Stereotactic Lung Radiotherapy (SBRT) vs. Wedge Resection for Stage I NSCLC

   The subject of stereotactic lung radiotherapy (SBRT) for cure of stage I disease has been extensively covered on GRACE with good cause: we may be witnessing a major change in how we treat early stage cancer. Multiple strategies for improved surveillance are being developed, and hopefully one or more will be successful, resulting in more frequent detection of early stage disease.  If so, we will have what my mentor calls a “delicious dilemma” – what is the best way to cure these early-stage patients?  Before turning to an important new article in JCO on the subject, I refer the curious reader to recent coverage on GRACE that leads up to the subject at hand:

Limited Resection vs. Radiation for Marginal Patients with Early Stage NSCLC : 11/15/2007 by Dr. Jack West
   o Review of evidence that older patients may do as well with a limited, smaller resection
   o Yendamuri / MD Anderson report from 2007 JTO: 160 patients with stage I NSCLC from 1988 to 2005 treated with either 3D-conformal radiation or limitted resection — surgery beat radiation in overall cohort but if you matched for similar characteristics, they were equivalent.

Dr. Le, Radiation Oncologist from Stanford, on Radiation Options for Early Stage NSCLC: 12/19/09
   o PET/CT can improve radiation planning
   o We have better control now for respiratory motion
   o Review of ongoing studies

Interview with Dr. Vivek Mehta, Radiation Oncologist: Early Stage and Locally Advanced NSCLC: 1/15/2009
   o Great review of the biologic difference between small fractions every day for seven weeks (traditional radiation) vs. giving a huge dose in 1-5 fractions (stereotactic radiation)
   o Simple-language review of why existing comparisons of surgery and radiation are not fair:
   o Surgery can show patients to be of a higher stage so stage I patients in a surgical group truly are stage I while in radiation studies, some patients are really more advanced
   o Since there is no randomization, radiation patients are sicker; they are often in this group because they are too sick for surgery and would die earlier no matter what you did
  o Postoperative radiation vs. brachytherapy

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Interview with Lung Cancer Pathologist Matthew Horton, Pt 1: Intro to NSCLC Subtypes

I had the opportunity to sit down with Dr. Matthew Horton, a pathologist who works with my own group at Swedish Cancer Institute in Seattle, at a pathology company called CellNetix.  He did subspecialty training in lung pathology and is a terrific resource for my colleagues and me, and now for a wider audience.

The first part of our discussion focused on the major subtypes (called histologies) of NSCLC, including adenocarcinomas, squamous cell carcinomas, large cell carcinomas, and the related large cell neuroendocrine carcinomas, along with a significant fraction of NSCLC tumors that can’t be classified despite our efforts.  So check out the links below for the audio and video versions of our discussion (the video with a few images of what we’re talking about), and the associated transcript and figures.

dr-horton-intro-to-lc-path-nsclc-subtypes-audio-podcast

dr-horton-intro-to-lc-path-nsclc-subtypes-transcript

dr-horton-intro-to-lc-path-nsclc-subtypes-figures

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Circulating Tumor Cells in Lung Cancer

Welcome back.  This is the second part of a discussion of the potential value of circulating tumor cells (CTCs) in cancer management.  Please see the prior post for a general introduction to the concept of CTCs and how they have been studied in various cancers.  We’ll now turn to research on CTCs in the setting of lung cancer.

CTCs in SCLC
Like breast cancer cells (described in the first part of this discussion), SCLC cells are DAPI and cytokeratin positive and CD45 negative (the pattern of particular proteins on the cells), making the cellsearch technology in its current form potentially applicable to them.  A British study sought to evaluate potential biomarkers in SCLC, including CTCs.  50 patients were evaluated and CTCs could be detected in all but 7—each of these 7 patients had limited stage disease.  Stated another way, 86% of patients overall, and 100% of patients with extensive stage disease, had detectable CTCs.  Median CTC number was much higher for patients with extensive-stage disease at 237 (range 1-44,896) compared to limited-stage disease at 2 (range 0-91).  CTCs were also assayed at 22 days after therapy; they fell to a median of 1 (range 0-2960).  In fact, at day 22, CTCs were detectable in only 60% of patients, compared to 86% at baseline.  The median survival for patients with >300 CTCs (highest quartile) was 134 days, compared to 443 days for patients with <2 CTCs (lowest quartile).  The number of CTCs at day 22 was also prognostic, with a hazard ratio of 1.43.

There is also an interesting case report about the use of CTCs for diagnosis of SCLC.  A 71 year old man presented with a lung nodule, with fine-needle aspiration (FNA) biopsy revealing a low-grade neuroendocrine tumor.  Staging was performed which demonstrated widespread metastatic disease, including liver and bone.  Noting that this is unusual for low-grade neuroendocrine tumors, his physicians dug deeper. They ran his blood for CTCs with cellsearch and 27 CTCs were detected.  Since neuroendocrine tumors (other than a rare type called Merkel carcinoma) don’t express EpCAM, they shouldn’t have CTCs detectable by cellsearch.  Liver biopsy was performed demonstrating that his cancer was really SCLC; he subsequently had a partial response to carbo/etoposide.

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Round Table Case-Based Discussion — Drs. Laskin and Sandler on First Line and Maintenance Chemo

  This is a continuation of the round table format, discussing real life case management with my colleagues who are lung cancer experts at other institutions,  This case is the second half of discussion centered around a never-smoking Asian woman who doesn’t have an EGFR mutation, and specifically the decision-making process of what first line chemotherapy-based treatment to recommend and whether to continue with maintenance therapy.  My guests for the discussion are Drs. Janessa Laskin, medical oncologist from British Columbia Cancer Agency in Vancouver, BC, and Alan Sandler, medical oncologist and Director of Hematology/Oncology at Oregon Health & Science University in Portland. 

Here is the video version, audio, transcript, and associated figures.

rt-laskin-sandler-never-smoker-egfr-wt-1st-line-chemo-and-maint-rx-audio-podcast

rt-laskin-sandler-never-smoker-egfr-wt-1st-line-chemo-and-maint-rx-transcript

rt-laskin-sandler-never-smoker-egfr-wt-1st-line-chemo-and-maint-rx-figures

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Podcast: Play in new window | Download

Case-Based Round Table in Webinar Format: Sign Up for Program on Wednesday, 1/27

We’ve got great interest in our upcoming program by Dr. Nathan Pennell on Molecular Markers in Lung Cancer, scheduled for January 20th, and many people signed up (by the way, register now if you’re interested, since it looks like we’re going to hit our cap).  Fortunately, we’re also going to be doing multiple live programs in a webinar format over time, so there will be plenty of chances for people who are interested to follow live programs with a wide range of experts.

In addition to the slide presentation/discussion that Dr. Pennell will be doing, we’re going to host a Case-Based Round Table Discussion with the Experts on Wednesday, January 27th at 8 PM EST/5 PM PST.   This will have some slides with images and a brief discussion of real cases that will provide points for discussion and debate among the participants.  I’m very pleased that many of my colleagues around the country have indicated their interest in being part of this series, and for the program in late January we have two great people joining me:

Dr. Julie Brahmer
Assistant Professor, Medical Oncologist
Sidney Kimmel Cancer Center at Johns Hopkins University
Baltimore, MD

and

Dr. Gregory Riely
Assistant Professor, Medical Oncologist
Memorial Sloan Kettering Cancer Center
New York, NY

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