Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma

Santiago A. Lozano-Calderón; Jose Ignacio Albergo; Olivier Q. Groot; Nelson A. Merchan; Jad M. El Abiad; Vanessa Salinas; Luis Carlos Gomez Mier; Camilo Soto Montoya; Marco L. Ferrone; John E. Ready; Francisco J. Linares; Adam S. Levin; Manuel Peleteiro Pensado; José Juan Pozo Kreilinger; Irene Barrientos Ruiz; Eduardo J. Ortiz-Cruz; Mark C. Gebhardt; Gregory M. Cote; Edwin Choy; Dimitrios Spentzos; Yin P. Hung; Vikram Deshpande; Ivan A. Chebib; Robert Allan McCulloch; Germán Farfalli; Luis Aponte Tinao; Carol D. Morris; Gunnlaugur Petur Nielsen; Megan E. Anderson; Lee M. Jeys

doi:10.1002/cncr.34506

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma

Santiago A. Lozano-Calderón
, Jose Ignacio Albergo
, Olivier Q. Groot
, Nelson A. Merchan
, Jad M. El Abiad
, Vanessa Salinas
, Luis Carlos Gomez Mier
, Camilo Soto Montoya
, Marco L. Ferrone
, John E. Ready
, Francisco J. Linares
, Adam S. Levin
, Manuel Peleteiro Pensado
, José Juan Pozo Kreilinger
, Irene Barrientos Ruiz
, Eduardo J. Ortiz-Cruz
, Mark C. Gebhardt
, Gregory M. Cote
, Edwin Choy
, Dimitrios Spentzos

Yin P. Hung, Vikram Deshpande, Ivan A. Chebib, Robert Allan McCulloch, Germán Farfalli, Luis Aponte Tinao, Carol D. Morris, Gunnlaugur Petur Nielsen, Megan E. Anderson, Lee M. Jeys

Harvard University
Hospital Italiano de Buenos Aires
Johns Hopkins University
Instituto Nacional de Cancerología - Colombia
Hospital Universitario San Ignacio
Hospital Universitario La Paz
Aston University

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma.

METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy.

RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response.

CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Original language	English
Pages (from-to)	60-70
Number of pages	11
Journal	Cancer
Volume	129
Issue number	1
DOIs	https://doi.org/10.1002/cncr.34506
State	Published - 01 Jan 2023
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Ewing sarcoma
bone tumor
cancer treatment
survival outcomes
tumor necrosis
Bone Neoplasms/pathology
Neoplasm Recurrence, Local/drug therapy
Humans
Neoadjuvant Therapy/adverse effects
Sarcoma, Ewing/drug therapy
Retrospective Studies
Necrosis/etiology

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10.1002/cncr.34506

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Lozano-Calderón, S. A., Albergo, J. I., Groot, O. Q., Merchan, N. A., El Abiad, J. M., Salinas, V., Gomez Mier, L. C., Montoya, C. S., Ferrone, M. L., Ready, J. E., Linares, F. J., Levin, A. S., Peleteiro Pensado, M., Pozo Kreilinger, J. J., Ruiz, I. B., Ortiz-Cruz, E. J., Gebhardt, M. C., Cote, G. M., Choy, E., ... Jeys, L. M. (2023). Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma. Cancer, 129(1), 60-70. https://doi.org/10.1002/cncr.34506

@article{7022f894719543c0a3da5b5684435cbf,

title = "Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma",

abstract = "BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma.METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy.RESULTS: Patients who had a complete (100\%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95\% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95\% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95\% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95\% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0\%-99\%) response.CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.",

keywords = "Ewing sarcoma, bone tumor, cancer treatment, survival outcomes, tumor necrosis, Bone Neoplasms/pathology, Neoplasm Recurrence, Local/drug therapy, Humans, Neoadjuvant Therapy/adverse effects, Sarcoma, Ewing/drug therapy, Retrospective Studies, Necrosis/etiology",

