International Journal of Radiation Oncology Biology Physics, Apr 1, 2018
Factors associated with worsened OS on UA were higher pathologic T stage (T3-T4) (PZ.003), lymph ... more Factors associated with worsened OS on UA were higher pathologic T stage (T3-T4) (PZ.003), lymph node positivity (P .001), higher tumor grade (G3-4) (PZ.002), positive margins (PZ.01), patients requiring adjuvant therapy (P .001), and recurrent disease (P .001). The same variables were also associated with a statistically significant worsened DFS on UA except for tumor grade and margin status. On MVA factors associated with worsened OS and DFS were higher pathologic T stage (PZ .008), lymph node positivity (P .001) and recurrent disease (P .001). Conclusion: The outcomes of this series continues to support treating young patients with primary oral cavity squamous cell carcinomas using a similar treatment paradigm to older adults. A decision-making strategy for adjuvant therapy based on pathologic criteria is justified.
Objective: The objective of this study was to examine tumor response with positron emission tomog... more Objective: The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer. Materials and Methods: Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years. Patients underwent a PET/MRI scan pretreatment and at fraction 10. Change in value of imaging means were analyzed by analysis of variance. K-means clustering with Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters. Linear regression was performed on all radiographic metrics using patient and disease characteristics. Results: Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Pretreatment imaging characteristics between LR and IR patients were similar. Patients with LR disease exhibited a larger reduction in maximum standardized uptake value (SUV) compared with IR patients (P<0.05). Cluster analysis defined 2 cohorts that exhibited a similar intratreatment response. Cluster 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cluster 2 contained 3 of 11 IR patients. Cluster 2 exhibited significant differences compared with cluster 1 in the change in primary tumor peak SUV and largest lymph node median SUV. Conclusions: We identified that IR p16-positive oropharynx cancers exhibit heterogeneity in their PET/MRI response to chemoradiotherapy. These data support further study of intratreatment imaging response as a potential mechanism to identify patients with IR oropharynx cancer suitable for treatment deintensification.
International Journal of Radiation Oncology*Biology*Physics, 2020
Background: Safety-net hospitals, treating a large proportion of uninsured, Medicaid, or other vu... more Background: Safety-net hospitals, treating a large proportion of uninsured, Medicaid, or other vulnerable populations, have previously been regarded with achieving inferior patient outcomes. Recent studies, however, have shown non-significant survival differences for rectal, hepatocellular, pancreatic, and esophageal cancer patients being treated at high burden safety-net facilities. In this study, we seek to specifically evaluate patients with oral cavity cancers treated at higher safety-net burden hospitals, because survival outcomes for this particular cancer population have been shown to be stratified by various socioeconomic factors. To date, a robust analysis of survival outcomes and hospital safety-net burden for oral cavity cancer patients has not yet been done. Objectives: To investigate the relationships between hospital safety-net burden, clinicopathologic characteristics, and overall survival in oral cavity cancer (OCC) patients. Methods: From the National Cancer Database, we identified 48,176 OCC patients diagnosed with oral cavity cancer between the years 2004 to 2015. Treatment facilities were defined as no safety-net burden hospitals (NBH), low safety-net burden hospitals (LBH), and high safety-net burden hospitals (HBH) based on percentiles of uninsured/Medicaid patients treated: 0-30%, >30-75%, and >75-100% defines treatment facilities as NBH, LBH, and HBH respectively. Social demographic and clinico-pathological variables assessed were age, distance to treatment facility, time to first treatment, gender, race, Hispanic origin, insurance status, median household income, year of diagnosis, Charlson-Deyo score, location of primary site, AJCC stage, facility type and volume, and treatment modality. Safety-net burden of treatment facilities was used as the primary independent predictor in this analysis and the primary outcome of interest was overall survival. Crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed using Cox regression modelling, where clustering of patients within facilities was accounted for using robust sandwich covariance matrix estimates. Results: There were 380 NBH (29.9%), 