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Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol
G Model
JORMAS-713; No. of Pages 2 J Stomatol Oral Maxillofac Surg xxx (2019) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Short communication
Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol A. Dinnoo a, F. Bidault b,c, N. Lassau b,c, M. Elmaalouf d, A. Moya-Plana a, A. Ruffier e, F. Janot a, N. Benmoussa a,* Department of Head and Neck Oncology, Gustave Roussy Institute, universite´ Paris-Saclay, 14, rue E´douard Vaillant, 94800 Villejuif, France Department of Radiology, Institut Gustave-Roussy, 14, rue E´douard Vaillant, 94800 Villejuif, France c IR4M, UMR 8081, CNRS, universite´ Paris-Sud, universite´ Paris-Saclay, 91400 Orsay, France d Department of Odontology, Gustave Roussy Institute, universite´ Paris-Saclay, 14, rue E´douard Vaillant, 94800 Villejuif, France e Department of Radiotherapy, Gustave Roussy Institute, universite´ Paris-Saclay, 14, rue E´douard Vaillant, 94800 Villejuif, France a
b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 16 June 2019 Accepted 21 June 2019
Osteoradionecrosis of the jaws (ORNJ) is a late complication of head and neck irradiation estimated at around 3% of irradiated patients. The PENTO protocol (Pentoxyfilline and Tocopherol), with the eventual adjunction of Clodronate (PENTOCLO), showed interesting results even in advanced ORNJ. The current literature does not describe the long-term outcomes and particularly after the completion of the protocol. The PENTO or PENTOCLO protocol should be prescribed as a life-long treatment or the outcome should be monitored at least as long as the duration of the protocol after its end.
C 2019 Elsevier Masson SAS. All rights reserved.
Keywords: Osteoradionecrosis PENTO PENTOCLO
Osteoradionecrosis of the jaws (ORNJ) is a late complication of head and neck radiotherapy defined clinically as the failure to heal of a previously irradiated zone of de-vitalized and exposed bone observed over a period of three to six months and in the absence of local neoplastic disease [1]. The incidence of this condition is estimated at around 3% of irradiated patients [2]. The prevention and management of ORNJ remains challenging because indications for conservative and surgical therapies are not yet defined. The PENTO protocol (Pentoxyfilline and Tocopherol), with the eventual adjunction of Clodronate (PENTOCLO), shows interesting results even in advanced ORNJ. Two studies show 89 to 100% of healing with the primary outcome being the reduction of SOMA (Subjective, Objective, Management, and Analytic evaluation of injury) score (discontinuation of analgesics, trismus, bone exposure, radiological improvement) [3,4]. A recent meta-analysis on seven studies showed a success for 62.7% of patients [95% confidence interval (CI) 55.8–69.1%] with the primary outcome being the full recovery or significant improvement not requiring further intervention [5]. This response rate is mainly measured during or at the end of the protocol [3,4,6] or is unclear [7,8]. We have observed that the average prescription duration for the protocol in the above-cited studies is 13.57 months. * Corresponding author. E-mail address: [email protected] (N. Benmoussa).
Our center experience on ORNJ shows four types of responses to this protocol: Healing (resolution of the symptoms and complete mucosal healing),stability (resolution or stabilization of symptoms and osteolysis with an incomplete mucosal coverage), progression (progression of symptoms, osteolysis or mucosal defect) or relapse (progression of symptoms, osteolysis or mucosal defect after a diagnosis of healing during the protocol). Delanian and al. also recognize relapses and rebound effect. They tend to pursue the protocol longer than the relief of symptoms or switch to another long-term treatment with Colchicin and Clodronate [9]. With these observations, we highlight that the current literature does not describe the long-term outcomes and particularly after the completion of the protocol. Therefore, two approaches can be considered: either the PENTO or PENTOCLO protocol should be prescribed as a life-long treatment or the outcome should be monitored at least as long as the duration of the protocol after its end. Disclosure of interest The authors declare that they have no competing interest. References [1] Nabil S, Samman N. Risk factors for osteoradionecrosis after head and neck radiation: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:54–69.
