Five-year outcomes of sparing level IB in node-positive, human papillomavirus-associated oropharyngeal carcinoma: A safety and efficacy analysis.

INTRODUCTION: The conformality of modern intensity modulated radiation therapy (IMRT) allows avoidance of the submandibular glands (SMG) in select patients, potentially improving late xerostomia. This study explores the safety and efficacy of this approach in select oropharyngeal carcinoma (OPC) patients. METHODS: Patients with T1-2N+ human papillomavirus (HPV)-associated OPC treated with definitive IMRT at one institution from 2009 to 2014 were identified. Patients were divided into 3 groups: bilateral level IB targeted (A, n = 16), a single level IB targeted (B, n = 61), and bilateral IB spared (C, n = 9). Outcomes were reviewed to identify the rate of level IB regional recurrence. Odds ratios were calculated for xerostomia between groups. RESULTS: Level Ib was targeted in 93 instances (54.1%) and avoided in 79 instances (45.9%). Mean SMG doses were significantly lower when level IB was spared compared to when targeted (37.5 Gy vs 67.5 Gy; P < 0.0001). Median doses to oral cavity decreased with increasing level Ib sparing (40.7 Gy [A] vs 35.4 Gy [B] vs 30.7 [C]; P = 0.002). The rate of late grade ≥2 xerostomia was significantly lower in patients with bilateral 1b sparing (53% in A vs 0% in C; P = 0.007). Sparing 1b unilaterally resulted in a non-significant decrease in late grade ≥2 xerostomia (P = 0.181). No regional failures were identified in levels IB (median follow up = 59.3 months). CONCLUSION: Sparing level IB is safe in T1-2N+ HPV+ OPC. Avoiding level Ib translates into significantly lower SMG and oral cavity doses. Larger studies are needed to validate these findings and the impact of this technique.

It is not just IMRT: Human papillomavirus related oropharynx squamous cell carcinoma is associated with better swallowing outcomes after definitive chemoradiotherapy.

OBJECTIVES: Long term swallowing dysfunction in patients with oropharynx squamous cell carcinoma (OPSCC) treated with concurrent chemoradiation (CRT) is declining. While the use of intensity modulated radiotherapy (IMRT) is commonly believed to be a potential cause, we hypothesize that the increasing incidence of human papillomavirus (HPV) related disease may also favorably impact this outcome. MATERIALS AND METHODS: We reviewed 130 HPV+ and 17 HPV- patients with stage III-IV OPSCC treated exclusively with conventional 3-field radiotherapy with chemotherapy between 2002 and 2010. The rates of normal diet, limited diet (significant restrictions in the types of foods eaten, and/or requiring nutritional supplementation for weight maintenance) and feeding tube dependence (FTD) were compared between HPV+ and HPV- patients. Cox proportional hazards modeling were used to perform univariate analysis (UVA) to examine predictors of a combined endpoint of dietary limitation, which included limited diet and/or FTD. These outcomes were also compared to our previously reported cohort of OPSCC patients treated between 1989 and 2002 to assess changes in toxicity over time given the changing disease epidemiology, in the setting of identical treatment regimens. RESULTS: With a median follow-up of 55 months, HPV+ patients more frequently had resumed a normal diet (87% vs. 65%) at last follow up and had lower rates of limited diet (9% vs. 18%) and FTD (4% vs. 18%) compared to HPV- patients (p=0.02). HPV status was the only significant predictor of reduced swallowing dysfunction on UVA (HR 0.19; p=0.008). When compared to our 1989-2002 cohort, patients treated between 2002 and 2010 had less FTD (7.5% vs. 34%, p<0.001) and dietary limitations (26% vs.46%, p<0.001) at 6 months post treatment. CONCLUSIONS: HPV+ patients with OPSCC have reduced late swallowing dysfunction after chemoradiation compared to HPV- patients. The changing epidemiology of OPSCC may play a role in toxicity reduction in these patients, independent of the increasing use of IMRT.

Comparison and predictors of rash associated with 15 antiepileptic drugs.

OBJECTIVE: To determine predictors and relative incidence of antiepileptic drug (AED)-related rash in patients taking all common AEDs. METHODS: We reviewed 1,890 outpatients. Eighty-one variables were tested as potential predictors of rash. We compared the rate of rash attributed to each AED (AED rash) with the average rate of rash attributed to the other AEDs in all adults (aged > or =16 years; n = 1,649) when taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproate (VPA), or zonisamide (ZNS). We repeated this analysis for patients with and without the identified nondrug predictors of AED rash. RESULTS: The average rate of AED rash was 2.8%. The only nondrug predictor significant in multivariate analysis was occurrence of another AED rash (odds ratio 3.1, 95% CI 1.8 to 5.1; p < 0.0001); the rate of rash in this subgroup was 8.8%, vs 1.7% in those without another AED rash. Higher AED rash rates were seen with PHT (5.9% overall, p = 0.0008; 25.0% in those with another AED rash, p = 0.001), LTG (4.8%, p = 0.00095; 14.4%, p = 0.025), and CBZ (3.7%, not significant; 16.5%, p = 0.01). Lower rates were seen with LEV (0.6% overall; p = 0.00042), GBP (0.3%, p = 0.00035), and VPA (0.7%, p = 0.01). Rash rates were also low (<1% overall) with FBM, PRM, TPM, and VGB (not significant). These AED differences remained similar in patients with and without other AED rashes. There were four cases of Stevens-Johnson syndrome involving four AEDs. CONCLUSIONS: The rate of an antiepileptic drug (AED) rash is approximately five times greater in patients with another AED rash (8.8%) vs those without (1.7%). Rash rates were highest with phenytoin, lamotrigine, and carbamazepine and low (<1%) with several AEDs.