Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial

Piotr Rutkowski, Louie Gaston, Aneta Borkowska, Silvia Stacchiotti, Hans Gelderblom, Giacomo Giulio Baldi, Emanuela Palmerini, Paolo Casali, Alessandro Gronchi, Michael Parry, Domenico Andrea Campanacci, Guido Scoccianti, Michal Wagrodzki, Stefano Ferrari, Sander Dijkstra, Andrzej Pieńkowski, Robert Grimer

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers.

METHODS: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery.

RESULTS: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw.

CONCLUSION: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.

Original languageEnglish
Pages (from-to)1384-1390
Number of pages7
JournalEuropean Journal of Surgical Oncology
Volume44
Issue number9
DOIs
Publication statusPublished - Sep 2018

Fingerprint

Giant Cell Tumor of Bone
Clinical Trials
Disease-Free Survival
Therapeutics
Curettage
Neoplasms
Retrospective Studies
Denosumab
Prosthesis Implantation
Recurrence
Neoadjuvant Therapy
Osteonecrosis
Case Management
Ribs
Jaw
Pelvis
Tibia
Skeleton
Upper Extremity
Femur

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents/administration & dosage
  • Bone Neoplasms/diagnosis
  • Denosumab/administration & dosage
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Europe/epidemiology
  • Female
  • Femur
  • Giant Cell Tumor of Bone/diagnosis
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Radiography
  • Retrospective Studies
  • Survival Rate/trends
  • Tibia
  • Treatment Outcome
  • Young Adult

Cite this

Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial. / Rutkowski, Piotr; Gaston, Louie; Borkowska, Aneta; Stacchiotti, Silvia; Gelderblom, Hans; Baldi, Giacomo Giulio; Palmerini, Emanuela; Casali, Paolo; Gronchi, Alessandro; Parry, Michael; Campanacci, Domenico Andrea; Scoccianti, Guido; Wagrodzki, Michal; Ferrari, Stefano; Dijkstra, Sander; Pieńkowski, Andrzej; Grimer, Robert.

In: European Journal of Surgical Oncology, Vol. 44, No. 9, 09.2018, p. 1384-1390.

Research output: Contribution to journalArticle

Rutkowski, P, Gaston, L, Borkowska, A, Stacchiotti, S, Gelderblom, H, Baldi, GG, Palmerini, E, Casali, P, Gronchi, A, Parry, M, Campanacci, DA, Scoccianti, G, Wagrodzki, M, Ferrari, S, Dijkstra, S, Pieńkowski, A & Grimer, R 2018, 'Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial', European Journal of Surgical Oncology, vol. 44, no. 9, pp. 1384-1390. https://doi.org/10.1016/j.ejso.2018.03.020
Rutkowski, Piotr ; Gaston, Louie ; Borkowska, Aneta ; Stacchiotti, Silvia ; Gelderblom, Hans ; Baldi, Giacomo Giulio ; Palmerini, Emanuela ; Casali, Paolo ; Gronchi, Alessandro ; Parry, Michael ; Campanacci, Domenico Andrea ; Scoccianti, Guido ; Wagrodzki, Michal ; Ferrari, Stefano ; Dijkstra, Sander ; Pieńkowski, Andrzej ; Grimer, Robert. / Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial. In: European Journal of Surgical Oncology. 2018 ; Vol. 44, No. 9. pp. 1384-1390.
@article{3626e54f8d724eed8bffc8db75432df0,
title = "Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial",
abstract = "BACKGROUND: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers.METHODS: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery.RESULTS: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38{\%}) - mostly in femur and tibia, in upper limb (34{\%}), and in pelvis/axial skeleton/ribs (28{\%}). 110 (80{\%}) patients had primary tumors, 28 (22{\%}) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98{\%} had clinical benefit from therapy. 39 (44{\%}) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56{\%}) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32{\%}); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81{\%}; 2-year EventFS (from surgery) was significantly better in WE group (93{\%}) vs 55{\%} in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw.CONCLUSION: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Bone Density Conservation Agents/administration & dosage, Bone Neoplasms/diagnosis, Denosumab/administration & dosage, Disease-Free Survival, Dose-Response Relationship, Drug, Europe/epidemiology, Female, Femur, Giant Cell Tumor of Bone/diagnosis, Humans, Male, Middle Aged, Neoplasm Staging, Radiography, Retrospective Studies, Survival Rate/trends, Tibia, Treatment Outcome, Young Adult",
author = "Piotr Rutkowski and Louie Gaston and Aneta Borkowska and Silvia Stacchiotti and Hans Gelderblom and Baldi, {Giacomo Giulio} and Emanuela Palmerini and Paolo Casali and Alessandro Gronchi and Michael Parry and Campanacci, {Domenico Andrea} and Guido Scoccianti and Michal Wagrodzki and Stefano Ferrari and Sander Dijkstra and Andrzej Pieńkowski and Robert Grimer",
note = "Copyright {\circledC} 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.",
year = "2018",
month = "9",
doi = "10.1016/j.ejso.2018.03.020",
language = "English",
volume = "44",
pages = "1384--1390",
journal = "European Journal of Surgical Oncology",
issn = "0748-7983",
publisher = "W.B. Saunders Ltd",
number = "9",

}

TY - JOUR

T1 - Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial

AU - Rutkowski, Piotr

AU - Gaston, Louie

AU - Borkowska, Aneta

AU - Stacchiotti, Silvia

AU - Gelderblom, Hans

AU - Baldi, Giacomo Giulio

AU - Palmerini, Emanuela

AU - Casali, Paolo

AU - Gronchi, Alessandro

AU - Parry, Michael

AU - Campanacci, Domenico Andrea

AU - Scoccianti, Guido

AU - Wagrodzki, Michal

AU - Ferrari, Stefano

AU - Dijkstra, Sander

AU - Pieńkowski, Andrzej

AU - Grimer, Robert

N1 - Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

PY - 2018/9

Y1 - 2018/9

N2 - BACKGROUND: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers.METHODS: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery.RESULTS: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw.CONCLUSION: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.

AB - BACKGROUND: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers.METHODS: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery.RESULTS: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw.CONCLUSION: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Bone Density Conservation Agents/administration & dosage

KW - Bone Neoplasms/diagnosis

KW - Denosumab/administration & dosage

KW - Disease-Free Survival

KW - Dose-Response Relationship, Drug

KW - Europe/epidemiology

KW - Female

KW - Femur

KW - Giant Cell Tumor of Bone/diagnosis

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Radiography

KW - Retrospective Studies

KW - Survival Rate/trends

KW - Tibia

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1016/j.ejso.2018.03.020

DO - 10.1016/j.ejso.2018.03.020

M3 - Article

C2 - 29650420

VL - 44

SP - 1384

EP - 1390

JO - European Journal of Surgical Oncology

JF - European Journal of Surgical Oncology

SN - 0748-7983

IS - 9

ER -