Ep 96: A Patient with a Lung Mass

Harrison's PodClass provides engaging, high-yield discussions of key topics commonly found on rotational and board exams in internal and family medicine. 

Transcript

0:00

[upbeat intro music][Dr. Handy] Hi, welcome to Harrison's PodClass, where we discuss important concepts in internal medicine. I'm Cathy Handy.[Dr. Wiener] And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine. Welcome to episode 96, a patient with a lung mass. Cathy, we're going to go with a slightly different format again today, and we're going to be focusing on typical patients and precision medicine oncology.[Dr. Handy] Well, good, one of my favorite topics, and I will put in a plug, I do think some of the work in oncology has really moved far towards utilizing precision medicine approaches. Although obviously we still have a long way to go.[Dr. Wiener] Yeah, I think we'll touch on some of those issues during this discussion. Here's the question. As an oncologist, you are considering treatment options for your patients with lung cancer, including small molecule therapy targeting the epidermal growth factor receptor or eGFR. Which of the following patients is most likely to have a tumor with a high degree of expression of the eGFR mutation? So your options are, A. a 23-year-old man with a hamartoma; B. a 33-year-old woman with carcinoid tumor; C. a 45-year-old woman who has never smoked and has an adenocarcinoma of the lung; D. is a 56-year-old man with a hundred pack year history of tobacco use and has small cell lung cancer; and E. is a 76-year-old man with a squamous cell carcinoma who also has a history of asbestos exposure and heavy cigarette smoking.[Dr. Handy] Okay, this is great because we've learned so much about the molecular characteristics of lung cancer and some of these are driving novel therapies. The key point is that these targeted therapies are only helpful in some patients, in this case with lung cancer, who have eGFR mutations that lead to overexpression.[Dr. Wiener] Okay, so you're telling me that some tumors do have expression of eGFR and some don't. Okay, which of the patients that I mentioned is most likely to have a tumor with a high expression of eGFR?[Dr. Handy] So the answer is C. the non-smoking woman with adenocarcinoma. This demographic of patients with lung cancer has grown dramatically in the U. S. as smoking has become less common. Traditionally, this was a group of patients who did very poorly with traditional chemotherapy. 10 to 15% of North American patients diagnosed with non-small cell lung cancer have cancers with eGFR mutations. Patients who are more likely to have these cancers are women, non-smokers, people from Asia, and patients with adenocarcinoma histopathology.[Dr. Wiener] Okay, well, tell me a little bit more about this targeted treatment.[Dr. Handy] Approximately 90% of these mutations are point mutations within the eGFR tyrosine kinase domain resulting in hyperactivation of both eGFR kinase activity and downstream signaling. Lung tumors that harbor activating mutations within the eGFR kinase domain display high sensitivity to small molecule eGFR tyrosine kinase inhibitors, or TKIs. Now, when these TKIs were used in unselected patient populations, they didn't show significant efficacy. However, in the subset of patients with eGFR mutations, these treatments are efficacious and represent the standard of care now.[Dr. Wiener] Okay, so what you're saying is that when they did broad studies with enrolling lots of patients with lung cancer, for trials of TKI, such as erlotinib, they did not necessarily show an effect, but they only showed an effect when they kind of filtered out for those who actually had the relevant mutations.[Dr. Handy] That's correct, in unselected, just general lung cancer population, these drugs are not really that efficacious but in the subset of patients who have these eGFR mutations, these drugs are very helpful.[Dr. Wiener] I think that's really interesting how these precision treatments not only have to redefine not only how we treat patients, but also how we design clinical trials, right?[Dr. Handy] Yeah, we're using more and more of these within oncology clinical trials and developing more targeted agents for patients.[Dr. Wiener] Okay, so you told us that the woman who has the adenocarcinoma is most likely to have eGFR mutations upregulated in her tumor, such that she would probably benefit from one of these TKIs, but let's talk about the other patients. Do the other patients have typical molecular defects that can help us define them or their therapy?[Dr. Handy] The first patient had a hamartoma, and we should remember that those are benign tumors, in fact, about 5 to 10% of lung solitary pulmonary nodules turn out to be hamartomas. Those are the most common benign lung nodules. That said, they can grow slowly, so should be on the differential of a slowly growing lung mass. And they're part of the neurofibromatosis type 1 or tuberous sclerosis syndrome.[Dr. Wiener] How about the woman with carcinoid tumor?[Dr. Handy] So carcinoids are neuroendocrine tumors and surgery is the mainstay of treatment. There aren't many recommended targeted molecular medications, although somatostatin analogs can be used in the treatment regimen for those types of cancers.[Dr. Wiener] Okay, well, let's move on. How about the man with small cell carcinoma?[Dr. Handy] So small cell lung cancer is typically very responsive initially to traditional chemotherapy, but the recurrence rates are high. The most common genetic mutation is in TP53, a common oncogene and there aren't any targeted treatments for that yet.[Dr. Wiener] Okay, and now, lastly, the asbestos squamous cell lung carcinoma in the smoker.[Dr. Handy] Thankfully, the frequency of asbestos-related tumors in the United States is declining with federal and state regulation, plus an increased awareness of the toxicity of asbestos. Squamous cell lung cancer has the strongest association with cigarette smoking and still accounts for about 20 to 30% of new lung cancers. A huge number of genetic mutations are common in squamous cell lung cancer. Unfortunately, targeted molecular therapies have not been as widely applied in these cancers. For example, eGFR mutations, which we started with today are much less frequent than in adenocarcinomas and have had disappointing results for squamous cell carcinoma of the lung. That being said, these tumors are often responsive to immunotherapies, another area where we need more science and clinical trials but a growing area of treatment.[Dr. Wiener] Okay, so the teaching points in this case are that molecular characterization of tumors, including lung cancer, is becoming part of our diagnostic and therapeutic armamentarium. Adenocarcinomas of the lung may express eGFR mutations and targeted therapy is effective in these tumors. There is also a growing role of immunotherapy in lung cancer beyond adenocarcinomas.[Dr. Handy] And you can read more about this in Harrison's chapters on cancer genetics and also the chapter on neoplasms of the lung.[upbeat outro music][Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. Go to accessmedicine.com to learn more.