573 LBH (45.2%), and 316 HBH (24.9%) identified among the 1,269 treatment facilities evaluated for their respective safety-net burden and survival outcomes in oral cavity cancer patients. The median percentage of uninsured/Medicaid patients treated was 23.5% (range 18.6-100%) at HBH, 11.6% (range 1.2-18.5%) at LBH, and 0% (range 0-0%) at NBH. Median follow-up in all surviving patients was 49.0 months. A total of 22,466 deaths were reported, and the overall 5year survival rate was 53.5% (median survivalZ69.7 months). Median survival for NBH, LBH and HBH was 68.6, 74.8 and 55.0 months, respectively (p<0.0001). However, compared to NBH and LBH, HBH facilities treated more late-staged cancers, racial and ethnic minorities, and patients of a lower socioeconomic status (SES). Thus, after adjusting for the aforementioned social demographic and clinico-pathological variables, no significant survival difference was noted in LBH (aHR 0.97 95% CI 0.91-1.04, pZ0.405) or HBH (aHR 1.05 95% CI 0.98-1.13, pZ0.175) when compared to patients treated at NBH facilities. Conclusions: While lower actuarial survival rates are observed in HBH compared to LBH and NBH, these findings may be driven by socioeconomic, and clinicopathologic characteristics. Racial and ethnic minorities are more likely to receive care at HBH. These findings suggest that high burden safety-net hospitals provide vital care to vulnerable populations with oral cavity cancer.
Objective The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemi... more Objective The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on head and neck oncologic care at a tertiary care facility. Study Design This was a cross-sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period. Secondary outcome measures were tumor conference volume, operative volume, and outpatient patient procedure and clinic volumes. Setting This single-center study was conducted at a tertiary care academic hospital in a large metropolitan area. Methods The study included a consecutive sample of adult subjects who were presented at a head and neck interdepartmental tumor conference during the study period. Patients were compared to historical controls based on review of operative data, outpatient procedures, and clinic volumes. Results In total, 117 patients were presented during the review period in 2020, compared to 69 in 2019. There was an...
Journal of the National Comprehensive Cancer Network, 2020
Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease,... more Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
e14619 Background: Patients with locally advanced adenocarcinoma of the gastroesophageal junction... more e14619 Background: Patients with locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) that undergo aggressive neoadjuvant chemoradiation therapy followed by an extensive oncologic resection have a 25-50% risk of developing locoregional recurrences and/or distant metastases. There is an unmet need for biomarkers that predict tumor behavior following neoadjuvant therapy that can be used to direct future therapy. CDX2, an intestine-specific transcription factor that regulates proliferation and differentiation, is ectopically expressed by epithelial cells lining the GEJ during intestinal metasplasia and retained by adenocarcinomas. To date, CDX2 has not been shown to contribute to the tumorigenic potential of GEJ adenocarciomas limiting its use as a predictive or prognostic marker. Methods: CDX2 mRNA from GEJ tissues were sequenced. Wild type and splice variant transcripts and proteins were analyzed by Western blot, RT-PCR, luciferase assays, and fluorescent IHC. In vi...
Background: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk struct... more Background: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk structures (DARS) using a direct gross tumor volume (GTV 70Gy) to planning target volume expansion (dPTV 70Gy) for patients with squamous cell carcinoma of the larynx (LSCC). Methods: A retrospective review was performed on patients with LSCC treated between 2003-2018. Clinical outcomes, toxicities, and dosimetric data were analyzed. Results: Seventy-three patients were identified. Overall survival at 5-years was 57.8%. Five-year local and regional control was 79.8% and 88.2%, respectively. Distant metastatic-only failure was 2.7%. Eighty percent of failures were 95% contained within the dPTV 70Gy. Mean dose and the volume of DARS receiving 70 Gy was significantly lower for dPTV 70Gy compared to a consensusdefined PTV 70Gy. Discussion: Judicious reduction in high-dose target volumes can preserve high tumor control rates while reducing dose to normal surrounding structures underscoring the potential benefit of this approach in enabling local therapy intensification to improve locoregional control.
Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh editi... more Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh edition staging system to prognosticate the overall survival of patients with human papillomavirus (HPV)–positive laryngeal squamous cell carcinoma. Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods Patients diagnosed with laryngeal squamous cell carcinoma who were treated with curative intent were identified in the National Cancer Database. Multivariate analysis was utilized to determine factors correlated with overall survival in the HPV-negative and HPV-positive cohorts. Unadjusted and propensity score–weighted Kaplan-Meier estimation was used to determine overall survival of HPV-negative and HPV-positive patients across AJCC stage groupings. Results We identified 3238 patients with laryngeal squamous cell carcinoma, of which 2812 were HPV negative and 426 were HPV positive. Overall survival adjusted for age, sex, and comorbidity status confirmed s...
International journal of radiation oncology, biology, physics, 2017
The patient was a 70-year-old man with a 6-month history of a progressively enlarging right neck ... more The patient was a 70-year-old man with a 6-month history of a progressively enlarging right neck mass. His medical history was significant for numerous basal cell carcinomas and chronic lymphocytic leukemia. He was a never-smoker and a social drinker. On examination, the mass was in level II, fixed, and nontender. Examination of the oral cavity and mucosal surfaces of the pharyngeal axis by endoscopy showed normal results. Computed tomography (CT) of the neck demonstrated a 2.4 Â 2.5 Â 2.0ecm cystic lesion in the right upper neck with infiltration of the sternocleidomastoid (Fig. 1).
The present study evaluated clinical outcomes for patients with head and neck squamous cell carci... more The present study evaluated clinical outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease. A retrospective analysis of N3 head and neck squamous cell carcinoma patients was performed. Pearson chi-square and Wilcoxon signed-rank tests were used to analyze patient demographics, disease characteristics, and treatment variables. Survival was evaluated using Kaplan-Meier curves with the log-rank test. Univariate analysis using Cox proportional hazards models was used to define factors associated with overall survival. Patient and tumor characteristics associated with treatment assignments were analyzed by univariate multinomial logistic regression. We identified 36 patients with radiographically-defined N3 disease. For the entire cohort, median follow-up was 23.6 (range 2.8-135.0) months, and overall survival was 60% at 2 years and 30% at 5 years. Overall survival was similar between patients receiving primary surgery, radiotherapy, or chemora...
Journal of Cancer Research and Clinical Oncology, 2017
Purpose-We examined overall survival in a large cohort of patients with human papillomavirus (HPV... more Purpose-We examined overall survival in a large cohort of patients with human papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell carcinoma of the head and neck (non-OPSCC). Methods-Patients diagnosed with non-OPSCC and known HPV status were identified in the National Cancer Database (NCDB). Multivariate logistic regression was applied to examine factors associated with HPV status. Multivariate analysis was utilized to determine factors correlated with overall survival. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in survival analyses. Multiple imputation method was used for sensitivity analysis. Results-We identified 19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median follow-up was 23.5 months. HPV-positive patients were more commonly male, white, with a lower comorbidity index score, presenting with T-stage <2, and N-stage ≥1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV-positive patients,
To evaluate treatment trends and overall survival of patients with small cell carcinoma of the he... more To evaluate treatment trends and overall survival of patients with small cell carcinoma of the head and neck region. Patients from 2004 to 2012 were identified from the National Cancer Database. Patient demographics and overall survival were analyzed. Multivariable analysis was used to identify predictors of survival. Among 347,252 head and neck patients a total of 1042 (0.3%) patients with small cell carcinoma were identified. 17% of patients were diagnosed as stage I/II, 61% as stage III/IVA/IVB and 22% as stage IVC disease. The distribution by anatomic site was 9% oral cavity, 12% oropharynx, 35% larynx, 4% hypopharynx, 10% nasopharynx and 30% nasal cavity and paranasal sinuses. The median overall survival by anatomical site was 20.8months for oral cavity, 23.7months for oropharynx, 17.9months for larynx/hypopharynx, 15.1months for nasopharynx and 36.4months for nasal cavity primary tumors. On multivariable analysis across stage, patients with nasal cavity and paranasal sinuses t...
