Hope and Realism: The Perfect Balance?
Authors: Shirish M. Gadgeel
Journal: Journal of Clinical Oncology (2011)

DOI: 10.1200/JCO.2010.34.5348 During my career as a thoracic oncologist, certain patients have left a lasting impression. Mrs R was one such patient: a woman in her early 50s who appeared younger than her age. When we first met, she greeted me with a smile that belied her underlying sense of anxiety. Mrs R had already been treated for lung cancer for more than 2 years before she was referred to my clinic. She had endured many chemotherapy regimens, including combinations with and without bevacizumab, and had also been treated with erlotinib twice without much benefit. Review of her records and scans revealed that her lungs were now filled with many metastases, some quite large, and that there was also disease in her liver and bones. After evaluating her, I was surprised by her continued good performance status. I even considered leaving the room to confirm that the scans I had just reviewed were actually hers. In the examination room, Mrs R was surrounded by numerous loving family members, including her husband and mother. She was a never-smoker, and before her lung cancer diagnosis, she had led a fulfilling life. She was one of those patients who make you wonder why such a calamity should befall such a warm person. I discussed with Mrs R and her family the available clinical trials at our center, with an assurance that probably conveyed a greater sense of optimism than her clinical condition warranted. In the lung cancer world, there is currently a great deal of buzz about patients with tumors that have alterations in the ALK gene and the exciting clinical benefit some such patients enrolled onto early-phase clinical trials have derived from therapy with an ALK inhibitor. I felt strongly that Mrs R’s tumor should be assessed for the presence of an ALK translocation. She was young and had never smoked, and her cancer had not responded well to erlotinib, making it unlikely that her tumor harbored an EGFR mutation. In such patients, available data suggest that there is approximately a 30% probability that their tumor will be positive for an ALK gene alteration, and among those with an ALK mutation, there is a 60% chance of response to ALK inhibition. Although I am sure that I quoted Mrs R and her family the correct probabilities, I later wondered whether my enthusiastic attitude in the consultation room had conveyed a much higher, and less realistic, likelihood that one of our trials could provide her with a lasting and meaningful clinical benefit. I myself experienced a sense of satisfaction that I had given hope to a patient who did not have many therapeutic options. We sent her diagnostic tumor tissue for ALK mutation testing. Unfortunately, after 2 weeks, the reference laboratory informed me that the available tumor material was not sufficient for ALK analysis. I decided that a computed tomography–guided biopsy of one of the many lung metastases would be appropriate. Although the incidence of complications after such a biopsy at our institution is quite low, she developed a pneumothorax that required hospitalization. She was clearly on an emotional rollercoaster, beginning with the optimism she had felt after her initial visit with me followed by the disappointment of learning that her available biopsy material was inadequate for testing and then the complication of the biopsy procedure. I am fairly certain that when she agreed to undergo the biopsy, she fully believed that her tumor would have an ALK mutation. Two weeks later, I obtained the results: the laboratory had not detected an ALK gene rearrangement. I felt a strong sense of failure, both for Mrs R and for myself. As promised, I called her as soon as I received the report. It was challenging for me to inform her of the negative results, but her immediate response was simply to ask what the next step would be. With a sigh of relief, I quickly moved on to discuss another clinical trial that might be appropriate for her. I scheduled her to come and see me again to discuss the other trial in person. During this visit, I noticed some whitish changes in her gums that did not seem consistent with oral candidiasis. I sent her to an oral surgeon who diagnosed osteonecrosis of the jaw. She had been on bisphosphonate therapy for more than 1 year for her bone metastases. The oral surgeon debrided her gums and prescribed a course of oral antibiotics, with plans for reevaluation in 3 weeks. I discussed her situation with the sponsor of the clinical trial I was considering for her and requested her inclusion in the trial. The JOURNAL OF CLINICAL ONCOLOGY T H E A R T O F O N C O L O G Y VOLUME 29 NUMBER 16 JUNE 1 2011