Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC

Hofman, Véronique; Heeke, Simon; Bontoux, Christophe; Chalabreysse, Lara; Barritault, Marc; Bringuier, Pierre Paul; Fenouil, Tanguy; Benzerdjeb, Nazim; Bégueret, Hugues; Merlio, Jean Philippe; Caumont, Charline; Piton, Nicolas; Sabourin, Jean‐Christophe; Evrard, Solène; Syrykh, Charlotte; Vigier, Anna; Brousset, Pierre; Long‐Mira, Elodie; Benzaquen, Jonathan; Boutros, Jacques; Allègra, Maryline; Tanga, Virginie; Lespinet‐Fabre, Virginie; Salah, Myriam; Bonnetaud, Christelle; Bordone, Olivier; Lassalle, Sandra; Marquette, Charles‐Hugo; Ilié, Marius; Hofman, Paul

doi:10.1016/j.jtocrr.2022.100457

Cited by 9 publications

(19 citation statements)

References 27 publications

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“…Therefore in future, the use of NGS-based gene panels will be essential if the indication of molecularly targeted drugs is to be considered based on co-mutation pro les. Improvements in technology to speed up the NGS testing process are currently underway (34,35), and it is expected that NGS tests with su ciently short TATs will be introduced in clinical practice in the near future.…”

Section: Discussionmentioning

confidence: 99%

The Race Against Time: Evaluating the Speed of Gene Panel Result Delivery in NSCLC Patient Management

Kunimasa,

Tamiya,

Inoue

et al. 2023

Preprint

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Background In this study, we aimed to compare the clinical utility of the Oncomine Dx® Target Test (Oncomine) with that of the AMOY Dx® Pan Lung Cancer PCR panel (AMOY), focusing on their turn-around times (TATs). Methods Data on the specimens, fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissue samples, the success rate and detected driver alterations, submitted for these gene panel analyses were also collected from medical records. Further, for the comparison of the two methods, TATs defined as: T1, the period from first visit to specimen submission at an external laboratory; T2, the period from first visit to when the attending physician ordered the gene panel test; and T3, the period from first visit until the availability of the analysis results, were measured. Results In total, 213 patients, with 157 and 56 who submitted specimens for Oncomine and AMOY, respectively, were enrolled. The success rate of the analyses were 98.0% for Oncomine and 100.0% for AMOY. Further, the detection rates of driver alterations were 57.9% and 50.9% for Oncomine and AMOY, respectively, and 95.9% specimens submitted for Oncomine were FFPE, while 78.2% of those submitted for AMOY were FF. Further, the TATs, T1, T2, and T3, tended to be significantly shorter in AMOY cases. Specifically, the median TAT for AMOY cases, particularly T3, was 12 days (range, 4–26 days). Conclusions AMOY showed shorter TATs and a higher success rate than Oncomine. Therefore, its application using FF specimens may be effectively utilized in oncologic emergencies.

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Section: Discussionmentioning

confidence: 99%

The Race Against Time: Evaluating the Speed of Gene Panel Result Delivery in NSCLC Patient Management

Kunimasa,

Tamiya,

Inoue

et al. 2023

Preprint

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“…This study showed that an ultrafast DNA and RNA NGS setting at the baseline can be greatly involved in reflex testing for ROS1 rearrangements in NS-NSCLC [ 16 , 17 ]. Here, the NGS results were obtained in an average of four working days and a positive result was confirmed in 15/16 cases by FISH.…”

