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Proton therapy through the use of the Bragg peak affords clinicians a tool with which highly conformal dose can be delivered to the target while minimizing integral dose to surrounding healthy tissue. To gain maximum benefit from proton therapy adequate patient immobilization must be maintained to ensure accurate dose delivery. While immobilization in external beam radiation therapy is designed to minimize inter- and intra-fraction target motion, in proton therapy there are other additional aspects which must be considered, chief of which is accurately determining and maintaining the targets water-equivalent depth along the beam axis. Over the past 23 years of treating with protons, the team at the James M. Slater Proton Treatment and Research Center at Loma Linda University Medical Center have developed and implemented extensive immobilization systems to address the specific needs of protons. In this publication we review the immobilization systems that are used at Loma Linda in the treatment of head and neck, prostate, upper GI, lung and breast disease, along with a description of the intracranial radiosurgery immobilization system used in the treatment of brain metastasis and arteriovenous malformations (AVM's)., (© The Author(s) 2014.)

Immobilization devices can impact not only the inter- and intra-fraction motion of the patient, but also the range uncertainty of the treatment beam in proton therapy. In order to limit additional range uncertainty, the water equivalent thickness (WET) of the immobilization device needs to be well known and accurately reflected in the calculations by the treatment planning system (TPS). The method presented here focusses on the use of a nozzle-mounted variable range shifter and precision-machined polystyrene blocks of known WET to evaluate commercial immobilization devices prior to clinical implementation. CT studies were also completed to evaluate the internal uniformity of the immobilization devices under study. Mul- tiple inserts of the kVue platform (Qfix Systems, Avondale, PA) were evaluated as part of this study. The results indicate that the inserts are largely interchangeable across a given design type and that the measured WET values agree with those generated by the TPS with a maxi- mum difference less than 1 mm. The WET of the devices, as determined by the TPS, was not impacted by CT beam hardening normally experienced during clinical use. The reproduc- ibility of the WET method was also determined to be better than ±0.02 mm. In conclusion, the testing of immobilization prior to implementation in proton therapy is essential in order to ascertain their impact on the proton treatment and the methodology described here can also be applied to other immobilization systems.

Proton therapy is rapidly developing as a mainstream modality for external beam radiation therapy. This development is largely due to the ability of protons to deposit much of their energy in a region known as the Bragg peak, minimizing the number of treatment fields and hence integral dose delivered to the patient. Immobilization in radiation therapy is a key component in the treatment process allowing for precise delivery of dose to the target volume and this is certainly true in proton therapy. In proton therapy immobilization needs to not only immobilize the patient, placing them in a stable and reproducible position for each treatment, but its impact on the depth dose distribution and range uncertainty must also be considered. The impact of immobilization on range is not a primary factor in X-ray radiation therapy, but it is a governing factor in proton therapy. This contribution describes the immobilization considerations in proton therapy which have been developed at Loma Linda over twenty plus years of clinical operation as a hospital based proton center.

Unlabelled: The purpose of this study was to compare the prognostic value of the percentage of positive biopsy cores (PPBC), the percentage of cancer volume (PCV), and the maximum involvement of biopsy cores (MIBC) as a prognostic factor in low- and intermediate-risk patients with clinically localized prostate cancer who received proton or photon beam therapy. Four hundred and fifty-nine patients with clinically localized prostate carcinoma who were treated with proton or photon beam therapy at Loma Linda University Medical Center were used for this analysis. Patients were treated with a median dose of 74.0 Gy (range 70.2-79.2) proton or combined proton/photon beam radiotherapy. Pathology reports were reviewed and PPBC, PCV, and MIBC were recorded. Analysis of biochemical no evidence of disease (bNED) outcome was assessed using Kaplan-Meier analyses. Cox regression multivariate analyses were performed to assess the impact of the biopsy factors on survival., Results: 285, 291, and 291 patients had biopsy information available for analysis, respectively. Survival analysis showed that a higher PPBC, PCV, and MIBC were each individually associated with an increased risk of biochemical failure on univariate analysis (p < 0.01). Only PPBC and PCV were associated with an increased risk of biochemical failure on multivariate analysis, adjusting for age, NCCN risk group, and dose (p < 0.01). When isolating the intermediate-risk group, only PPBC and PCV were statistically significant on multivariate analysis. Multivariate analysis of the intermediate-risk group comparing PPBC and PCV showed that PPBC was not a significant predictor of biochemical failure, while PCV was a significant predictor of biochemical failure (p = 0.37 and p = 0.03, respectively)., Conclusion: PPBC and PCV can potentially be used for additional risk stratification of intermediate-risk patients with PCV potentially being the most clinically relevant predictor bNED survival. MIBC was not found to have utility in the prognosis of low- and intermediate-risk patients.

