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Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown.NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities.3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality.There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment.

PURPOSE This work aims to reduce dose delivery time of pencil beam scanning (PBS) proton plans, which is the dominant factor of total plan delivery time. A proton PBS system, such as Varian ProBeam proton therapy system, can be equipped with the proton dose rate that is linearly proportional to the minimum monitor unit (MU) (i.e., number of protons) of PBS spots before saturation. Thus dose delivery time can be potentially reduced by increasing the MU threshold. However, commercially available treatment planning systems and current methods only allow for a single MU threshold globally for all PBS spots (i.e., all energy layers), and consequently the room to increase this minimum-MU for reducing dose delivery time is very limited since higher minimum-MU can greatly degrade treatment plan quality. METHODS Two major innovations of this work are the proposal of using variable MU thresholds locally adaptive to each energy layer, that is, minimum-MU-per-energy-layer (MMPEL), for reducing dose delivery time, and the joint optimization of plan delivery time and plan quality. Minimum-MU-per-energy-layer is formulated as a constrained optimization problem with objectives of dose-volume-histogram based planning constraints and plan delivery time, and minimum-MU constraints per energy layer for deliverable PBS spots. Minimum-MU-per-energy-layer is solved by iterative convex relaxations via alternating direction method of multipliers. RESULTS Representative prostate, lung, brain, head-and-neck, breast, liver and pancreas cases were used to validate MMPEL. Minimum-MU-per-energy-layer reduced dose delivery time to 53%, 67%, 67%, 53%, 54%, 32%, and 14% respectively while maintaining a similar plan quality. Accepting a slightly degraded plan quality that still met all physician planning constraints, the treatment time could be further reduced to 26%, 35%, 41%, 34%, 32%, 16%, and 11% respectively, or in another word MMPEL accelerated the PBS plan delivery by 2-10 fold. CONCLUSIONS A new proton PBS treatment planning method MMPEL with variable energy-adaptive MU thresholds is developed to optimize dose delivery time jointly with plan quality. The preliminary results suggest that MMPEL could substantially reduce dose delivery time.

Purpose In intensity-modulated proton therapy (IMPT), protons are used to deliver highly conformal dose distributions, targeting tumors, and sparing organs-at-risk. However, due to uncertainties in both patient setup and relative stopping power (RSP) calculation, margins are added to the treatment volume during treatment planning, leading to higher doses to normal tissues. Cone-beam computed tomography (CBCT) images are taken daily before treatment; however, the poor image quality of CBCT limits the use of these images for online dose calculation. In this work, we use a deep-learning-based method to predict RSP maps from daily CBCT images, allowing for online dose calculation in a step toward adaptive radiation therapy. Methods Twenty-three head-and-neck cancer patients were simulated using a Siemens TwinBeam dual-energy CT (DECT) scanner. Mixed-energy scans (equivalent to a 120 kVp single-energy CT scan) were converted to RSP maps for treatment planning. Cone-beam computed tomography images were taken on the first day of treatment, and the planning RSP maps were registered to these images. A deep learning network based on a cycle-GAN architecture, relying on a compound loss function designed for structural and contrast preservation, was then trained to create an RSP map from a CBCT image. Leave-one-out and holdout cross validations were used for evaluation, and mean absolute error (MAE), mean error (ME), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM) were used to quantify the differences between the CT-based and CBCT-based RSP maps. The proposed method was compared to a deformable image registration-based method which was taken as the ground truth and two other deep learning methods. For one patient who underwent resimulation, the new planning RSP maps and CBCT images were used for further evaluation and validation. Results The CBCT-based RSP generation method was evaluated on 23 head-and-neck cancer patients. From leave-one-out testing, the MAE between CT-based and CBCT-based RSP was 0.06 ± 0.01 and the ME was -0.01 ± 0.01. The proposed method statistically outperformed the comparison DL methods in terms of MAE and ME when compared to the planning CT. In terms of dose comparison, the mean gamma passing rate at 3%/3 mm was 94% when three-dimensional (3D) gamma index was calculated per plan and 96% when gamma index was calculated per field. Conclusions The proposed method provides sufficiently accurate RSP map generation from CBCT images, allowing for evaluation of daily dose based on CBCT and possibly allowing for CBCT-guided adaptive treatment planning for IMPT.

