Optimizing GRID and Lattice Spatially Fractionated Radiation Therapy: Innovative Strategies for Radioresistant and Bulky Tumor Management.

Treating radioresistant and bulky tumors is challenging due to their inherent resistance to standard therapies and their large size. GRID and lattice spatially fractionated radiation therapy (simply referred to GRID RT and LRT) offer promising techniques to tackle these issues. Both approaches deliver radiation in a grid-like or lattice pattern, creating high-dose peaks surrounded by low-dose valleys. This pattern enables the destruction of significant portions of the tumor while sparing healthy tissue. GRID RT uses a 2-dimensional pattern of high-dose peaks (15-20 Gy), while LRT delivers a three-dimensional array of high-dose vertices (10-20 Gy) spaced 2-5 cm apart. These techniques are beneficial for treating a variety of cancers, including soft tissue sarcomas, osteosarcomas, renal cell carcinoma, melanoma, gastrointestinal stromal tumors (GISTs), pancreatic cancer, glioblastoma, and hepatocellular carcinoma. The specific grid and lattice patterns must be carefully tailored for each cancer type to maximize the peak-to-valley dose ratio while protecting critical organs and minimizing collateral damage. For gynecologic cancers, the treatment plan should align with the international consensus guidelines, incorporating concurrent chemotherapy for optimal outcomes. Despite the challenges of precise dosimetry and patient selection, GRID RT and LRT can be cost-effective using existing radiation equipment, including particle therapy systems, to deliver targeted high-dose radiation peaks. This phased approach of partial high-dose induction radiation therapy with standard fractionated radiation therapy maximizes immune modulation and tumor control while reducing toxicity. Comprehensive treatment plans using these advanced techniques offer a valuable framework for radiation oncologists, ensuring safe and effective delivery of therapy for radioresistant and bulky tumors. Further clinical trials data and standardized guidelines will refine these strategies, helping expand access to innovative cancer treatments.

Practice Patterns of Spatially Fractionated Radiation Therapy: A Clinical Practice Survey.

Purpose: Spatially fractionated radiation therapy (SFRT) is increasingly used for bulky advanced tumors, but specifics of clinical SFRT practice remain elusive. This study aimed to determine practice patterns of GRID and Lattice radiation therapy (LRT)-based SFRT. Methods and Materials: A survey was designed to identify radiation oncologists' practice patterns of patient selection for SFRT, dosing/planning, dosimetric parameter use, SFRT platforms/techniques, combinations of SFRT with conventional external beam radiation therapy (cERT) and multimodality therapies, and physicists' technical implementation, delivery, and quality procedures. Data were summarized using descriptive statistics. Group comparisons were analyzed with permutation tests. Results: The majority of practicing radiation oncologists (United States, 100%; global, 72.7%) considered SFRT an accepted standard-of-care radiation therapy option for bulky/advanced tumors. Treatment of metastases/recurrences and nonmetastatic primary tumors, predominantly head and neck, lung cancer and sarcoma, was commonly practiced. In palliative SFRT, regimens of 15 to 18 Gy/1 fraction predominated (51.3%), and in curative-intent treatment of nonmetastatic tumors, 15 Gy/1 fraction (28.0%) and fractionated SFRT (24.0%) were most common. SFRT was combined with cERT commonly but not always in palliative (78.6%) and curative-intent (85.7%) treatment. SFRT-cERT time sequencing and cERT dose adjustments were variable. In curative-intent treatment, concurrent chemotherapy and immunotherapy were found acceptable by 54.5% and 28.6%, respectively. Use of SFRT dosimetric parameters was highly variable and differed between GRID and LRT. SFRT heterogeneity dosimetric parameters were more commonly used (P = .008) and more commonly thought to influence local control (peak dose, P = .008) in LRT than in GRID therapy. Conclusions: SFRT has already evolved as a clinical practice pattern for advanced/bulky tumors. Major treatment approaches are consistent and follow the literature, but SFRT-cERT combination/sequencing and clinical utilization of dosimetric parameters are variable. These areas may benefit from targeted education and standardization, and knowledge gaps may be filled by incorporating identified inconsistencies into future clinical research.

