Long-Term Outcomes Following Definitive or Adjuvant Proton Radiotherapy for Adenoid Cystic Carcinoma.

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive (n = 9) or adjuvant PT (n = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement. Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension (P = .003) and gross residual tumor (P = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% (n = 13). Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

Boswellia serrata Enhances Passive Range-of-Motion Exercises in Radiation-Induced Trismus: A Case Report.

Trismus is a common, extremely detrimental side effect following definitive radiotherapy for head and neck malignancies. Existing therapeutic modalities (active and passive range-of-motion exercises and systemic therapies) offer only modest, slow improvements in jaw opening; thus, there is a need for additional treatment options. Boswellia serrata (BS) ("Indian frankincense") is a tree native to West Asia and North Africa that produces resin-containing "boswellic" acids. These have been shown to have in vitro and in vivo anti-inflammatory effects and have previously been found to be an effective treatment for asthma, colitis, arthritis, and post-radiation edema. Herein we report the case of a 54-year-old male with severe post-radiation trismus who experienced a dramatic resolution with BS/Therabite® combination therapy. His trismus improved from 6 mm to 45 mm over 10 weeks (0.46 mm/day), far exceeding previous rates of improvement documented in the literature. There were no ill effects. Given the dearth of effective treatments for post-radiation trismus, BS is a promising agent deserving of further study.

Low contralateral failure rate with unilateral proton beam radiotherapy for oropharyngeal squamous cell carcinoma: A multi-institutional prospective study from the proton collaborative group.

INTRODUCTION: Unilateral radiation therapy is appropriate for select patients with oropharyngeal squamous cell carcinoma (OPSCC). The use of proton beam therapy (PBT) in the unilateral setting decreases the dose to the contralateral neck and organs at risk. This study aims to evaluate contralateral recurrences in patients who received ipsilateral PBT. METHODS: We evaluated the Proton Collaborative Group database for patients treated with PBT for head and neck squamous cell carcinoma between the years 2015-2020 at 12 institutions. Dosimetric analysis was performed in five cases. RESULTS: Our analysis included 41 patients that received ipsilateral PBT with a mean follow-up of 14.7 months. 37% patients (n = 15) were treated for recurrent disease, and 63% (n = 26) were treated for de novo disease. Oropharyngeal sites included tonsillar fossa (n = 30) and base of tongue (n = 11). The median dose and BED delivered were 69.96 CGE and 84 Gy, respectively. Eight (20%) patients experienced at least one grade 3 dysphagia (n = 4) or esophagitis (n = 4) toxicity. No grade ≥ 4 toxicities were reported. There was one (2.4%) failure in the contralateral neck. The 1-year locoregional control was 88.9% and the freedom from distant metastasis was 95.5% (n = 2). The dosimetric analysis demonstrated similar ipsilateral level II cervical nodal region doses, whereas contralateral doses were higher with photon plans, mean: 15.5 Gy and 0.7CGE, D5%: 25.1 Gy and 6.6CGE. CONCLUSIONS: Our series is the first to report outcomes for patients with OPSCC receiving unilateral PBT. The contralateral neck failure rate was excellent and comparable to failure rates with photon irradiation.

The role of chemotherapy in the management of olfactory neuroblastoma: A 40-year surveillance, epidemiology, and end results registry study.

BACKGROUND: In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory neuroblastoma (ON), an exceedingly rare sino-nasal tumor typically treated with surgery and/or radiation therapy (RT). METHODS: We analyzed all patients in the SEER registry diagnosed with a single primary malignancy of ON, a primary tumor site within the nasal cavity or surrounding sinuses, sufficient staging information to derive Kadish staging, and >0 days of survival, ensuring follow-up data. Receipt of CT in the SEER registry was documented as either Yes or No/Unknown. RESULTS: Six hundred and thirty-six patients were identified. One hundred and ninety-five patients received CT as part of their treatment for ON. Following propensity score matching and inverse probability of treatment weighting, there was inferior overall survival (OS) (HR 1.7, 95% CI: 1.3-2.2, P = .001) and cancer-specific survival (CSS) (HR 1.8, 95% CI: 1.3-2.4, P < .001) for patients who received CT compared to those who were not treated with CT or had unknown CT status. On subgroup analysis, the only patient population that derived benefit from CT were patients who did not receive surgery and were treated with CT and/or RT (HR 0.3, 95% CI: 0.14-0.61, P < .001). CONCLUSIONS: Based on this retrospective SEER registry analysis, the use of CT in the management of ON is associated with decreased OS. Our analysis suggests that patients who are considered nonsurgical candidates may benefit from the addition of CT.

Radiotherapy alone or combined with chemotherapy as definitive treatment for squamous cell carcinoma of the tonsil.

