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RESEARCH PRODUCT
Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
Stefan FröhlingAlbrecht StenzingerIvo BuchhalterPeter HohenbergerSebastian BauerUlrich KeilholzAndreas MockAndreas MockDaniel B. LipkaBenedikt BrorsMichael AllgäuerAndreas RumpStephan WolfMelanie BoerriesKlaus Schulze-osthoffGunnar FolprechtKatrin PfützeChristof Von KalleChristian BrandtsMichael BitzerLaura GieldonLaura GieldonArne JahnPeter SchirmacherOlaf NeumannMatthias KroissMatthias KroissBarbara KlinkDaniela RichterSebastian UhrigPeter HorakUlrike WinterNikolas Von BubnoffBarbara HutterWalter E. AulitzkyWilko WeichertJennifer HülleinPhilipp J. JostPhilipp J. JostVeronica TeleanuVeronica TeleanuThomas KindlerLeo RuhnkeMartina FröhlichChristoph E. HeiligKatja BeckKarsten SpiekermannVolker EndrisEvelin SchröckFrederick KlauschenDorothea HanfSimon KreutzfeldtDaniel HübschmannJens T. SivekeBettina MeißburgerLino MöhrmannRichard F. SchlenkAndreas LaßmannAnna Lena IllertRoland PenzelChristina GeörgChristoph HeiningMarinela AugustinHanno Glimmsubject
Oncologymedicine.medical_specialtybusiness.industryGenetic counselingMEDLINEMedizinCancermedicine.diseaseClinical trialTranscriptomeOncologyInternal medicineMedicineClinical significanceObservational studybusinessExomedescription
Abstract The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. Significance: Rare cancers are difficult to treat; in particular, molecular pathogenesis–oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials. See related commentary by Eggermont et al., p. 2677. This article is highlighted in the In This Issue feature, p. 2659
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-06-10 |