https://doi.org/10.1016/j.jormas.2019.06.007 C 2019 Elsevier Masson SAS. All rights reserved. 2468-7855/
Please cite this article in press as: Dinnoo A, et al. Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.06.007
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JORMAS-713; No. of Pages 2 2
A. Dinnoo et al. / J Stomatol Oral Maxillofac Surg xxx (2019) xxx–xxx
[2] Wahl MJ. Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys 2006;64:661–9. [3] Delanian S, Depondt J, Lefaix J-L. Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck 2005;27:114–23. [4] Delanian S, Chatel C, Porcher R, Depondt J, Lefaix J-L. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys 2011;80:832–9. [5] Kolokythas A, Rasmussen JT, Reardon J, Feng C. Management of osteoradionecrosis of the jaws with pentoxifylline-tocopherol: a systematic review of the literature and meta-analysis. Int J Oral Maxillofac Surg 2019;48:173–80.
[6] Robard L, Louis M-Y, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis 2014;131:333–8. [7] McLeod NMH, Pratt CA, Mellor TK, Brennan PA. Pentoxifylline and tocopherol in the management of patients with osteoradionecrosis, the Portsmouth experience. Br J Oral Maxillofac Surg 2012;50:41–4. [8] D’Souza J, Lowe D, Rogers SN. Changing trends and the role of medical management on the outcome of patients treated for osteoradionecrosis of the mandible: experience from a regional head and neck unit. Br J Oral Maxillofac Surg 2014;52:356–62. [9] Delanian S. Fracture mandibulaire sur oste´oradione´crose: option conservatrice me´dicale « Pentoclo »? Cancer/Radiothe´rapie 2014;18:629.
Please cite this article in press as: Dinnoo A, et al. Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.06.007
JORMAS-713; No. of Pages 2 J Stomatol Oral Maxillofac Surg xxx (2019) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Short communication
Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol A. Dinnoo a, F. Bidault b,c, N. Lassau b,c, M. Elmaalouf d, A. Moya-Plana a, A. Ruffier e, F. Janot a, N. Benmoussa a,* Department of Head and Neck Oncology, Gustave Roussy Institute, universite´ Paris-Saclay, 14, rue E´douard Vaillant, 94800 Villejuif, France Department of Radiology, Institut Gustave-Roussy, 14, rue E´douard Vaillant, 94800 Villejuif, France c IR4M, UMR 8081, CNRS, universite´ Paris-Sud, universite´ Paris-Saclay, 91400 Orsay, France d Department of Odontology, Gustave Roussy Institute, universite´ Paris-Saclay, 14, rue E´douard Vaillant, 94800 Villejuif, France e Department of Radiotherapy, Gustave Roussy Institute, universite´ Paris-Saclay, 14, rue E´douard Vaillant, 94800 Villejuif, France a
b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 16 June 2019 Accepted 21 June 2019
Osteoradionecrosis of the jaws (ORNJ) is a late complication of head and neck irradiation estimated at around 3% of irradiated patients. The PENTO protocol (Pentoxyfilline and Tocopherol), with the eventual adjunction of Clodronate (PENTOCLO), showed interesting results even in advanced ORNJ. The current literature does not describe the long-term outcomes and particularly after the completion of the protocol. The PENTO or PENTOCLO protocol should be prescribed as a life-long treatment or the outcome should be monitored at least as long as the duration of the protocol after its end.
C 2019 Elsevier Masson SAS. All rights reserved.