Journal of the National Comprehensive Cancer Network : JNCCN, Jun 1, 2017
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers pro... more The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.
To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated ar... more To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer.
International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 2014
We evaluated the feasibility of combined hippocampal-and scalp-sparing intensity-modulated radiot... more We evaluated the feasibility of combined hippocampal-and scalp-sparing intensity-modulated radiotherapy (IMRT) plans. This study included 7 patients who received conventional palliative whole brain radiation treatment (WBRT) for brain metastasis. The brain, hippocampus, and scalp were contoured and replanned with intensity modulated radiation therapy. The prescription dose was 30 Gray (Gy) in 10 fractions with hippocampus and normal structure constraints per the Radiation Therapy Oncology Group (RTOG) 0933 protocol. Further planning was done to minimize the scalp dose while maintaining the dose constraints for the hippocampus. Dose volume histograms were obtained from conventional opposed lateral fields, IMRT and compared. Planning target volume (PTV) coverage for all plans fell within the RTOG 0933 critical structure acceptable variation category. When compared to traditional opposed lateral fields, the IMRT plan with combined hippocampal-and scalp-sparing constraints was able to significantly reduce the max and mean scalp dose as well as the percentage of scalp receiving 10 and 20 Gy by 46% and 35%, respectively, while maintaining acceptable RTOG 0933 hippocampal dose variations. We conclude that acceptable PTV coverage and sparing of the scalp and hippocampus can be accomplished using a 9-field non-coplanar IMRT plan. Prospective study is warranted to understand the impact on radiation induced alopecia.
Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini r... more Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.
International Journal of Radiation Oncology*Biology*Physics, 2012
To evaluate the clinical outcomes of stereotactic body radiation therapy for lung cancer in octog... more To evaluate the clinical outcomes of stereotactic body radiation therapy for lung cancer in octogenarians. Materials/Methods: Thirty-one patients who were over 80 years old at the time of therapy and 33 lesions, treated between September 2006 and February 2011, were included in this study. Seventeen patients had Stage IA lung cancer, 7 had Stage I B, one patient had Stage IIIA (the metastasis of a different lobe of the ipsilateral side and no lymph node metastasis), one patient had Stage IV (contralateral lung metastasis and no lymph node metastasis) and the other 5 had recurrence within the first 5 years after surgery for lung cancer. Threedimensional treatment planning using 7-8 non-coplanar beams was performed to maintain the target dose homogeneity and to decrease the irradiated lung volume >20 grays (Gy). All but one patient received five single, high doses of radiation of 10 Gy at the isocenter for 5-8 days. The median follow-up period was 32 months (range, 13-60 months). Results: Ten patients died during the follow-up period: Six of these died of lung cancer, and the remaining 4 died of other causes. No patients died of the radiation therapy itself. Ten patients had recurrence: 3 local recurrences, 3 regional lymph node metastases and 4 distal metastases. Overall survival rates, cause-specific survival rates and local control after 1 year/2 years were 93.5%/ 66.6%, 100%/79.6% and 93.8%/90.0%, respectively. One patient had radiation-induced pneumonitis of Grade 3 (G3). Three patients had rib fracture in line with the radiation field. Three patients had G1 atelectasis. With regard to radiodermatitis, 7 patients had G1 skin pigmentation and 2 patients had G1 induration or G1 atrophy. No other vascular, cardiac, esophageal or neurologic toxicities were encountered. Conclusions: We believe that stereotactic body radiation therapy for primary lung cancer in octogenarians is safe and minimally invasive.
International Journal of Radiation Oncology*Biology*Physics, 2013
Conclusions: Results provide evidence that, besides prolonging survival with a good safety profil... more Conclusions: Results provide evidence that, besides prolonging survival with a good safety profile, Ra-223 delays time to first SRE, in particular, time to first use of EBRT and use of opioids. In addition, Ra-223 reduces pain and opioid use in CRPC patients with bone mets. Importantly, the study showed that Ra-223 could be given safely with concomitant EBRT.
