Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review

Elizabeth A Connolly; Vivek A Bhadri; Johnathon Wake; Katrina M Ingley; Jeremy Lewin; Susie Bae; Daniel D Wong; Anne P Long; David Pryor; Stephen R Thompson; Madeleine C Strach; Peter S Grimison; Annabelle Mahar; Fiona Bonar; Fiona Maclean; Angela Hong

doi:10.1002/cam4.4580

Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review

Elizabeth A Connolly, Vivek A Bhadri, Johnathon Wake, Katrina M Ingley, Jeremy Lewin, Susie Bae, Daniel D Wong, Anne P Long, David Pryor, Stephen R Thompson, Madeleine C Strach, Peter S Grimison, Annabelle Mahar, Fiona Bonar, Fiona Maclean, Angela Hong

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31 Citations (Scopus)

Abstract

UNLABELLED: CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes.

METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019.

RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1-20.1), 1-year OS was 57%. Median progression-free survival was 5.8 months (95% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen.

CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.

Original language	English
Pages (from-to)	1805-1816
Number of pages	12
Journal	Cancer Medicine
Volume	11
Issue number	8
DOIs	https://doi.org/10.1002/cam4.4580
Publication status	Published - Apr 2022

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Connolly, E. A., Bhadri, V. A., Wake, J., Ingley, K. M., Lewin, J., Bae, S., Wong, D. D., Long, A. P., Pryor, D., Thompson, S. R., Strach, M. C., Grimison, P. S., Mahar, A., Bonar, F., Maclean, F., & Hong, A. (2022). Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review. Cancer Medicine, 11(8), 1805-1816. https://doi.org/10.1002/cam4.4580

@article{ef529fe13a0749ecbec85914fc6f7c30,

title = "Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review",

abstract = "UNLABELLED: CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes.METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019.RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56\%), 11 patients (61\%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82\%, 64\% and 34\% respectively. Nine patients (82\%) underwent surgery (all had R0 resections), 8 (73\%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73\%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55\% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95\% CI 5.1-20.1), 1-year OS was 57\%. Median progression-free survival was 5.8 months (95\% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen.CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.",

keywords = "Adolescent, Adult, Female, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Sarcoma/genetics, Sarcoma, Small Cell/pathology, Soft Tissue Neoplasms, Young Adult",

author = "Connolly, \{Elizabeth A\} and Bhadri, \{Vivek A\} and Johnathon Wake and Ingley, \{Katrina M\} and Jeremy Lewin and Susie Bae and Wong, \{Daniel D\} and Long, \{Anne P\} and David Pryor and Thompson, \{Stephen R\} and Strach, \{Madeleine C\} and Grimison, \{Peter S\} and Annabelle Mahar and Fiona Bonar and Fiona Maclean and Angela Hong",

note = "{\textcopyright} 2022 The Authors. Cancer Medicine published by John Wiley \& Sons Ltd.",

year = "2022",

month = apr,

doi = "10.1002/cam4.4580",

language = "English",

volume = "11",

pages = "1805--1816",

journal = "Cancer Medicine",

issn = "2045-7634",

publisher = "John Wiley \& Sons",

number = "8",

}

Connolly, EA, Bhadri, VA, Wake, J, Ingley, KM, Lewin, J, Bae, S, Wong, DD, Long, AP, Pryor, D, Thompson, SR, Strach, MC, Grimison, PS, Mahar, A, Bonar, F, Maclean, F & Hong, A 2022, 'Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review', Cancer Medicine, vol. 11, no. 8, pp. 1805-1816. https://doi.org/10.1002/cam4.4580

TY - JOUR

T1 - Systemic treatments and outcomes in CIC-rearranged Sarcoma

T2 - A national multi-centre clinicopathological series and literature review

AU - Connolly, Elizabeth A

AU - Bhadri, Vivek A

AU - Wake, Johnathon

AU - Ingley, Katrina M

AU - Lewin, Jeremy

AU - Bae, Susie

AU - Wong, Daniel D

AU - Long, Anne P

AU - Pryor, David

AU - Thompson, Stephen R

AU - Strach, Madeleine C

AU - Grimison, Peter S

AU - Mahar, Annabelle

AU - Bonar, Fiona

AU - Maclean, Fiona

AU - Hong, Angela

PY - 2022/4

Y1 - 2022/4

N2 - UNLABELLED: CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes.METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019.RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1-20.1), 1-year OS was 57%. Median progression-free survival was 5.8 months (95% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen.CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.

AB - UNLABELLED: CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes.METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019.RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1-20.1), 1-year OS was 57%. Median progression-free survival was 5.8 months (95% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen.CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.

KW - Adolescent

KW - Adult

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Retrospective Studies

KW - Sarcoma/genetics

KW - Sarcoma, Small Cell/pathology

KW - Soft Tissue Neoplasms

KW - Young Adult

UR - https://www.scopus.com/pages/publications/85125055519

U2 - 10.1002/cam4.4580

DO - 10.1002/cam4.4580

M3 - Article

C2 - 35178869

SN - 2045-7634

VL - 11

SP - 1805

EP - 1816

JO - Cancer Medicine

JF - Cancer Medicine

IS - 8

ER -

Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review

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