Quality assurance computed tomography (QACT) is the current clinical practice in proton therapy to evaluate the needs for replan. QACT could falsely indicate replan because of setup issues that would be solved on the treatment machine. Deforming the treatment planning CT (TPCT) to the pretreatment CBCT may eliminate this issue. We investigated the performance of replan evaluation based on deformed TPCT (TPCTdir) for proton head and neck (HN) therapy.Twenty-eight HN datasets along with pretreatment CBCT and QACT were used to validate the method. The changes in body volume were analyzed between the no-replan and replan groups. The dose on the TPCTdir, the deformed QACT (QACTdir), and the QACT were calculated by applying the clinical plans to these image sets. Dosimetric parameters' changes, including ΔD95, ΔDmean, and ΔD1 for the clinical target volumes (CTVs) were calculated. Receiver operating characteristic curves for replan evaluation based on ΔD95 on QACT and TPCTdir were calculated, using ΔD95 on QACTdir as the reference. A threshold for replan based on ΔD95 on TPCTdir is proposed. The specificities for the proposed method were calculated.The changes in the body contour were 95.8 ± 83.8 cc versus 305.0 ± 235.0 cc (p 0.01) for the no-replan and replan groups, respectively. The ΔD95, ΔDmean, and ΔD1 are all comparable for all the evaluations. The differences between TPCTdir and QACTdir evaluations were 0.30% ± 0.86%, 0.00 ± 0.22 Gy, and -0.17 ± 0.61 Gy for CTV ΔD95, ΔDmean, and ΔD1, respectively. The corresponding differences between the QACT and QACTdir were 0.12% ± 1.1%, 0.02 ± 0.32 Gy, and -0.01 ± 0.71 Gy. CTV ΔD95 2.6% in TPCTdir was chosen as the threshold to trigger QACT/replan. The corresponding specificity was 94% and 98% for the clinical practice and the proposed method, respectively.The replan evaluation based on TPCTdir provides better specificity than that based on the QACT.

OBJECTIVES/HYPOTHESIS For locally advanced oral squamous cell carcinoma (OSCC) treated by surgery and adjuvant therapy, consensus has yet to be reached on whether the optimal time to initiate surveillance positron emission tomography/computed tomography (PET/CT) scan is before or after adjuvant therapy. In this study, we characterize the utility of PET/CT scans obtained 3 months after adjuvant therapy. STUDY DESIGN PET/CT scans were obtained for 220 patients with stage III, IVA, or IVB OSCC who underwent resection followed by adjuvant radiotherapy or chemoradiotherapy. METHODS Using the Neck Imaging Reporting and Data System, PET/CT scans were dichotomized as suspicious (primary or neck category ≥3, or distant lesion present) versus nonsuspicious. We then computed differences in locoregional progression, distant progression, and overall survival; positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity; and success rate of salvage. RESULTS Sixty-seven patients (30%) had suspicious PET/CT scans, which were significantly associated with local failure (hazard ratio [HR] 14.0, 95% confidence interval [CI] 7.3-26.6), distant failure (HR 18.4, 95% CI 9.6-35.3), and poorer overall survival (HR 9.5, 95% CI 5.0-17.9). Overall PPV, locoregional PPV, NPV, sensitivity, and specificity were 85%, 79%, 73%, 58%, and 92%, respectively. Among those with biopsy-confirmed progression, 37 patients (65%) underwent salvage therapy; four (11%) were without evidence of disease at last follow-up. CONCLUSIONS For locally advanced OSCC, PET/CT scan 3 months after adjuvant therapy is strongly predictive of disease recurrence and survival, demonstrating improved performance over postoperative imaging in previous studies. Following a suspicious post-adjuvant therapy PET/CT scan, cure of locoregional recurrence is possible but unlikely. LEVEL OF EVIDENCE 4 Laryngoscope, 2020.

BACKGROUND: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with HPV associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx METHODS: Under a shared use agreement, 547 RTOG 0129 and 0522 patients with non. metastatic oropharyngeal squamous cell cancers who had known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. Factors analyzed included p16 status, gender, T stage, N Stage, age, and smoking history. RESULTS: Multivariable analysis of 547 patients with a median follow-up of 4.6 years revealed that age ≥ 50 (HR=3.28, p=0.003), smoking > 0 pack-years (HR=3.09, p

