James Ohr

A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

PURPOSE Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. METHODS AND MATERIALS From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m(2) on day -7 and then 250 mg/m(2) on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. RESULTS Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. CONCLUSIONS SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.

Prospective evaluation of patient-reported quality-of-life outcomes following SBRT ± cetuximab for locally-recurrent, previously-irradiated head and neck cancer

PURPOSE Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for unresectable, previously-irradiated recurrent squamous cell carcinomas of the head and neck (rSCCHN). Here-in, we report the first prospective evaluation of patient-reported quality-of-life (PR-QoL) following re-irradiation with SBRT±cetuximab for rSCCHN. MATERIALS AND METHODS From November 2004 to May 2011, 150 patients with unresectable, rSCCHN in a previously-irradiated field receiving >40 Gy were treated with SBRT to 40-50 Gy in 5 fractions ± concurrent cetuximab. PR-QoL was prospectively acquired using the University of Washington Quality-of-Life Revised (UW-QoL-R). RESULTS Overall PR-QoL, health-related PR-QoL, and select domains commonly affected by re-irradiation progressively increase following an initial 1-month decline with statistically significant improvements noted in swallowing (p=0.025), speech (p=0.017), saliva (p=0.041), activity (p=0.032) and recreation (p=0.039). CONCLUSIONS Especially for patients surviving >1-year, improved tumor control associated with SBRT re-irradiation may ameliorate decreased PR-QoL resulting from rSCCHN. These improvements in PR-QoL transcend all measured domains in a validated PR-QoL assessment tool independent of age, use of cetuximab, tumor volume, and interval since prior irradiation.

Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck

Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for patients with recurrent, previously irradiated head and neck cancer; however, data are limited predominantly to squamous cell carcinomas. Herein, we report the efficacy of SBRT in recurrent, nonsquamous cell cancers of the head and neck (NSCHNs).

Negative Predictive Value of Surveillance PET/CT in Head and Neck Squamous Cell Cancer

BACKGROUND AND PURPOSE: Optimizing the utilization of surveillance PET/CT in treated HNSCC is an area of ongoing research. Our aim was to determine the negative predictive value of PET/CT in patients with treated head and neck squamous cell cancer and to determine whether negative PET/CT reduces the need for further imaging surveillance. MATERIALS AND METHODS: We evaluated patients with treated HNSCC who underwent posttreatment surveillance PET/CT. During routine clinical readouts, scans were categorized as having negative, probably negative, probably malignant, or malignant findings. We followed patients clinically and radiographically for at least 12 months from their last PET/CT (mean, 26 months; median, 28 months; range, 12–89 months) to determine recurrence rates. All suspected recurrences underwent biopsy for confirmation. RESULTS: Five hundred twelve patients (1553 scans) were included in the study. Two hundred fourteen patients had at least 1 PET/CT with negative findings. Of the 214 patients with a scan with negative findings, 19 (9%) eventually experienced recurrence, resulting in a NPV of 91%. In addition, a subgroup of 114 patients with 2 consecutive PET/CT examinations with negative findings within a 6-month period was identified. Only 2 recurrences were found in this group, giving a NPV of 98%. CONCLUSIONS: In patients treated for HNSCC, a single PET/CT with negative findings carries a NPV of 91%, which is not adequate to defer further radiologic surveillance. Two consecutive PET/CT examinations with negative findings within a 6-month period, however, resulted in a NPV of 98%, which could obviate further radiologic imaging in the absence of clinical signs of recurrence.

Examining tumor control and toxicity after stereotactic body radiotherapy in locally recurrent previously irradiated head and neck cancers: Implications of treatment duration and tumor volume

Stereotactic body radiotherapy (SBRT) has been studied in locally recurrent previously‐irradiated head and neck cancers; however, the optimum fractionation and patient selection continues to be defined.

Oncologic and Functional Outcomes of Partial Laryngeal Surgery for Intermediate-Stage Laryngeal Cancer

Objective To evaluate the oncologic and functional outcomes of partial laryngeal surgery (PLS) using transoral laser microsurgery (TLM) and supracricoid laryngectomy (SCL) in patients with intermediate-stage laryngeal squamous cell carcinoma (LSCC). Study Design Historical cohort study. Setting Single tertiary care center. Subjects and Methods Retrospective review of oncologic and functional outcomes in intermediate-stage (T2-3/N0-1, stage II and III) LSCC patients who underwent TLM or SCL from 1998 to 2010. Results Sixty patients were included, of whom 28 (47%) underwent TLM and 32 (53%) underwent SCL. For the entire cohort, 2- and 5-year probabilities were 86.2% (95% confidence interval [CI], 73.0%-93.2%) and 72.9% (95% CI, 52.4%-85.6%), respectively, for overall survival (OS) and 79.3% (95% CI, 65.6%-88.0%) and 62.4% (95% CI, 41.9%-77.4%), respectively, for recurrence-free survival (RFS). There was no difference between the TLM and SCL cohorts in OS (P = .542) or RFS (P = .483). More than 75% of patients avoided adjuvant therapy. Communication Scale and Functional Outcome Swallowing Scale scores at median follow-up of 33 months were 2 or better in 97% and 91% of patients, respectively, reflecting functional voice and swallowing postoperatively. Eighty-eight percent of patients retained a functional larynx. Conclusion PLS provides excellent oncologic and functional outcomes for intermediate-stage LSCC and should be considered an alternative to chemoradiation or total laryngectomy in selected patients.

