MedWorm provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest medical blog items that have been tagged with 'cell lung cancer'. Sat, 03 Sep 2011 02:26:30 +0100 http://www.medworm.com/index.php?rid=5159878&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-more-genomics.html This study showed the potential for using DNA methylation profiles in targeted therapy profiles.  This seemed like a lot of fancy razzle-dazzle in this context and I'm unclear what it would really add in a practical sense; it seems to me most of the work on DNA methylation patterns in lung cancer has been focused on identifying markers for early diagnosis in serum. (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5159878 Tue, 23 Aug 2011 20:12:54 +0100 5159878 http://www.medworm.com/index.php?rid=5125976&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-squamous-cell-carcinoma.html This study involved a tissue microarray constructed from 568 patients with stage 1 NSCLC with detailed histopathological and clinical data.  SOX2 gene data was determined by FISH and SOX2 protein expression was assessed by IHC.  This data was correlated then with clinicopathological findings and OS and cancer-specific survival. Increased SOX2 gene amplification or polysomy was found in 4% of (17/429) evaluable samples but 16/17 (94%) were associated with non-ADC histology.  SOX2 protein expression was found in 48% of NSCLC and was associated with non-ADC histology (P<0.001): SOX2 expression was identified in 78% of SQC specimens (178/227) but only in 15% of ADC (29/191).  Further, SOX2 protein expression was significantly associated with high grade tumors, patien... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5125976 Fri, 12 Aug 2011 12:05:00 +0100 5125976 http://www.medworm.com/index.php?rid=5119014&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-genomics.html This study provides some preliminary benchmarking data to discuss with clinicians, although I would provide a caveat that there is likely to be a referral bias (since this is a single-institutional study from one of the world’s most reknown cancer centers) that overestimates the frequency of driver mutations in ADC. Finally, O016.06 is another presentation from the MSKCC that examined the prognostic impact of driver mutations in lung ADC with respect to smoking history.  There is important background that puts this study in context, namely, the demonstration of an independent dose-dependent relationship between smoking history and survival in patients with advanced stage NSCLC with never-smokers living 50% longer than smokers (Janjigian et al., Cancer 2010).  The authors revi... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5119014 Wed, 10 Aug 2011 12:09:27 +0100 5119014 http://www.medworm.com/index.php?rid=5086570&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-tumor-microenvironment.html This study highlights the importance of localization of immune cell response but also underscores the challenge for future studies to use more refined quantitative assessments of immune cell subpopulations and relative expression of IHC staining intesity (such as utilizing digital imaging and image analysis).  MO 22.04, also from session VIII, presented interesting complementary data to the above presentation. This study examined 196 resected stage 1-3A NSCLC using IHC for infiltrating CD8+ and FOXP3+ cells.  They counted cells expressing these markers in tumor and stromal regions in five "randomly selected" high-power-fields and reported their data as the number of cells per mm2 for each region.  They used median cell count as the cutoff to define patient subgr... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5086570 Tue, 02 Aug 2011 10:01:00 +0100 5086570 http://www.medworm.com/index.php?rid=4768264&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F04%2Fasco-issues-provisional-clinical-opinion-on-egfr-testing-in-non-small-cell-lung-cancer.html Hot off the electronic press is the PCO issued by ASCO recommending that patients with advanced stage NSCLC should have their tumors tested for EGFR mutation if they are being considered candidates for EGFR-TKI therapy.  Read here  for the abstract or Download ASCO EGFR testing in NSCLC for more deets. Provisional Clinical OpinionOn the basis of the results of five phase III randomized controlled trials, patients withNSCLC who are being considered for first-line therapy with an EGFR TKI (patients who havenot previously received chemotherapy or an EGFR TKI) should have their tumor tested forEGFR mutations to determine whether an EGFR TKI or chemotherapy is the appropriatefirst-line therapy. If you haven't been following this topic, the paper nicely summarizes the clinic... