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ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

Scheffler M, Schultheis A, Teixido C, Michels S, Morales-Espinosa D, Viteri S, Hartmann W, Merkelbach-Bruse S, Fischer R, Schildhaus HU, Fassunke J, Sebastian M, Serke M, Kaminsky B, Randerath W, Gerigk U, Ko YD, Krüger S, Schnell R, Rothe A, Kropf-Sanchen C, Heukamp L, Rosell R, Büttner R, Wolf J - Oncotarget (2015)

Bottom Line: Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement.Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far.

View Article: PubMed Central - PubMed

Affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.

ABSTRACT

Background: While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.

Patients and methods: 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients.

Results: 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.

Conclusion: ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.

No MeSH data available.


Related in: MedlinePlus

(A)ROS1-rearranged case with clear split signals and additional green signals(B)ROS1-rearranged case with primarily additional green signals and few clear split signals. (C)ROS1-rearranged case with only additional green signals indicating an unbalanced translocation.
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Figure 1: (A)ROS1-rearranged case with clear split signals and additional green signals(B)ROS1-rearranged case with primarily additional green signals and few clear split signals. (C)ROS1-rearranged case with only additional green signals indicating an unbalanced translocation.

Mentions: ROS1 status was evaluable in 1035 out of 1137 (91.0%) patients, whereof 19 patients (1.8%) had a ROS1 rearrangement. ROS1 signals were homogeneously distributed in all analyzed tumors. The amount of cells showing aberrant signals ranged between 23% and 100% (mean 66%, median 67%). In all rearranged cases we observed an even signal distribution over the entire tumor with no “hot spot” areas. However, among different rearranged tumors, we observed a certain variation in the signal patterns. Some tumors showed only additional 3′ signals with no or few split signals, indicating an unbalanced translocation. In contrast, other tumors showed a homogenous split signal pattern in all tumor cells (see Figure 1).


ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

Scheffler M, Schultheis A, Teixido C, Michels S, Morales-Espinosa D, Viteri S, Hartmann W, Merkelbach-Bruse S, Fischer R, Schildhaus HU, Fassunke J, Sebastian M, Serke M, Kaminsky B, Randerath W, Gerigk U, Ko YD, Krüger S, Schnell R, Rothe A, Kropf-Sanchen C, Heukamp L, Rosell R, Büttner R, Wolf J - Oncotarget (2015)

(A)ROS1-rearranged case with clear split signals and additional green signals(B)ROS1-rearranged case with primarily additional green signals and few clear split signals. (C)ROS1-rearranged case with only additional green signals indicating an unbalanced translocation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496376&req=5

Figure 1: (A)ROS1-rearranged case with clear split signals and additional green signals(B)ROS1-rearranged case with primarily additional green signals and few clear split signals. (C)ROS1-rearranged case with only additional green signals indicating an unbalanced translocation.
Mentions: ROS1 status was evaluable in 1035 out of 1137 (91.0%) patients, whereof 19 patients (1.8%) had a ROS1 rearrangement. ROS1 signals were homogeneously distributed in all analyzed tumors. The amount of cells showing aberrant signals ranged between 23% and 100% (mean 66%, median 67%). In all rearranged cases we observed an even signal distribution over the entire tumor with no “hot spot” areas. However, among different rearranged tumors, we observed a certain variation in the signal patterns. Some tumors showed only additional 3′ signals with no or few split signals, indicating an unbalanced translocation. In contrast, other tumors showed a homogenous split signal pattern in all tumor cells (see Figure 1).

Bottom Line: Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement.Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far.

View Article: PubMed Central - PubMed

Affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.

ABSTRACT

Background: While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.

Patients and methods: 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients.

Results: 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.

Conclusion: ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.

No MeSH data available.


Related in: MedlinePlus