A retrospective, deformable registration analysis of the impact of PET-CT planning on patterns of failure in stereotactic body radiation therapy for recurrent head and neck cancer

BackgroundStereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for selected patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). PET-CT may be advantageous for tumor delineation and evaluation of treatment failures in SBRT. We analyzed the patterns of failure following SBRT for rSCCHN and assessed the impact of PET-CT treatment planning on these patterns of failure.MethodsWe retrospectively reviewed 96 patients with rSCCHN treated with SBRT. Seven patients (7%) were treated after surgical resection of rSCCHN and 89 patients (93%) were treated definitively. PET-CT treatment planning was used for 45 patients whereas non-PET-CT planning was used for 51 patients. Categories of failure were assigned by comparing recurrences on post-treatment scans to the planning target volume (PTV) from planning scans using the deformable registration function of VelocityAI™. Failures were defined: In-field (>75% inside PTV), Overlap (20-75% inside PTV), Marginal (<20% inside PTV but closest edge within 1cm of PTV), or Regional/Distant (more than 1cm from PTV).ResultsMedian follow-up was 7.4 months (range, 2.6–52 months). Of 96 patients, 47 (49%) developed post-SBRT failure. Failure distribution was: In-field–12.3%, Overlap–24.6%, Marginal–36.8%, Regional/Distant–26.3%. There was a significant improvement in overall failure-free survival (log rank p = 0.037) and combined Overlap/Marginal failure-free survival (log rank p = 0.037) for those receiving PET-CT planning vs. non-PET-CT planning in the overall cohort (n = 96). Analysis of the definitive SBRT subgroup (n = 89) increased the significance of these findings (overall failure: p = 0.008, Overlap/Marginal failure: p = 0.009). There were no significant differences in age, gender, time from prior radiation, dose, use of cetuximab with SBRT, tumor differentiation, and tumor volume between the PET-CT and non-PET-CT groups.ConclusionsMost failures after SBRT treatment for rSCCHN were near misses, i.e. Overlap/Marginal failures (61.4%), suggesting an opportunity to improve outcomes with more sensitive imaging. PET-CT treatment planning showed the lowest rate of overall and near miss failures and is beneficial for SBRT treatment planning.

Stereotactic body radiotherapy for recurrent oropharyngeal cancer - Influence of HPV status and smoking history

PURPOSE HPV status and smoking history stratifies patients into 3 distinct risk groups for survival following definitive chemoradiotherapy. Local-regional recurrences are common patterns of failure across all 3 risk-groups. SBRT±cetuximab has emerged as a promising salvage strategy for unresectable locally-recurrent, previously-irradiated head-and-neck cancer (rHNC) relative to conventional re-irradiation±chemotherapy. However the influence of HPV and smoking remains unknown in the setting of re-irradiation. METHODS/MATERIALS Patients (n=30) with rHNC of the oropharynx salvaged with SBRT±cetuximab from August 2002 through August 2013 were retrospectively reviewed; HPV status was determined based on p16 staining of primary pathology. RESULTS At a median follow-up of 10months for surviving patients, the mean overall survival for all patients was 12.6 months. HPV positivity was a significant predictor of overall survival (13.6 vs. 6.88 months, p=0.024), while smoking status did not significantly impact overall survival (p=0.707). CONCLUSION HPV status remains a significant predictor of overall survival in the re-irradiation setting with HPV positive rHNC demonstrating superior overall survival following salvage SBRT±cetuximab.

Adjuvant stereotactic body radiotherapy ± cetuximab following salvage surgery in previously irradiated head and neck cancer

Locoregional recurrence remains the primary failure pattern following salvage surgery for previously irradiated head and neck cancer; randomized trials have suggested a complimentary role for adjuvant chemotherapy and conventional reirradiation at the expense of significant increases in toxicity. We aimed to identify if stereotactic body radiotherapy (SBRT) ± cetuximab improves tumor control while reducing treatment‐related toxicity following salvage surgery.

Incidence of hospitalization in patients with head and neck cancer treated with intensity‐modulated radiation therapy

Patients with primary head and neck cancer managed with radiation therapy (RT) +/‐ chemotherapy may experience significant treatment‐related toxicities. We assessed hospitalization as a metric for severe treatment‐related toxicities and evaluated patient and treatment factors for possible association.