b'Redefining Research & Caretrial in which UT Southwestern partici-pated combined nivolumab with a second immunotherapy drug, ipilimumab. The phaseFEATURED KIDNEY CANCER COLLABORATOR3 clinical trial (CheckMate 214), for whichA group of specialists and collaborating medical oncologist Dr. Hammers was aphysicians works with kidney cancer principal investigator, reported 42 percentoncologists to address misdirected response rates in patients with aggressiveattacks from the immune system to disease (intermediate and poor risk groups),tissues other than the cancer. They as well as disappearance of the cancerinclude experts in gastroenterology, in 9 percent of the patients. This studyendocrinology, and rheumatology, was based on a prior clinical trial led bysuch as Dr. Bonnie Bermas, who, Dr. Hammers and published in the Journal ofafter fellowship training at the National Clinical Oncology, showing promising resultsInstitutes of Health, was on faculty at in a smaller number of patients.Brigham and Womens Hospital/Harvard The combination of ipilimumab andDr. Bonnie Bermas is a specialist in complex nivolumab can, however, result in significantMedical School and is now at UTsystemic rheumatic diseases.side effects. Side effects occur in aboutSouthwestern.30-40 percent of patients. They arise when the immune system fights not just cancer cells, but also normal cells. This causes inflammation in many organs such as theDr. Raquibul lungs (pneumonitis), the bowel (colitis), orHannan explaining Joe Ungeheier and his family consulting with immunotherapy leader Dr. Hans Hammers. Teamthe liver (hepatitis). The reaction can bestereotactic radiation. Ungeheier, in memory of Joe, has been instrumental in raising awareness and philanthropic funds for the Kidney Cancer Program. severe, requiring high doses of steroids or other immunosuppressive drugs. Expert management is imperative. (Motzer et al., N Engl J Med, 2015; Hammers et al., J Clin Oncol, 2017; Motzer et al., N Engl J Med, Immunotherapy and Novel Approaches 2018) Immunotherapy has been used to treatgrew back. Thus, it was clear that otherInnovation: Exposing thekidney cancer since the 1980s. IL-2 (interleu- treatments were needed.Enemy with Radiationkin-2), a substance produced by the bodysThe Nobel Prize-winning discoveriesSIX FACTORSTraditionally considered an ineffective treat-immune cells, can stall cancer progressionof Drs. James Allison at MD AndersonASSOCIATED WITHment with limited use in kidney cancer, the in about 30 percent of the patients whenCancer Center and Tasuku Honjo at Kyotoefficacy of radiotherapy has improved mark-administered in high doses. In 7 percent ofUniversity in Japan ushered in a new eraWORSE METASTATICedly. Advancements have been driven in part patients, it can induce a complete responseof immunotherapy. In 2015, nivolumabKIDNEY CANCER by UT Southwesterns renowned team of (eliminating all traces of cancer), which canwas approved by the FDA. The approval1. Need for drug therapy within aradiation oncologists (see page 52).last for many years. IL-2 is administeredwas based on a phase 3, randomizedyear from initial diagnosis High-dose, precisely targeted radia-intravenously, typically in an intensive careclinical trial (called CheckMate 025) oftion beams from various anglescalled unit. It activates the immune systems821 patients, including participants at2. Debilitation SBRTcan kill kidney tumors while min-killer cells. This process of activation andUT Southwestern Kidney Cancer Program.3. Anemia imizing radiation damage to surrounding mobilization of killer cells is accompaniedThe study showed that 25 percent ofhealthy tissues. by whole-body inflammation. The FDApatients receiving nivolumab had their4. High neutrophil counts (cell typeAnimal studies by Drs. Yair Lotan and approved IL-2 in 1992.tumors shrink substantially. This rate wasin the blood) Timmerman showed that SBRT, unlike Subsequently, several drugs werefive times higher than that of patients5. High platelet countsconventional radiation, can kill kidney cancer approved that blocked either blood vesselsreceiving standard-of-care everolimus.6. High blood calciumcells. As shown by Dr. Hannan and others, or mTOR. The drugs controlled the cancerNivolumab also extended patient survivalthe immune system begins to recognize the and helped patients live longer. However,by 25 percent. These results are quite sig- Number of factors: 0 (good risk),radiated tumor cells as enemy invaders. they did not cure patients. The drugs alsonificant, says Dr. Hammers, an author of1-2 (intermediate risk), 3 or moreIn exposing cancer cells for what they had adverse side effects and lowered qualitythe clinical trial report, which was published(high risk) are, radiation may improve immunotherapy. of life. Further, they had to be taken contin- in the New England Journal of Medicine. (Walsh et al., Eur Urol, 2006; Takeshima et uously. If the drug was stopped, the cancerAnother major immunotherapy clinicalal., Proc Natl Acad Sci USA, 2016) 46 47'