Objectives The patterns of care for salivary gland adenoid cystic carcinomas (ACC) are unknown. We sought to assess predictors of receiving postoperative radiation and/or chemotherapy for patients with nonmetastatic, definitively resected ACC, as well as report unexpected nodal disease. Methods The National Cancer Data Base was queried for definitively resected nonmetastatic ACC from 2004 to 2014. Logistic regression, Kaplan-Meier, and Cox proportional-hazard models were utilized. Propensity-score matched analysis was employed to reduce confounding variables. Results A total of 3,136 patients met entry criteria: 2,252 (71.8%) received postoperative radiation, with 223 (7.4%) also receiving concurrent chemotherapy. Median follow-up was 4.87 years. In clinically lymph node negative (cN0) patients, 7.4% had pathologically positive lymph nodes (pN) + after elective neck dissection. Patients who lived closer to their treatment facility and had positive margins were more likely to receive postoperative radiation. Black patients and uninsured patients were less likely to receive radiation. Older age, male sex, advancing stage, and positive surgical margins were associated with worse overall survival (OS). With limited follow-up, receipt of radiation or chemotherapy was not associated with OS. Conclusion Postoperative radiation was frequently given for resected ACC, with a minority receiving chemotherapy. Black patients and uninsured patients were less likely to receive radiation. Postoperative radiation and/or chemotherapy had no association with OS but were given in greater frequency in more advanced disease, and our series is limited by short follow-up. The disparity findings for this rare disease need to be addressed in future studies. Level of evidence 2c Laryngoscope, 129:377-386, 2019.

Summary The coleopteran insect western corn rootworm (WCR, Diabrotica virgifera virgifera) is an economically important pest in North America and Europe. Transgenic corn plants producing Bacillus thuringiensis (Bt) insecticidal proteins have been useful against this devastating pest, but evolution of resistance has reduced their efficacy. Here, we report the discovery of a novel insecticidal protein, PIP‐47Aa, from an isolate of Pseudomonas mosselii. PIP‐47Aa sequence shows no shared motifs, domains or signatures with other known proteins. Recombinant PIP‐47Aa kills WCR, two other corn rootworm pests (Diabrotica barberi and Diabrotica undecimpunctata howardi) and two other beetle species (Diabrotica speciosa and Phyllotreta cruciferae), but it was not toxic to the spotted lady beetle (Coleomegilla maculata) or seven species of Lepidoptera and Hemiptera. Transgenic corn plants expressing PIP‐47Aa show significant protection from root damage by WCR. PIP‐47Aa kills a WCR strain resistant to mCry3A and does not share rootworm midgut binding sites with mCry3A or AfIP‐1A/1B from Alcaligenes that acts like Cry34Ab1/Cry35Ab1. Our results indicate that PIP‐47Aa is a novel insecticidal protein for controlling the corn rootworm pests.

BACKGROUND Octogenarians and nonagenarians with stage II/III rectal adenocarcinomas are underrepresented in the randomized trials that have established the standard-of-care therapy of preoperative chemoradiation followed by definitive resection (ie, chemoradiation and then surgery [CRT+S]). The purpose of this study was to evaluate the impact of therapies on overall survival (OS) for patients with stage II/III rectal cancers and determine predictors of therapy within the National Cancer Data Base (NCDB). METHODS In the NCDB, patients who were 80 years old or older and had clinical stage II/III rectal adenocarcinoma from 2004 to 2013 were queried. Kaplan-Meier analysis, log-rank testing, logistic regression, Cox proportional hazards regression, interaction effect testing, and propensity score–matched analysis were conducted. RESULTS The criteria were met by 2723 patients: 14.9% received no treatment, 29.7% had surgery alone, 5.0% underwent short-course radiation and then surgery (RT+S), 45.3% underwent CRT+S, and 5.1% underwent surgery and then chemoradiation (S+CRT). African American race and residence in a less educated county were associated with not receiving treatment. Male sex, older age, worsening comorbidities, and receiving no treatment or undergoing surgery alone were associated with worse OS. There was no statistical difference in OS between RT+S, S+CRT, and CRT+S. Interaction testing found that CRT+S improved OS independently of age, comorbidity status, sex, race, and tumor stage. In the propensity score–matched analysis, CRT+S was associated with improved OS in comparison with surgery alone. CONCLUSIONS A significant portion of octogenarians and nonagenarians with stage II/III rectal adenocarcinomas do not receive treatment. African American race and living in a less educated community are associated with not receiving therapy. This series suggests that CRT+S is a reasonable strategy for elderly patients who can tolerate therapy. Cancer 2017;123:4325-36. © 2017 American Cancer Society.

