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M.L. Dalurzo
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MTE28 - Implementation of Precision Medicine in Routine Practice: The Latin American Experience (Ticketed Session) (ID 321)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 07:30 - 08:30, Lehar 3-4
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MTE28.01 - Implementation of Precision Medicine in Routine Practice: The Latin American Experience (ID 6590)
07:30 - 08:00 | Author(s): M.L. Dalurzo
- Abstract
- Presentation
Abstract:
Implementation of Precision Medicine in Routine Practice: The Latin American Experience – Part 2 Technology for molecular testing in lung cancer is a highly demanding aspect to tackle in the LATAM countries. Molecular testing requires incorporation of new technologies usually involving expensive equipment, reagents and supplies. Moreover, these items are commonly imported from other countries and are subjected to custom regulation and heavy taxes. Therefore, LATAM labs commonly face unpredictable delays in the legal processing of purchase orders, are constantly adjusting to changes in regulations and in the country’s financial status, and suffer from slow and sometimes poor support from companies that do not see them as preferred clients. As an example of consequences of some of this points, in Argentina the agents Nivolumab and Pembrolizumab were approved by government agencies for immunotherapy for NSCLC before the molecular testing laboratories had conditions to purchase the DAKO platform and the CDx antibodies for appropriate IHC testing. Some technical devices such as automated IHC platforms are more widely available. They were initially integrated onto large pathology labs in the main cities of several countries but smaller automated platforms are currently available in a number of other cities. There are laboratories equipped for fluorescence in situ hybridization (FISH) and for DNA sequencing in most countries. Sanger sequencing is still commonly used, but the main laboratories already incorporated newer technologies such as RT-PCR allele-specific technology (usually Cobas platform) and tailored panels of next generation sequencing (NGS) or have them in the short list for implementation. Additionally to the challenges in the laboratories organization, two other main issues obstruct the implementation of lung cancer molecular testing in the LATAM countries: the lack of a stable logistic infra-structure necessary to ship biological samples to the molecular laboratories in a cheap, reliable and rapid way, and the hurdle of cost reimbursement for the tests. In the past 10 years, expenses and logistics for transfer of biological specimens and reimbursement for molecular test costs, in most countries such as Mexico, Brazil and Argentina, were sponsored by pharmaceutical companies. Companies such as AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer have acted through clinical trials or special access programs. In a smaller scale, molecular tests have been supported by governmental health agencies or covered by private health care insurance companies. A restricted number of patients are paying the tests out of the pocket, mostly sending to US laboratories. Least but not least, the implementation of lung cancer molecular testing relies in the adequate quantity and, most importantly, in the good quality of the available biological sample. Subsequent to the intense interdisciplinary work by the laboratory personnel, significant progress has been detected in the last years in the amount of tumor cells present in the testing specimens. However, proper quality is only achieved in a fraction of specimens. Most LATAM countries do not have local regulations for quality control (QC) of pathology laboratories, and a limited number of those laboratories are taken external QC certification. Moreover, there is no financial support for the adequate validation of the assays at their implementation and for the competency checking periodically thereafter. In consequence, the risk of having laboratories testing in substandard quality conditions is high. Institutions that are well-structured administratively, technically and scientifically and that handle large volumes of clinical specimens usually participate in external QC for molecular tests. They engage in accredited proficiency testing activities or, at least, send material to reference laboratories for investigation of reproducibility of results. Unfortunately, this does not occur in the majority of the LATAM laboratories. Therefore, it is critical to reach potential sponsors to assist the LATAM molecular testing laboratories in overcoming these challenges and rapidly jump to the future. Efforts leading to improve tissue quality, to facilitate local optimization of assays and to ensure assay validation by international standards are needed. A group of regional laboratories have been trying to organize a collaborative project to face these issues and also to come up with an affordable strategy to ensure good quality in pathology and molecular laboratories. Multiple barriers are making it difficult to succeed in this effort. The patient advocate groups have proved effective in sensitizing governments and regulatory agencies in the USA, but those groups are still very under-represented in LATAM. Professional institutions such as the IASLC are specially tailored to help. IASLC congregates internationally conscious personnel and lung cancer experts and would excel, for instance, in matching experts with laboratories requesting specific assistance and in coordinating a regional consortium of laboratories interested in rounds of specimen exchange for proficiency testing and in validated sets of control specimens for implementation of new tests. Data from at least 15 of the highest populated LATAM countries regarding their lung cancer test menu, the technical platforms used, and efforts for investigation of the assay performance characteristics have been surveyed and results will be discussed.
