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Purpose: The superior soft-tissue contrast of MRI-guided radiotherapy offers enhanced localization accuracy of the spinal cord in spine Stereotactic Body Radiotherapy (SBRT). This work includes a planning study for spine-SBRT on an MR-Linac. Additionally, a patient with spine metastasis was treated using an adaptive radiation therapy workflow. We report our initial experience of targeting accuracy, image-guided localization, on-line adaptive planning, and treatment with real-time intrafraction imaging with automatic beam gating.Methods: Six spine-SBRT patients were retrospectively re-planned to 18 Gy in 1-fraction on a commercial, Monte Carlo-based MR-Linac treatment planning system. Plans were generated using 9–13 step-and-shoot intensity-modulated radiation therapy 6 MV-flattening filter free beams and optimized to achieve plan quality criteria recommended by RTOG-0631. One thoracic vertebral body clinical case was treated to 27 Gy in 3-fractions utilizing ART, where daily anatomical changes were accounted for via re-planning and treatment in an on-line manner to account for limited ability to correct rotational setup uncertainties.Results: Plans met all critical-tissue constraints outlined in RTOG-0631 and AAPM Task Group-101, while covering 90% of the target with the prescription dose. Clinically, visibility of the spinal cord allowed for patient setup focusing on spinal cord-alignment. Utilization of the online ART workflow, while re-contouring the target and spinal cord, enabled an increase in prescription dose coverage from 89 to 95% in two of three fractions while maintaining acceptable doses to organs-at-risk. Real-time MR-cine imaging demonstrated sufficient quality for the automatic beam gating algorithm to provide intrafraction motion management of the spinal canal utilizing a 3.0 mm gating boundary and 1–2% region of excursion allowance, in the sagittal plane. A decrease in coverage, below the 95% threshold was noted in post-treatment volumetric imaging due to lateral movement not observed during real-time gating.Conclusion: Achieved plan quality and deliverability was within accepted standards. MR-guidance with an on-line ART workflow offered increased accuracy in the localization of the spinal cord at the time of treatment to enhance both tissue sparing and target volume coverage. Increased spatial resolution of cine-images, and tracking in three-dimensions would be beneficial for future spine-SBRT treatments on the MR-Linac.

Abstract Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract. Advanced organ motion management, image guidance, and adaptive planning techniques enable delivery of ablative doses of radiation (> = 100Gy BED) when more protracted hypofractionated regimens or advanced image guidance and adaptive planning are used. This approach has resulted in encouraging improvements in survival in several studies. This review will summarize the evolution of the radiation technique over time from conventional to ablative and describe the practical aspects of delivering ablative doses near the GI tract using cone beam CT image (CBCT) guidance and online adaptive MRI guidance.

Purpose: Magnetic resonance image guided radiation therapy (MR-IGRT) has been used at our institution since 2014. We report on more than 2 years of clinical experience in treating patients with the world's first MR-IGRT system. Methods and materials: A clinical service was opened for MR-IGRT in January 2014 with an MR-IGRT system consisting of a split 0.35T magnetic resonance scanner that straddles a ring gantry with 3 multileaf collimator-equipped 60Co heads. The service was expanded to include online adaptive radiation therapy (ART) MR-IGRT and cine gating after 6 and 9 months, respectively. Patients selected for MR-IGRT were enrolled in a prospective registry between January 2014 and June 2016. Patients were treated with a variety of radiation therapy techniques including intensity modulated radiation therapy and stereotactic body radiation therapy (SBRT). When applicable, online ART was performed and gating on sagittal 2-dimensional cine MR was used. The charts of patients treated with MR-IGRT were reviewed to report on the clinical and treatment characteristics of the initial patients who were treated with this novel technique. Results: A total of 316 patients have been treated with the MR-IGRT system, which has been integrated into a high-volume clinic. The cases were most commonly selected for improved soft tissue visualization, ART, and cine gating. Seventy-six patients were treated with 3-dimensional conformal radiation therapy, 146 patients with intensity modulated radiation therapy, and 94 patients with SBRT. The most commonly treated disease sites were the abdomen (28%), breast (26%), pelvis (22%), thorax (19%), and head and neck (5%). Sixty-seven patients were treated with online ART over a total of 244 adapted fractions. Cine treatment gating was used for a total of 81 patients. Conclusions: MR-IGRT has been successfully implemented in a high-volume radiation clinic and provides unique advantages in the treatment of a variety of malignancies. Additional clinical trials are in development to formally evaluate MR-IGRT in the treatment of multiple disease sites with techniques such as SBRT and ART.

