Mark Zaki

PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous cell carcinoma: a case report

BackgroundImmunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated.Case presentationWe report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy.ConclusionT cell activation induced by checkpoint inhibition may dramatically improve tumor response to radiation. More data are needed to identify the toxicity and efficacy of sequential or concurrent checkpoint inhibitors and radiotherapy.

Target Volume Heterogeneity Index, a Potentially Valuable Metric in IMRT Prostate Cancer Treatment Planning

Abstract Purpose/Objectives: Heterogeneity index (HI) has been described in the literature as a tool for evaluating dose gradients within a planning target volume (PTV). HI may be expressed as D1/D95 where D1 and D95 equal the dose encompassing 1% and 95% of the target volume. The purpose of this study is to evaluate the effect of target volume dose heterogeneity on dose received by local organs at risk in the treatment of low and intermediate risk prostate cancer. Materials/Methods: Treatment plans were reviewed for 157 patients with low or intermediate risk prostate cancer treated with dose-escalated radiation therapy between 6/2007 and 2/2012. Patients treated in the post-operative setting or receiving pelvic nodal irradiation were excluded. Patients were treated with either standard intensity modulation (IMRT) using 7 or 8 fields or 2-arc volumetric modulated arc therapy (VMAT). All patients had daily image-guidance. PTV HI (D1/D95) and dose-volume histogram (DVH) data at 8 dose levels for rectum and bladder were recorded. Patients were categorized into two groups (low HI or high HI) with respect to median index score. A two-tailed t-test was used to test for differences in dose received by rectum and bladder for the two groups. Results: For the 157 plans evaluated, mean PTV volume was 164cc and mean prescription dose was 7833cGy. Median HI was 1.04 (range 1.0-1.08). Low HI (≤1.04) was found to correlate with significantly lower rectal V50 (p=0.02), V55 (p=0.01), V60 (p=0.01), V65 (p=0.01), and V70 (p=0.01). There was no significant correlation with dose received by bladder at any dose level. HI was similar for patients treated with standard IMRT and VMAT (p=0.85). Conclusions: Target volume HI ≤1.04 is associated with more favorable rectal doses at clinically relevant dose-levels. We believe HI may serve as a valuable metric in prostate cancer treatment planning. Further work is needed to correlate these dosimetric findings with clinical outcomes.

Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.

Abstract Background. Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. Materials and methods. We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher’s exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. Results. A total of 132 patients met the inclusion criteria with a median age of 62 (range 36–80) and median follow-up of 28 months (range 4–128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p = 0.01) and close/positive margins (p < 0.01). Regional nodal failure was correlated with fewer LN assessed (p < 0.01) and larger pretreatment tumor size (p = 0.04). Patients with ≤13 LN evaluated had an inferior locoregional RFS versus patients with >13 LN evaluated (p = 0.003). Distant recurrence was correlated with higher pathologic nodal stage (p < 0.001), ulceration (p = 0.017), perineural invasion (p = 0.029), residual disease (p = 0.004), and higher post-treatment PET SUV max (p = 0.049). Patients with a pathologic complete response (OR 0.19, 95% CI 0.05–0.68) were less likely to experience distant recurrence. Conclusion. Tumor and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients.

Radiotherapy and radioembolization for liver metastases

Liver metastases are a common source of cancer-related morbidity. While systemic palliative chemotherapy is an option for patients with significant metastatic disease burden, radiotherapy (RT) is a safe, well-tolerated local treatment that can offer durable tumor control and relief of symptoms. Innovations in RT delivery now allow for treatment of liver metastases in one to five sessions with high local control rates. There is a growing body of Phase I-II data supporting the use of such RT techniques, including stereotactic body radiotherapy (SBRT) and radioembolization for the treatment of liver metastases. While there are a variety of local therapies available to patients with liver metastases, RT should be strongly considered in patients with liver metastasis related pain or oligometastatic disease not amenable to surgery. We recommend a multidisciplinary approach when weighing the risks and benefits of the available local treatment modalities for each patient.

Unresectable Extraskeletal Myxoid Chondrosarcoma of the Neck: Early Tumor Response to Chemoradiotherapy

Extraskeletal myxoid chondrosarcoma (EMC) rarely occurs in the head and neck and is generally managed with primary surgery. To our knowledge, no cases of unresectable EMC of the neck have been reported. We present a case of an unresectable EMC treated with chemotherapy and radiation, and highlight the exceptional early response to therapy.

