CAD/CAM-assisted ablative surgery and intraoperative brachytherapy for pediatric skull-base sarcomas.

BACKGROUND: Head and neck (H&N) sarcomas in children can poise numerous challenges to the surgical oncologist and require multidisciplinary input and meticulous surgical planning. The application of computer-assisted design/computer-assisted manufacturing (CAD/CAM) has been extensively examined in H&N reconstruction in adults, but its utility in ablative oncologic surgery in children warrants further examination. We present preliminary results utilizing CAD/CAM techniques to assist in planning tumor resections and the application of intra-operative radiation in children with skull-base sarcomas. METHODS: A retrospective cohort review of all pediatric patients who presented to a tertiary care cancer center for surgical resection of a skull-base malignancy was performed between 1980 and 2021. All children under 18 years of age with diagnosis of a skull-base sarcoma as confirmed with imaging and pathology were analyzed. RESULTS: A total of 21 children were identified but only four children with skull-base sarcomas had diagnostic imaging available in whom computer-assisted volumetric analyses were generated. In these cases, CAD/CAM was used to plan surgical approaches and intraoperative radiotherapy, significantly aiding in treatment for these complicated pediatric cases. CONCLUSION: CAD/CAM planning for oncologic resection has huge potential. Here we have shown its utility in pre-operative surgical planning and for administration of intraoperative radiation therapy. Future studies are needed to examine its value in facilitating intraoperative surgical management and patient outcomes, as well as cost effectiveness.

Use of Ultrasmall Core-Shell Fluorescent Silica Nanoparticles for Image-Guided Sentinel Lymph Node Biopsy in Head and Neck Melanoma: A Nonrandomized Clinical Trial.

Importance: Sentinel lymph node (SLN) mapping agents approved for current surgical practice lack sufficient brightness and target specificity for high-contrast, sensitive nodal visualization. Objective: To evaluate whether an ultrasmall, molecularly targeted core-shell silica nanoparticle (Cornell prime dots) can safely and reliably identify optically avid SLNs in head and neck melanoma during fluorescence-guided biopsy. Design, Setting, and Participants: This nonrandomized clinical trial enrolled patients aged 18 years or older with histologically confirmed melanoma in whom SLN mapping was indicated. Exclusion criteria included known pregnancy, breast-feeding, or medical illness unrelated to the tumor. The trial was conducted between February 2015 and March 2018 at Memorial Sloan Kettering Cancer Center, with postoperative follow-up of 2 years. Data analysis was conducted from February 2015 to March 2018. Interventions: Patients received standard-of-care technetium Tc 99m sulfur colloid followed by a microdose administration of integrin-targeting, dye-encapsulated nanoparticles, surface modified with polyethylene glycol chains and cyclic arginine-glycine-aspartic acid-tyrosine peptides (cRGDY-PEG-Cy5.5-nanoparticles) intradermally. Main Outcomes and Measures: The primary end points were safety, procedural feasibility, lowest particle dose and volume for maximizing nodal fluorescence signal, and proportion of nodes identified by technetium Tc 99m sulfur colloid that were optically visualized by cRGDY-PEG-Cy5.5-nanoparticles. Secondary end points included proportion of patients in whom the surgical approach or extent of dissection was altered because of nodal visualization. Results: Of 24 consecutive patients enrolled (median [interquartile range] age, 64 [51-71] years), 18 (75%) were men. In 24 surgical procedures, 40 SLNs were excised. Preoperative localization of SLNs with technetium Tc 99m sulfur colloid was followed by particle dose-escalation studies, yielding optimized doses and volumes of 2 nmol and 0.4 mL, respectively, and maximum SLN signal-to-background ratios of 40. No adverse events were observed. The concordance rate of evaluable SLNs by technetium Tc 99m sulfur colloid and cRGDY-PEG-Cy5.5-nanoparticles was 90% (95% CI, 74%-98%), 5 of which were metastatic. Ultrabright nanoparticle fluorescence enabled high-sensitivity SLN visualization (including difficult-to-access anatomic sites), deep tissue imaging, and, in some instances, detection through intact skin, thereby facilitating intraoperative identification without extensive dissection of adjacent normal tissue or nerves. Conclusions and Relevance: This study found that nanoparticle-based fluorescence-guided SLN biopsy in head and neck melanoma was feasible and safe. This technology holds promise for improving lymphatic mapping and SLN biopsy procedures, while potentially mitigating procedural risks. This study serves as a first step toward developing new multimodal approaches for perioperative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02106598.

Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline.

PURPOSE: To provide evidence-based recommendations to practicing physicians and other health care providers on the diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck (SCCUP). METHODS: The American Society of Clinical Oncology convened an Expert Panel of medical oncology, surgery, radiation oncology, radiology, pathology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2008 through 2019. Outcomes of interest included survival, local and regional disease control, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 100 relevant studies to inform the evidence base for this guideline. Four main clinical questions were addressed, which included subquestions on preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate pathology techniques, and adjuvant therapy. RECOMMENDATIONS: Evidence-based recommendations were developed to address preoperative evaluation for patients with a neck mass, surgical diagnostic and therapeutic procedures, appropriate treatment options in unilateral versus bilateral SCCUP.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Imaging in oral cancers: A comprehensive review.

This review aims at simplifying the relevant imaging anatomy, guiding the optimal imaging method and highlighting the key imaging findings that influence prognosis and management of oral cavity squamous cell carcinoma (OSCC). Early OSCC can be treated with either surgery alone while advanced cancers are treated with a combination of surgery, radiotherapy and/or chemotherapy. Considering the complex anatomy of the oral cavity and its surrounding structures, imaging plays an indispensable role not only in locoregional staging but also in the distant metastatic work-up and post treatment follow-up. Knowledge of the anatomy with understanding of common routes of spread of cancer, allows the radiologist to accurately determine disease extent and augment clinical findings to plan appropriate therapy. This review aims at simplifying the relevant imaging anatomy, guiding the optimal imaging method and highlighting the key imaging findings that influence prognosis and management.

Dynamic contrast-enhanced MRI model selection for predicting tumor aggressiveness in papillary thyroid cancers.

The purpose of this study was to identify the optimal tracer kinetic model from T1 -weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data and evaluate whether parameters estimated from the optimal model predict tumor aggressiveness determined from histopathology in patients with papillary thyroid carcinoma (PTC) prior to surgery. In this prospective study, 18 PTC patients underwent pretreatment DCE-MRI on a 3 T MR scanner prior to thyroidectomy. This study was approved by the institutional review board and informed consent was obtained from all patients. The two-compartment exchange model, compartmental tissue uptake model, extended Tofts model (ETM) and standard Tofts model were compared on a voxel-wise basis to determine the optimal model using the corrected Akaike information criterion (AICc) for PTC. The optimal model is the one with the lowest AICc. Statistical analysis included paired and unpaired t-tests and a one-way analysis of variance. Bonferroni correction was applied for multiple comparisons. Receiver operating characteristic (ROC) curves were generated from the optimal model parameters to differentiate PTC with and without aggressive features, and AUCs were compared. ETM performed best with the lowest AICc and the highest Akaike weight (0.44) among the four models. ETM was preferred in 44% of all 3419 voxels. The ETM estimates of Ktrans in PTCs with the aggressive feature extrathyroidal extension (ETE) were significantly higher than those without ETE (0.78 ± 0.29 vs. 0.34 ± 0.18 min-1 , P = 0.005). From ROC analysis, cut-off values of Ktrans , ve and vp , which discriminated between PTCs with and without ETE, were determined at 0.45 min-1 , 0.28 and 0.014 respectively. The sensitivities and specificities were 86 and 82% (Ktrans ), 71 and 82% (ve ), and 86 and 55% (vp ), respectively. Their respective AUCs were 0.90, 0.71 and 0.71. We conclude that ETM Ktrans has shown potential to classify tumors with and without aggressive ETE in patients with PTC.

Molecular phenotyping and image-guided surgical treatment of melanoma using spectrally distinct ultrasmall core-shell silica nanoparticles.

Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

Quantitative Non-Gaussian Intravoxel Incoherent Motion Diffusion-Weighted Imaging Metrics and Surgical Pathology for Stratifying Tumor Aggressiveness in Papillary Thyroid Carcinomas.

