.0000000000001946.02. Epub ahead of print. PMID: 34383588. https://www.auajournals.org/doi/10.1097/JU.0000000000001946.02
2020
Duthie, C.J., Calich, H.J., Rapsey, C.M., & Wibowo, E. (2020). Maintenance of sexual activity following androgen deprivation in males. Critical Reviews in Oncology/Hematology, 153. [Online ahead of print]. https://doi.org/10.1016/j.critrevonc.2020.103064
Wibowo, E., Wassersug, R.J., Robinson, J.W., Matthew, A., McLeod, D.L., Walker, L.M. (2020). An Educational Program Designed to Prepare Patients for Adapting to Androgen Deprivation Therapy Side Effects: Feasibility, Acceptability, and Preliminary Outcomes. American Journal of Men’s Health, 14(1). doi: 10.1177/1557988319898991. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005977/
Walker, L.M. & Santos-Iglesias, P. (2020). On the relationship between erectile function and sexual distress in men with prostate cancer. Archives of Sexual Behavior. [Online ahead of print]. doi: 10.1007/s10508-019-01603-y. https://pubmed.ncbi.nlm.nih.gov/32072396/?from_term=Santos-Iglesias+P&from_filter=ds1.y_1&from_pos=3
Mathew, S., Rapsey, C. M., & Wibowo, E. (2020). Psychosocial Barriers and Enablers for Prostate Cancer Patients in Starting a Relationship. Journal of sex & marital therapy, 46(8), 736–746. https://doi.org/10.1080/0092623X.2020.1808549
Delpachitra, S., Campbell, A., & Wibowo, E. (2020). Preference for sleep management strategies among prostate cancer patients: An Aotearoa/New Zealand perspective✰. Cancer Treatment and Research Communications, 25, 100219. https://doi.org/10.1016/j.ctarc.2020.100219
2019
Wibowo, E., Wassersug, R. J., Robinson, J. W., Matthew, A., McLeod, D. L., Walker, L. M. (2019). How are patients with prostate cancer managing Androgen Deprivation Therapy side effects? Clinical Genitourinary Cancer, 17(3), e408-e419. doi: 10.1016/j.clgc.2018.12.006. https://www.ncbi.nlm.nih.gov/pubmed/30745202
Elterman, D.S., Petrella, A.R., Walker, L.M., Van Asseldonk, B., Jamnicky, L., Brock, G.B., Elliott, D., Finelli, A., Gajewski, J.B., Jarvi, K.A., Robinson, J.W., Ellis, J., Curtis, A., Shepherd, S., Matthew, A. (2019). Canadian Consensus Algorithm for Erectile Rehabilitation Following Prostate Cancer Treatment. Canadian Urological Association Journal, 13(8), 239-245. http://dx.doi.org/10.5489/cuaj.5653
Walker, L.M. & Santos-Iglesias, P. (2019). A Systematic Review of Sexual Satisfaction in Prostate Cancer Patients. Sexual Medicine Reviews, pii: S2050-0521(19)30094-0. doi: 10.1016/j.sxmr.2019.09.001. https://www.ncbi.nlm.nih.gov/pubmed/31653439
2018
Wibowo, E., Wassersug, R. J., Robinson, J. W., Matthew, A., McLeod, D. L., Walker, L. M. (2018). The influence of an Androgen Deprivation Therapy Educational Program on dyadic quality and intimacy for prostate cancer patients and their partners. J Clin Oncol. 36 (Suppl 7S): abstr 178. Presented at the 2018 Cancer Survivorship Symposium, Orlando, FL.
Walker, L. M., Santos-Iglesias, P. (2018). Psychometric Validation of the Sexual Distress Scale in Men with Prostate Cancer, Journal of Sexual Medicine, 15(7), 1010-1020. doi: 10.1016/j.jsxm.2018.05.015. https://www.ncbi.nlm.nih.gov/pubmed/29960626
Walker, L. M., Santos-Iglesias, P., & Robinson, J.W. (2018) Mood, Sexuality, and Relational Intimacy after starting Androgen Deprivation Therapy: Implications for Couples, Journal of Supportive Care in Cancer, 26(11), 3835-3842. doi: 10.1007/s00520-018-4251-9. https://link.springer.com/article/10.1007%2Fs00520-018-4251-9
Santos-Iglesias, P., Mohamed, B., & Walker, L. M. (2018) A systematic review of sexual distress measures. Journal of Sexual Medicine, 15(5), 625-644. doi: 10.1016/j.jsxm.2018.02.020. https://www.jsm.jsexmed.org/article/S1743-6095(18)30141-3/fulltext
2017
Wassersug, R. J., Wibowo, E. (2017). Non-pharmacological and non-surgical strategies for sexual recovery by men with erectile dysfunction. (Invited review) Trans Androl Urol. 6(Suppl. 5):S776-794. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715194/
Wibowo, E., Wassersug, R. J., Robinson, J. W., Matthew, A., McLeod, D. L., Wilyman, S., Walker, L. M. (2017). A preliminary evaluation of the TrueNTH androgen deprivation therapy educational program. J Clin Oncol. 35(Suppl 5S):abstr 219. Presented at the 2017 Cancer Survivorship Symposium, San Diego, CA.
