Normal Tissue Complication Probability (NTCP) Prediction Model for Osteoradionecrosis of the Mandible in Patients With Head and Neck Cancer After Radiation Therapy: Large-Scale Observational Cohort

Dijk, Lisanne V. van; Abusaif, Abdelrahman; Rigert, Jillian; Naser, Mohamed A.; Hutcheson, Katherine A.; Lai, Stephen Y.; Fuller, Clifton D.; Mohamed, Abdallah S.R.

doi:10.1016/j.ijrobp.2021.04.042

Cited by 26 publications

(29 citation statements)

References 32 publications

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“…DVCs with moderate dose indices (V40Gy[RBE], V50Gy[RBE], and V60Gy[RBE]), instead of the DVCs with high dose indices (V70Gy[RBE] and V75Gy[RBE]), were found to have statistically significant differences between the ORN group and control group for both VMAT and PBSPT (Table 2). For VMAT, this dose volume effect at moderate doses has been reported in multiple studies related to ORN (32)(33)(34)(35)(36)(37). The derived DVCs for VMAT are consistent with the reported results (Table 3).…”

Section: Discussionsupporting

confidence: 90%

Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated With Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study

et al. 2022

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PurposeTo retrospectively investigate empirical relative biological effectiveness (RBE) for mandible osteoradionecrosis (ORN) in head and neck (H&N) cancer patients treated with pencil-beam-scanning proton therapy (PBSPT).MethodsWe included 1,266 H&N cancer patients, of which, 931 patients were treated with volumetric-modulated arc therapy (VMAT) and 335 were treated with PBSPT. Among them, 26 VMAT and 9 PBSPT patients experienced mandible ORN (ORN group), while all others were included in the control group. To minimize the impact of the possible imbalance in clinical factors between VMAT and PBSPT patients in the dosimetric comparison between these two modalities and the resulting RBE quantification, we formed a 1:1 case-matched patient cohort (335 VMAT patients and 335 PBSPT patients including both the ORN and control groups) using the greedy nearest neighbor matching of propensity scores. Mandible dosimetric metrics were extracted from the case-matched patient cohort and statistically tested to evaluate the association with mandibular ORN to derive dose volume constraints (DVCs) for VMAT and PBSPT, respectively. We sought the equivalent constraint doses for VMAT so that the critical volumes of VMAT were equal to those of PBSPT at different physical doses. Empirical RBEs of PBSPT for ORN were obtained by calculating the ratio between the derived equivalent constraint doses and physical doses of PBSPT. Bootstrapping was further used to get the confidence intervals.ResultsClinical variables of age, gender, tumor stage, prescription dose, chemotherapy, hypertension or diabetes, dental extraction, smoking history, or current smoker were not statistically related to the incidence of ORN in the overall patient cohort. Smoking history was found to be significantly associated with the ORN incidence in PBSPT patients only. V40Gy[RBE], V50Gy[RBE], and V60Gy[RBE] were statistically different (p<0.05) between the ORN and control group for VMAT and PBSPT. Empirical RBEs of 1.58(95%CI: 1.34-1.64), 1.34(95%CI: 1.23-1.40), and 1.24(95%: 1.15-1.26) were obtained for proton dose at 40 Gy[RBE=1.1], 50 Gy[RBE=1.1] and 60 Gy[RBE=1.1], respectively.ConclusionsOur study suggested that RBEs were larger than 1.1 at moderate doses (between 40 and 60 Gy[RBE=1.1]) with high LET for mandible ORN. RBEs are underestimated in current clinical practice in PBSPT. The derived DVCs can be used for PBSPT plan evaluation and optimization to minimize the incidence rate of mandible ORN.

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Section: Discussionsupporting

confidence: 90%

Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated With Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study

et al. 2022

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“…A subset analysis generated for the current manuscript demonstrated that 123/826 oropharyngeal cancer patients (14.9%) developed all grade ORN and 42/825 (5.1%) developed grade 4 ORN. 33 In the current cohort, Veterans who developed ORN were more likely to have pre-EBRT extractions (Table 3). No other variables reached statistical significance (Tables 1, 3).…”

Section: Discussionmentioning

confidence: 90%

Early detection of mandible osteoradionecrosis risk in a high comorbidity Veteran population

Wilde

Kansara

Sapienza

et al. 2022

Preprint

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Objective: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively. Study design: Retrospective analysis of prospective cohort. Setting: Tertiary care Veterans Health Administration (VHA) medical center. Methods: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively analyzed this patient cohort and extracted clinical and pathologic data for 164 patients with SCC of the oral cavity, oropharynx, larynx and hypopharynx who received definitive or adjuvant EBRT (2016-2020). Results: Most patients were dentate and 80% underwent dental extractions prior to EBRT of which 16 (16%) had complications. The rate of ORN was 3.7% for oral cavity SCC patients and 8.1% for oropharyngeal SCC patients. Median time to ORN development was 156 days and the earliest case was detected at 127 days post EBRT completion. All ORN patients were dentate and underwent extraction prior to EBRT start. Conclusion: ORN development can occur early following EBRT in a Veteran population with significant comorbid conditions but overall rates are in line with the general population. Prospective tracking of HNSCC patients throughout the post-treatment surveillance period is critical to early detection of this devastating EBRT complication.

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“…The risk factors for ORN [12][13][14]17], such as the RT dose to the whole or to a nonanatomically defined proportion of the mandible [18][19], do not fully explain the occurrence of severe ORN events. Different mandibular topographies may range in their proclivity for the development of severe ORN.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible

Sapienza

Thomas

Mai

et al. 2022

Rep Pract Oncol Radiother.

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Background:The purpose of this study was to describe the topography, extension (volume), and timing of severe osteoradionecrosis (ORN) that required mandible resection in patients previously treated for head and neck cancer at a high-volume Veterans Affairs Medical Center. Materials and methods:The records from a reference hyperbaric oxygen clinic were retrospectively analyzed (n = 50, 2018-2021). Inclusion criteria were: I) severe ORN defined as progressive ORN that required resection; II) pathologic confirmation of ORN; and III) availability of pre-operative CT-imaging. Using a radiotherapy (RT) imaging software, we performed a detailed volumetric (3D) analysis of the bone involvement by ORN. Time intervals from RT to surgery for ORN and from surgery to the last follow-up were calculated.Results: All patients that met inclusion criteria (n = 10) were male with significant smoking history (median 47.5 pack-years) and a median age of 57 years old at the time of RT. The primary tumors were: oropharynx (n = 6), oral cavity (n = 3) and nasopharynx (n = 1). The median time from RT to ORN surgery was 8 years. The most common ORN location was the posterior lateral body (molar) and six patients had associated fractures. The mean ORN volume was 3.6 cc (range: 0.6-8.3), corresponding to a mean 6.3% (range: 0.7-14) of the total mandibular volume. After a median follow-up of 13.5 months, no recurrence of ORN occurred.Three patients died of non-cancer and non-ORN-recurrence related causes (1 y OS 77.1%). Conclusion:Severe ORN occurred after a median of 8 years from the previous RT and usually affected the posterior lateral body. Surgical resection achieved excellent ORN control.

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Normal Tissue Complication Probability (NTCP) Prediction Model for Osteoradionecrosis of the Mandible in Patients With Head and Neck Cancer After Radiation Therapy: Large-Scale Observational Cohort

Cited by 26 publications

References 32 publications

Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated With Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study

Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated With Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study

Early detection of mandible osteoradionecrosis risk in a high comorbidity Veteran population

Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible

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