author = "Lozano-Calder{\'o}n, \{Santiago A.\} and Albergo, \{Jose Ignacio\} and Groot, \{Olivier Q.\} and Merchan, \{Nelson A.\} and \{El Abiad\}, \{Jad M.\} and Vanessa Salinas and \{Gomez Mier\}, \{Luis Carlos\} and Montoya, \{Camilo Soto\} and Ferrone, \{Marco L.\} and Ready, \{John E.\} and Linares, \{Francisco J.\} and Levin, \{Adam S.\} and \{Peleteiro Pensado\}, Manuel and \{Pozo Kreilinger\}, \{Jos{\'e} Juan\} and Ruiz, \{Irene Barrientos\} and Ortiz-Cruz, \{Eduardo J.\} and Gebhardt, \{Mark C.\} and Cote, \{Gregory M.\} and Edwin Choy and Dimitrios Spentzos and Hung, \{Yin P.\} and Vikram Deshpande and Chebib, \{Ivan A.\} and McCulloch, \{Robert Allan\} and Germ{\'a}n Farfalli and \{Aponte Tinao\}, Luis and Morris, \{Carol D.\} and \{Petur Nielsen\}, Gunnlaugur and Anderson, \{Megan E.\} and Jeys, \{Lee M.\}",

note = "Publisher Copyright: {\textcopyright} 2022 American Cancer Society.",

year = "2023",

month = jan,

day = "1",

doi = "10.1002/cncr.34506",

language = "English",

volume = "129",

pages = "60--70",

journal = "Cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "1",

}

Lozano-Calderón, SA, Albergo, JI, Groot, OQ, Merchan, NA, El Abiad, JM, Salinas, V, Gomez Mier, LC, Montoya, CS, Ferrone, ML, Ready, JE, Linares, FJ, Levin, AS, Peleteiro Pensado, M, Pozo Kreilinger, JJ, Ruiz, IB, Ortiz-Cruz, EJ, Gebhardt, MC, Cote, GM, Choy, E, Spentzos, D, Hung, YP, Deshpande, V, Chebib, IA, McCulloch, RA, Farfalli, G, Aponte Tinao, L, Morris, CD, Petur Nielsen, G, Anderson, ME & Jeys, LM 2023, 'Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma', Cancer, vol. 129, no. 1, pp. 60-70. https://doi.org/10.1002/cncr.34506

TY - JOUR

T1 - Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma

AU - Lozano-Calderón, Santiago A.

AU - Albergo, Jose Ignacio

AU - Groot, Olivier Q.

AU - Merchan, Nelson A.

AU - El Abiad, Jad M.

AU - Salinas, Vanessa

AU - Gomez Mier, Luis Carlos

AU - Montoya, Camilo Soto

AU - Ferrone, Marco L.

AU - Ready, John E.

AU - Linares, Francisco J.

AU - Levin, Adam S.

AU - Peleteiro Pensado, Manuel

AU - Pozo Kreilinger, José Juan

AU - Ruiz, Irene Barrientos

AU - Ortiz-Cruz, Eduardo J.

AU - Gebhardt, Mark C.

AU - Cote, Gregory M.

AU - Choy, Edwin

AU - Spentzos, Dimitrios

AU - Hung, Yin P.

AU - Deshpande, Vikram

AU - Chebib, Ivan A.

AU - McCulloch, Robert Allan

AU - Farfalli, Germán

AU - Aponte Tinao, Luis

AU - Morris, Carol D.

AU - Petur Nielsen, Gunnlaugur

AU - Anderson, Megan E.

AU - Jeys, Lee M.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma.METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy.RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response.CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

AB - BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma.METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy.RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response.CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

KW - Ewing sarcoma

KW - bone tumor

KW - cancer treatment

KW - survival outcomes

KW - tumor necrosis

KW - Bone Neoplasms/pathology

KW - Neoplasm Recurrence, Local/drug therapy

KW - Humans

KW - Neoadjuvant Therapy/adverse effects

KW - Sarcoma, Ewing/drug therapy

KW - Retrospective Studies

KW - Necrosis/etiology

UR - https://www.scopus.com/pages/publications/85141378159

U2 - 10.1002/cncr.34506

DO - 10.1002/cncr.34506

M3 - Article

C2 - 36305090

AN - SCOPUS:85141378159

SN - 0008-543X

VL - 129

SP - 60

EP - 70

JO - Cancer

JF - Cancer

IS - 1

ER -

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma

Abstract

UN SDGs

Keywords

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