Proton beam therapy of periorbital sinonasal squamous cell carcinoma: Two case reports and review of literature

BACKGROUND Sinonasal malignancies are rare but demanding due to complex anatomy,usually late diagnosis,and inconsistent therapy strategy based on multimodality approaches.Squamous cell carcinoma(SCC)is the most common histology,with poorer prognosis.In the setting of orbital invasion,an orbital exenteration may be required.However,in case of primary rejection of disfiguring surgery or unresectable disease,proton beam therapy(PBT)should be largely considered,allowing for better sparing of neighboring critical structures and improved outcomes by dose escalation.CASE SUMMARY A 62-year-old male presented with a recurrent SCC in the nasal septum abutting frontal skull base and bilateral orbits at 7 mo after primary partial nasal amputation.Because of refusal of face-deforming surgery and considerable adverse effects of conventional radiotherapy,the patient underwent a PBT by hyperfractionated accelerated scheme,resulting in complete response and moderate toxicities.After 2 years,a nasal reconstruction was implemented with satisfactory appearance and recurrence-freedom to date.Another patient with an initially extended sinonasal SCC,invading right orbit and facial soft tissue,declined an orbital exenteration and was treated with a normofractionated PBT to the gross tumor and elective cervical lymphatics.The follow-up showed a continuous tumor remission with reasonable late toxicities,such as cataract and telangiectasia on the right.Despite T4a stage and disapproval of concurrent chemotherapy owing to individual choice,both patients still achieved outstanding treatment outcomes with PBT alone.CONCLUSION PBT enabled orbit preservation and excellent tumor control without severe adverse effects on both presented patients with locally advanced sinonasal SCC.

In Vivo Dosimetry of an Anthropomorphic Phantom Using the RADPOS for Proton Beam Therapy

The radiation positioning system (RADPOS) combines an electromagnetic positioning sensor with metal oxide semiconductor field-effect transistor (MOSFET) dosimetry, enabling simultaneous online measurement of dose and spatial position. Evaluation points can be determined with the RADPOS. The accuracy of in-vivo proton dosimetry was evaluated using the RADPOS and an anthropomorphic head and neck phantom. MOSFET doses measured at 3D positions obtained with the RADPOS were compared with treatment plan values calculated using a simplified Monte Carlo (SMC) method. MOSFET responses, which depend strongly on the linear energy transfer of the proton beam, were corrected using the SMC method. The SMC method was used to calculate only dose deposition determined by the experimental depth-dose distribution and lateral displacement of protons due to the multiple scattering effect in materials and incident angle. This method thus enabled rapid calculation of accurate doses in even heterogeneities. In vivo dosimetry using the RADPOS, as well as MOSFET doses, agreed with SMC calculations in the range of ?3.0% to 8.3%. Most measurement errors occurred because of uncertainties in dose calculations due to the 1-mm position error. The results indicate that uncertainties in measurement position can be controlled successfully within 1 mm when using the RADPOS with in-vivo proton dosimetry.

Proton Beam Therapy for Hepatocellular Carcinoma after the Fontan Procedure

Background: Hepatocellular carcinoma (HCC) is more likely to occur in patients with a history of Fontan surgery, possibly due to long-term liver congestion. Proton beam therapy (PBT) may be effective for HCC that develops after Fontan surgery. Methods: Six lesions in 5 patients (3 females, 2 males) received PBT. The median age of the patients was 33 (range 21 - 42) years, and the median age at the time of the Fontan procedure was 6 (5 - 13) years. Four patients had multiple HCC at the time of PBT. The median tumor size was 57 (22 - 80) mm and 4 patients were classified as Child-Pugh B. Two patients received transcatheter arterial chemoembolization before PBT. The schedule of PBT was 66 Gy (RBE) in 10 fractions for 2 lesions, 72.6 Gy (RBE) in 22 fractions for 2 lesions, and 74 GyE (RBE) in 37 fractions for 2 lesions. Results: The median follow-up period was 31 (10 - 46) months, and the numbers of survivors, deaths from primary diseases, and deaths from other diseases were 3, 1, and 1, respectively. There were no local recurrences, one intrahepatic metastasis, one lung metastasis, and one intrathoracic metastasis. Conclusion: Although experiences on a small number of patients cannot conclude things, we believe that PBT can be a reasonable choice of radical treatment for HCC occurring after the Fontan procedure.