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4768264 Fri, 29 Apr 2011 16:50:41 +0100 4768264 http://www.medworm.com/index.php?rid=4684777&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F04%2Faberrant-wnt1-and-beta-catenin-expression-in-nsclc.html This month's April 2011 Journal of Thoracic Oncology has an interesting paper by Xu and colleagues (abstract) that examines Wnt1 expression in non-small cell lung cancer (NSCLC) in relation to downstream Wnt signaling molecules, including beta-catenin, and correlates different marker expression with traditional clinicopathological parameters. This is an immunohistochemical study of a tissue microarray composed of 262 NSCLC resected specimens.    The authors define aberrant beta-catenin expression as: 1) decreased membranous pattern in less than 70% of tumor cells, 2) cytoplasmic pattern of expression, or 3) nuclear pattern of expression.  As expected, the majority of patients are stage 1 or 2 but nearly 36% of the study population are never-smokers--over 50% in ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4684777 Tue, 05 Apr 2011 19:55:50 +0100 4684777 http://www.medworm.com/index.php?rid=4455482&cid=t_249460_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FuEu4Ajq_SyY%2F In 2005, AstraZeneca ran into a problem with its Iressa cancer drug, which had been approved two years earlier to treat non-small cell lung cancer as part of the FDA accelerated approval program. This meant the drugmaker was required to conduct so-called confirmatory studies, but the follow-up failed to show a survival benefit and Iressa was withdrawn, except for patients already being treated. In fact, this turned out to be the first of five instances in which such follow-up trials flopped and a drug was subsequently yanked or new restrictions were imposed. This was a distinction that, no doubt, AstraZeneca would like to forget. Of course, the drugmaker was not helped after receiving reports of serious illness and deaths due to a lung disease associated with the med in Japan. However, con... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4455482 Wed, 09 Feb 2011 22:11:48 +0100 4455482 http://www.medworm.com/index.php?rid=4275599&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F12%2Foptimal-panel-for-differentiating-nsclc-in-small-specimens.html This study makes several practical points that can be nicely summarized as bullets: For ADC the most sensitive marker and best negative predictor is CK7: 93% sensitivity, 91% NPV. For ADC the most specific marker and best positive predictor is Napsin A: 94% specificity, 90% PPV. TTF-1 has similar specificity as Napsin A for ADC. For SQC the most sensitive marker and best negative predictor is p63: 84% sensitivity, 86% NPV. For SQC the most spepcific marker and best positive predictor is NTKR2 (a neurotrophic tyrosine kinase receptor, rarely used outside of research labs) but CK5/6 has a nearly identical specificity and PPV: about 95% specificity, about 95% PPV. No single marker is BOTH highly sensitive and specific for either ADC or SQC. The authors identified a 6-marker panel that inclu... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4275599 Tue, 21 Dec 2010 12:22:00 +0100 4275599 http://www.medworm.com/index.php?rid=4238160&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F12%2Fa-consensus-statement-of-egfr-mutation-testing-in-nsclc.html The International Association for the Study of Lung Cancer (IASLC) and European Thoracic Oncology Platform recently published a consensus statement regarding EGFR mutation testng in NSCLC.  There was agreement that the decision to request EGFR mutation testing should be made by the treating physician.  The worskshop group underscored that the most important issue is cooperation and communication between the various disciplines with regard to tumor specimen handling.  The group did not reach a consensus on a preferred methodology but did stress the need for good laboratory practice with regard to validation and standardization of whatever methodology is used.  