Fiducial markers for stereotactic lung radiation therapy: review of the transthoracic, endovascular and endobronchial approaches

Stereotactic body radiation therapy is an alternative to surgery for early-stage, inoperable peripheral non-small cell lung cancer. As opposed to linear accelerator (linac)-based (e.g. gating) and free-breathing techniques, CyberKnife® with Synchrony® technology allows accurate radiation delivery by means of a real-time respiratory motion tracking system using, in most cases, metal fiducial markers (FMs) placed in the vicinity of the target. The aims of this review are as follows. First, to describe the safety and efficacy of the transthoracic, endovascular and endobronchial FM insertion techniques for peripheral pulmonary lesions (PPLs). Second, to analyse performance in terms of the migration and tracking rates of different FM types. Recent developments in FM tracking for central lesions will also be reviewed. In conclusion, for PPLs, the endobronchial approach provides a low rate of pneumothorax, offers the possibility of concurrent diagnostic sampling for both the PPL and the lymph nodes, and, finally, reduces the intervention time compared to other techniques. In this context, coil-tailed and coil-spring FMs have shown the lowest migration rate with a consequently high tracking rate.

Variation in isocentre location of an Elekta Unity MR-linac through full gantry rotation

Objective: The objective of this study was to separately quantify the stability of the megavoltage imager (MVI) and radiation head of an Elekta Unity MRL, throughout full gantry rotation. Approach: A ball-bearing (BB) phantom was attached to the radiation head of the Unity, while a single BB was placed at isocentre. Images were acquired during rotation, using the MVI. These images were processed using an in-house developed MATLAB program to reduce the errors resulted by noise, and the positions of the BBs in the images were analysed to extract MVI and radiation head sag data. Main results: The results returned by this method showed reproducibility, with a mean standard deviation of 7 µm for the position of BBs across all gantry angles. The radiation head was found to sag throughout rotation, with a maximum course of movement of 0.59 mm. The sag pattern was stable over a period greater than a year but showed some dependence on gantry rotation direction. Significance: As MRL is a relatively new system, it is promising to have data supporting the high level of precision on one Elekta Unity machine. Isolating and quantifying the sources of uncertainty in radiation delivery may allow more sophisticated analysis of how the system performance may be improved.

IL-1 SRS Without the Bunker: Introduction and Clinical Experience of ZAP-X Gyroscopic Radiosurgery

Each year more than two million patients worldwide are potential candidates for SRS, yet due to the significant costs and complexities of historical delivery systems, only 150,000 patients currently receive such treatment. Japan Shonin-cleared in 2020, ZAP Surgical’s ZAP-X Gyroscopic Radiosurgery platform was designed to solve this challenge, and ultimately bring world-class SRS to more patients in more places. ZAP-X is recognized for being the first and only vault-free SRS delivery system, thereby typically eliminating the need for providers to build costly shielded radiation treatment rooms. Utilizing a modern linear accelerator to produce radiation, ZAP-X is also the first and only dedicated radiosurgery system to no longer require Cobalt-60 radioactive sources, thereby eliminating the significant costs to license, secure and regularly replace live radioactive isotopes. Built on a distinctive dual-gimbaled gantry design, the ZAP-X system uses gyroscopic mobility to direct radiosurgical beams from hundreds of unique angles to precisely concentrate radiation on the tumor target. This pioneering approach supports the clinical objective of protecting healthy brain tissue and patient neuro-cognitive function, as well as enable future potential SRS re-treatments without the unnecessary risks associated with multi-purpose radiation delivery technologies.

