Proton Therapy for Head and Neck Cancer.

OPINION STATEMENT: The application of proton beam radiation therapy in the treatment of head and neck cancer has grown tremendously in the past few years. Globally, widespread interest in proton beam therapy has led to multiple research efforts regarding its therapeutic value and cost-effectiveness. The current standard of care using modern photon radiation technology has demonstrated excellent treatment outcomes, yet there are some situations where disease control remains suboptimal with the potential for detrimental acute and chronic toxicities. Due to the advantageous physical properties of the proton beam, proton beam therapy may be superior to photon therapy in some patient subsets for both disease control and patient quality of life. As enthusiasm and excitement for proton beam therapy continue to increase, clinical research and widespread adoption will elucidate the true value of proton beam therapy and give a greater understanding of the full risks and benefits of proton therapy in head and neck cancer.

Discontinuation/Dose Reduction of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers during Acute Decompensated Heart Failure in African-American Patients with Reduced Left-Ventricular Ejection Fraction.

OBJECTIVES: Patients with heart failure (HF) and reduced left-ventricular ejection fraction (LVEF) benefit from angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) therapy. While dose reduction/discontinuation (r/d) of ß-blockers (BB) and furosemide in acute decompensated HF (ADHF) worsen outcomes, data on ACEI/ARB are lacking. METHODS: To determine the frequency and reasons for ACEI/ARB therapy r/d in ADHF patients, we studied 174 patients with LVEF <40% on ACEI/ARB and BB therapy upon admission over 1 year. RESULTS: ACEI/ARB doses were r/d in 17.2% because of acute kidney injury (56.7%), hypotension (23.3%), and hyperkalemia (10%). Clinical characteristics were similar between patients with r/d and continued therapy. Admission and discharge creatinine (Cr) levels were higher in the r/d group. On multivariate analysis, admission Cr and admission systolic blood pressures were independent predictors of r/d. Among patients with renal dysfunction cited as the r/d reason, Cr did not significantly rise in 23.5%. The r/d group had a longer length of stay (LOS). CONCLUSIONS: ACEI/ARB dose is reduced and/or discontinued in nearly one-fifth of all ADHF admissions, and LOS is longer in the ACEI/ARB r/d group. While impaired renal function is the most frequently cited reason, nearly one-fourth of the patients had stable renal function. ACEI/ARB r/d therapy in the setting of ADHF merits further study.

Hip fusion takedown to a total hip arthroplasty-is it worth it? A systematic review.

INTRODUCTION: Patients with surgically or spontaneously fused hips are often dissatisfied with their overall function and the debilitating effect on adjacent joints. Therefore, in properly selected patients, hip fusion-takedown and conversion to total hip arthroplasty (THA) can result in improved function and decreased pain. We aimed to (1) evaluate the indications for conversion, (2) evaluate the clinical outcomes, (3) analyze the overall complications, and (4) identify the overall satisfaction following the procedure. METHODS: A systematic and comprehensive literature search was performed to analyze studies evaluating conversion of hip fusion to THA. After reviewing 3,882 studies, 27 total studies (1,104 hips) met our inclusion/exclusion criteria and were included in our final analysis. A weighted mean of rates was determined for each complication, including infection, instability, loosening, nerve-related, abductor-related, venous thrombotic event, and revision. RESULTS: The study population consisted of 53.2% male and 46.8% female subjects. The mean age at time of conversion was 52 years (range 36-65 years), the mean time until follow-up was 9.2 years (range 2.5-17.3), and the mean duration of arthrodesis was 27.7 years (range 11-40.2). As measured by Harris Hip Score, overall clinical outcomes improved from 58.1 points (range 42.4-70 points) pre-operatively to 80.0 (range 62-93.5) post-operatively. The specific complication rates were 5.3% (range 0-43.6%) for infection, 2.6% (range 0-15.4%) for instability, 6.2% (range 0-17.2%) for loosening, 4.7% (range 0-13%) for nerve-related complications, 13.1% (range 0-87%) for abductor-related complications, and 1.2% (range 0-13%) for venous thrombotic events. The revision rate was 12.0% (range 0-43.6%). CONCLUSION: Takedown of a fused-hip can be a challenging procedure. Although patients can benefit functionally, both patients and surgeons need to be aware of the complications and increased risk of further revision procedures, which should be an important part of the pre-operative discussion.