Section: Discussionmentioning

confidence: 99%

“…One previous limitation to the use of only NGS for ROS1 rearrangement evaluation was the delay in obtaining the results, which would not be suitable for the administration of a targeted therapy according to the organization, workflow of the samples, and sequencing approaches. However, the development of a new ultrafast NGS system has allowed us to obtain, in another study, the results in an average of four days for positive cases, which is even faster than the TAT when sequentially using ROS1 IHC and then ROS1 FISH [ 16 , 17 ]. It is also noteworthy that RNA NGS can lead to the identification of all the fusion partners of ROS1 and allow the detection of short deletions sometimes not visible with ROS1 FISH [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Second, even if available, access to some NGS approaches could be limited, due to the cost and absence of reimbursement of costs, and can also be associated with a long TAT to obtain the results, which is not compatible with international guidelines [ 15 ]. Due to the lower cost and the shorter TAT, IHC and/or rapid RT-PCR can be easily performed as an alternative for ROS1 status assessment [ 16 , 36 , 37 , 38 ]. More importantly, IHC and FISH methods can sometimes be the only approaches that detect some therapeutic targets in very small tissue biopsies and/or, if only a low percentage of tumor cells are present, knowing that NGS can lead to some false negative results due to the low quantity and/or quality of the extracted nucleic acid [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, the present study demonstrated that performing IHC to evaluate the ROS1 rearrangement status in advanced NS-NSCLC should be abandoned nowadays in favor of ultrafast RNA NGS reflex testing [ 16 , 17 , 43 ]. ROS1 FISH is still useful for validation of the diagnosis in the case of uncertain NGS results and/or of very small tissue biopsies with a few tumor cells.…”

Section: Discussionmentioning

confidence: 99%

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A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

Hofman

Goffinet

Bontoux

et al. 2023

JPM

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The detection of ROS1 rearrangements in metastatic non-squamous non-small cell lung carcinoma (NS-NSCLC) permits administration of efficient targeted therapy. Detection is based on a testing algorithm associated with ROS1 immunohistochemistry (IHC) screening followed by ROS1 FISH and/or next generation sequencing (NGS) to confirm positivity. However, (i) ROS1 rearrangements are rare (1–2% of NS-NSCLC), (ii) the specificity of ROS1 IHC is not optimal, and (iii) ROS1 FISH is not widely available, making this algorithm challenging to interpret time-consuming. We evaluated RNA NGS, which was used as reflex testing for ROS1 rearrangements in NS-NSCLC with the aim of replacing ROS1 IHC as a screening method. ROS1 IHC and RNA NGS were prospectively performed in 810 NS-NSCLC. Positive results were analyzed by ROS1 FISH. ROS1 IHC was positive in 36/810 (4.4%) cases that showed variable staining intensity while NGS detected ROS1 rearrangements in 16/810 (1.9%) cases. ROS1 FISH was positive in 15/810 (1.8%) of ROS1 IHC positive cases and in all positive ROS1 NGS cases. Obtaining both ROS1 IHC and ROS1 FISH reports took an average of 6 days, while obtaining ROS1 IHC and RNA NGS reports took an average of 3 days. These results showed that systematic screening for the ROS1 status using IHC must be replaced by NGS reflex testing.

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Current challenges and practical aspects of molecular pathology for non-small cell lung cancers

Hofman,

Berezowska,

Kazdal

et al. 2023

Virchows Arch

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The continuing evolution of treatment options in thoracic oncology requires the pathologist to regularly update diagnostic algorithms for management of tumor samples. It is essential to decide on the best way to use tissue biopsies, cytological samples, as well as liquid biopsies to identify the different mandatory predictive biomarkers of lung cancers in a short turnaround time. However, biological resources and laboratory member workforce are limited and may be not sufficient for the increased complexity of molecular pathological analyses and for complementary translational research development. In this context, the surgical pathologist is the only one who makes the decisions whether or not to send specimens to immunohistochemical and molecular pathology platforms. Moreover, the pathologist can rapidly contact the oncologist to obtain a new tissue biopsy and/or a liquid biopsy if he/she considers that the biological material is not sufficient in quantity or quality for assessment of predictive biomarkers. Inadequate control of algorithms and sampling workflow may lead to false negative, inconclusive, and incomplete findings, resulting in inappropriate choice of therapeutic strategy and potentially poor outcome for patients. International guidelines for lung cancer treatment are based on the results of the expression of different proteins and on genomic alterations. These guidelines have been established taking into consideration the best practices to be set up in clinical and molecular pathology laboratories. This review addresses the current predictive biomarkers and algorithms for use in thoracic oncology molecular pathology as well as the central role of the pathologist, notably in the molecular tumor board and her/his participation in the treatment decision-making. The perspectives in this setting will be discussed.

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Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC

Cited by 9 publications

References 27 publications

The Race Against Time: Evaluating the Speed of Gene Panel Result Delivery in NSCLC Patient Management

The Race Against Time: Evaluating the Speed of Gene Panel Result Delivery in NSCLC Patient Management

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

Current challenges and practical aspects of molecular pathology for non-small cell lung cancers

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