RADT-15. FIRST EXPERIENCE WITH MAXIMAL SAFE RESECTION AND GAMMATILE BRACHYTHERAPY AS TREATMENT FOR RECURRENT GLIOBLASTOMA

INTRODUCTION Gammatile (GT) is a recently FDA-cleared brachytherapy platform with 131Cs seeds imbedded into a resorbable collagen carrier for surgically targeted radiation delivery. We report the first experience for recurrent glioblastoma patients who underwent GT treatment following surgical resection. METHODS Twenty-two consecutive patients with 23 isocitrate dehydrogenase (IDH) wild-type glioblastomas (14 second; eight third recurrence) who underwent intra-operative MRI/5-ALA guided maximal safe resection followed by GT placement were prospectively followed. There were 6 methylguanine-DNA-methyltransferase promoter methylated (MGMTm) and 17 unmethylated (MGMTu) glioblastomas. RESULTS The median hospital stay was one day (range:1-15 days). There was one 30-day readmission (4.5%) for a cerebrospinal fluid leak from the incision site, which resolved with lumbar drainage. There were no other wound complications. One patient (4.5%) suffered new post-operative seizure. Eight patients experienced worsened neurological deficit (8/22 or 36%). While all deficits improved by the 30-day follow-up, 7 of these 8 patients suffered KPS decline due to persistent deficits. There was one 30-day mortality (4.5%) from intracranial hemorrhage secondary to heparinization for an ischemic limb. The median follow-up after GT placement for the remaining 21 patients was 296 days (range:111-931 days). Six months local control (LC) was achieved in ~75% of the patients irrespective of MGMT status. Median overall survival (OS) was 715 days for the MGMTu patients, and not reached (>1000 days) for MGMTm patients. These outcomes compared favorably to the published literature (LC: 3-49%; OS MGMTu: 135-285 days; OS MGMTm: 174-564 days) and an age, KPS, extent of resection matched glioblastoma cohort who underwent maximal safe resection without GT at our institution (LC: 52%; OS MGMTu: 462 days; OS MGMTm: 821 days; p=0.0089 and p=0.0271, respectively when compared to the GT treated patients). CONCLUSION This clinical experience supports the safety and efficacy of GT brachytherapy as a treatment option for recurrent glioblastomas.

Focused Versus Conventional Radiotherapy in Spinal Oncology: Is There any Difference in Fusion Rates and Pseudoarthrosis?

IntroductionRadiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newerfocused radiotherapy strategies with enhanced conformalitycould offer improved fusion rates for these patients, but this has not been confirmed.MethodsWe performed a retrospective analysis of patients at three tertiary care academic institutions withprimary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used theLenke fusion score to grade fusion status at6 and 12-months after surgery. Secondary outcomes includedclinical pseudoarthrosis, wound complications, and the effect of radiation timing, radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location,and use of autograft on fusion outcomes.ResultsAfter reviewof 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy,20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such assmoking status,obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p=0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p=0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohortcompared to patients in the focused radiotherapy cohort (19.1% versus 0%,p=0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use ofintra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p=0.043). ConclusionFocused radiotherapy may be associated withan improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategiesin patients with spinal tumors.Use of autograft at the time of surgery may be associated with improved 12-month fusion rates.Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Analysis of a novel X-ray lens for converging beam radiotherapy

We describe the development and analysis of a new teletherapy modality that, through a novel approach to targeted radiation delivery, has the potential to provide greater conformality than conventional photon-based treatments. The proposed system uses an X-ray lens to reflect photons from a conventional X-ray tube toward a focal spot. The resulting dose distributions have a highly localized peak dose, with lower doses in the converging radiation cone. Physical principles governing the design of this system are presented, along with a series of measurements analyzing various characteristics of the converging beam. The beam was designed to be nearly monoenergetic (~ 59 keV), with an energy bandwidth of approximately 10 keV allowing for treatment energies lower than conventional therapies. The focal spot was measured to be approximately 2.5 cm long and 4 mm wide. Mounting the proposed X-ray delivery system on a robotic arm would allow sub-millimeter accuracy in focal spot positioning, resulting in highly conformal dose distribution via the optimal placement of individual focal spots within the target volume. Aspects of this novel radiation beam are discussed considering their possible clinical application as a treatment approach that takes maximum advantage of the unique properties afforded by converging X-ray beam therapy.