Keywords: Osteoradionecrosis PENTO PENTOCLO
Osteoradionecrosis of the jaws (ORNJ) is a late complication of head and neck radiotherapy defined clinically as the failure to heal of a previously irradiated zone of de-vitalized and exposed bone observed over a period of three to six months and in the absence of local neoplastic disease [1]. The incidence of this condition is estimated at around 3% of irradiated patients [2]. The prevention and management of ORNJ remains challenging because indications for conservative and surgical therapies are not yet defined. The PENTO protocol (Pentoxyfilline and Tocopherol), with the eventual adjunction of Clodronate (PENTOCLO), shows interesting results even in advanced ORNJ. Two studies show 89 to 100% of healing with the primary outcome being the reduction of SOMA (Subjective, Objective, Management, and Analytic evaluation of injury) score (discontinuation of analgesics, trismus, bone exposure, radiological improvement) [3,4]. A recent meta-analysis on seven studies showed a success for 62.7% of patients [95% confidence interval (CI) 55.8–69.1%] with the primary outcome being the full recovery or significant improvement not requiring further intervention [5]. This response rate is mainly measured during or at the end of the protocol [3,4,6] or is unclear [7,8]. We have observed that the average prescription duration for the protocol in the above-cited studies is 13.57 months. * Corresponding author. E-mail address: [email protected] (N. Benmoussa).
Our center experience on ORNJ shows four types of responses to this protocol: Healing (resolution of the symptoms and complete mucosal healing),stability (resolution or stabilization of symptoms and osteolysis with an incomplete mucosal coverage), progression (progression of symptoms, osteolysis or mucosal defect) or relapse (progression of symptoms, osteolysis or mucosal defect after a diagnosis of healing during the protocol). Delanian and al. also recognize relapses and rebound effect. They tend to pursue the protocol longer than the relief of symptoms or switch to another long-term treatment with Colchicin and Clodronate [9]. With these observations, we highlight that the current literature does not describe the long-term outcomes and particularly after the completion of the protocol. Therefore, two approaches can be considered: either the PENTO or PENTOCLO protocol should be prescribed as a life-long treatment or the outcome should be monitored at least as long as the duration of the protocol after its end. Disclosure of interest The authors declare that they have no competing interest. References [1] Nabil S, Samman N. Risk factors for osteoradionecrosis after head and neck radiation: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:54–69.
https://doi.org/10.1016/j.jormas.2019.06.007 C 2019 Elsevier Masson SAS. All rights reserved. 2468-7855/
Please cite this article in press as: Dinnoo A, et al. Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.06.007
G Model
JORMAS-713; No. of Pages 2 2
A. Dinnoo et al. / J Stomatol Oral Maxillofac Surg xxx (2019) xxx–xxx
[2] Wahl MJ. Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys 2006;64:661–9. [3] Delanian S, Depondt J, Lefaix J-L. Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck 2005;27:114–23. [4] Delanian S, Chatel C, Porcher R, Depondt J, Lefaix J-L. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys 2011;80:832–9. [5] Kolokythas A, Rasmussen JT, Reardon J, Feng C. Management of osteoradionecrosis of the jaws with pentoxifylline-tocopherol: a systematic review of the literature and meta-analysis. Int J Oral Maxillofac Surg 2019;48:173–80.
[6] Robard L, Louis M-Y, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis 2014;131:333–8. [7] McLeod NMH, Pratt CA, Mellor TK, Brennan PA. Pentoxifylline and tocopherol in the management of patients with osteoradionecrosis, the Portsmouth experience. Br J Oral Maxillofac Surg 2012;50:41–4. [8] D’Souza J, Lowe D, Rogers SN. Changing trends and the role of medical management on the outcome of patients treated for osteoradionecrosis of the mandible: experience from a regional head and neck unit. Br J Oral Maxillofac Surg 2014;52:356–62. [9] Delanian S. Fracture mandibulaire sur oste´oradione´crose: option conservatrice me´dicale « Pentoclo »? Cancer/Radiothe´rapie 2014;18:629.
Please cite this article in press as: Dinnoo A, et al. Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.06.007