The Proton Treatment Center at Loma Linda University Medical Center, the world's first hospital-based proton facility, opened in 1990 after two decades of development. Its early years were marked by a deliberately cautious approach in clinical utilization of protons, with intent to establish hospital-based proton therapy on a scientific basis. The facility was designed to be upgradeable, and development since 1990 has proceeded in three distinct phases of upgrades, both in technology and clinical applications. Upgrades continue, all of them based on an underlying program of basic and clinical research; future new applications of proton radiation therapy are expected to follow.

Primary B cell lymphomas of the skull base are uncommon and lack well-defined treatment guidelines. We report a case of diffuse, large B-cell lymphoma of the cavernous sinus with sphenoid sinus and clivial extension, treated with partial resection, chemotherapy, and proton beam irradiation. To our knowledge, this is the first report of a skull-base lymphoma treated with protons. A 53-year-old female presented with a two-month history of diplopia, persistent headaches, and paresthesia over the left side of her mouth. A skull MRI revealed an enhancing mass in the right cavernous sinus and right sphenoid sinus. Transsphenoidal subtotal resection of the mass confirmed the presence of a diffuse, large B-cell lymphoma. Treatment consisted of CHOP-R chemotherapy and locoregional radiation with protons. Locoregional radiation of the lesion required moderate doses, below the radiation tolerance of adjacent normal structures. Conformal protons were utilized to minimize the volume of normal brain receiving radiation. Conformal proton beam radiotherapy to a moderate dose proved valuable in this case because it minimized the volume of normal brain receiving low to moderate doses of radiation.

Proton radiation therapy has been used at Loma Linda University Medical Center for 15 years, sometimes in combination with photon irradiation, surgery, and chemotherapy, but often as the sole modality. Our initial experience was based on established studies showing the utility of protons for certain management problems, but since then we have engaged in a planned program to exploit the capabilities of proton radiation and expand its applications in accordance with progressively accumulating clinical data. Our cumulative experience has confirmed that protons are a superb tool for delivering conformal radiation treatments, enabling delivery of effective doses of radiation and sparing normal tissues from radiation exposure.

Replacement of current CT-based, three-dimensional (3D) treatment planning systems by newer versions capable of automated multi-modality image registration may be economically prohibitive for most radiation oncology clinics. We present a low-cost technique for MR-CT image registration on a "first generation" CT-based, 3D treatment planning system for intracranial tumors. The technique begins with fabrication of a standard treatment mask. A second truncated mask, the "minimask," is then made, using the standard mask as a mold. Two orthogonal leveling vials glued onto the minimask detect angular deviations in pitch and roll. Preservation of yaw is verified by referencing a line marked according to the CT laser on the craniocaudal axis. The treatment mask immobilizes the patient's head for CT. The minimask reproduces this CT-based angular treatment position, which is then maintained by taping the appropriately positioned head to the MR head coil for MR scanning. All CT and MR images, in DICOM 3.0 format, are entered into the treatment planning system via a computer network. Interactive registration of MR to CT images is controlled by real-time visual feedback on the computer monitor. Translational misalignments at the target are eliminated or minimized by iterative use of qualitative visual inspection. In this study, rotational errors were measured in a retrospective series of 20 consecutive patients who had undergone CT-MR image registration using this technique. Anatomic structures defined the three CT orthogonal axes from which angular errors on MR image were measured. Translational errors at the target isocenter were within pixel size, as judged by visual inspection. Clinical setup using the minimask resulted in overall average angular deviation of 3 degrees +/-2 degrees (mean +/- SD) and translational deviation within the edges of the target volume of typically less than 2 mm. The accuracy of this registration technique for target delineation of intracranial tumors is compatible with practice guidelines. This method, then, provides a cost-effective means to register MR and CT images for target delineation of intracranial tumors.