2016
Rot I, Wassersug RJ, Walker LM. (2016). What do urologists think patients need to know when starting on androgen deprivation therapy? The perspective from Canada versus countries with lower gross domestic product. Transl Androl Urol. 5:235-247. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837317/
Wassersug RJ. (2016). Maintaining intimacy for prostate cancer patients on androgen deprivation therapy. Curr Opin Support Palliat Care 10:55-65. www.ncbi.nlm.nih.gov/pubmed/26761788
Walker, L.M., King, N., Kwasny, Z., Robinson, J.W. (2016). Intimacy after Prostate Cancer: A Brief Couples’ Workshop is Associated with Improvements in Sexual Function and Relationship Distress. PsychoOncology, Sep;26(9):1336-1346. doi: 10.1002/pon.4147. https://onlinelibrary.wiley.com/doi/abs/10.1002/pon.4147
Robinson, J., Wassersug, R. J., Walker, L. M., McLeod, D. L., Matthew, A., Wibowo E. (2016). The androgen-deprivation therapy educational program: A Canadian True NTH initiative. Psychooncology. 25(Sp. S 3):21. Abstr 60. Presented at the International Psychooncology Society Congress, Dublin, Ireland.
Robinson, J. W., Wassersug, R. J., Walker, L. M., Wibowo, E., Matthew, A., McLeod, D. L. (2016). The androgen deprivation therapy educational program: A Canadian TrueNTH initiative. CUAJ. 10(Suppl 1):S79, Abstract: UP-07.10. Presented at the 2016 Canadian Urological Association Annual Meeting, Vancouver, BC.
Wibowo, E., Walker, L. M., Wilyman, S., Matthew, A., McLeod, D. L., Wassersug, R. J., Robinson, J. W. (2016). Androgen deprivation therapy educational program: A Canadian True NTH initiative. J Clin Oncol. 34(Suppl 3S):abstr 243. Presented at Cancer Survivorship Symposium, San Francisco, CA.
2015
Lee TK, Handy AB, Kwan W, Oliffe JL, Brotto LA, Wassersug RJ, Dowsett GW. (2015). Impact of prostate cancer treatment on the sexual quality of life for men-who-have-sex-with-men. J Sex Med 12:2378-86. www.ncbi.nlm.nih.gov/pubmed/26537853
Hamilton LD, Van Dam D, Wassersug RJ. (2015). The perspective of prostate cancer patients and patients' partners on the psychological burden of androgen deprivation and the dyadic adjustment of prostate cancer couples. Psychooncology 25:823-31. www.ncbi.nlm.nih.gov/pubmed/26411285
Donovan KA, Walker LM, Wassersug RJ, Thompson LM, Robinson JW. (2015). Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners. Cancer 121:4286-99. www.ncbi.nlm.nih.gov/pubmed/26372364
Van Dam D, Wassersug RJ, Hamilton LD. (2015). Androgen deprivation therapy’s impact on the mood of prostate cancer patients as perceived by patients and the partners of patients. Psycho-Oncology 25:848-56. www.ncbi.nlm.nih.gov/pubmed/26332203
Walker LM, Wassersug RJ, Robinson JW. (2015). Psychosocial perspectives on sexual recovery after prostate cancer treatment. Nat Rev Urol 12:167-176. http://www.ncbi.nlm.nih.gov/pubmed/25753250
2014
McLeod DL, Walker LM, Wassersug RJ, Matthew A, Robinson JW. (2014). The sexual and other supportive care needs of Canadian prostate cancer patients and their partners: Defining the problem and developing interventions. Canadian Oncology Nursing Journal 24:272-278. http://www.canadianoncologynursingjournal.com/index.php/conj/article/view/59
Tran S, Walker LM, Wassersug RW, Matthew AG, McLeod DL, Robinson JW. (2014). What do Canadian uro-oncologists believe patients should know about androgen deprivation therapy? J Oncol Pharm Pract. 20:199-209. http://www.ncbi.nlm.nih.gov/pubmed/2412285
2013