Proton therapy for prostate cancer: current state and future perspectives

Objective: Localized prostate cancer can be treated with several radiotherapeutic approaches. Proton therapy (PT) can precisely target tumors, thus sparing normal tissues and reducing side-effects without sacrificing cancer control. However, PT is a costly treatment compared with conventional photon radiotherapy, which may undermine its overall efficacy. In this review, we summarize current data on the dosimetric rationale, clinical benefits, and cost of PT for prostate cancer. Methods: An extensive literature review of PT for prostate cancer was performed with emphasis on studies investigating dosimetric advantage, clinical outcomes, cost-effective strategies, and novel technology trends. Results: PT is safe, and its efficacy is comparable to that of standard photon-based therapy or brachytherapy. Data on gastrointestinal, genitourinary, and sexual function toxicity profiles are conflicting; however, PT is associated with a low risk of second cancer and has no effects on testosterone levels. Regarding cost-effectiveness, PT is suboptimal, although evolving trends in radiation delivery and construction of PT centers may help reduce the cost. Conclusion: PT has several advantages over conventional photon radiotherapy, and novel approaches may increase its efficacy and safety. Large prospective randomized trials comparing photon therapy with proton-based treatments are ongoing and may provide data on the differences in efficacy, toxicity profile, and quality of life between proton- and photon-based treatments for prostate cancer in the modern era. Advances in knowledge: PT provides excellent physical advantages and has a superior dose profile compared with X-ray radiotherapy. Further evidence from clinical trials and research studies will clarify the role of PT in the treatment of prostate cancer, and facilitate the implementation of PT in a more accessible, affordable, efficient, and safe way.

Extreme Hypofractionation with SBRT in Localized Prostate Cancer

Prostate cancer is the most commonly diagnosed cancer among men around the world. Radiotherapy is a standard of care treatment option for men with localized prostate cancer. Over the years, radiation delivery modalities have contributed to increased precision of treatment, employing radiobiological insights to shorten the overall treatment time, improving the control of the disease without increasing toxicities. Stereotactic body radiation therapy (SBRT) represents an extreme form of hypofractionated radiotherapy in which treatment is usually delivered in 1–5 fractions. This review assesses the main efficacy and toxicity data of SBRT in non-metastatic prostate cancer and discusses the potential to implement this scheme in routine clinical practice.

Exploiting Radiation Therapy to Restore Immune Reactivity of Glioblastoma

Glioblastoma (GBM) is among the most aggressive of brain tumors and confers a dismal prognosis despite advances in surgical technique, radiation delivery methods, chemotherapy, and tumor-treating fields. While immunotherapy (IT) has improved the care of several adult cancers with previously dismal prognoses, monotherapy with IT in GBM has shown minimal response in first recurrence. Recent discoveries in lymphatics and evaluation of blood brain barrier offer insight to improve the use of ITs and determine the best combinations of therapies, including radiation. We highlight important features of the tumor immune microenvironment in GBM and potential for combining radiation and immunotherapy to improve prognosis in this devastating disease.

Radiation-Induced Immunity and Toxicities: The Versatility of the cGAS-STING Pathway

In the past decade, radiation therapy (RT) entered the era of personalized medicine, following the striking improvements in radiation delivery and treatment planning optimization, and in the understanding of the cancer response, including the immunological response. The next challenge is to identify the optimal radiation regimen(s) to induce a clinically relevant anti-tumor immunity response. Organs at risks and the tumor microenvironment (e.g. endothelial cells, macrophages and fibroblasts) often limit the radiation regimen effects due to adverse toxicities. Here, we reviewed how RT can modulate the immune response involved in the tumor control and side effects associated with inflammatory processes. Moreover, we discussed the versatile roles of tumor microenvironment components during RT, how the innate immune sensing of RT-induced genotoxicity, through the cGAS-STING pathway, might link the anti-tumor immune response, radiation-induced necrosis and radiation-induced fibrosis, and how a better understanding of the switch between favorable and deleterious events might help to define innovative approaches to increase RT benefits in patients with cancer.