We assessed a priori aggressive features using quantitative diffusion-weighted imaging metrics to preclude an active surveillance management approach in patients with papillary thyroid cancer (PTC) with tumor size 1-2 cm. This prospective study enrolled 24 patients with PTC who underwent pretreatment multi-b-value diffusion-weighted imaging on a GE 3 T magnetic resonance imaging scanner. The apparent diffusion coefficient (ADC) metric was calculated from monoexponential model, and the perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), and diffusion kurtosis coefficient (K) metrics were estimated using the non-Gaussian intravoxel incoherent motion model. Neck ultrasonography examination data were used to calculate tumor size. The receiver operating characteristic curve assessed the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. Multivariate logistic regression analysis was performed on metrics using a leave-1-out cross-validation method. Tumor aggressiveness was defined by surgical histopathology. Tumors with aggressive features had significantly lower ADC and D values than tumors without tumor-aggressive features (P < .05). The absolute relative change was 46% in K metric value between the 2 tumor types. In total, 14 patients were in the critical size range (1-2 cm) measured by ultrasonography, and the ADC and D were significantly different and able to differentiate between the 2 tumor types (P < .05). ADC and D can distinguish tumors with aggressive histological features to preclude an active surveillance management approach in patients with PTC with tumors measuring 1-2 cm.

Novel intraoperative radiotherapy utilizing prefabricated custom three-dimensionally printed high-dose-rate applicators.

BACKGROUND: Intraoperative radiotherapy (IORT) is an effective strategy for the delivery of high doses of radiotherapy to a residual tumor or resection cavity with relative sparing of nearby healthy tissues. This strategy is an important component of the multimodality management of pediatric soft tissue sarcomas, particularly in cases where patients have received prior courses of external beam radiotherapy. PURPOSE: Tumor beds with significant topographic irregularity remain a therapeutic challenge because existing IORT technologies are typically most reliable with flat surfaces. To address this limitation, we have developed a novel strategy to create custom, prefabricated high-dose-rate (HDR)-IORT applicators designed to match the shape of an anticipated surgical cavity. METHODS AND MATERIALS: Silastic applicators are constructed using three-dimensional (3D) printing and are derived from volumetric segmentation of preoperative imaging. RESULTS: HDR preplanning with the applicators improves dosimetric accuracy and minimizes incremental operative time. In this report, we describe the fabrication process for the 3D-printed applicators and detail our experience utilizing this strategy in two pediatric patients who underwent HDR-IORT as part of complex base of skull sarcoma resections. CONCLUSIONS: Early experience suggests that usage of the custom applicators is feasible, versatile for a variety of clinical situations, and enables the uniform delivery of high superficial doses of radiotherapy to irregularly shaped surgical cavities.

Texture analysis on parametric maps derived from dynamic contrast-enhanced magnetic resonance imaging in head and neck cancer.

AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: In this retrospective study, 19 HNSCC patients underwent pre- and intra-treatment DCE-MRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images, generating maps of volume transfer rate (K(trans)) and volume fraction of the extravascular extracellular space (ve). Image texture analysis was then employed on maps of K(trans) and ve, generating two texture measures: Energy (E) and homogeneity. RESULTS: No significant changes were found for the mean and standard deviation for K(trans) and ve between pre- and intra-treatment (P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans, relative to pretreatment scans (P < 0.04). CONCLUSION: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.

Multi-institutional validation of a novel textural analysis tool for preoperative stratification of suspected thyroid tumors on diffusion-weighted MRI.

PURPOSE: Ultrasound-guided fine needle aspirate cytology fails to diagnose many malignant thyroid nodules; consequently, patients may undergo diagnostic lobectomy. This study assessed whether textural analysis (TA) could noninvasively stratify thyroid nodules accurately using diffusion-weighted MRI (DW-MRI). METHODS: This multi-institutional study examined 3T DW-MRI images obtained with spin echo echo planar imaging sequences. The training data set included 26 patients from Cambridge, United Kingdom, and the test data set included 18 thyroid cancer patients from Memorial Sloan Kettering Cancer Center (New York, New York, USA). Apparent diffusion coefficients (ADCs) were compared over regions of interest (ROIs) defined on thyroid nodules. TA, linear discriminant analysis (LDA), and feature reduction were performed using the 21 MaZda-generated texture parameters that best distinguished benign and malignant ROIs. RESULTS: Training data set mean ADC values were significantly different for benign and malignant nodules (P = 0.02) with a sensitivity and specificity of 70% and 63%, respectively, and a receiver operator characteristic (ROC) area under the curve (AUC) of 0.73. The LDA model of the top 21 textural features correctly classified 89/94 DW-MRI ROIs with 92% sensitivity, 96% specificity, and an AUC of 0.97. This algorithm correctly classified 16/18 (89%) patients in the independently obtained test set of thyroid DW-MRI scans. CONCLUSION: TA classifies thyroid nodules with high sensitivity and specificity on multi-institutional DW-MRI data sets. This method requires further validation in a larger prospective study. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