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-029 - Infrequent Staining Patterns in ALK Immunohistochemistry: Correlation with Fish Analysis (ID 5208)
14:30 - 14:30 | Author(s): M.L. Dalurzo
- Abstract
Background:
AKL gene rearrangements are predictive alterations in non small cell lung carcinomas (NSCLC). Immunohistochemistry (IHC) has become a valuable tool in assessing ALK status, however unusual staining patterns, such as heterogeneous diffuse moderate and focal intense stains, may occur and can make evaluation difficult.
Methods:
We correlated immunohistochemistry unusual staining patterns with ALK status by fluorescence in situ hybridization (FISH). Of 851 cases tested, we found 14 (1.6%) cases with inconclusive staining patterns that can be summarized in: a) diffuse granular cytoplasmic moderate stain, with or without background mucin stain (10 cases) b) focal intense granular cytoplasmic stain in overall negative or weakly positive tumors (4 cases). IHC was performed on an automatized Benchmark staining module using Ventana ALK (D5F3) CDx assay with Optiview amplification kit. FISH was performed using ALK break-apart probe set (Vysis LSI ALK Dual Color, Abbott Molecular). Cases were considered ALK-FISH positive if ≥15% tumor cells showed split red and green signals (separation of 2 diameters or more) and/or single red signals
Results:
Of 10 moderate granular cytoplasmic stain cases, 4 had also abundant mucin backround stain 6 where markedly heterogeneous with areas of weak and moderate cytoplasmic granular stain. Nine were FISH negative, one yielded no signals (uninformative result) and one specimen corresponded to an acid decalcified specimen and was not evaluated by FISH. Focal intense stain was observed in 5 samples, 3 corresponded to surgical specimens and the rest to small needle biopsies, one of the surgical specimens was FISH positive and the rest, negative.
Conclusion:
Since FDA approval of Ventana ALK (D5F3) IHC CDx Assay, IHC has become a widely used tool for assessing ALK status. Guidelines suggest that weak granular stain should be interpreted as negative and focal intense granular stain in any number of cells, as positive. Even though our sample is small, moderate granular stain was consistently negative by FISH analysis, however, focal intense stain shows more discordant results between tests. To date, no suggestions are made on what should be the minimum amount of tumor in a sample to report an IHC assay. Even though some of these patients with IHC positive/FISH negative results have been reported as responders to Crizotinib, further studies are needed. One specimen with moderate cytoplasmic IHC stain was uninformative due to lack of signals. This raises the issue of the need to standardize preanalytical variables, which can be difficult in some areas of Latin America.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-070 - NSCLC with Detectable EGFR Mutation: Institutional Experience (ID 6238)
14:30 - 14:30 | Author(s): M.L. Dalurzo
- Abstract
Background:
Background: EGFR is one of the most commonly mutated proto-oncogenes in lung cancer. The frequency of such mutations varies from approximately 10% of lung adenocarcinomas in North American and European populations to as high as 50% in Asia. The leucine to arginine substitution at position 858 (L858R) in exon 21 and short in-frame deletions in exon 19 are the most common sensitizing mutations, comprising approximately 90% of cases. Approximately 50% of EGFR TKI resistance is due to a second site mutation, the T790M mutation occurring within exon 20. We describe our experience in patients with lung cancer with detectable EGFR mutation.
Methods:
Describe the epidemiological characteristics and the incidence of mutations in patients diagnosed with advanced NSCLC in our institution. Analyze toxicities and adherence to treatment. Evaluate treatments performed and the problem of the analysis of the biopsy. We analyzed patients from June 2012 to date.
Results:
We found 61 /326 ( 18.7%) patients with detectable EGFR mutation, 47 women (77 %) and 39% smokers, 47 patients had advanced or unresectable disease. The most common sites of metastases were bone and lymph nodes. 27 of the 61 patients had mutation of exon 19, 27 patients with mutation of exon 21, others in 18 and 20. Five of them with detectable T790M mutation confirmed by repeat biopsy after progressing to ITK. The most common side effects were diarrhea and rash, 12 patients had toxicities which had to reduce dose or discontinue treatment.
Conclusion:
The most common side effects were diarrhea and rash, 12 patients had toxicities which had to reduce dose or discontinue treatment. We had a low incidence of invalid or not evaluable biopsies. although not all patients with detectable mutation were treated with ITK , who received such treatment had good adhesion and a low percentage of patients had to discontinue treatment
