from advances at mass general Cancer Center Fall 2013

technologies are meant to decrease A Landmark Study toxicity and perhaps reduce the rare risk of developing a second cancer. Compares Proton Beam Unlike IMRT, PBT delivers radiation by using a more focused beam to the Therapy with Standard targeted tumor, with less of a low-dose bath for the pelvis and no “exit” dose Radiation Therapy irradiating tissue beyond the tumor. Theoretically, PBT may thus cause fewer side effects than IMRT.2 What is the value of proton Two Innovative Technologies beam therapy? Of the some 200,000 men who are Scant Evidence of PBT’s diagnosed with prostate cancer Benefit in Prostate Cancer assachusetts General annually, many will suffer lifelong The theoretical advantage of PBT Hospital, along with the morbidities resulting from treatment. seemed particularly relevant to the University of Pennsylvania PBT and IMRT are both targeted prostate, which lies close to the bowel, M and several other proton advanced radiation technologies bladder and rectum, which all may be centers, is leading a trial that may help that are capable of delivering higher affected by scattered radiation. But it settle a long-standing debate: Is proton doses of radiation more directly to the is also possible that protons are not beam therapy (PBT) more effective prostate than do older techniques, as sharp at the depth of deep-seated than intensity-modulated radiotherapy leading to higher cure rates. By sparing tumors like the prostate, and there are (IMRT) for prostate cancer? surrounding tissue and organs, these other potential (continued on page 2) The trial, Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL),1 is the first large Phase III randomized clinical Standard Radiotherapy vs. Proton Beam Therapy trial to directly compare PBT with For prostate cancer, intensity-modulated radiotherapy and IMRT in prostate cancer. The five-year proton beam therapy each have pros and cons. multicenter study, which opened IMPBTRT: in July 2012, is sponsored by Mass General and the National Cancer Pro: Having no exit dose makes Institute and is still accruing patients. it potentially possible to deliver higher tumor In recent years, the Agency for doses with lower doses Healthcare Research and Quality, to surrounding normal tissues, especially tissues Institute of Medicine, Centers for beyond the tumor. Medicare & Medicaid Services, other ConS: federal agencies, policymakers, With current delivery clinicians, researchers and the techniques, doses to the hips may be higher with media have called for a rigorous IMIMRT:RT PBT and the beam is a comparative evaluation of these little less sharp with deep- Pro: seated tumors such as the two treatments prior to PBT’s wider Targeting of the tumor prostate; the high-dose adoption. The study’s principal is very accurate, and region to the rectum is IMRT can be sculpted to likely similar to IMRT; it investigator, Jason A. Efstathiou, MD, the prostate to limit the may cost up to twice as exposure of high doses to much as IMRT. DPhil, says that the results will help neighboring organs such prostate cancer patients and their as the rectum. Costs: median Medicare reimbursement4 physicians make better informed Con: decisions regarding the most effective Lower-dose radiation is unavoidably deposited in therapy with the least burdensome normal tissues beyond quality-of-life (QOL) issues, while the tumor because of the increased number of also contributing to the larger debate beam angles. This creates about the investment in and impact of a low-dose radiation “bath” over a larger region arl D eTorres

C innovative technologies. of the pelvis.

1

massgeneral.org/cancer The Proton Therapy Boom By 2016 Prostate cancer has been a major driving force behind the [20] establishment of new proton beam facilities.

O perating hospital-based proton therapy centers nationwide

Under development, scheduled to open

2009 2012 [6] [10]

2006 [5]

2003 2000 [2] [1]

(continued from page 2) advantages to IMRT. gastrointestinal and urinary problems, point is bowel function because it is the The few studies comparing PBT but after two years QOL outcomes were most specific long-term side effect. The with IMRT in prostate cancer have similar to IMRT. study will also: been retrospective, uncontrolled and conflicting. A 2012 study in JAMA3 The Controversy • Develop predictive models of the found that patients treated with According to the 2012 JNCI study, association between radiation dose IMRT had decreased bowel toxicity median Medicare reimbursement for distribution and patient-reported compared with those treated with PBT, PBT is $32,428, compared with $18,575 bowel, urinary and erectile functions while a 2012 study in the Journal of for IMRT. Despite the lack of well- the National Cancer Institute (JNCI)4 designed prospective comparative • Identify and evaluate biomarkers, found that patients treated with PBT studies to date and the higher cost, including circulating tumor cells, had improved urinary function in the many men choose PBT over IMRT for the response to PBT and IMRT to short term. However, both studies relied because of the assumption that guide future personalized medicine on data from physician billing codes it reduces long-term side effects. decisionmaking rather than patient reports. In Cancer Prostate cancer has been a driving this year, Dr. Efstathiou and colleagues force behind the establishment of • Assess longer-term survival rates and described patient-reported outcomes new proton beam facilities, which late effects following PBT, IMRT or 3-D conformal may double in three years and whose radiotherapy. PBT initially caused fewer patient load in some cases may include • Compare cost-effectiveness at current up to 75 percent prostate patients. and future pricing schemes

1 http://clinicaltrials.gov/ct2/show/NCT01617161 The Aims of PARTIQoL “Despite a clear benefit in some

2 Efstathiou, J.A., P.J. Gray and A.L. Zietman. The PARTIQoL trial is looking at cancers, such as pediatric malignancies, “Proton Beam Therapy and Localised Prostate patient-reported QOL outcomes and the rapid adoption of PBT may be Cancer: Current Status and Controversies.” British Journal of Cancer 108, no. 6 (April 2, 2013): other end points. The primary QOL end happening before its effectiveness and 1225–1230. comparative value has been rigorously 3 Sheets, N.C. et al. “Intensity-Modulated Radiation evaluated in all disease sites,” noted Dr. Therapy, Proton Therapy, or Conformal Radiation Contributor Efstathiou. He hopes PARTIQoL will Therapy and Morbidity and Disease Control in Localized Prostate Cancer.” JAMA 2012; 307(15): serve as a model for evaluating costly Jason A. Efstathiou, MD, DPhil 1611-1620. yet promising medical technologies. ■ Assistant Professor of Radiation Oncology, 4 Yu, J.B. et al. “Proton Versus Intensity-Modulated Department of Radiation Oncology, Radiotherapy for Prostate Cancer: Patterns of For more information on the PARTIQoL Care and Early Toxicity.” Journal of the National Massachusetts General Hospital Cancer Institute, 2013 Jan 2; 105(1): 25-32. [email protected] trial, please call 617-726-5866.

2 Advances at Mass General Cancer Center | Fall 2013