High-dose-rate brachytherapy in scrotal extramammary Paget's disease: A case report.

PURPOSE: Extramammary Paget's disease (EMPD) is a rare but lethal intraepithelial malignancy without standardized guidelines concerning diagnostic or therapeutic approaches. We report a case of EMPD of the scrotum treated with excellent results using high-dose brachytherapy. METHODS AND MATERIALS: A 76-year-old male originally presented in 2015 with pruritus and erythema of the right scrotum, biopsy proved to represent extramammary Paget's disease. He was treated for a year with topical creams without sustained relief. In July 2016 he underwent a right hemiscrotectomy which revealed stage 1 EMPD of the right scrotum and the medial thigh with positive margins but no deep invasion. Brachytherapy was selected as the most appropriate treatment option and carried out in December 2016 using HDR with a H.A.M. applicator and CT treatment planning. RESULTS: On December 2021, at 5 years of clinical and pathological follow up, the patient remains NED with minimal skin toxicity. CONCLUSIONS: High-Dose-Rate Brachytherapy appears to be a feasible treatment alternative as adjuvant therapy in patients with EMPD with incomplete resection.

An International Consensus on the Design of Prospective Clinical-Translational Trials in Spatially Fractionated Radiation Therapy for Advanced Gynecologic Cancer.

Despite the unexpectedly high tumor responses and limited treatment-related toxicities observed with SFRT, prospective multi-institutional clinical trials of SFRT are still lacking. High variability of SFRT technologies and methods, unfamiliar complex dose and prescription concepts for heterogeneous dose and uncertainty regarding systemic therapies present major obstacles towards clinical trial development. To address these challenges, the consensus guideline reported here aimed at facilitating trial development and feasibility through a priori harmonization of treatment approach and the full range of clinical trial design parameters for SFRT trials in gynecologic cancer. Gynecologic cancers were evaluated for the status of SFRT pilot experience. A multi-disciplinary SFRT expert panel for gynecologic cancer was established to develop the consensus through formal panel review/discussions, appropriateness rank voting and public comment solicitation/review. The trial design parameters included eligibility/exclusions, endpoints, SFRT technology/technique, dose/dosimetric parameters, systemic therapies, patient evaluations, and embedded translational science. Cervical cancer was determined as the most suitable gynecologic tumor for an SFRT trial. Consensus emphasized standardization of SFRT dosimetry/physics parameters, biologic dose modeling, and specimen collection for translational/biological endpoints, which may be uniquely feasible in cervical cancer. Incorporation of brachytherapy into the SFRT regimen requires additional pre-trial pilot investigations. Specific consensus recommendations are presented and discussed.

The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT).

The concept of spatially fractionated radiation therapy (SFRT) was conceived over 100 years ago, first in the form of GRID, which has been applied to clinical practice since its early inception and continued to the present even with markedly improved instrumentation in radiation therapy. LATTICE radiation therapy (LRT) was introduced in 2010 as a conceptual 3D extension of GRID therapy with several uniquely different features. Since 2014, when the first patient was treated, over 150 patients with bulky tumors worldwide have received LRT. Through a brief review of the basic principles and the analysis of the collective clinical experience, a set of technical recommendations and guidelines are proposed for the clinical implementation of LRT. It is to be recognized that the current clinical practice of SFRT (GRID or LRT) is still largely based on the heuristic principles. With advancements in basic biological research and the anticipated clinical trials to systemically assess the efficacy and risk, progressively robust optimizations of the technical parameters are essential for the broader application of SFRT in clinical practice.

Spatially Fractionated Radiation Therapy Using Lattice Radiation in Far-advanced Bulky Cervical Cancer: A Clinical and Molecular Imaging and Outcome Study.