An Overview of the Control System for Dose Delivery at the UCSF Dedicated Ocular Proton Beam

Since 1978, the University of California San Francisco (UCSF) Ocular Tumor Program has been using particle therapy for treating ocular patients with malignant as well as benign eye disease. Helium ion beams were used initially and were produced by two synchrotron-based systems: first by the 184-inch synchro-cyclotron and later by the Bevalac, at the Lawrence Berkeley National Laboratory (LBNL). Since 1994, protons, produced by a cyclotron-based system at the Crocker Nuclear Laboratory (CNL) Eye Treatment Facility (ETF), have been used for this purpose. The CNL cyclotron produces a 67.5 MeV beam, allowing for a uniquely homogeneous beam for eye treatment, without degradation of the beam or manipulation of the beam line. This paper describes, in detail, the control system for beam delivery, as implemented for measuring and delivering the radiation to ocular tumors at CNL. The control system allows for optimal delivery and rapid termination of the irradiation after the desired dose is achieved. In addition, several safeguard systems are discussed, as these are essential for such a system in the event of failure of software, electronics, or other hardware. The QA analysis shows that the total range of the proton beam is 30.7 ± 1.0 mm in water at iso-center. The beam distal penumbra (80% - 20%) is 1.1 mm for a range-modulated beam at a collimator to iso-center distance of 50 mm. Daily QA checks confirm that the range and modulation is within 0.1 mm. The beam flatness and symmetry in a 25 mm diameter beam are ±1% - 2%. Variation in the daily dosimetry system, as compared to standard dosimetry, is within ±3.5%, with a mean variation of 0.72(±1.9)% and 0.85(±2.3)% for segmented transmission ionization chambers IC1 (upstream) and IC2 (downstream), respectively. From May 1994 to the end of 2015, UCSF has treated 1838 proton ocular patients at the Davis ETF. During this period, no treatments were missed due to any cyclotron or control system failures. The overall performance, maintenance, and quality assurance of the cyclotron and the ocular control system have been excellent.

Proton beam therapy for downstaging hepatocellular carcinoma with lobar portal vein tumor thrombosis to living donor liver transplantation

Introduction Liver transplantation(LT)is considered as the definitive standard treatment for hepatocellular carcinoma(HCC)with the advantage of addressing both malignancy and the underlying cirrhosis,thus,providing the best overall and recurrence-free survival.Unfortunately,only 20-25%of patients meet the eligibility criteria for LT.

Radiotherapy and the cellular DNA damage response: current and future perspectives on head and neck cancer treatment

Incidences of head and neck squamous cell carcinoma(HNSCC)have been on the rise in the last few decades,with a significant risk factor being human papillomavirus(HPV)type-16/18 infection,particularly in the development of oropharyngeal cancers.Radiotherapy(RT)is an important treatment modality for HNSCC,where it promotes extensive cellular DNA damage leading to the therapeutic effect.It has been well-established that HPV-positive HNSCC display better response rates and improved survival following RT compared to HPV-negative HNSCC.The differential radiosensitivity has been largely associated with altered cellular DNA damage response mechanisms in HPV-positive HNSCC,and particularly with the signaling and repair of DNA double strand breaks.However,other factors,particularly hypoxia present within the solid cancer,have a major impact on relative radioresistance.Consequently,recent approaches aimed at enhancing the radiosensitivity of HNSCC have largely centered on targeting key proteins involved in DNA repair,DNA damage checkpoint activation,and hypoxia signaling.These studies have utilised in vitro and in vivo models of HPV-positive and HPV-negative HNSCC and examined the impact of specific inhibitors against the targets in combination with radiation in suppressing HNSCC cell growth and survival.Here,accumulating evidence has shown that targeting enzymes including poly(ADP-ribose)polymerase,ataxia telangiectasia and Rad-3 related,DNA-dependent protein kinase catalytic subunit,and checkpoint kinase 1 can radiosensitise HNSCC cells which should be taken forward in further preclinical studies,with the goal of optimizing the future effective RT treatment of HNSCC.