International Journal of Radiation Oncology Biology Physics, Apr 1, 2018
Factors associated with worsened OS on UA were higher pathologic T stage (T3-T4) (PZ.003), lymph ... more Factors associated with worsened OS on UA were higher pathologic T stage (T3-T4) (PZ.003), lymph node positivity (P .001), higher tumor grade (G3-4) (PZ.002), positive margins (PZ.01), patients requiring adjuvant therapy (P .001), and recurrent disease (P .001). The same variables were also associated with a statistically significant worsened DFS on UA except for tumor grade and margin status. On MVA factors associated with worsened OS and DFS were higher pathologic T stage (PZ .008), lymph node positivity (P .001) and recurrent disease (P .001). Conclusion: The outcomes of this series continues to support treating young patients with primary oral cavity squamous cell carcinomas using a similar treatment paradigm to older adults. A decision-making strategy for adjuvant therapy based on pathologic criteria is justified.
Objective: The objective of this study was to examine tumor response with positron emission tomog... more Objective: The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer. Materials and Methods: Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years. Patients underwent a PET/MRI scan pretreatment and at fraction 10. Change in value of imaging means were analyzed by analysis of variance. K-means clustering with Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters. Linear regression was performed on all radiographic metrics using patient and disease characteristics. Results: Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Pretreatment imaging characteristics between LR and IR patients were similar. Patients with LR disease exhibited a larger reduction in maximum standardized uptake value (SUV) compared with IR patients (P<0.05). Cluster analysis defined 2 cohorts that exhibited a similar intratreatment response. Cluster 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cluster 2 contained 3 of 11 IR patients. Cluster 2 exhibited significant differences compared with cluster 1 in the change in primary tumor peak SUV and largest lymph node median SUV. Conclusions: We identified that IR p16-positive oropharynx cancers exhibit heterogeneity in their PET/MRI response to chemoradiotherapy. These data support further study of intratreatment imaging response as a potential mechanism to identify patients with IR oropharynx cancer suitable for treatment deintensification.
International Journal of Radiation Oncology*Biology*Physics, 2020
Background: Safety-net hospitals, treating a large proportion of uninsured, Medicaid, or other vu... more Background: Safety-net hospitals, treating a large proportion of uninsured, Medicaid, or other vulnerable populations, have previously been regarded with achieving inferior patient outcomes. Recent studies, however, have shown non-significant survival differences for rectal, hepatocellular, pancreatic, and esophageal cancer patients being treated at high burden safety-net facilities. In this study, we seek to specifically evaluate patients with oral cavity cancers treated at higher safety-net burden hospitals, because survival outcomes for this particular cancer population have been shown to be stratified by various socioeconomic factors. To date, a robust analysis of survival outcomes and hospital safety-net burden for oral cavity cancer patients has not yet been done. Objectives: To investigate the relationships between hospital safety-net burden, clinicopathologic characteristics, and overall survival in oral cavity cancer (OCC) patients. Methods: From the National Cancer Database, we identified 48,176 OCC patients diagnosed with oral cavity cancer between the years 2004 to 2015. Treatment facilities were defined as no safety-net burden hospitals (NBH), low safety-net burden hospitals (LBH), and high safety-net burden hospitals (HBH) based on percentiles of uninsured/Medicaid patients treated: 0-30%, >30-75%, and >75-100% defines treatment facilities as NBH, LBH, and HBH respectively. Social demographic and clinico-pathological variables assessed were age, distance to treatment facility, time to first treatment, gender, race, Hispanic origin, insurance status, median household income, year of diagnosis, Charlson-Deyo score, location of primary site, AJCC stage, facility type and volume, and treatment modality. Safety-net burden of treatment facilities was used as the primary independent predictor in this analysis and the primary outcome of interest was overall survival. Crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed using Cox regression modelling, where clustering of patients within facilities was accounted for using robust sandwich covariance matrix estimates. Results: There were 380 NBH (29.9%), 