Background Aggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking. Methods The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results The American College of Radiology Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC. Conclusion Multidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 175–182, 2016

The purpose of this study was to investigate the effect of dose perturbations for two metallic spinal screw implants in proton beam therapy in the perpendicular and parallel beam geometry. A 5.5 mm (diameter) by 45 mm (length) stainless steel (SS) screw and a 5.5 mm by 35 mm titanium (Ti) screw commonly used for spinal fixation were CT‐scanned in a hybrid phantom of water and solid water. The CT data were processed with an orthopedic metal artifact reduction (O‐MAR) algorithm. Treatment plans were generated for each metal screw with a proton beam oriented, first parallel and then perpendicular, to the longitudinal axis of the screw. The calculated dose profiles were compared with measured results from a plane‐parallel ion chamber and Gafchromic EBT2 films. For the perpendicular setup, the measured dose immediately downstream from the screw exhibited dose enhancement up to 12% for SS and 8% for Ti, respectively, but such dose perturbation was not observed outside the lateral edges of the screws. The TPS showed 5% and 2% dose reductions immediately at the interface for the SS and Ti screws, respectively, and up to 9% dose enhancements within 1 cm outside of the lateral edges of the screws. The measured dose enhancement was only observed within 5 mm from the interface along the beam path. At deeper depths, the lateral dose profiles appeared to be similar between the measurement and TPS, with dose reduction in the screw shadow region and dose enhancement within 1–2 cm outside of the lateral edges of the metals. For the parallel setup, no significant dose perturbation was detected at lateral distance beyond 3 mm away from both screws. Significant dose discrepancies exist between TPS calculations and ion chamber and film measurements in close proximity of high‐Z inhomogeneities. The observed dose enhancement effect with proton therapy is not correctly modeled by TPS. An extra measure of caution should be taken when evaluating dosimetry with spinal metallic implants. PACS number: 87.50.sj

Background The purpose of this study was to report outcomes of proton therapy in head and neck adenoid cystic carcinoma. Methods We conducted a retrospective analysis of 26 patients treated between 2004 and 2012. Twenty patients (77%) had base of skull involvement; 19 (73%) were treated for initial disease and 7 (27%) for recurrent disease. Twenty patients were treated postoperatively, 6 after biopsy alone and 24 had positive margins or gross residual disease. Median dose delivered was 72 Gy (relative biological effectiveness [RBE]). Results Median follow-up was 25 months (range, 7–50 months). The 2-year overall survival was 93% for initial disease course and 57% for recurrent disease (p = .19). The 2-year local control was 95% for initial disease and 86% for recurrent disease (p = .48). The 2-year distant metastatic rate was 25%. Late toxicity of grade 0 or 1 was seen in 17 patients, grade 2 in 5, grade 3 in 2, grade 4 in 1, and grade 5 in 1. Conclusion Initial outcomes of proton therapy are encouraging. Longer follow-up is required. © 2014 Wiley Periodicals, Inc. Head Neck 37: 117–124, 2015

Background Controversy surrounds the appropriate therapy for T1 glottic cancer. Both transoral endolaryngeal resection and radiation offer excellent local control and voice quality; some lesions are best addressed with resection and others with radiation. Methods The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guideline development includes an analysis of current literature from peer reviewed journals and the well-established “modified Delphi” consensus methodology to rate the appropriateness of treatment. Where evidence is not definitive, expert opinion informed recommendations. Results The ACR Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for treatment of T1 glottic cancer. Treatment planning is complex and decisions nuanced. Conclusion Best treatment for a particular cancer cannot be defined without consideration of the lesion's location, extent, depth of invasion, and quality of surgical exposure during direct laryngoscopy. © 2013 American College of Radiology. Head & Neck © 2013 Wiley Periodicals, Inc. Head Neck 36: 3–8, 2014

Background Controversy exists as to the criteria for selecting patients with carcinoma of the tonsil for treatment with ipsilateral radiotherapy (RT). Methods The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of treatment procedures by the panel. In those instances where evidence is not definitive, expert opinion may be used to recommend treatment. Results The ACR Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for selecting patients with tonsillar carcinoma for ipsilateral RT. Conclusion Patients that are appropriate for ipsilateral RT have less than 1 cm of tumor invasion into the soft palate or base of tongue, and nodal stage of N0 to 1. © 2012 American College of Radiology. Head Neck, 2012

Takayasu's arteritis is a rare idiopathic arteriopathy that produces narrowing and eventually closure of affected blood vessels. Ocular symptoms typically occur late in the disease process in those individuals who have severe involvement of the aortic arch and the carotid arteries. Visual loss typically occurs as a result of either systemic hypertension or concomitant ocular hypo-perfusion. We describe an unusual case of Takayasu's arteritis presenting in a child who complained of painful blurred vision. In this individual, no carotid artery disease was identified on vascular imaging and no evidence of impairment of ocular perfusion was demonstrable. Vision loss in this instance was due to anterior uveitis and cystoid maculopathy. These are atypical and rarely described features of Takayasu's arteritis. The patient responded well to anti-inflammatory treatment and his symptoms resolved. The clinical significance of these findings are discussed and the relevant literature reviewed.

