Surgical organ displacement: what is the best “materials and methods” for proton radiotherapy?

In the mid 1940s, Robert Wilson （1） hypothesized that a highly localized deposition of energy from a proton beam could be used to increase the radiation dose to tumors while minimizing radiation to adjacent normal tissues. The depth- dose distribution of a proton beam differs significantly from that of a photon beam. Protons show increasing energy deposition with penetration distance, reaching a maximum- named the Bragg peak-near the end of the range of the proton beam. In front of the Bragg peak, the dose level is modest compared to photon beams; beyond the Bragg peak, the dose decreases to nearly zero. By choosing the appropriate proton beam energy, the depth of the Bragg peak can be adjusted to match the depth and extent of the target volume. Therefore, excellent conformality can be achieved, in contrast to conventional or intensity-modulated radiotherapy （IMRT）.

Proton therapy for hepatocellular carcinoma

Proton radiotherapy has seen an increasing role in the treatment of hepatocellular carcinoma （HCC）. Historically, external beam radiotherapy has played a very limited role in HCC due to a high incidence of toxicity to surrounding normal structures. The ability to deliver a high dose of radiation to the tumor is a key factor in improving outcomes in HCC. Advances in photon radiotherapy have improved dose conformity and allowed dose escalation to the tumor. However, despite these advances there is still a large volume of normal liver that receives a considerable radiation dose during treatment. Proton beams do not have an exit dose along the beam path once they enter the body. The inherent physical attributes of proton radiotherapy offer a way to maximize tumor control via dose escalation while avoiding excessive radiation to the remaining liver, thus increasing biological effectiveness. In this review we discuss the physical attributes and rationale for proton radiotherapy in HCC. We also review recent literature regarding clinical outcomes of using proton radiotherapy for the treatment of I-ICC.

Carbon ion radiotherapy boost in the treatment of glioblastoma:a randomized phase Ⅰ/Ⅲ clinical trial

Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy. Methods and design: Patients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose-escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM-only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradia-tion with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long-term). Secondary endpoints are progression-free survival (PFS), and tumor response (based upon assess-ment with C-methionine/fluoro-ethyl-tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). We hypothesize that the induction CIRT boost will result in a greater initial tumor-killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates. Discussion: The prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malig-nancy is its chronic state of tumor hypoxia, which promotes both immunosuppression/immunologic evasion and radio-resistance. The unique physical and biological properties of CIRT are expected to overcome these microenviron-mental limitations to confer an improved tumor-killing ability and anti-tumor immune response, which could result in an improvement in OS with minimal toxicity. Trial registration number This trial has been registered with the China Clinical Trials Registry, and was allocated the number ChiCTR-OID-17013702.