Mehran Yusuf

High-dose versus weekly cisplatin definitive chemoradiotherapy for HPV-related oropharyngeal squamous cell carcinoma of the head and neck

OBJECTIVES To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). METHODS All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). RESULTS Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m2. Both cohorts received a median total dose of cisplatin of 200mg/m2. At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. CONCLUSIONS HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar.

Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: An analysis of the National Cancer Data Base

The objectives of this study were to characterize patterns of care and to identify predictors for adjuvant therapy in elderly patients with glioblastoma in the modern era. METHODS. The National Cancer Data Base was queried for patients aged 70 years and older with glioblastoma diagnosed from January 1, 2004 through December 31, 2012. Multinomial logistic regression was used to identify predictors for receiving adjuvant therapy. Survival outcomes were estimated using the Kaplan‐Meier method and were analyzed using Cox regression models and the log‐rank test.

Dose-Volume Response Relationship for Brain Metastases Treated with Frameless Single-Fraction Linear Accelerator-Based Stereotactic Radiosurgery

Background: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). Methods: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. Results: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 – 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. Conclusions: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control.

Interim Results of a Phase II Study of Hypofractionated Radiotherapy with Concurrent Temozolomide Followed by Adjuvant Temozolomide in Patients over 70 Years Old with Newly Diagnosed Glioblastoma

Objective: In this phase II study, we investigate clinical outcomes and tolerability of hypofractionated radiotherapy (HRT) combined with temozolomide (TMZ) to treat elderly patients with glioblastoma (GBM). Methods: Patients 70 years of age or older with newly diagnosed GBM received HRT to a dose of 34 Gy given in ten fractions over 2 weeks, delivered with concurrent and adjuvant TMZ. Results: In this interim analysis, ten patients were enrolled on trial from 12/1/2015 to 4/5/2017. With a median follow-up of 9 months (range 3–12 months), median progression-free survival (PFS) was 6 months. The median overall survival (OS) has not been reached. Estimated 1-year OS and PFS rates were 53.3 and 44.4%, respectively. All patients completed the full course of RT, with no patients developing grade 3 or higher adverse events from treatment. Conclusions: The preliminary results of our phase II trial suggest HRT delivered over 2 weeks with concurrent and adjuvant TMZ is well tolerated in elderly patients with GBM without compromising clinical outcomes.

Effect of time to simulation and treatment for patients with oropharyngeal cancer receiving definitive radiotherapy in the era of risk stratification using smoking and human papillomavirus status

The effect of increasing time to definitive radiotherapy (RT) for patients with oropharyngeal squamous cell carcinoma (SCC) is unknown.

A Dose–Volume Response Model for Brain Metastases Treated With Frameless Single-Fraction Robotic Radiosurgery: Seeking to Better Predict Response to Treatment

Purpose/Objective(s): To establish a dose–volume response relationship for brain metastases treated with single-fraction robotic stereotactic radiosurgery and identify predictors of local control. Materials/Methods: We reviewed a prospective institutional database of all patients treated for intact brain metastases with stereotactic radiosurgery alone using the CyberKnife robotic radiosurgery system from 2012 to 2015. Tumor response was determined based on Response Evaluation Criteria In Solid Tumors version 1.1. Survival was estimated using the Kaplan-Meier method. Logistic regression modeling was used to identify predictors of outcome and establish a dose–volume response relationship. Receiver operating characteristic curves were constructed to evaluate the predictive capability of the relationship. Results: There were 357 metastases evaluated in 111 patients with a median diameter of 8.14 mm (2.00-40.77 mm). At 6 and 12 months, local control was 86.9% and 82.2%, respectively. For lesions of similar volumes, higher maximum dose, mean dose, and minimum dose (all P values <.05) predicted for better local control. Tumor volume and diameter were strongly correlated, and a dose–volume response relationship was constructed using mean dose per lesion diameter (Gy/mm) that was predictive of local control (odds ratio: 1.34, 95% confidence interval: 1.06-1.70). Area under the receiver operating characteristic curve for local control and mean dose by volume was 0.6199 with a threshold of 2.05 Gy/mm (local failure 7.6% above and 17.3% below 2.05 Gy/mm). Conclusion: A dose–volume response relationship exists for brain metastases treated with robotic stereotactic radiosurgery. Mean dose per volume is strongly predictive of local control and can be potentially useful during stereotactic radiosurgery plan evaluation while respecting previously established dose constraints.

Neck dissection for unknown cancer of the head and neck in the era of chemoradiation

PURPOSE To report outcomes for patients with cervical lymph node metastases from an unknown primary site of the head and neck treated with either non-operative therapy or neck dissection followed by adjuvant therapy. MATERIALS AND METHODS All patients with squamous cell carcinoma of an unknown primary site of the head or neck seen between 2003 and 2013 were reviewed. The Kaplan-Meier method was used to estimate overall survival, local recurrence free survival, loco-regional recurrence free survival, and progression free survival. The log-rank test and proportional hazards regression were used to analyze factors influencing outcomes. RESULTS Of 2258 patients with a new diagnosis of head and neck cancer, no primary site was identified in 66 patients. Twenty-nine patients were treated with definitive non-operative therapy (15 with chemoradiation and 14 with radiation alone). Thirty-seven patients received an upfront neck dissection followed by adjuvant radiation or chemoradiation. Three-year loco-regional recurrence free survival, progression free survival, and overall survival were 55.9%, 55.4%, and 69.4% respectively. Patients treated with preoperative neck dissection had improved local recurrence free survival (96.7% vs 54.1%, p=0.003) and loco-regional recurrence free survival (82.2% vs 46.4%, p=0.068) compared to patients treated with definitive chemoradiation with no difference in overall survival (p=0.641). CONCLUSIONS Neck dissection improved local and regional control but not overall survival in patients with unknown primary squamous cell carcinoma of the head and neck over non-operative therapy alone.

Organ preservation with neoadjuvant chemoradiation in patients with orbit invasive sinonasal cancer otherwise requiring exenteration.

Purpose We sought to determine if organ preservation (OP) with neoadjuvant chemoradiation (CRT) was feasible in patients with sinonasal cancer determined to require exenteration. Materials and Methods Twenty patients were determined to require exenteration for definitive treatment from 2005 to 2014. Fourteen patients underwent OP and 6 patients received exenteration with adjuvant CRT. Exenteration free survival (EFS), locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were estimated. Results Five patients (36%) receiving OP had complete disease response at time of surgery. With a median follow-up of 18.8 months, EFS was 62% at 2 years for patients undergoing OP. At 2 years, there were no significant differences in LRC, PFS or OS (all all p > 0.050) between the groups. Less grade 3 or greater toxicity was seen in patients undergoing OP (p = 0.003). Visual function was preserved in all patients undergoing OP. Conclusion For patients with sinonasal cancer, OP may avoid exenteration, offering similar disease control and improved toxicity.