Aims The aim of this study was to determine whether young, normotensive blacks who have been recently demonstrated to have a venodilator response to isoprenaline decreased compared with whites, also have an decreased vasodilatory response to bradykinin. Methods Eleven black and 11 white subjects were studied. Full dose-response curves to bradykinin (dosing range 0.5–500 ng min−1 ) were generated in hand veins preconstricted with phenylephrine (dosing range 20–6800 ng min−1 ). Results The groups had a similar maximal response to bradykinin (57.6±32.2%vs 67.8±49.3%, P=NS 95% confidence interval for the difference (CI): −47.3, 26.8). Also, the log of the dose that produced half maximal response to bradykinin was similar for the two groups (0.89±0.58 vs 0.78±0.61 ng min−1, P=NS, 95% CI: −0.42, 0.64). There was no difference between the two groups in the log dose of phenylephrine necessary to produce 80% constriction of the hand vein. Conclusion Diminished vasodilatory response to endothelium-derived relaxing factor (EDRF) does not seem to be associated with the increased prevalence of hypertension in blacks.

Purpose: To investigate the effect of dose perturbations for different spinal metallic screws in proton beam therapy. Methods: A 5.5mm (diameter) × 45mm (length) stainless steel (SS) screw and a 5.5mm × 35mm titanium (Ti) screw used for spinal fixation were CT‐scanned in a small water phantom. The CT data was processed with a metal artifact reduction (MAR) software. Two treatment plans were generated using Eclipse treatment planning system (TPS) for each metal screw with a proton beam parallel and perpendicular to the longitudinal axis of the metal, respectively. The calculated dose profiles were compared with measured ion chamber and EBT2 films results. Results: With the perpendicular setup, the measured dose immediately downstream from the screw exhibited dose enhancement up to 12% and 8% for SS and Ti respectively, but such dose perturbation was not observed outside the lateral shadow of the screws. The TPS showed 5% and 2% dose reductions immediately at the interface for the SS and Ti screws respectively and up to 9% dose enhancements within 1cm outside of the lateral shadow of the screws. The measured dose enhancement was only observed within 5mm from the interface along the beam path. At deeper depths, the lateral dose profiles appeared to be similar between the measurement and TPS, with dose reduction in the screw shadow region and dose enhancement within 1–2cm outside of the lateral edge of the metals. For the parallel setup, no significant dose perturbation was detected at lateral distance beyond 3 mm away from both screws. Conclusion: Streaking artifacts in CT images are significantly reduced with MAR but significant dose discrepancies between measurements and TPS in close proximity of the high‐Z inhomogeneities are clearly visible. Dose enhancement effect is not correctly modeled by TPS, thus extra caution should be given for dosimetry with metallic implants.

Purpose: Stereotactic radiosurgery (SRS) is a non‐invasive treatment modality appropriate for a wide array of tumors. Particularly in patients with benign tumors receiving proton SRS (pSRS), the generation of secondary neutrons from brass apertures may be associated with higher risk of secondary radiation‐induced tumors. A specially designed revolving titanium alloy collimator system with multiple sized collimator openings in circular and elliptical shapes is proposed and investigated in this study. Methods: Simulations of the passage of a proton beam through the proposed collimator system was performed using the FLUKA Monte Carlo general purpose code with treatment nozzle model implemented. The set of materials potentially applicable for the collimator fabrication, i.e. brass, stainless steel (SS), tungsten alloy (WA) and titanium alloy (TiA) (Ti‐6A1‐4V Grade 5) were simulated. The neutron fluence, dose equivalent, activation of the collimator material, the cooling times and beam shaping properties are analyzed. Results: Utilization of TiA results in less neutron dose equivalent at the patient compared to brass, WA or SS. The neutron flux spectra for TiA is an order of magnitude lower than those for the other materials in the energy interval with the maximum neutron weighting factor. The activation of TiA is lower and the cooling time 10 times shorter compared to WA. Dose shaping with the pSRS collimator is similar to a brass aperture. Dose enhancement at shallow depths for small proton fields limits the practical collimator opening size. Conclusion: The specially designed revolving pSRS titanium alloy collimator proposed in this study may reduce secondary neutron dose to the patient compared to other collimator materials investigated. This may reduce the risk of secondary tumors and malignancies and reduce late effects to the patient. The pSRS collimator allows the establishment of a pSRS system and methodology without the need for a dedicated pSRS treatment vault.