SaeHee K. Yom

The prevalence and risk factors associated with osteoradionecrosis of the jaw in oral and oropharyngeal cancer patients treated with intensity-modulated radiation therapy (IMRT): The Memorial Sloan Kettering Cancer Center experience

OBJECTIVE To determine the prevalence and correlation of various risk factors [radiation dose, periodontal status, alcohol and smoking] to the development of osteoradionecrosis (ORN). PATIENTS AND METHODS The records of 1023 patients treated with IMRT for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) between 2004 and 2013 were retrospectively reviewed to identify patients who developed ORN. Fisher exact tests were used to analyze patient characteristics between ORN patients with OCC and OPC. Paired Wilcoxon tests were used to compare the dose volumes to the ORN and contralateral non-ORN sites. To evaluate an association between ORN and risk factors, a case-control comparison was performed. One to 2 ORN-free patients were selected to match each ORN patient by gender, tumor site and size. General estimation equations models were used to compare the risk factors in ORN cases and matched controls. RESULTS 44 (4.3%) patients developed ORN during a median follow-up time of 52.5months. In 82% of patients, ORN occurred spontaneously. Patients with OPC are prone to develop ORN earlier compared to patients with OCC (P=0.03). OPC patients received a higher Dmax compared to OCC patients (P=0.01). In the matched case-control analysis the significant risk factors on univariate analysis were poor periodontal status, history of alcohol use and radiation dose (P=0.03, 0.002 and 0.009, respectively) and on multivariate analysis were alcohol use and radiation dose (P=0.004 and 0.026, respectively). CONCLUSION In our study, higher radiation dose, poor periodontal status and alcohol use are significantly related to the risk of developing ORN.

Radiographic osteoradionecrosis of the jaw with intact mucosa: Proposal of clinical guidelines for early identification of this condition

Osteoradionecrosis (ORN) remains an unintended debilitating complication of radiation therapy despite the advent of intensity-modulated radiation therapy (IMRT) which aims to deliver doses of radiation to the tumor site while minimizing doses to healthy tissues [[1], [2], [3], [4]. The etiopathogenesis of ORN has been attributed to the avascular effect of radiation to the bone resulting in hypoxia, hypovascularity, and hypocellularity [5], [6]. Radiation-induced fibrosis has also been implicated in the pathophysiology of ORN [7. Recent studies have placed reported incidences of ORN at 1–30% [2], [8], [9], [10], [11]. ORN of the jaw was defined as an area of exposed necrotic bone greater than 1 cm in an area of previous irradiation that failed to heal after 6 months [5]. This definition of ORN has been used for years and still remains the most widely used clinical criterion for the diagnosis of ORN though it fails to incorporate cases with radiologic evidence of necrosis with intact mucosa [5], [12], [13], [14], [15]. Although a report by Van Merkesteyn et al. described a case of ORN of the jaw with intact mucosa [16], subsequently only two series have likewise reported this condition. In 2000, Store and Boysen reported 17 patients with radiographic osteoradionecrosis of the jaw (rORN) with intact mucosa at initial diagnosis as did He et al. in a recent article where they described 16 patients presenting with rORN with intact mucosa [17], [18]Thus, it appears that rORN with intact mucosa is underdiagnosed. The objectives of this article are to: 1. Describe new cases of rORN with intact mucosa. 2. Correlate the dosimetric analyses of the involved area with the radiographic presentation and to determine the best predictor of rORN with intact mucosa. 3. Propose modification of Store and Boysen’s staging system of ORN. 4. Propose clinical guidelines for early identification of rORN with intact mucosa.

A clinicopathologic study on SS18 fusion positive head and neck synovial sarcomas

OBJECTIVE To determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma. PATIENTS AND METHODS We retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996-2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS). Fisher exact test was performed to evaluate variables related to local recurrence. RESULTS Thirty-four patients (20 males and 14 females, mean of 31years) with SS18-SSX fusion-positive SS-HN were identified. The parapharyngeal region of the neck was the most common site. The mean tumor size was 4.8cm (0.8-10cm). Two-thirds (n=23) of cases had a monophasic histology. The 2, 5 and 10-year DSS rates were 97%, 79% and 68%. The 5-year DSS rates for the adult/pediatric cohort were 74%/88%. Recurrence showed significant effect on DSS (p=0.021). There was no significant effect on DSS with age, therapy modality, tumor site, surgical margin, tumor size (⩽5cm vs. >5cm) and histopathologic subtype. Tumor site (i.e. skull base/paranasal sinus region) was associated with local recurrence (p=0.003). CONCLUSION In our cohort DSS rate was associated with recurrence. Tumors located in the skull base/paranasal sinus region were associated with a higher rate of local recurrence. Thus appropriate selection of high risk patients who can benefit from multimodality therapies might improve survival.

