A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆
Background: Tumor molecular profiling (TMP) for pancreatic cancer (PC) is recommended by current international guidelines, yet no testing standards exist. Moreover, the magnitude of benefit and the cost-effectiveness of comprehensive next-generation sequencing panels for PC are under debate. Materia...
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Elsevier
2025-03-01
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| Series: | ESMO Gastrointestinal Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949819825000032 |
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| author | S. Hussung D. Akhoundova C. Pistoni D. Lenggenhager A. Töpfer C. Pauli B. Pestalozzi C. Britschgi M. Zoche M. Rechsteiner H. Moch A. Weber R. Fritsch |
| author_facet | S. Hussung D. Akhoundova C. Pistoni D. Lenggenhager A. Töpfer C. Pauli B. Pestalozzi C. Britschgi M. Zoche M. Rechsteiner H. Moch A. Weber R. Fritsch |
| author_sort | S. Hussung |
| collection | DOAJ |
| description | Background: Tumor molecular profiling (TMP) for pancreatic cancer (PC) is recommended by current international guidelines, yet no testing standards exist. Moreover, the magnitude of benefit and the cost-effectiveness of comprehensive next-generation sequencing panels for PC are under debate. Materials and methods: We implemented a stratified two-stage TMP algorithm for advanced PC. Stage 1 comprised immunohistochemistry for mismatch repair deficiency and targeted sequencing employing a 33-gene next-generation sequencing panel covering common PC drivers and DNA damage response genes. Based on pre-specified events (KRAS wild type, mismatch repair deficiency, molecular tumor board recommendation), subsequent comprehensive molecular testing was carried out (stage 2). We report molecular findings and patient outcomes. Results: A total of 94 PC patients were included in the study. Some 63/94 (67.0%) patients underwent TMP according to the algorithm, of which 5/63 (7.9%) fulfilled criteria for subsequent stage 2 comprehensive testing. A total of 31/94 (33%) patients underwent upfront comprehensive molecular testing outside the algorithm based on referring physician’s request. Compared with algorithm testing, upfront comprehensive testing detected a higher number of pathogenic molecular alterations/patient (median: five versus three, P = 0.0005), however no additional actionable alterations. Actionable alterations were identified in 25/94 (26.6%) cases, including DNA damage response gene alterations, KRAS G12C and targetable drivers in KRAS wild type tumors. Patients receiving targeted therapy based on molecular profile showed superior survival (progression-free survival, overall survival) compared with patients without targeted treatment. Conclusions: Stratified two-stage TMP reliably identifies actionable alterations in PC patients, with potential therapeutic benefit. The proposed TMP algorithm might be as effective, yet more feasible and economic compared with comprehensive upfront testing. |
| format | Article |
| id | doaj-art-89f81c3167254019b9baf0a8217db36c |
| institution | Kabale University |
| issn | 2949-8198 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-89f81c3167254019b9baf0a8217db36c2025-02-12T05:33:13ZengElsevierESMO Gastrointestinal Oncology2949-81982025-03-017100134A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆S. Hussung0D. Akhoundova1C. Pistoni2D. Lenggenhager3A. Töpfer4C. Pauli5B. Pestalozzi6C. Britschgi7M. Zoche8M. Rechsteiner9H. Moch10A. Weber11R. Fritsch12University Hospital Zurich, Department of Medical Oncology and Hematology, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, SwitzerlandDepartment of Medical Oncology, Inselspital, University Hospital of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, SwitzerlandUniversity Hospital Zurich, Department of Medical Oncology and Hematology, Zurich, SwitzerlandFaculty of Medicine, University of Zurich, Zurich, Switzerland; University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, SwitzerlandFaculty of Medicine, University of Zurich, Zurich, Switzerland; University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Medical Oncology and Hematology, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Medical Oncology and Hematology, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, SwitzerlandFaculty of Medicine, University of Zurich, Zurich, Switzerland; University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, Switzerland; Institute of Molecular Cancer Research (IMCR), University of Zurich, Zurich, SwitzerlandUniversity Hospital Zurich, Department of Medical Oncology and Hematology, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland; Correspondence to: Dr Ralph Fritsch, Raemistrasse 100, 8091 Zürich, Switzerland. Tel: +41-44-255111Background: Tumor molecular profiling (TMP) for pancreatic cancer (PC) is recommended by current international guidelines, yet no testing standards exist. Moreover, the magnitude of benefit and the cost-effectiveness of comprehensive next-generation sequencing panels for PC are under debate. Materials and methods: We implemented a stratified two-stage TMP algorithm for advanced PC. Stage 1 comprised immunohistochemistry for mismatch repair deficiency and targeted sequencing employing a 33-gene next-generation sequencing panel covering common PC drivers and DNA damage response genes. Based on pre-specified events (KRAS wild type, mismatch repair deficiency, molecular tumor board recommendation), subsequent comprehensive molecular testing was carried out (stage 2). We report molecular findings and patient outcomes. Results: A total of 94 PC patients were included in the study. Some 63/94 (67.0%) patients underwent TMP according to the algorithm, of which 5/63 (7.9%) fulfilled criteria for subsequent stage 2 comprehensive testing. A total of 31/94 (33%) patients underwent upfront comprehensive molecular testing outside the algorithm based on referring physician’s request. Compared with algorithm testing, upfront comprehensive testing detected a higher number of pathogenic molecular alterations/patient (median: five versus three, P = 0.0005), however no additional actionable alterations. Actionable alterations were identified in 25/94 (26.6%) cases, including DNA damage response gene alterations, KRAS G12C and targetable drivers in KRAS wild type tumors. Patients receiving targeted therapy based on molecular profile showed superior survival (progression-free survival, overall survival) compared with patients without targeted treatment. Conclusions: Stratified two-stage TMP reliably identifies actionable alterations in PC patients, with potential therapeutic benefit. The proposed TMP algorithm might be as effective, yet more feasible and economic compared with comprehensive upfront testing.http://www.sciencedirect.com/science/article/pii/S2949819825000032pancreatic cancertumor molecular profilingmolecular tumor boardpersonalized treatmentprecision oncology |
| spellingShingle | S. Hussung D. Akhoundova C. Pistoni D. Lenggenhager A. Töpfer C. Pauli B. Pestalozzi C. Britschgi M. Zoche M. Rechsteiner H. Moch A. Weber R. Fritsch A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ ESMO Gastrointestinal Oncology pancreatic cancer tumor molecular profiling molecular tumor board personalized treatment precision oncology |
| title | A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ |
| title_full | A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ |
| title_fullStr | A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ |
| title_full_unstemmed | A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ |
| title_short | A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ |
| title_sort | stratified two stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆ |
| topic | pancreatic cancer tumor molecular profiling molecular tumor board personalized treatment precision oncology |
| url | http://www.sciencedirect.com/science/article/pii/S2949819825000032 |
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