You can read more in the October 2010 Journal of Thoracic Oncology. This is interesting because of the fact ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4238160 Tue, 07 Dec 2010 12:25:00 +0100 4238160 http://www.medworm.com/index.php?rid=4175981&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F11%2Fassociation-between-egfr-mutations-and-ercc1-expression-in-nsclc.html Gandara and colleagues from UC Davis Cancer Center have published ahead-of-print on October 21, 2010 in Journal of Thoracic Oncology an interesting article examining the association between EGFR activating mutations and ERCC1 gene expression in NSCLC. NSCLC tumors that show EGFR activating mutations are also more likely to show low expression of ERCC1 mRNA levels according to this study.  This might explain (at least in part) the clinical observation that suggest enhanced efficacy of platinum-based chemotherapy in patients with EGFR-mutant NSCLCs. The authors performed microdissection of tumors from 1207 patients with NSCLC and analyzed EGFR mutation by allele-specific by PCR and ERCC1 mRNA expression by RT-PCR. Median ERCC1 expression was histology-related: adenocarcinoma (ADC... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4175981 Wed, 17 Nov 2010 12:04:00 +0100 4175981 http://www.medworm.com/index.php?rid=4125295&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F11%2Fdetecting-alk-in-endobronchial.html The October 15, 2010 issue of Clinical Cancer Research has an intriguing article that could have major implications for staging and prognostication in lung cancer.  Sakairi and colleagues from Chiba Cancer Center in Japan show the feasibility of using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain specimens suitable for testing for EML4-ALK fusion gene in NSCLC lung cancer patients with proven hilar and/or mediastinal lymph node metastasis. The protocol for this study involved chest CT followed by EBUS-TBNA for lymph nodes >5 mm.  They obtained a histologic core using a 22-gauge needle and divided the specimen into two parts with one part placed in 20% (!) formalin and the other half placed in a cryopreservative solution and then froze... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4125295 Mon, 01 Nov 2010 11:45:00 +0100 4125295 http://www.medworm.com/index.php?rid=4119713&cid=t_249460_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2Fiqx9Ideosb4%2F There’s nothing like a nasty battle over the rights to a drug under development to make for interesting reading. And so we present you with some intense legal haggling over a molecule known as WZ4002, which was discovered by researchers at the Dana-Farber Cancer Institute in Boston for combating non small-cell lung cancer with specific gene mutations. The compound is potentially quite valuable because it may be able to treat patients who don’t respond to existing cancer pills. The dispute, however, is not your run-of-the-mill spat over development rights. Instead, the lawsuit peels back the curtain on some of the jockeying that occurs among universities, drugmakers and scientists when potentially lucrative intellectual property rights are in play. Here’s why: the legal ba... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4119713 Fri, 29 Oct 2010 14:35:42 +0100 4119713 http://www.medworm.com/index.php?rid=4119748&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F10%2Falk-inhibition-in-nsclc.html Great stuff in this week's NEJM! Today's (October 28, 2010) New England Journal of Medicine has no less than three articles reporting the use of small molecule ALK tyrosine kinase inhibitor crizotinib (PF-02341066, Pfizer) in non-small-cell lung cancers harboring the oncogenic fusion gene EML4-ALK and in a patient with ALK-rearrangement positive inflammatory myofibroblastic tumor, a distinctive but uncommon soft tissue neoplasm.   Pathologists should be familiar with these articles--at least so you can suggest appropriate testing for ALK rearrangement but also that you might "shine" at your next Tumor Conference ; )  BTW, the article by Kwak et al. presents in paper form the data that rocked this past summer's ASCO Annual Meeting regarding criz... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4119748 Fri, 29 Oct 2010 04:51:39 +0100 4119748 http://www.medworm.com/index.php?rid=4086528&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F10%2Fa-little-bit-more-about-bac-of-lung.html Literally within minutes of publishing my previous post following up on a digital case challenge on bronchioloalveolar carcinoma (BAC) of the lung, I discover this month's (October 2010) Archives of Pathology and Laboratory Medicine on my desk which contains a nice article by Lindsay Schmidt and Jeffrey Myers titled, "Bronchioloalveolar Carcinoma and the Significance of Invasion: Predicting Biologic Behavior" (Arch Pathol Lab Med 2010;134:1450-1454). The issue is how to designate tumors that show stromal invasion but are mostly BAC (think Miracle Max from The Princess Bride: "It just so happens that your friend here is only MOSTLY dead. There's a big difference between mostly dead and all dead.").  