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Semiquantitative Assessment of Tumor Spread through Air Spaces (STAS) in Early-Stage Lung Adenocarcinomas
Hironori Uruga MD, PhD, Takeshi Fujii MD, PhD, Sakashi Fujimori MD, PhD, Tadasu Kohno MD, PhD, Kazuma Kishi MD, PhD.Journal of Thoracic Oncology, July 2017, Volume 12, Issue 7, Pages 1046-1051
Commentary by Nir Peled
Air-born spread of cancer cells considered being safe, however there is no proven evidence associated with that assumption. Seeding ability of cancer cells as well mesenchymal to epithelial transition may play a role in this process. Although the numerous limitations of this study, it provides an early evidence for the importance of air-born spread of cancer cells and their ability to survive without a trivial seeding capacity.
Aberrant signaling through the HER2-ERK1/2 pathway is predictive of reduced disease-free and overall survival in early stage non-small cell lung cancer (NSCLC) patients
Marianna Scrima, Federica Zito Marino, Duarte Mendes Oliveira et al.Journal of Cancer 2017; 8(2):227-239
Commentary by Nir Peled
Mutation in HER2 gene is identified in 2-4% of the lung adenocarcinomas, while the incidence of HER2 overexpression is 7-32% in this population. The clinical evidence supporting HER2 as an important therapeutic target in lung cancer is growing, however with disappointing response rates in comparison to the excellent success seen in breast cancer. This study screened HER2 overexpression and its downstream signaling pathway (ERK1/2) in TMA from 132 NSCLC patients indicating that the HER2 pathway may be activated through the ERK1/2 mechanism (and not through AKT) and its overexpression is a negative prognostic factor in NSCLC. There is definitely a need for therapeutic studies considering the total coverage of the HER2 pathway.
The challenge of molecular testing for clinical trials in advanced non-small cell lung cancer patients: Analysis of a prospective database
Vrancken A, Lepers S, Peeters L, Oyen C, Dooms C, Nackaerts K, Verbeken E, Wauters I, Weynand B, Vansteenkiste JLung Cancer, Volume 102, 1 December 2016, Pages 96-100
Commentary by Tom Stinchcombe
Many clinical trials require tumor samples with central laboratory testing for a biomarker for enrollment in the trial. This requirement can contribute to significant delays in enrollment in trials, starting therapy, and many patients are subsequently determined to be ineligible for the clinical trial due to the lack of the biomarker or interval decline in performance status. Unfortunately, many of us have experienced these issues, and this retrospective analysis by Vrancken and colleagues is very timely and clinically relevant. In this analysis of 250 patients, 227 patients had sample sent for central testing and 20 patients had a failure of central biomarker analysis due to insufficient quantity or quality. Results were obtained were available on 207 patients, and 91 patients had the biomarker of interest and 116 did not have the biomarker of interest. Of the 91 patients with the biomarker of interest, 34 patients were included in the trial, 20 patients were excluded due to decline in performance status, 5 patients were not eligible due to other eligibility criteria, 14 patients were loss to follow up, and 18 patients did not participate because a trial spot was not available. This led to a trial enrollment rate of 15%. The mean waiting time between informed consent and receipt of biomarker results from the central lab was 24 calendar days. The mean time for patients with archival or newly taken biopsies was 21.9 and 22.1 days, respectively. The authors recommend the use of local testing with central confirmation as one method of addressing the situation
Many patients have high hopes of participating in a clinical trial and the delays can cause significant patient frustration and anxiety. The need to screen a significant number of patients to enroll a few, and to track the status of the biopsies increases the labor of the clinical research staff. The causes of the delay are multifactorial (i.e. time in preparation of the sample, sending sample, testing sample, etc.) so it is unlikely one solution will address the problem. The importance of these biopsies in understanding of tumor biology and drug development is well recognized, but as we field we will have to address the barrier to trial enrollment they have created. I have started reviewing the trial tissue and biopsy requirements and the prevalence of the biomarker of interest more closely to ensure the trial is feasible before committing to trial participation.
ALK-Testing in non-small cell lung cancer (NSCLC): Immunohistochemistry (IHC) and/or fluorescence in-situ Hybridisation (FISH)?: Statement of the Germany Society for Pathology (DGP) and the Working Group Thoracic Oncology (AIO)
Laffert M, Schirmacher P, Warth A, Weichert W, Büttner R, Huber RM, Wolf J, Griesinger F, Dietel M, Grohé CLung Cancer, Volume 103, 1 January 2017, Pages 1-5
Commentary by Nir Peled
ALK(+) NSCLC may have targeted thearpies for the 1st, 2nd and even 3rd line therapies with overall response rates of 60-80% and significant prolongation of PFS, excellent QOL and accumulatd prolongatoin of survival. Therefore, highly sensitive approach to detect this subgroup of patients, 5-7% of the NSCLC adenocarcinomas, must be in highers priority. Screening for IHC became standard procedure in many countries, followed by FISH validation in IHC borderline cases. The German Statment summerizes the three algorithems IHC first (D5F3 vs. 5A4) followed by FISH for borderline cases, with a relatively more binaric approach when using D5F3; and FISH first with a validation by IHC in borderline cases. In all tracks, further technologies are recommended in borderline cases with high clinical suspecious (e.g. NGS). This statement describes an easier algorithm with upfront IHC (vs. FISH) and provides additional confirmation to treat patient based on a strong IHC positivity as a single test.