573 LBH (45.2%), and 316 HBH (24.9%) identified among the 1,269 treatment facilities evaluated for their respective safety-net burden and survival outcomes in oral cavity cancer patients. The median percentage of uninsured/Medicaid patients treated was 23.5% (range 18.6-100%) at HBH, 11.6% (range 1.2-18.5%) at LBH, and 0% (range 0-0%) at NBH. Median follow-up in all surviving patients was 49.0 months. A total of 22,466 deaths were reported, and the overall 5year survival rate was 53.5% (median survivalZ69.7 months). Median survival for NBH, LBH and HBH was 68.6, 74.8 and 55.0 months, respectively (p<0.0001). However, compared to NBH and LBH, HBH facilities treated more late-staged cancers, racial and ethnic minorities, and patients of a lower socioeconomic status (SES). Thus, after adjusting for the aforementioned social demographic and clinico-pathological variables, no significant survival difference was noted in LBH (aHR 0.97 95% CI 0.91-1.04, pZ0.405) or HBH (aHR 1.05 95% CI 0.98-1.13, pZ0.175) when compared to patients treated at NBH facilities. Conclusions: While lower actuarial survival rates are observed in HBH compared to LBH and NBH, these findings may be driven by socioeconomic, and clinicopathologic characteristics. Racial and ethnic minorities are more likely to receive care at HBH. These findings suggest that high burden safety-net hospitals provide vital care to vulnerable populations with oral cavity cancer.
Objective The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemi... more Objective The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on head and neck oncologic care at a tertiary care facility. Study Design This was a cross-sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period. Secondary outcome measures were tumor conference volume, operative volume, and outpatient patient procedure and clinic volumes. Setting This single-center study was conducted at a tertiary care academic hospital in a large metropolitan area. Methods The study included a consecutive sample of adult subjects who were presented at a head and neck interdepartmental tumor conference during the study period. Patients were compared to historical controls based on review of operative data, outpatient procedures, and clinic volumes. Results In total, 117 patients were presented during the review period in 2020, compared to 69 in 2019. There was an...
Journal of the National Comprehensive Cancer Network, 2020
Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease,... more Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
e14619 Background: Patients with locally advanced adenocarcinoma of the gastroesophageal junction... more e14619 Background: Patients with locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) that undergo aggressive neoadjuvant chemoradiation therapy followed by an extensive oncologic resection have a 25-50% risk of developing locoregional recurrences and/or distant metastases. There is an unmet need for biomarkers that predict tumor behavior following neoadjuvant therapy that can be used to direct future therapy. CDX2, an intestine-specific transcription factor that regulates proliferation and differentiation, is ectopically expressed by epithelial cells lining the GEJ during intestinal metasplasia and retained by adenocarcinomas. To date, CDX2 has not been shown to contribute to the tumorigenic potential of GEJ adenocarciomas limiting its use as a predictive or prognostic marker. Methods: CDX2 mRNA from GEJ tissues were sequenced. Wild type and splice variant transcripts and proteins were analyzed by Western blot, RT-PCR, luciferase assays, and fluorescent IHC. In vi...
Background: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk struct... more Background: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk structures (DARS) using a direct gross tumor volume (GTV 70Gy) to planning target volume expansion (dPTV 70Gy) for patients with squamous cell carcinoma of the larynx (LSCC). Methods: A retrospective review was performed on patients with LSCC treated between 2003-2018. Clinical outcomes, toxicities, and dosimetric data were analyzed. Results: Seventy-three patients were identified. Overall survival at 5-years was 57.8%. Five-year local and regional control was 79.8% and 88.2%, respectively. Distant metastatic-only failure was 2.7%. Eighty percent of failures were 95% contained within the dPTV 70Gy. Mean dose and the volume of DARS receiving 70 Gy was significantly lower for dPTV 70Gy compared to a consensusdefined PTV 70Gy. Discussion: Judicious reduction in high-dose target volumes can preserve high tumor control rates while reducing dose to normal surrounding structures underscoring the potential benefit of this approach in enabling local therapy intensification to improve locoregional control.
Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh editi... more Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh edition staging system to prognosticate the overall survival of patients with human papillomavirus (HPV)–positive laryngeal squamous cell carcinoma. Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods Patients diagnosed with laryngeal squamous cell carcinoma who were treated with curative intent were identified in the National Cancer Database. Multivariate analysis was utilized to determine factors correlated with overall survival in the HPV-negative and HPV-positive cohorts. Unadjusted and propensity score–weighted Kaplan-Meier estimation was used to determine overall survival of HPV-negative and HPV-positive patients across AJCC stage groupings. Results We identified 3238 patients with laryngeal squamous cell carcinoma, of which 2812 were HPV negative and 426 were HPV positive. Overall survival adjusted for age, sex, and comorbidity status confirmed s...
International journal of radiation oncology, biology, physics, 2017
The patient was a 70-year-old man with a 6-month history of a progressively enlarging right neck ... more The patient was a 70-year-old man with a 6-month history of a progressively enlarging right neck mass. His medical history was significant for numerous basal cell carcinomas and chronic lymphocytic leukemia. He was a never-smoker and a social drinker. On examination, the mass was in level II, fixed, and nontender. Examination of the oral cavity and mucosal surfaces of the pharyngeal axis by endoscopy showed normal results. Computed tomography (CT) of the neck demonstrated a 2.4 Â 2.5 Â 2.0ecm cystic lesion in the right upper neck with infiltration of the sternocleidomastoid (Fig. 1).
The present study evaluated clinical outcomes for patients with head and neck squamous cell carci... more The present study evaluated clinical outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease. A retrospective analysis of N3 head and neck squamous cell carcinoma patients was performed. Pearson chi-square and Wilcoxon signed-rank tests were used to analyze patient demographics, disease characteristics, and treatment variables. Survival was evaluated using Kaplan-Meier curves with the log-rank test. Univariate analysis using Cox proportional hazards models was used to define factors associated with overall survival. Patient and tumor characteristics associated with treatment assignments were analyzed by univariate multinomial logistic regression. We identified 36 patients with radiographically-defined N3 disease. For the entire cohort, median follow-up was 23.6 (range 2.8-135.0) months, and overall survival was 60% at 2 years and 30% at 5 years. Overall survival was similar between patients receiving primary surgery, radiotherapy, or chemora...
Journal of Cancer Research and Clinical Oncology, 2017
Purpose-We examined overall survival in a large cohort of patients with human papillomavirus (HPV... more Purpose-We examined overall survival in a large cohort of patients with human papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell carcinoma of the head and neck (non-OPSCC). Methods-Patients diagnosed with non-OPSCC and known HPV status were identified in the National Cancer Database (NCDB). Multivariate logistic regression was applied to examine factors associated with HPV status. Multivariate analysis was utilized to determine factors correlated with overall survival. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in survival analyses. Multiple imputation method was used for sensitivity analysis. Results-We identified 19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median follow-up was 23.5 months. HPV-positive patients were more commonly male, white, with a lower comorbidity index score, presenting with T-stage <2, and N-stage ≥1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV-positive patients,
To evaluate treatment trends and overall survival of patients with small cell carcinoma of the he... more To evaluate treatment trends and overall survival of patients with small cell carcinoma of the head and neck region. Patients from 2004 to 2012 were identified from the National Cancer Database. Patient demographics and overall survival were analyzed. Multivariable analysis was used to identify predictors of survival. Among 347,252 head and neck patients a total of 1042 (0.3%) patients with small cell carcinoma were identified. 17% of patients were diagnosed as stage I/II, 61% as stage III/IVA/IVB and 22% as stage IVC disease. The distribution by anatomic site was 9% oral cavity, 12% oropharynx, 35% larynx, 4% hypopharynx, 10% nasopharynx and 30% nasal cavity and paranasal sinuses. The median overall survival by anatomical site was 20.8months for oral cavity, 23.7months for oropharynx, 17.9months for larynx/hypopharynx, 15.1months for nasopharynx and 36.4months for nasal cavity primary tumors. On multivariable analysis across stage, patients with nasal cavity and paranasal sinuses t...