Walker LM, Tran S, Wassersug RJ, Thomas B, Robinson JW. (2013). Patients and partners lack knowledge of androgen deprivation therapy side effects. Urol Oncol 31:1098-1105. http://www.ncbi.nlm.nih.gov/pubmed/22285008
Walker LM, Tran S, Robinson JW. (2013). Luteinizing hormone—releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects. Clin Genitourin Cancer. 11:375-384. http://www.ncbi.nlm.nih.gov/pubmed/23891497
Kukula KC, Jackowich RA, Wassersug RW. (2013). Eroticization as a factor influencing ED treatment effectiveness. Inter J Impotence Res. 26:1-6. http://www.ncbi.nlm.nih.gov/pubmed/23823215
Wassersug RJ. (2013). Extending the case for oestradiol in androgen-sensitive prostate cancer. Lancet Oncol. 14:e242-3. http://www.ncbi.nlm.nih.gov/pubmed/23725706
Walker LM, Hampton AJ, Wassersug RJ, Thomas BC, Robinson RJ. (2013). Androgen deprivation therapy and maintenance of intimacy: A randomized controlled pilot study of an educational intervention for patients and their partners. Contemp Clinical Trials 34:227-231. http://www.ncbi.nlm.nih.gov/pubmed/23220254
2012
Wibowo E, Deurveilher S, Wassersug RJ, Semba K. (2012). Estradiol treatment modulates spontaneous sleep and sleep recovery after sleep deprivation in castrated male rats. Behav Brain Res. 226:456-464. http://www.ncbi.nlm.nih.gov/pubmed/22004978
Walker L, Tran S, Wassersug RJ, Thomas B, Robinson J. (2012). Patients and partners lack knowledge of androgen deprivation therapy side effects. Urol Oncol. 31:1098-105. http://www.ncbi.nlm.nih.gov/pubmed/22285008
Rot I, Ogah I, Wassersug RJ. (2012). The language of prostate cancer treatments and implications for informed decision making by patients and their partners. Eur J Cancer Care. 21:766-775. http://www.ncbi.nlm.nih.gov/pubmed/22574619
Wibowo E, Wassersug R, Warkentin K, Walker L, Robinson J, Brotto L, Johnson T. (2012). Impact of androgen deprivation therapy on sexual function: A response. Asian J Androl. 14:793-794. http://www.ncbi.nlm.nih.gov/pubmed/22796736
Phillips JL, Wassersug RJ, McLeod D. (2012). Systemic bias in the medical literature on androgen deprivation therapy and its implication to clinical practice. Int J Clin Practice. 66:1189-1196. http://www.ncbi.nlm.nih.gov/pubmed/23163498
Ogah I, Wassersug RJ. (2012). How reliable are "reputable sources" for medical information on the internet?—The case of hormonal therapy to treat prostate cancer. Urol Oncol. 31:1546-1552. http://www.ncbi.nlm.nih.gov/pubmed/23141782
Aning JJ, RJ Wassersug RJ, Goldenberg LS. (2012). Patient preferences and the impact of decision-making aids on prostate cancer treatment choices and post-intervention regret. Current Oncol. 19:S37-S44. http://www.ncbi.nlm.nih.gov/pubmed/23355792
2011
Murphy R, Wassersug RJ, Dechman G. (2011). The role of exercise in managing the adverse effects of androgen deprivation therapy in men with prostate cancer. Phys Therapy Rev. 16:269-277. http://www.maneyonline.com/doi/abs/10.1179/1743288X11Y.0000000029
Wibowo E, Schellhammer P, Wassersug RJ. (2011). Role of estrogen in normal male function: Clinical implications for patients with prostate cancer on androgen deprivation therapy. J Urol, 185:17-23. http://www.ncbi.nlm.nih.gov/pubmed/21074215
2010
Elliott S, Latini DM, Walker LM, Wassersug RJ, Robinson JW. (2010). Androgen deprivation therapy for prostate cancer: Recommendations to improve patient and partner quality of life. J Sex Med. 7: 2996–3010. http://www.ncbi.nlm.nih.gov/pubmed/20626600
2009
Wassersug RJ. (2009). Mastering emasculation. J Clin Oncol. 27:634-636. http://jco.ascopubs.org/content/27/4/634.full