Using diffusion-weighted MRI to predict aggressive histological features in papillary thyroid carcinoma: a novel tool for pre-operative risk stratification in thyroid cancer.

BACKGROUND: Initial management recommendations of papillary thyroid carcinoma (PTC) are very dependent on preoperative studies designed to evaluate the presence of PTC with aggressive features. The purpose of this study was to evaluate whether diffusion-weighted magnetic resonance imaging (DW-MRI) before surgery can be used as a tool to stratify tumor aggressiveness in patients with PTC. METHODS: In this prospective study, 28 patients with PTC underwent DW-MRI studies on a three Tesla MR scanner prior to thyroidectomy. Due to image quality, 21 patients were finally suitable for further analysis. Apparent diffusion coefficients (ADCs) of normal thyroid tissues and PTCs for 21 patients were calculated. Tumor aggressiveness was defined by surgical histopathology. The Mann-Whitney U test was used to compare the difference in ADCs among groups of normal thyroid tissues and PTCs with and without features of tumor aggressiveness. Receiver operating characteristic (ROC) analysis was performed to assess the discriminative specificity, sensitivity, and accuracy of and determine the cutoff value for the ADC in stratifying PTCs with tumor aggressiveness. RESULTS: There was no significant difference in ADC values between normal thyroid tissues and PTCs. However, ADC values of PTCs with extrathyroidal extension (ETE; 1.53±0.25×10(-3) mm2/s) were significantly lower than corresponding values from PTCs without ETE (2.37±0.67×10(-3) mm2/s; p<0.005). ADC values identified 3 papillary carcinoma patients with extrathyroidal extension that would have otherwise been candidates for observation based on ultrasound evaluations. The cutoff value of ADC to discriminate PTCs with and without ETE was determined at 1.85×10(-3) mm2/s with a sensitivity of 85%, specificity of 85%, and ROC curve area of 0.85. CONCLUSION: ADC value derived from DW-MRI before surgery has the potential to stratify ETE in patients with PTCs.

Repeatability Investigation of Reduced Field-of-View Diffusion-Weighted Magnetic Resonance Imaging on Thyroid Glands.

OBJECTIVE: To investigate the repeatability of the quantitative magnetic resonance imaging (MRI) metric (apparent diffusion coefficient [ADC]) derived from reduced field-of-view diffusion-weighted (rFOV DWI) on thyroid glands in a clinical setting. MATERIALS AND METHODS: Ten healthy human volunteers were enrolled in MRI studies performed on a 3-T MRI scanner. Each volunteer was designed to undergo 3 longitudinal examinations (2 weeks apart) with 2 repetitive sessions within each examination, which included rFOV and conventional full field-of-view (fFOV) DWI scans. Diffusion-weighted images were assessed and scored based on image characteristics. Apparent diffusion coefficient values of thyroid glands from all participants were calculated based on regions of interest. Repeatability analysis was performed based on the framework proposed by the Quantitative Imaging Biomarker Alliance, generating 4 repeatability metrics: within-participant variance ((Equation is included in full-text article.)), repeatability coefficients, intraclass correlation coefficient, and within-participant coefficient of variation. Student t test was used to compare the performance difference between rFOV and fFOV DWI. RESULTS: The overall image quality from rFOV DWI was significantly higher than that from fFOV DWI (P = 0.04). The ADC values calculated from rFOV DWI were significantly lower than corresponding values from fFOV DWI (P < 0.001). There was no significant difference in ADC values across sessions and examinations in either rFOV or fFOV DWI (P > 0.05). Reduced field-of-view DWI had lower values of (Equation is included in full-text article.), repeatability coefficient, and within-participant coefficient of variation and had a higher value of intraclass correlation coefficient compared with fFOV DWI across either sessions or examinations. CONCLUSIONS: This study demonstrated that rFOV DWI produced more superior-quality DWI images and more repeatable ADC measurements compared with fFOV DWI, thus providing a feasible quantitative imaging tool for investigating thyroid glands in clinical settings.