Journal of the National Comprehensive Cancer Network : JNCCN, Jun 1, 2017
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers pro... more The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.
To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated ar... more To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer.
International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 2014
We evaluated the feasibility of combined hippocampal-and scalp-sparing intensity-modulated radiot... more We evaluated the feasibility of combined hippocampal-and scalp-sparing intensity-modulated radiotherapy (IMRT) plans. This study included 7 patients who received conventional palliative whole brain radiation treatment (WBRT) for brain metastasis. The brain, hippocampus, and scalp were contoured and replanned with intensity modulated radiation therapy. The prescription dose was 30 Gray (Gy) in 10 fractions with hippocampus and normal structure constraints per the Radiation Therapy Oncology Group (RTOG) 0933 protocol. Further planning was done to minimize the scalp dose while maintaining the dose constraints for the hippocampus. Dose volume histograms were obtained from conventional opposed lateral fields, IMRT and compared. Planning target volume (PTV) coverage for all plans fell within the RTOG 0933 critical structure acceptable variation category. When compared to traditional opposed lateral fields, the IMRT plan with combined hippocampal-and scalp-sparing constraints was able to significantly reduce the max and mean scalp dose as well as the percentage of scalp receiving 10 and 20 Gy by 46% and 35%, respectively, while maintaining acceptable RTOG 0933 hippocampal dose variations. We conclude that acceptable PTV coverage and sparing of the scalp and hippocampus can be accomplished using a 9-field non-coplanar IMRT plan. Prospective study is warranted to understand the impact on radiation induced alopecia.
Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini r... more Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.
International Journal of Radiation Oncology*Biology*Physics, 2012
To evaluate the clinical outcomes of stereotactic body radiation therapy for lung cancer in octog... more To evaluate the clinical outcomes of stereotactic body radiation therapy for lung cancer in octogenarians. Materials/Methods: Thirty-one patients who were over 80 years old at the time of therapy and 33 lesions, treated between September 2006 and February 2011, were included in this study. Seventeen patients had Stage IA lung cancer, 7 had Stage I B, one patient had Stage IIIA (the metastasis of a different lobe of the ipsilateral side and no lymph node metastasis), one patient had Stage IV (contralateral lung metastasis and no lymph node metastasis) and the other 5 had recurrence within the first 5 years after surgery for lung cancer. Threedimensional treatment planning using 7-8 non-coplanar beams was performed to maintain the target dose homogeneity and to decrease the irradiated lung volume >20 grays (Gy). All but one patient received five single, high doses of radiation of 10 Gy at the isocenter for 5-8 days. The median follow-up period was 32 months (range, 13-60 months). Results: Ten patients died during the follow-up period: Six of these died of lung cancer, and the remaining 4 died of other causes. No patients died of the radiation therapy itself. Ten patients had recurrence: 3 local recurrences, 3 regional lymph node metastases and 4 distal metastases. Overall survival rates, cause-specific survival rates and local control after 1 year/2 years were 93.5%/ 66.6%, 100%/79.6% and 93.8%/90.0%, respectively. One patient had radiation-induced pneumonitis of Grade 3 (G3). Three patients had rib fracture in line with the radiation field. Three patients had G1 atelectasis. With regard to radiodermatitis, 7 patients had G1 skin pigmentation and 2 patients had G1 induration or G1 atrophy. No other vascular, cardiac, esophageal or neurologic toxicities were encountered. Conclusions: We believe that stereotactic body radiation therapy for primary lung cancer in octogenarians is safe and minimally invasive.
International Journal of Radiation Oncology*Biology*Physics, 2013
Conclusions: Results provide evidence that, besides prolonging survival with a good safety profil... more Conclusions: Results provide evidence that, besides prolonging survival with a good safety profile, Ra-223 delays time to first SRE, in particular, time to first use of EBRT and use of opioids. In addition, Ra-223 reduces pain and opioid use in CRPC patients with bone mets. Importantly, the study showed that Ra-223 could be given safely with concomitant EBRT.
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Papers by Matthew Witek