Ah, but how much is mostly?  This ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4086528 Wed, 20 Oct 2010 10:56:00 +0100 4086528 http://www.medworm.com/index.php?rid=4061078&cid=t_249460_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FJm5q94WjWFs%2F Rise and shine, everyone. Another day has arrived. We have gotten off to a reasonable start by hustling one of the short people to the schoolhouse on time. Of course, there is still much to do. So join us as we peruse the news of the world and celebrate the passing of another year with a cup of stimulation. Hope your day goes well and do stay in touch… Lundbeck Buys Rights To Merck’s Bipolar Disorder Drug (Bloomberg News) Halozyme Cuts Workforce By 25 Percent (InPharma-Technologist) Sara Bloom Fights Health Care Fraud (The Washington Post) Four Big Drugmakers Bid For Paras Pharma (The Business Standard) Pfizer Reports Promising Data On NSCLC Drug (PharmaTimes) Turkey’s Biofarma May Be For Sale (Reuters) (Source: Pharmalot) Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4061078 Tue, 12 Oct 2010 12:05:00 +0100 4061078 http://www.medworm.com/index.php?rid=4045403&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F10%2Fi-pulled-this-from-fiercebiotech-news-which-i-thought-you-who-are-interested-in-breast-and-lung-cancer-should-note-hours.html I pulled this from FierceBiotech news which I thought you who are interested in breast and lung cancer should note: Hours ahead of the 2010 European Society for Medical Oncology meeting in Milan, Roche CEO Severin Schwan is talking up data from two of his company's cancer drugs: T-DM1, a breast cancer treatment, and MetMab, a drug for lung cancer. "I think a lot of people will be very excited about what we have to present," said Schwan, as quoted by Reuters. "I think the T-DM1 results are stunning; MetMab results are stunning." The remarks were made at a press and analyst event in Tokyo. In a head-to-head Phase II study, T-DM1 demonstrated a higher response rate and lower toxicity than Roche's blockbuster Herceptin. TheStreet notes that ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4045403 Fri, 08 Oct 2010 19:59:41 +0100 4045403 http://www.medworm.com/index.php?rid=4036956&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F10%2Ffollow-up-on-adenocarcinoma-with-bac-features.html My last post was a "Digital Case Challenge" presenting a case of pulmonary adenocarcinoma with non-mucinous bronchioloalveolar (BAC) features. Here's my synopsis of 3 recent papers on bronchioloalveolar carcinoma that focus on the clinicopathological, histological, and molecular differences between the two subtypes, non-mucinous and mucinous, as well as the practical importance in distinguishing these two subtypes. 1.  Wislez et al, in a recently published paper in Lung Cancer (2010;68:185-191), studied 50 cases of non-resectable adenocarcinoma with bronchioloalveolar (ADC-BAC) features who were enrolled in a multicenter study to evaluate gefitinib as a first-line therapy for non-resectable ADC-BAC.  Previous trials (SWOG S0126 and IFCT0401) have shown that ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4036956 Wed, 06 Oct 2010 21:13:32 +0100 4036956 http://www.medworm.com/index.php?rid=3954493&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F09%2Fgrading-system-for-lung-adenocarcinoma-still-elusive.html The August 2010 issue of American Journal of Surgical Pathology features an article from the Memorial Sloan Kettering Cancer Center group proposing a grading system for lung adenocarcinoma in stage 1 cancer. Sica G, Yoshizawa A, Sima CS, et al.  A grading system of lung adenocarcinoma based on histologic pattern is predictive of disease recurrence in stage I tumors.  Am J Surg Pathol 2010;34:1155-1162. The authors articulate the frustration pathologists experience in dealing with the histological heterogeneity of lung adenocarcinoma (ACa) since the vast majority are mixed subtype as well as the lack of an objective, clinically relevant grading system for lung ACa.  Recent literature has shown that mixed subtype tumors with solid or micropapillary components appear to ha... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3954493 Thu, 09 Sep 2010 11:20:00 +0100 3954493 http://www.medworm.com/index.php?rid=3907795&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F08%2Flung-adenocarcinoma-variants.html There are five common types of adenocarcinoma (actually I would say four since "mixed" doesn't seem to me a specific 'type") recognized in the WHO classification of lung cancer.  But this classification also includes five rare but distinctive variants: fetal adenocarcinoma, mucin-producing adencarcinomas (mucinous "colloid" adenocarcinoma, mucinous cystadenocarcinoma, and signet ring adenocarcinoma), and clear cell adenocarcinoma.  While rare to exceedingly rare as pure tumors, the variant patterns are important to be aware of because they occur much more commonly as a component of mixed type adenocarcinomas, are associated with particular clinicopathologic features, and often require the exclusion of a different primary site.  Anoth... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3907795 Thu, 26 Aug 2010 11:20:00 +0100 3907795 http://www.medworm.com/index.php?rid=3876910&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F08%2Fscreening-for-egfr-and-kras-mutations-by-clinicopathologic-featuresa-contraposition.html Dr. Sonia Dacic and the lung pathology group at University of Pittsburgh Medical Center recently published in Modern Pathology an article (full text here), "Clinicopathologic predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas."  The authors state that the aim of the study was "to determine whether clinicopathological characteristics and morphology of lung adenocarcinomas might be used as predictors of tumor mutational status, which then may be implemented as the selection criteria for molecular profiling of lung adenocarcinomas in clinical practice."  Implicit in this statement are the assumptions that molecular testing of lung adenocarcinoma is expensive and that screening cases for molecular testing by morphological criteria would be... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3876910 Tue, 17 Aug 2010 11:30:00 +0100 3876910 http://www.medworm.com/index.php?rid=3807528&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F07%2Fmrna-subtypes-in-lung-squamous-cell-carcinoma.html With all the recent studies looking at various distinct histological and molecular subtypes in lung adenocarcinoma, lung squamous cell carcinoma has been somewhat neglected.  Pathologists have recognized variability in morphological appearances in squamous cell carcinomas and there is a wide range of clinical outcomes.  Although the recent WHO classification recognizes four uncommon histological variants, their biological and clinical significance is not clear.  Moreover, clinical differences between other less-defined morphological patterns are unknown.A paper published online on July 19, 2010 on Clinical Cancer Research by Wilkerson et al. from University of North Carolina sheds a new light of lung squamous cell carcinoma (abstract).  They describe four novel repr... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3807528 Sat, 31 Jul 2010 14:19:12 +0100 3807528 http://www.medworm.com/index.php?rid=3767335&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F07%2Fmucinous-bronchioloalveolar-carcinoma-of-lung-and-alk-mutation.html In this study, 96% of responders had adenocarcinoma histology--primarily signet ring morphology.This is surely a very exceptional case since mucinous ACa/BAC is a very distinctive histological subtype and has been also characterized at the molecular level as being associated with KRAS mutation.  The point is that histology is not a perfect predictor of potentially druggable molecular pathologies.  If targeted therapy is being contemplated in NSCLC, we should adopt a systematic approach to all NSCLC regardless of histology.  At this point, while we are identifying patients who may potentially benefit from targeted therapy, we are building a database that will allow a more full appreciation of the relationship between histological type and molecular pathology.Thanks t... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3767335 Tue, 20 Jul 2010 04:06:14 +0100 3767335 http://www.medworm.com/index.php?rid=3636043&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F06%2Fasco-2010-erlotinib-plus-novel-cmet-inhibitor-in-nsclc.html I was attending the 2010 ASCO Annual Meeting this past weekend, June 5-6, and will post some blogs about my "highlights."  