Outcomes of Elderly Patients Who Receive Combined Modality Therapy for Locally Advanced Non–Small-Cell Lung Cancer

Background: The objective of this study was to review our institutions experience among patients with locally advanced non–small‐cell lung cancer (LA‐NSCLC) treated with chemotherapy and radiation and to determine the prognostic significance of age. Patients and Methods: Patients were included if they underwent sequential or concurrent chemoradiotherapy from 2006 to 2014 for LA‐NSCLC. Patients were stratified according to age ≤70 and >70 years. Kaplan–Meier and Cox regression methods were performed to evaluate overall survival (OS) and progression‐free survival (PFS). Results: One hundred twenty‐three patients were identified. Ninety‐eight patients were 70 years of age or younger and 25 patients were older than 70 years of age. The median radiotherapy dose was 6660 cGy (range, 3780–7600 cGy). A greater percentage of elderly patients were men, 72% (18 patients) versus 39% (38 patients) (P = .006) and received carboplatin/paclitaxel‐based chemotherapy, 60% (15 patients) versus 21% (20 patients) (P < .001). Median follow‐up for OS was 25.9 (95% confidence interval [CI], 21.3–33.9) months. There was no difference in the PFS of older patients versus younger patients (hazard ratio [HR], 1.15; P = .64), adjusted for significant covariates. The 1‐year PFS rate for patients 70 years of age or younger was 51% (95% CI, 42%‐63%) versus 45% (95% CI, 28%‐71%) in patients older than 70 years. After adjusting for significant covariates, there was no difference in the OS of older patients compared with younger patients (HR, 1.18; P = .65). The 1‐year OS rate for patients 70 years of age or younger was 77% (95% CI, 68%‐86%) versus 56% (95% CI, 39%‐81%) in patients younger than 70 years. Conclusion: Chemoradiotherapy is an effective treatment in elderly patients with LA‐NSCLC, with outcomes similar to that in younger patients. Appropriately selected elderly patients should be considered for chemoradiation. Micro‐Abstract: Our objective was to determine the significance of age in patients treated with sequential or concurrent chemoradiotherapy for locally advanced non–small‐cell lung cancer (LA‐NSCLC). Ninety‐eight patients were 70 years of age or younger and 25 were older than 70 years. In multivariable analysis, there was no difference in the progression‐free survival (hazard ratio [HR], 1.15; P = .64) or overall survival (HR, 1.18; P = .65) of older versus younger patients. Chemoradiotherapy is an effective treatment in elderly patients with LA‐NSCLC, with outcomes similar to that in younger patients.

Definitive chemoradiotherapy with carboplatin for squamous cell carcinoma of the head and neck: Chemoradiotherapy with Carboplatin for HNSCC

Definitive concurrent chemoradiotherapy (CRT) is considered the standard of care for organ preservation and is the only potentially curative therapy for surgically unresectable patients with stage III to IVb locally advanced squamous cell carcinoma of the head and neck. In patients with high risks for adverse events utilizing cisplatin, carboplatin has been empirically substituted. The objective of this study was to estimate the locoregional control rate, progression‐free survival, overall survival, and adverse events in locally advanced squamous cell carcinoma of the head and neck patients treated with CRT utilizing carboplatin.

Cervical osteoradionecrosis following accelerated fractionation radiation therapy for laryngeal cancer

Osteoradionecrosis is a serious complication that may occur following radiation therapy, particularly head and neck–directed radiation therapy. A very limited number of cases of cervical-spine osteoradionecrosis have been reported1-6 and only 2 involve altered fractionation radiation therapy.6 We present a patient with extensive osteoradionecrosis 9 years after receiving accelerated fractionation radiation therapy with concurrent chemotherapy.

Patterns of failure following tri-modality therapy for locally advanced esophageal cancer.

203 Background: Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. Methods: Following IRB approval, we retrospectively reviewed all pts who underwent chemoradiation followed by esophagectomy at two NCI-designated cancer centers from 2000-2013. Patient and treatment factors were analyzed for failure patterns. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher’s exact test and non-parametric Wilcoxon rank-sum test. Results: A total of 132 patients met the inclusion criteria with a median age of 62 (range 36-80) and median follow-up of 28 months (range 4-128). The majority of patients had T3 (82%), N1 (64%), or M0/M1a (92%) disease. At the time of last follow-up there were a total of 6 (4.5%) local, 13 (10%) regional nodal, ...