Medication-related osteonecrosis of the jaw (MRONJ): an update on the Memorial Sloan Kettering Cancer Center (MSKCC) experience and the role of pre-medication dental evaluation in the prevention of MRONJ

OBJECTIVE The aim of this study was to investigate the relationship between type of antiresorptive medication and medication-related osteonecrosis of the jaw (MRONJ) onset and the role of premedication dental evaluation (PMDE) in the prevention of MRONJ. STUDY DESIGN Our database of patients with MRONJ was reviewed. The Kruskal-Wallis test was used to analyze the onset dose of the 3 frequent medication types associated with MRONJ. To evaluate the role of PMDE in the prevention of MRONJ, all patients on antiresorptive and/or antiangiogenic medications seen in the Dental Service of Memorial Sloan Kettering Cancer Center during a 10-year period were subclassified into 2 groups. Group I comprised patients seen for PMDE before the commencement of A/A and group II patients seen after prior exposure to antiresorptive and/or antiangiogenic medications. Fischers exact test was used to compare the incidence of MRONJ in both groups. RESULTS Patients on denosumab developed MRONJ earlier compared with zoledronate and pamidronate (P = .003). Group I had a significantly reduced incidence of MRONJ (0.9%) compared with group II (10.5%) (P < .0001). Dentoalveolar trauma as a precipitating factor between groups I and II was not statistically significant. CONCLUSIONS Denosumab was associated with an earlier occurrence of MRONJ compared with zoledronate and pamidronate. The role of PMDE may be an effective preventive strategy in reducing the incidence of MRONJ.

WE-AB-207B-08: Exploring and Refining the QUANTEC Guideline to Reduce Severe Hyposalivation Following IMRT for Head and Neck Cancer

PURPOSE The aim of this study was to investigate the usefulness of the QUANTEC guideline to prevent xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) with respect to follow-up time. In addition, we explored alternative guidelines to further reduce xerostomia. METHODS The QUANTEC guideline suggests a mean dose to the contralateral (Dmeancontra) parotid<20 Gy, or Dmeancontra and Dmean to the ipsilateral parotid (Dmeanipsi)<25 Gy. Stimulated whole mouth saliva flow measurements (WMSFM) were conducted at a median of 11 (3-24) months for 63 patients treated with IMRT for HNC to a median dose of 70 Gy in 2006-2015. Severe hyposalivation/xerostomia was defined as WMSFM ≤25% post- relative to pre-RT. Patients were stratified into a <6m (xerostomia: 27% (n=15)), and a 6-24m (xerostomia: 19% (n=10)) follow-up group. Dose-response modeling was performed using logistic regression including Dmeancontra, or Dmeancontra and Dmeanipsi. The area under the receiver-operating characteristics curve (AUC) was used to assess discriminative ability, and the agreement between the estimated and observed rate of xerostomia was given by Spearmans rank correlation coefficient (Rs), and related p-values. RESULTS Of the non-xerostomia patients, 65% (<6m) and 56% (6-24m) fulfilled Dmeancontra<20 Gy. The estimated and observed rate of xerostomia agreed at <6m (AUC=0.78; Rs=0.46; p=0.001), and was 28% at Dmeancontra=20 Gy. A smaller number of non-xerostomia patients fulfilled the two-gland guideline (33% (<6m) and 26% (6-24m)), but the AUC was higher than using Dmeancontra only (<6m: AUC=0.90; Rs=0.63; p<0.0001; 6-24m: AUC=0.84; Rs=0.25; p=0.08), and the following amendment of the two-gland guideline was suggested: (0.17*Dmeancontra+0.11*Dmeanipsi-8.13)<-1.60 (<6m), and (0.05*Dmeancontra+0.02*Dmeanipsi-3.10)<-1.60 (6-24m). CONCLUSION The QUANTEC guideline is effective to prevent xerostomia <6m post-RT, but its usefulness is reduced at later follow-up times. The suggested amendment to the two-gland QUANTEC guideline should be further investigated in an independent cohort of HNC patients treated with IMRT.