Regional nodal irradiation (RNI) in breast cancer patients with residual isolated tumor cells or micrometastatic nodal disease after neoadjuvant chemotherapy.

Background/Purpose: The optimal management of residual micrometastases and isolated tumor cells (ITC) in patients with invasive breast cancer who undergo neoadjuvant chemotherapy (NAC) followed by definitive surgery is not well-studied. We evaluated the role of regional nodal irradiation (RNI) in clinically node-positive (cN1) breast cancer patients with residual low-volume nodal disease following NAC. Methods/Materials: We queried the National Cancer Database (NCDB) and included patients with cN1 invasive breast cancer diagnosed from 2004 to 2016 who were treated with NAC and definitive surgery and had residual micrometastases (ypN1mi) or ITC (ypN0i+). We used univariable (UVA) and multivariable (MVA) Cox regression analyses to determine prognostic factors and Kaplan-Meier (KM) methods to evaluate overall survival (OS). We used inverse probability treatment weighting (IPTW) to reweight data to account for confounding factors. Results: Our final cohort included 1980 patients, including 527 patients with ypN0i + disease and 1453 patients with ypN1mi disease. 1101 patients (45.0%) received RNI in the overall cohort with a higher proportion of ypN1mi patients receiving RNI (56.5%) compared to 53.1% of ypN0i + patients. There was no significant difference in OS between ypN0i + and ypN1mi patients. RNI had no significant effect on OS in the overall cohort using Cox MVA and KM methods. With separate subset analysis of ypN0i + and ypN1mi patients, there was no significant effect of RNI on OS. This was confirmed with IPTW. Conclusions: In a national hospital-based study of cN1 invasive breast cancer patients with residual ITC or micrometastases after NAC, RNI did not have a significant effect on OS.

Repeat re-irradiation with interstitial HDR-brachytherapy for an in-field isolated nodal recurrence in a patient with HPV-positive squamous cell carcinoma of the head and neck.

PURPOSE: Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. METHODS AND MATERIALS: In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. RESULTS: Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. CONCLUSION: Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year.

Patterns of Care and Outcomes of Low-Lying Adenocarcinoma and Squamous Cell Carcinoma of the Rectum.

PURPOSE: Squamous cell carcinoma (SCC) of the rectum is a unique entity that lacks definitive guidelines regarding prognosis and treatment. This study aimed to analyze patterns of care and survival for SCC and adenocarcinoma (AC) of the rectum. METHODS: This was a retrospective analysis of patients with stage I-III SCC or AC of the rectum treated from 2004 to 2016 from the National Cancer Database. The treatment groups analyzed were surgery alone (S), chemoradiation followed by surgery (CRT + S), surgery followed by chemoradiation (S + CRT), and definitive chemoradiation (CRT). Patient- and clinical-related factors were compared. Overall survival was assessed with the Kaplan-Meier method and Cox proportional regression models. RESULTS: Of the patients studied, 21,587 (97.1%) were AC and 640 (2.9%) were SCC. Among patients with AC, most (n = 8549, 59.4%) received chemoradiation followed by surgery; those with SCC (n = 305, 66.4%) received definitive chemoradiation. Among patients who received surgery, the majority (69.2%) with AC histology had a low anterior resection while the majority (52.1%) of SCC had an abdominoperineal resection. Five-year overall survival of AC versus SCC in the entire cohort was 61.6% versus 56.1%, respectively (p < 0.001). On multivariable analysis for AC, CRT + S (HR 0.61, p < 0.001), or S + CRT (HR 0.67, p < 0.001) had improved survival compared to S alone while those who had definitive CRT (HR 1.55, p < 0.001) had worse survival. CONCLUSIONS: SCC of the rectum tends to be treated like anal cancers with definitive chemoradiation, with similar survival to historical reports of anal cancer. AC of the rectum is most commonly treated under the rectal cancer paradigm.

Stereotactic body radiation therapy for an unresectable FGF23-secreting tumor of the cervical spine: A case report and literature review.

We present the case of a 65-year-old male with tumor-induced osteomalacia (TIO) caused by an FGF23-secreting phosphaturic tumor of C2 treated definitively with stereotactic body radiation therapy (SBRT) and kyphoplasty. The patient exhibited notable reduction in FGF23 6 weeks following radiotherapy. He also received a dose of the FGF23 monoclonal antibody, burosumab. We discuss the case with emphasis on radiation in the management of TIO. This case demonstrates SBRT as a well-tolerated local treatment option for the management of unresectable FGF23-producing tumors.