This study is aimed at updating our institution's experience with definitive radiotherapy (RT) for squamous cell carcinoma of the tonsil. We reviewed 531 patients treated between 1983 and 2012 with definitive RT for squamous cell carcinoma of the tonsil. Of these, 179 patients were treated with either induction (n = 19) or concomitant (n = 160) chemotherapy. Planned neck dissection was performed on 217 patients: unilaterally in 199 and bilaterally in 18 patients. Median follow-up was 5.2 years for all patients (range 0.1-31.6 years) and 8.2 years for living patients (range 1.9-31.6 years). The 5-year local control rates by T stage were as follows: T1, 94 %; T2, 87 %; T3 79 %; T4, 70 %; and overall, 83 %. Multivariate analysis revealed that local control was significantly influenced by T stage and neck dissection. The 5-year cause-specific survival rates by overall stage were as follows: I, 94 %; II, 88 %; III, 87 %; IVA, 75 %; IVB, 52 %; and overall, 78 %. Multivariate analysis revealed that cause-specific survival was significantly influenced by T stage, N stage, overall stage, fractionation, neck dissection, sex, and ethnicity. Of 77 patients treated with ipsilateral fields only, contralateral neck failure occurred in 1 %. The rate of severe complications was 12 %. Definitive RT for patients with tonsillar squamous cell carcinoma provides control rates equivalent to other modalities with a comparatively low incidence of late complications. Patients with anterior tonsillar pillar or tonsillar fossa primaries that are well lateralized with no base of tongue or soft palate extension may be treated with ipsilateral fields.

Ipsilateral radiotherapy for squamous cell carcinoma of the tonsil.

The purpose of this study is to update our institution's experience with ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n = 41, 54 %) or cT2 (n = 35, 46 %) primaries and cN0 (n = 27, 36 %), cN1 (n = 15, 20 %), cN2a (n = 8, 11 %), or cN2b (n = 26, 34 %) nodal disease. Of these, 32 (42 %) patients underwent a planned neck dissection and 21 (28 %) patients received concomitant chemotherapy. Median follow-up for all patients was 7.1 years (range 0.1-27.2) and 7.8 years (range 2.1-27.2 years) for living patients. The 2- and 5-year control and survival rates were as follows: local control, 98.6 and 96.9 %; local-regional control 95.8 and 92.6 %; cause-specific survival 95.9 and 93.1 %; and overall survival, 92.1 and 83.8 %. One patient failed in the contralateral, non-radiated neck 3 years after primary treatment. Univariate analysis revealed that overall survival was significantly influenced by whether the patient had a primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with the latter performing better. The incidence of severe late complications was 16 %. Ipsilateral RT for patients with squamous cell carcinoma of the anterior tonsillar pillar or tonsillar fossa with no base of tongue or soft palate extension is an efficacious treatment that provides excellent control rates with a relatively low incidence of late complications.

Proton therapy for skull base chordomas: an outcome study from the university of Florida proton therapy institute.

Objectives Skull base chordoma is a rare, locally aggressive tumor located adjacent to critical structures. Gross total resection is difficult to achieve, and proton therapy has the conformal advantage of delivering a high postoperative dose to the tumor bed. We present our experience using proton therapy to treat 33 patients with skull base chordomas. Design Retrospective outcomes study. Setting University of Florida Proton Therapy Institute; 2007 to 2011. Participants A total of 33 patients with skull base chordomas received postoperative three-dimensional conformal proton therapy. The patients were 79% male and 6% diabetic; 27% had received a gross total resection. Main Outcome Measures The gross tumor/tumor bed received a dose between 77.4 CGE and 79.4 CGE. Local control and overall survival were tracked, and radiation toxicity was assessed using a modified Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme. Results Median follow-up for all patients was 21 months. Local control and overall survival rates at 2 years were 86% and 92%, respectively. Grade 2 toxicity was observed in 18% of our cohort in the form of unilateral hearing loss partially corrected with a hearing aid. No grade 2 or higher optic or brainstem toxicities were observed. Conclusions Proton therapy is an effective treatment modality for skull base chordomas.

Synergistic effects of multiple natural products in pancreatic cancer cells.

Pancreatic cancer (PC) remains the fourth most common cause of cancer related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Numerous dietary and pharmacological agents have been proposed as alternative strategies for the prevention and/or treatment of PC. Isoflavone is a prominent flavonoid found in soy products and has been proposed to be responsible for lowering the incidence of PC in Asians. Similarly, curcumin, an active ingredient of turmeric, that inhibits growth of malignant neoplasms, has a promising role in the prevention and/or treatment of PC. Here we examined whether isoflavone together with curcumin could elicit a greater inhibition of growth of PC cells than either agent alone, and also sought to determine the molecular mechanism of action. We found that the inhibition of cell growth and induction of apoptosis was significantly greater in the combination group than that could be achieved by either agent alone. These changes were associated with decreased Notch-1 expression and DNA binding activity of NF-kappaB and its target genes such as Cyclin D1, Bcl-2, and Bcl-xL. Moreover, we found that the combination of four natural agents at lower concentration was much more effective. Collectively, our results suggest that diet containing multiple natural products should be preferable over single agents for the prevention and/or treatment of PC. The superior effects of the combinatorial treatment could partly be attributed to the inhibition of constitutive activation of Notch-1 and NF-kappaB signaling pathways.