Breast Irradiation Therapy Innovations Forgo Permanent Marks, Minimize Treatment
Authors: A. Azvolinsky
Journal: JNCI Journal of the National Cancer Institute (2015)

Many women who had radiotherapy for breast cancer bear small, dark ink dots on their chest—a permanent reminder of diagnosis and treatment. Radiation oncologists use these to mark the area to irradiate. But many patients are reluctant to receive these permanent body markings, which can be visible in bathing suits and other clothing. Steven Landeg, M.Sc., senior radiographer, and colleagues at the Royal Marsden Hospital in London found a solution: tattoos visible only under ultraviolet (UV) lighting. The UV light excites the dye, making it fluoresce. At the National Cancer Research Institute Cancer Conference 2014, the researchers presented their 46-patient randomized study comparing traditional black tattoos with the new invisible one (http://conference.ncri.org.uk/ abstracts/2014/abstracts/B291.html). Both types yield equally accurate delivery of radiotherapy. Although the fluorescent dye had been used to mark the site of a tumor biopsy before surgery to reduce risk of error, this is the first time the dye was used in breast cancer radiotherapy. Applying fluorescent tattoos to guide radiotherapy modestly increased average pretreatment time, from 19 minutes, 3 seconds to 21 minutes, 4 seconds (P = 0.37; not statistically significant). Likewise, treatment time increased modestly, from 10 minutes, 5 seconds to 11 minutes, 4 seconds (P = 0.06; not statistically significant). “I am glad my tattoos will only be visible under special lights and I will be able to complete my radiotherapy with no lasting signs,” one anonymous patient wrote. Fifty-six percent of patients receiving the fluorescent tattoo had improved body image satisfaction 1 month after treatment, compared with 14% who received a dark-ink tattoo. A worse body image satisfaction at 1 month occurred in 22% and 50% of patients who received fluorescent and conventional tattoos, respectively. The researchers will soon submit full efficacy data and their approach for publication. Now they work to implement the new technique in routine practice, because the data are sufficient evidence that the fluorescent ink does not compromise consistent delivery of radiation, Landeg said. “This is a cost effective alternative that is likely to improve the experience of breast radiotherapy for a proportion of this large population of women so we endeavor to implement invisible tattoos into routine clinical practice in early 2015,” he said. “A lot of women complain about the [permanent] tattoos. Having something that is invisible except under a certain type of light is great,” said Michael D. Alvarado, M.D., associate professor of surgery at the University of California, San Francisco. (He was not involved in the study.) Alvarado said he would still like to see data on how long the fluorescent tattoos last to ensure the marks are still there at least 5 years after application in case retreatment or treatment of the other breast is necessary. Reshma Jagsi, M.D., D.Phil., associate professor of radiation oncology at the University of Michigan Health System in Ann Arbor, who also was not involved in the study, agreed. “This is an important pilot study. We need to do everything possible to minimize the long-term impact of breast cancer treatment on our patients as many patients go on to long-term survivorship.” patients stopped treatment because of toxic effects, and one patient died from colitis-related multiorgan failure. Scientists at ASCO’s 2014 meeting discussed preliminary results of a phase I trial in metastatic renal cell cancer with the same combination at two doses. The objective response rate was 29% with a higher dose of nivolumab and 39% for a higher dose of ipilimumab; duration of response was 4.1–22.1 weeks and 6.1– 18.3 weeks, respectively. An expansion trial at these doses and at a third, equal high dose is ongoing. A phase III trial comparing the combination with each drug alone is under way. Researchers are now seeing checkpoint blocker activity outside melanoma and renal cell carcinoma, Herbst said. Lung cancer, once thought nonimmunogenic, is also the subject of several ipilimumab trials. A phase II study combining ipilimumab with paclitaxel and carboplatin showed a median overall survival of 12.2 months for phased ipilimumab, 9.7 months for concurrent ipilimumab, and 8.3 months for control in untreated patients. Those results serve as the basis for an ongoing phase III trial in non–small-cell lung cancer (NSCLC) and SCLC. It is also in phase II testing with chemotherapy before surgery for NSCLC and in a phase I trial with the targeted drugs erlotinib or crizotinib for patients with stage IV NSCLC who also have mutations in the gene for epidermal growth factor receptor or anaplastic lymphoma kinase. A phase I trial of ipilimumab plus imatinib (Gleevec), a c-Kit inhibitor, is ongoing for patients with advanced cancers, including lung cancer. Ovarian cancer and other trials are also under way, including a phase II study with ipilimumab and a phase I with tremelimumab and MEDI4736, an anti–PD-L1 immunotherapy in advanced solid tumors, including colorectal cancers. Combination nivolumab and ipilimumab is in a phase II clinical trial for recurrent glioblastoma. Ipilimumab is also in two phase I trials in adults with Hodgkin lymphoma and a phase II trial in mesothelioma. “Despite many, many unanswered questions, I think that it is safe to say that we have finally, after decades of research, begun to open an important new chapter in the treatment of cancer via the manipulation of the immune system,” Klausner said. “That said, we are still in the early days of the therapeutic potential of immunotherapy—and the rules, the generalizability, and the persistence of therapeutic benefit are all questions whose answers are ahead of us,” he added.