Update of Radiation Techniques Using Photons for Anterior Skull Base Tumors.

Anterior skull base tumors represent a challenge for radiation therapy (RT) planning given the close proximity of the target lesion to numerous critical structures in this complex anatomic location. Despite this challenge, surgery followed by postoperative RT is a common treatment paradigm for malignant sinonasal tumors that has been associated with improved outcomes compared to single-modality treatment. Therefore, technological advancements allowing for increasingly conformal target coverage and sparing of organs at risk are important to accomplish the goal of delivering RT with the highest therapeutic ratio possible. Such advances include both intensity-modulated RT and volumetric-modulated arc therapy, which allow RT to be delivered more precisely than ever before. Furthermore, stereotactic radiosurgery can deliver highly conformal doses of external beam RT in a single or limited number of fractions for the definitive or postoperative management of benign lesions of the anterior base of the skull. These sophisticated photon-based RT strategies have allowed for exciting advances in the contemporary treatment of anterior skull base tumors that will continue to improve patient outcomes and reduce toxicity for years to come.

Patterns of Radiotherapy Use and Outcomes in Head and Neck Soft-Tissue Sarcoma in a National Cohort.

OBJECTIVES/HYPOTHESIS: We used the National Cancer Database to identify the patterns of care and prognostic factors in adult patients with head and neck soft-tissue sarcoma (HNSTS). STUDY DESIGN: Retrospective cohort analysis. METHODS: Using the National Cancer Database, we identified patients age ≥ 18 years who were diagnosed with HNSTS between 2004 and 2013. Both χ2 and multivariate logistic regression were used to identify factors associated with radiation therapy (RT) utilization. Kaplan-Meier methods were used to estimate overall survival (OS) and Cox proportional regression was used to determine significant contributors to OS. RESULTS: Our final cohort included 1,282 patients (682 treated with surgery only, 199 treated with RT only, and 401 treated with surgery and RT). Patients with younger age, poor tumor grade, rhabdomyosarcoma histology, and chemotherapy treatment were more likely to receive RT alone without surgery. Among the 1,083 surgical patients, RT utilization was associated with positive margins (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.36-3.48), poor grade (OR: 2.92, 95% CI: 1.95-4.38), and chemotherapy use (OR: 1.78, 95% CI: 1.15-2.76). Radiotherapy utilization among surgical patients was not affected by demographic factors (age, sex, or ethnicity) or treatment institution (academic or community). For surgical patients, poor grade, large tumor size, and rhabdomyosarcoma histology were associated with worse OS on multivariate analysis. CONCLUSIONS: In this analysis of HNSTS, younger patients with poor tumor grade and rhabdomyosarcoma histology were more likely to receive RT without surgery. Among surgical patients, adjuvant RT was more likely to be used for positive margins and poor grade, with no demographic disparities identified. Poor grade and rhabdomyosarcoma histology were negative prognostic factors for surgical patients. LEVEL OF EVIDENCE: NA Laryngoscope, 130:120-127, 2020.

Cardiac Metastasis in a Patient with Head and Neck Cancer: A Case Report and Review of the Literature.

Cardiac metastasis from a primary head and neck cancer is a rare finding. Most patients with cardiac metastases have nonspecific symptoms that may vary depending on the severity and location of the lesion. Due to the infrequency of reported cases, there are no clear guidelines for the diagnosis or management of cardiac metastasis in head and neck cancer patients. In this report, we discuss the case of a patient with a primary diagnosis of oral tongue cancer who developed a cardiac metastasis that was detected antemortem.

Spontaneous Hemorrhage Followed by Paraparesis in a Patient with a Spinal Meningioma.

BACKGROUND: Although rare, spinal meningiomas may cause motor and sensory deficits or difficulty with bladder or bowel function due to spinal cord compression. Although hemorrhage of intracranial meningiomas is well documented, there are very few cases of hemorrhage or hematoma associated with spinal meningiomas in the literature. Spinal meningiomas have been reported to be associated with subdural, epidural, intratumoral, and subarachnoid hemorrhage, and usually in the setting of an inciting event such as lumbar puncture or anticoagulation therapy. CASE DESCRIPTION: A 68-year-old women presented to the emergency room with acute onset of paraparesis in the lower extremities. Magnetic resonance imaging findings were inconclusive for cause but showed spinal cord compression. Intraoperative findings demonstrated an intratumoral hemorrhage and pathology was consistent with meningioma. CONCLUSIONS: To the best of our knowledge, this is the first report in English literature of a patient who first develops symptoms from a spinal meningioma with spontaneous intratumoral hemorrhage presenting with acute paraparesis. Magnetic resonance imaging findings in retrospect match surgical intraoperative findings. Prompt surgical intervention can result in complete resolution of neurologic deficits.