Perineural tumor spread involving the central skull base region.

Perineural spread of tumor is defined as extension of the primary tumor along tissues of the neural sheath (epineurium and perineurium) of a named nerve. Given the density of cranial nerves in the central skull base region and their extracranial communications, perineural tumor spread from a variety of sources can affect the central skull base region. Common malignancies with perineural tumor spread to central skull base include mucosal squamous cell carcinoma, adenoid cystic carcinoma, and cutaneous malignancies including melanoma. The presence and extent of tumor spread influence selection of treatment and prognosis. Appropriate imaging and interpretation, therefore, play a crucial role in detection and management of perineural tumor spread in the central skull base region.

Comparing primary tumors and metastatic nodes in head and neck cancer using intravoxel incoherent motion imaging: a preliminary experience.

OBJECTIVE: This study aimed to use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and to evaluate IVIM efficacy in predicting outcome. METHODS: Sixteen patients with head and neck cancer underwent IVIM diffusion-weighted imaging on a 1.5-T magnetic resonance imaging scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: In comparison with metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (P < 0.0009) and lower diffusion coefficient (D) (P < 0.0002). Patients with lower SD for D had prolonged progression-free survival and overall survival (P < 0.05). CONCLUSIONS: Pretreatment IVIM measures were feasible in investigating the physiologic differences between the 2 tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care.

Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions.

Early diagnosis and treatment of melanoma are essential to minimizing morbidity and mortality. The presence of lymph node metastases is a vital prognostic predictor, and accurate identification by imaging has important implications for disease staging, prognosis, and clinical outcome. Sentinel lymph node (SLN) mapping procedures are limited by a lack of intraoperative visualization tools that can aid accurate determination of disease spread and delineate nodes from adjacent critical neural and vascular structures. Newer methods for circumventing these issues can exploit a variety of imaging tools, including biocompatible particle-based platforms coupled with portable device technologies for use with image-guided surgical and interventional procedures. We describe herein a clinically-translated, integrin-targeting platform for use with both PET and optical imaging that meets a number of key design criteria for improving SLN tissue localization and retention, target-to-background ratios, and clearance from the site of injection and the body. The use of such agents for selectively probing critical cancer targets may elucidate important insights into cellular and molecular processes that govern metastatic disease spread. Coupled with portable, real-time optical camera systems, we show that pre-operative PET imaging findings for mapping metastatic disease in clinically-relevant larger-animal models can be readily translated into the intraoperative setting for direct visualization of the draining tumor lymphatics and fluorescent SLN/s with histologic correlation. The specificity of this platform, relative to the standard-of-care radiotracer, (18)F-FDG, for potentially discriminating metastatic disease from inflammatory processes is also discussed in the setting of surgically-based or interventionally-driven therapies.

Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer.

PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from eight patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the eight neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3-79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.

A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage III/IVB head and neck squamous cell cancer.

BACKGROUND: For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. METHODS: Planned treatment consisted of definitive intensity-modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m(2) on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2-year progression-free survival (PFS), and overall survival (OS) was a secondary endpoint. RESULTS: Forty-two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27-75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow-up was approximately 31.8 months (range, <3 to 51 months). The 2-year PFS rate was 75.9% (95% confidence interval, 63.9%-90.1%), and the 2-year OS rate was 88% (95% confidence interval, 78.6%-98.4%). Among 32 patients for whom post-treatment Head and Neck Performance Status Scores were obtained (median, 5.6 months after completing radiation therapy), scores of 100 for eating, speech, and diet, respectively, were recorded among 75%, 84%, and 50% of patients. BACKGROUND: The addition of bevacizumab to high-dose cisplatin plus IMRT did not appear to increase toxicity to unacceptable levels among patients with HNSCC, and the efficacy results were encouraging.