This is a perk of living in Chicago since the meetings were here from 2006-2008 and will be here for the next ten meetings!Dr. Joan H. Schiller, from the University of Texas Southwestern Medical Center, presented the findings of the the ARQ 197-209 Clinical Trial Group during Saturday’s Clinical Science Symposium on “Molecularly Targeted Trials in Lung Cancer” (Abstract LBA7502).  ARQ 197-209 is an investigational agent that is an inhibitor of c-MET, a high-affinity tyrosine kinase receptor for hepatocyte growth factor.  The c-MET receptor is an attractive anticancer target in NSCLC given that c-MET gene amplification correlates with a... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3636043 Mon, 07 Jun 2010 12:50:55 +0100 3636043 http://www.medworm.com/index.php?rid=3607842&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F05%2Fmutations-amok-in-lung-cancer.html A team from Genentech reports their findings in this week's Nature 465, 473-477 (27 May 2010) of direct tumor sequencing of a 51-year-old man with a 19-pack-year smoking history.  Note the greater than 50,000 mutations compared with paired "normal" lung. (egads!!!)  Not surprisingly, they found mutation of KRAS.  The magnitude and breadth of mutations is staggering and was surprising to the researchers.  Certainly give pause to ongoing efforts to identify oncogene-addicted tumors amenable to targeted therapy.excerpt from abstract:Here we present the complete sequences of a primary lung tumour (60× coverage) and adjacent normal tissue (46×). Comparing the two genomes, we identify a wide variety of somatic variations, including >50,000 high-confi... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3607842 Thu, 27 May 2010 20:30:00 +0100 3607842 http://www.medworm.com/index.php?rid=3416325&cid=t_249460_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FAbTi8QEjMfs%2F Welcome back. We hope you had a nice weekend filled with relaxing moments and pleasant escapades. Now, though, the routine has resumed as meetings and deadlines beckon. As usual, we prepare by clutching the mandatory cup of stimulation. Grab your own or, perhaps, a bottle of water and greet the day. Here are a few items to help you on your way. Have a great day, everyone… Antisoma Halts Phase III Lung-Cancer Drug Trial (MarketWatch) Germany To Move Quickly To Enact Price Cuts (Reuters) Eisai Hit By Delay In Filing Sepsis Drug (Seeking Alpha) Roche To Cut 500 NJ Jobs (Dow Jones) Test Predicts Which Patients Benefit From MS Drugs (Bloomberg News) Merck Is A Bigger Beast To Feed (PharmaTimes) KV Pharma Sees Shipment Resuming In Fourth Quarter (St. Louis Today) (Source: Pharmalot) Pharmalot blogs http://www.medworm.com/rss/comments.php?id=3416325 Mon, 29 Mar 2010 11:45:17 +0100 3416325 http://www.medworm.com/index.php?rid=3408672&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F03%2Fmolecular-markers-for-targeted-therapy-in-lung-cancer-uscap-2010.html I attended the Special Course at USCAP 2010, "Basic Principles and Practice of Molecular Pathology in Cancer."  One of the talks was given by Dr. Marc Ladanyi from MSKCC and one of the leaders in the field of molecular pathology of lung cancer.  The title of his presentation was "Molecular Predictive Markers for Targeted Therapies in Lung Cancer."  Here's my "take-home" points from the talk: Term: "lung adenocarcinoma oncogenome"--(I like this) and he presented a pie chart illustrating the different (and (generally) mutually exclusive) mutations found so far in lung ACa  KRAS EGFR BRAF ERBB2 (HER2) ALK fusions (especially, ALK-EML4) MEK1 NF1 but still about one-third of lung ACa have an unknown mutation Although there a... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3408672 Fri, 26 Mar 2010 15:04:27 +0100 3408672 http://www.medworm.com/index.php?rid=3294829&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F02%2Fmixed-adenocarcinomas-of-the-lung.html Continuing with the last post, Chilosi and Murer in the January 2010 Arch Pathol Lab Med also argue for the need of a new classification of mixed adenocarcinoma of the lung based on morphology, immunophenotyping, and molecular features.Chilosi M, Murer B.  Mixed adenocarcinoma of the lung: place in new proposals in classification, mandatory for target therapy.  Arch Pathol Lab Med 2010;134:55-65.Currently, we do not know the clinical relevance of distinguishing between different subtypes of ACa--let alone the significance of assigning percentages of different recognizable subtypes.  And the latter is of much more practical significance since 80% or so of lung ACa are "mixed."  The article by Okudela et al previously posted could be helpful in r... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3294829 Mon, 22 Feb 2010 04:19:23 +0100 3294829 http://www.medworm.com/index.php?rid=3292028&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F02%2Fpushing-the-boundaries-of-histology-in-nsclc.html This study is a remarkable attempt to wrestle with a heterogenous, "harmoniously confused" (Alexander Pope) group of tumors.  While it may prove unwieldy to use in practice, I think their classification of the various features is what we basically already do in daily practice (although perhaps not so consciously).  The authors stated that they determined the percentages of the different histologic patterns (but do not report this data) and this paper's findings support the idea of reporting percentages of different histologic patterns and confirms the finding that most ACa are "mixed" type.  I think it is especially important to routinely report the proportion of a tumor that is BAC-like as well as "solid" since these patterns (which are ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3292028 Sun, 21 Feb 2010 04:45:33 +0100 3292028 http://www.medworm.com/index.php?rid=3271212&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F02%2Fgene-expression-profiling-in-nsclcage-and-sexspecific-differences.html This week's JAMA (February 10, 20100 has a paper by Mostertz et al., "Age- and Sex-Specific Genomic Profiles in Non-Small Cell Lung Cancer," that examines pathway activation profiles in a retrospective series of patients with NSCLC to identify differences in underlying biology that might explain clinically relevant differences observed with respect to age and sex.  Check it out--good stuff!Mostertz W, Stevenson M, Acharya C, et al.  Age- and Sex-Specific Genomic Profiles in Non-Small Cell Lung Cancer.  JAMA 2010;303:535-543.This is a retrospective study from a single institution of 787 "patient tumor samples" from "early-stage" (1-3A) NSCLC and at least 60 months of follow-up combined from four independent microarray gen... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3271212 Sun, 14 Feb 2010 03:34:31 +0100 3271212 http://www.medworm.com/index.php?rid=3267221&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F02%2Fnotable-abstracts-from-6th-biennial-pulmonary-pathology-society-meeting-2009.html This study takes 12 "expert pathologists" (EP) and 12 "community pathologists" (CP) and measured the interobserver reproducibility (IOR) by the kappa statistic using H&E "virtual slides" from 96 lung tumors based on the 2004 WHO classification.  The authors report comparisons between various major classes (SqCa versus non-SqCa, AdCa versus non-AdCa, EP versus CP) and categories accounting for "grade" (non-poorly differentiated SqCa versus non-SqCa, pdSqCa versus non-SqCa, non-pdAdCa versus non-AdCa, pdAdCa versus non-AdCa).  Not surprisingly, EPs have a higher degree of agreement than CPs in every category, although even in the "basic" binary comparisons (SqCa vs. non-SqCa and AdCa vs. non-AdCa), the "best" agreeme... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3267221 Fri, 12 Feb 2010 05:29:37 +0100 3267221 http://www.medworm.com/index.php?rid=3176138&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F01%2Frelationship-between-growth-patterns-and-survival-in-nsclc-news-from-aacriaslc.html Medscape (registration required) reports a study presented at the joint American Association for Cancer Research-International Association for the Study of Lung Cancer (AACR-IASLC) in which Sardari Nia et al from University of Antwerp, Belgium in which researchers from the University of Antwerp, Belgium identify tumor growth patterns in lung cancer that are independent predictors of disease-free survival, disease-specific survival, and overall survival.They report having previously identified three growth patterns--destructive, alveolar, and papillary.  These patterns do not describe histological subtypes (despite the confusing terminology).  The "papillary" type ("normal lung tissue is preserved in the presence of a new microenvironment") seems to be ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3176138 Fri, 15 Jan 2010 04:12:50 +0100 3176138 http://www.medworm.com/index.php?rid=3083203&cid=t_249460_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F12%2Fnew-therapeutic-approaches-for-sclc.html This article specifically discusses agents targeting the bcl-2 protein family.  The prognosis for SCLC remains pretty dismal but there is a lot of interest in this malignancy because of the better understanding of pathways involved in SCLC and the development of "targeted" therapies.Hurwitz J, McCoy F, Scullin P, Fennell D. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009;14(10):986-994. (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3083203 Sun, 13 Dec 2009 16:11:59 +0100 3083203 http://www.medworm.com/index.php?rid=2593220&cid=t_249460_136_f&fid=35300&url=http%3A%2F%2Fwww.metastaticlivercancer.org%2F2009-06-15-cancer-treatment%2Fsmall-cell-carcinoma-of-the-lungs%2F What do you do when your oncologist gives you a small cell lung cancer prognosis of 6 months with chemotherapy and half as long without chemotherapy?   Gary wants to know. Please share your experience like we share ours.   Small cell lung cancer prognosis and secondary liver cancer   As far as I have experienced: as soon as doctors and oncologists hear "secondary liver cancer", they reason that:   "with a normal effort" there is no cancer treatment.   We stress "with normal effort". With a huge extra effort and doing everything right, our few secondary cancer survivors are living proof that you can survive secondary liver cancer much longer than the prognosis done in your hospital.   If you want to go the "do everything rig... Metastatic liver cancer blogs http://www.medworm.com/rss/comments.php?id=2593220 Mon, 15 Jun 2009 08:09:21 +0100 2593220 http://www.medworm.com/index.php?rid=1349623&cid=t_249460_131_f&fid=34989&url=http%3A%2F%2Ffeeds.b5media.com%2F%7Er%2Fb5media%2FGeneticsHealth%2F%7E3%2F264009127%2F A research team comprising scientists from MD Anderson, Johns Hopkins University and the Insitutute for Cancer Research and the University of Cambridge, UK have identified two inherited genetic variations (SNPs) on chromosome 15 associated with increased risk of lung cancer for smokers and former smokers. Individuals who have ever smoked and who have one or two copies of either of these SNPs have increased risks ranging from 28% to 81% of developing lung cancer. The findings are a major step forward in identifying those at high risk for non-small cell lung cancer and for understanding how smoking and genetic factors interact to cause the disease. The team’s findings might also provide support for a growing body of evidence suggesting that nicotine, long known as the prime addictive c... Genetics and Health blogs http://www.medworm.com/rss/comments.php?id=1349623 Fri, 04 Apr 2008 14:18:29 +0100 1349623 http://www.medworm.com/index.php?rid=956131&cid=t_249460_97_f&fid=35050&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmaGazette%2F%7E3%2F170721317%2Fglaxosmithkline_gets_fda_appro.html The FDA approved GlaxoSmithKline's (NYSE:GSK) oral Hycamtin (topotcan) for the treatment of relapsed small cell lung cancer. The capsules are indicated for patients who had a complete or partial response to chemotherapy and who are at least 45 days from the end of their treatment."The approval of HYCAMTIN capsules is particularly important forpatients with relapsed small cell lung cancer as they now have an effective treatment option that has been shown to provide a survival benefit and can be conveniently taken at home," said Debasish Roychowdhury, M.D., Vice President, Global Clinical Development, Oncology Medicine Development Center, GSK.Small Cell Lung Cancer (SCLC) is caused by uncontrollable growth of cancer cells on the bronchi and tends to spread to the rest of the bo... PharmaGazette blogs http://www.medworm.com/rss/comments.php?id=956131 Tue, 16 Oct 2007 17:45:20 +0100 956131 http://www.medworm.com/index.php?rid=486511&cid=t_249460_131_f&fid=34996&url=http%3A%2F%2Ftalk.genesanddrugs.com%2F2007%2F01%2F06%2Fusing-genesto-predict-clinical-outcome-in-non-small-cell-lungcancer%2F Cancer staging is an important clinical tool. At the very least, agreement on a staging system allows us to compare treatment regimens and choose the best one for our patients. But classical staging—based on anatomical and pathological criteria as in the TNM system–doesn’t always predict response to treatment. Modern genotyping techniques offer an alternative to classical staging. In the latest issue of The New England Journal of Medicine (356(1), January 4, 2007), a group of researchers from Taiwan report on a using gene signatures for determining clinical outcome in non-small cell lung cancer (NSCLC) (Chen, HY et al.: A five-gene signature and clinical outcome in non-small cell lung cancer). The Taiwan group used microarrays to look at some 672 genes that were associated with i... Genes & Drugs Blog blogs http://www.medworm.com/rss/comments.php?id=486511 Sat, 06 Jan 2007 18:52:16 +0100 486511