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Poster session 17

112P - Clinical, genomic and transcriptomic characteristics of young-onset biliary tract cancers

Date

21 Oct 2023

Session

Poster session 17

Topics

Cancer in Adolescents and Young Adults (AYA); Genetic and Genomic Testing

Tumour Site

Hepatobiliary Cancers

Presenters

Thomas Pudlarz

Citation

Annals of Oncology (2023) 34 (suppl_2): S215-S232. 10.1016/S0923-7534(23)01929-4

Authors

T. Pudlarz¹, L. Antoun², A. Rousseau³, R. Nicolle⁴, M. Gelli⁵, E. Fernandez de Sevilla⁶, S. Cosconea¹, L. Tselikas⁷, R. Barbe⁸, A. Turpin⁹, M. Deloger¹, A. Italiano¹⁰, M. Valery¹¹, A.A. Tarabay¹², V. Boige¹³, D. Malka¹⁴, C. Smolenschi¹⁵, A. hollebecque¹⁶, M.P. Ducreux¹⁷, A. Boileve¹⁸

Author affiliations

¹ Département De Médecine Oncologique, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
² Gustave Roussy Cancer Campus, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
³ Paris, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
⁴ Programme Carte D'identité Des Tumeurs, Ligue Contre le Cancer, 75013 - Paris/FR
⁵ Surgery, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
⁶ Département D'anesthésie, Chirurgie Et Interventionnel, Gustave Roussy, 94800 - Villejuif/FR
⁷ Interventional Radiology Department, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
⁸ Diagnostic Imaging, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
⁹ Oncologie Médicale, Hopital Claude Huriez, 59037 - Lille/FR
¹⁰ Ditep, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
¹¹ Medical Oncology Department, Gustave Roussy, 94805 - Villejuif, Cedex/FR
¹² Medical Oncology Department - Gi, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
¹³ Département De Médecine Oncologique, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
¹⁴ 75, Institut mutaliste Montsouris, 75013 - Paris/FR
¹⁵ Département De Médecine Oncologique, Gustave Roussy, 94805 - VILLEJUIF/FR
¹⁶ Ditep, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
¹⁷ Medical Oncology Department, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
¹⁸ Département De Médecine Oncologique, Institut Gustave Roussy, 94805 - Villejuif/FR

Resources

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Abstract 112P

Background

Biliary tract cancers (BTC), including cholangiocarcinomas (CCA) are rare but aggressive cancers primarily affecting patients (pts) >70 years (median age at diagnosis : 72-78 years). However, there has been a rise in the incidence of CCA among younger individuals (<50 years). This study aimed to investigate clinical, genomic and transcriptomic characteristics and outcomes of young-onset BTC/CCA (YOC) pts.

Methods

We identified all consecutive patients with histologically confirmed CCA treated at Gustave Roussy (France) between 2015 and 2021 as part of the ACABI-PRONOBIL multicenter cohort study. Clinical data were extracted from medical records. Genomic data were obtained through in-house or Foundation Medicine® panels. Transcriptomic analyses were performed for 58 pts (13 YOC) at metastatic diagnosis.

Results

Of the 546 pts with CCA, 92 (16.8%) had YOC (median age, 42 years; range, 27-50). Median overall survival (mOS) from 1^st line therapy was 22.7 months (mo) (95%CI: 18.3-27.6) for YOC patients vs 19.2 mo (95%CI: 18.0-22.0) for non-YOC patients (p=0.14). Molecular profiling was more often performed for YOC pts (68% vs 55%, p<0.05). Rates of actionable molecular alterations (IDH1/2, BRAF, FGFR2, NTRK, HER2, MSI) and targeted therapies administration did not differ between YOC and non-YOC pts. CDKN2A alterations were less frequent in YOC than in non-YOC pts (12.6% vs 25.2%, p<0.05). Differentially expressed genes between YOC and non-YOC pts with Gene Set Enrichment Analysis were mostly genes involved in immunity and WNT signaling pathways. Table: 112P

Genomic characteristics		Age <=50 n=92	age>50 n=454[BA1]
		n	%	n	%
Molecular profile available	No	29	32%	204	45%
	Yes	63	68%	250	55%
Actionable alteration	No	41	65%	141	56%
	Yes	22	35%	109	44%
Main actionable alterations	No alteration	11	17%	43	17%
	Mutation IDH1/2	8	13%	40	16%
	Fusion FGFR 1-4	8	13%	21	8%
	Amplification HER2	3	5%	15	6%
	Mutation BRAF V600E	0	0%	10	4%
	EGFR	2	3%	7	3%
	Fusion NTRK	6	10%	11	4%
	Mutation KRAS G12C	1	2%	3	1%
Other relevant alterations	KRAS	16	25%	40	16%
	TP53	25	40%	91	36%
	CDKN2A/B	8	13%	63	25%
MMR status (n=199)	dMMR/MSI	0	0%	11	7%
	pMMR/MSS	47	100%	141	93%
Targeted therapies administration	No	41	65%	141	56%
	Yes	22	35%	109	44%

Conclusions

Although tending to have a more advanced disease at diagnosis, YOC patients had OS similar to that of non-YOC pts, and no more actionable molecular alterations. Our findings suggest that the biological mechanisms driving CCA in YOC patients may be different from those in older patients and warrant further investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Gercor.

Disclosure

All authors have declared no conflicts of interest.