A new device for measuring esophageal variceal pressure.

BACKGROUND: Esophageal varices are a frequent source of bleeding in patients with cirrhosis. Elevated intravariceal pressure is associated with variceal bleeding. There is no simple, easy-to-use device for noninvasive measurement of intravariceal pressure. The purposes of this study were to develop a noninvasive method for measuring intravariceal pressure, and to develop a model of esophageal varices that can be used to test this pressure measurement device. METHODS: A variceal pressure measurement device was constructed by placing a 20 MHz US transducer in a latex balloon catheter sheath and attaching the catheter to a pressure transducer. The pressure measurement device was passed though the accessory channel of a large-channel endoscope and tested in blinded fashion by using tip deflection to compress each of 4 variceal models with the device. The pressure within each model was measured 10 times by 2 separate investigators blinded to the actual pressures. The mean (SD) pressure was calculated for each model. The variceal models were made of nitrocellulose dialysis tubing filled with water. Each "varix" had the same diameter but a different intraluminal pressure (5.5, 10, 15, 21.5 mm Hg). OBSERVATIONS: The correlation coefficient between the actual and measured "varix" pressures for the first investigator (L.S.M.) was r = 0.96: 99% CI [0.93, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 9.5, 3.9, 5.1, and 0.7. The correlation coefficient between the actual and measured varix pressures for the second investigator (Q.D.) was r = 0.97: 99% CI [0.94, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 10.3, 3.4, 9.8, and 1.1. The correlation coefficient between the 2 investigators (L.S.M., Q.D.) for the varix model pressures was r = 0.97: 99% CI [0.95, 0.99]. CONCLUSION: The variceal pressure measuring device developed for this study measured intravariceal pressure in a model varix with a low percent error and high correlation to the actual pressures. Intraobserver and interobserver variability was low.

A new ultrasound-guided esophageal variceal pressure-measuring device.

OBJECTIVE: To develop a noninvasive method and device to determine intravariceal pressure and variceal wall tension by measuring the variables of the Laplace equation and test this device in a model of esophageal varices. METHODS: Two variceal pressure measurement devices were constructed. The first device consists of an Olympus 20 MHz ultrasound transducer placed next to a latex balloon catheter attached to a pressure transducer. The second device was constructed by placing the same ultrasound transducer inside a latex condom balloon attached to a pressure transducer. These pressure measurement devices were tested blindly in varix models with different intravariceal pressures, by inflating the balloon to flatten the varix models. Each variceal pressure was measured 10 times by two separate investigators blinded to the actual pressures. The mean intravariceal pressures were calculated. The variceal models were made of a latex balloon filled with water and coffeemate. RESULTS: The correlation coefficient between the actual and measured varix pressures for both devices was 0.99. The percent error ranged from 0 to 10%. The correlation coefficient between the investigators making the blinded measurements for both devices was 0.98. CONCLUSION: Two pressure-measuring devices were developed to determine intravariceal pressure in a model varix system. These devices demonstrate a low percent error and a high correlation to the actual variceal pressures with low intra- and interobserver variability. These devices have the potential to measure all the variables of the Laplace equation for wall tension. We plan to test these devices in human subjects.

Evaluation of the upper esophageal sphincter (UES) using simultaneous high-resolution endoluminal sonography (HRES) and manometry.

The aim of this study was to characterize the motion, morphology, and pressure of the upper esophageal sphincter (UES). The UES and its surrounding structures were evaluated in seven normal subjects and four human cadavers, using simultaneous high-resolution endoluminal sonography and manometry. The UES musculature on ultrasound is a C-shaped structure with an angle of 107 +/- 19 degrees. The mean peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA) of 0.87 +/- 0.33 cm2. During swallowing, the UES moved in an orad direction. Localizing the UES sonographically, the peak UES pressure in the cadavers was 19.7 +/- 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than the upper esophageal body. In the cadaver studies, the UES was imaged in conjunction with a significant increase in pressure, indicating that the pressure is due to passive mechanical conformational changes.

Mechanics and hemodynamics of esophageal varices during peristaltic contraction.

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.