An international group of 22 liver cancer experts from 18 institutions met in Miami, Florida to discuss the optimal utilization of proton beam therapy (PBT) for primary and metastatic liver cancer. There was consensus that PBT may be preferred for liver cancer patients expected to have a suboptimal therapeutic ratio from XRT, but that PBT should not be preferred for all patients. Various clinical scenarios demonstrating appropriateness of PBT vs. XRT were reviewed.

SUMMARY: BACKGROUND The immune system of advanced stage head and neck cancer patients is frequently suppressed. Poor immune function has been correlated with poor clinical outcome. Immunotherapeutic strategies have been previously attempted in an effort to enhance immune function and improve survival. Previous studies have shown surgical suture can be transformed into an immune stimulant capable of activating the T lymphocytes of cancer patients. The development of a process for covalently linking proteins and cytokines to suture could have enormous potential for the in vivo manipulation of the immune system.HYPOTHESIS We hypothesize proteins and cytokines can be covalently linked to surgical suture while preserving their functional properties.STUDY DESIGN Prospective study testing normal donor and head and neck squamous cell carcinoma (HNSCC) patient lymphocytes.METHOD Polyester suture was acid hydrolyzed followed by reacting with 1-ethyl-3(-3-dimethylamino propyl carbodiimide) (EDAC) to create a suture-EDAC intermediate. Next, selected proteins (horseradish peroxidase [HRP] or bovine serum albumin [BSA]) or cytokines (interleukin [IL]-2 or interferon [IFN]-γ) were reacted with the suture-EDAC intermediate to test the covalent linkage of the selected protein or cytokine to suture. Functional activity of the linked proteins was measured spectrophotometrically. The linking of cytokines to suture was tested by stimulating normal donor peripheral blood lymphocytes (PBL) or HNSCC patients'' lymphocytes. The functional activity was confirmed by proliferation, enzyme linked immunoadsorbent assay (ELISA), and phenotype expression of T cells.RESULTS The conditions for optimally linking a protein to polyester suture were defined using HRP as a model protein. HRP retained its enzymatic activity. The optimal conditions for linking IL-2 or IFN-γ were defined. The covalently linked cytokines retained their immune enhancing properties for stimulating PBL and lymph node lymphocytes (LNL) from HNSCC patients to proliferate, generate a TH1 immunologic profile of cytokines (IL-2, IL-12, IFN-γ), and stimulate T lymphocytes.CONCLUSION This is the first report to demonstrate that cytokines can be covalently linked to surgical sutures and retain their immune-stimulating properties. Proteins linked to suture also retained their enzymatic activity. The clinical implications of functionally active cytokines or proteins linked to surgical suture may be very significant in the future for manipulating the immune system in vivo or enhancing wound healing. [ABSTRACT FROM AUTHOR]

In radiation therapy, fiducial markers are often implanted near tumors and used for patient positioning and respiratory gating purposes. These markers are then used to manually align the patients by matching the markers in the cone beam computed tomography (CBCT) reconstruction to those in the planning CT. This step is time-intensive and user-dependent, and often results in a suboptimal patient setup. We propose a fully automated, robust method based on dynamic programming (DP) for segmenting radiopaque fiducial markers in CBCT projection images, which are then used to automatically optimize the treatment couch position and/or gating window bounds. The mean of the absolute 2D segmentation error of our DP algorithm is mm for 87 markers on 39 patients. Intrafraction images were acquired every 3 s during treatment at two different institutions. For gated patients from Institution A (8 patients, 40 fractions), the DP algorithm increased the delivery accuracy ( versus , p  <  0.01) compared to the manual setup using kV fluoroscopy. For non-gated patients from Institution B (6 patients, 16 fractions), the DP algorithm performed similarly ( mm versus mm, p  =  0.48) compared to the manual setup matching the fiducial markers in the CBCT to the mean position. Our proposed automated patient setup algorithm only takes 1–2 s to run, requires no user intervention, and performs as well as or better than the current clinical setup. [ABSTRACT FROM AUTHOR]