Spatially fractionated radiation therapy (SFRT) has shown promise in generating high tumor response and local control in the treatment of various palliative and locally advanced bulky tumors. SFRT has not yet been studied systematically in cancer of the cervix. Here we report the first series of patients receiving SFRT for advanced/bulky cervical cancer. Ten patients with far-advanced bulky cervical cancer, stage IIIB-IVA (seven squamous cell and three adeno/adenosquamous carcinomas) received lattice radiation therapy (LRT), a variant of SFRT. The LRT regimen consisted of a dose of 24 Gy in three fractions, given to an average of five high-dose spheres within the gross tumor volume (GTV). The dose in the peripheral GTV was limited to 9 Gy in three fractions, using the volumetric modulated arc therapy (VMAT) technique. LRT was followed subsequently by conventionally fractionated external beam irradiation to 44.28 Gy (range: 39.60-45.00 Gy in 1.8 Gy fractions). All patients received concurrent cisplatin chemotherapy. Tumor response was assessed clinically, by morphological imaging (CT, MRI) and 18FDG PET/CT. Tumor control and survival rates were estimated using Kaplan-Meier analysis. All patients had local control at a median follow-up of 16 months (1-77). The two-year disease-specific survival rate was 53.3%. All cancer deaths were due to metastatic failure with local control maintained. Among the three patients who died of disease, all had adeno- or adenosquamous carcinoma histology, and no deaths from disease occurred among the patients with squamous cell carcinoma (P = 0.010). There were no grade ≥3 short-term or long-term treatment-related complications. Intra-treatment morphological tumor regression was highly variable (mean: 54%, range: 6-91%). After therapy, the complete metabolic response was 88.9% (8/9), and one patient out of the nine patients with post-treatment PET-CT had partial response (11.1%). Our preliminary data suggest that LRT-based SFRT is well tolerated in patients with far-advanced bulky cervical cancer and results in favorable tumor responses and high local control. These observations confirm prior reports of favorable tumor control and toxicity outcomes with SFRT in other advanced/bulky malignancies. Our findings are corroborated by high molecular-imaging-based tumor response. These encouraging hypothesis-generating results require cautious interpretation and confirmation with larger patient cohorts, preferably through a multi-institutional controlled randomized clinical trial.

Safety and Efficacy of Lattice Radiotherapy in Voluminous Non-small Cell Lung Cancer.

Objective Lattice radiotherapy (LRT) is a novel technique of delivering heterogeneous doses of radiation to voluminous tumors not amenable to surgery. Built from the conventional two-dimensional grid, LRT utilizes the power of new technology, three-dimensional radiation allowing the delivery of higher doses of radiation to small spheres, also called vertices, inside bulky tumors while limiting exposure to surrounding healthy tissue. The main goals of the study were the evaluation of tumor response and the overall safety of LRT in this cohort of patients with bulky non-small cell lung cancer. Materials and methods During a seven-year period, 10 patients with non-small cell lung cancer (NSCLC), who presented with bulky, unresectable tumors, were treated using a single fraction of LRT followed by conventionally fractionated radiation. Patients received one initial LRT fraction of 18 Gy in the vertices and 3 Gy in the periphery. After the LRT, all patients continued with conventional radiation: 25 to 29 daily fractions of 1.8 Gy to 2 Gy. Results With a median follow-up of six months (range: one to 71 months), the mean decrease in tumor volume was 42%. The overall survival of the entire group ranged from four to 86 months (mean 22, median 16). There was no mortality related to LRT. No significant acute or chronic toxicity was noted. Conclusion In this small cohort, LRT appears to be a safe and effective modality to treat bulky NSCLC. Further research is needed to establish its efficacy in the management of voluminous NSCLC.

Improved outcome of treating locally advanced lung cancer with the use of Lattice Radiotherapy (LRT): A case report.

The Lattice Radiotherapy (LRT) technique is mainly based on the GRID technology with the improved feature of the 3D treatment delivery. A 72 year old male presented with left shoulder pain due to a 6 cm pulmonary mass in the left upper lobe (LUL) histologically proven Non-Small Cell Lung Cancer (NSCLC) stage IIIA. In July 2011 he was treated in our center with LRT followed by conventional fractionated Volumetric Modulated Arc Therapy (VMAT) combined with chemotherapy. Clinical and imaging follow up of 6 years demonstrated continued improvement and the patient is currently with no evidence of disease (NED). This outstanding result obtained in our first lung cancer patient treated with this approach corroborates its potential in the treatment of locally advanced lung cancer. In a period of 7 years we have treated more than 30 patients with LRT for different diagnosis and sites; 12 of them NSCLC patients, with markedly improved local control and minimal toxicity.