Volumetric Modulated Arc Therapy Enabled Total Body Irradiation (VMAT-TBI): Six-year Clinical Experience and Treatment Outcomes.

Total body irradiation is an important part of the conditioning regimens frequently used to prepare patients for allogeneic hematopoietic stem cell transplantation (SCT). Volumetric-modulated arc therapy enabled total body irradiation (VMAT-TBI), an alternative to conventional TBI (cTBI), is a novel radiotherapy treatment technique that has been implemented and investigated in our institution. The purpose of this study is to (1) report our six-year clinical experience in terms of treatment planning strategy and delivery time and (2) evaluate the clinical outcomes and toxicities in our cohort of patients treated with VMAT-TBI. This is a retrospective single center study. Forty-four patients at our institution received VMAT-TBI and chemotherapy conditioning followed by allogeneic SCT between 2014 and 2020. Thirty-two patients (73%) received standard-dose TBI (12-13.2 Gy in 6-8 fractions twice daily), whereas 12 (27%) received low-dose TBI (2-4 Gy in one fraction). Treatment planning, delivery, and treatment outcome data including overall survival (OS), relapse-free survival (RFS), and toxicities were analyzed. The developed VMAT-TBI planning strategy consistently generated plans satisfying our dose constraints, with planning target volume coverage >90%, mean lung dose ∼50% to 75% of prescription dose, and minimal hotspots in critical organs. Most of the treatment deliveries were <100 minutes (range 33-147, mean 72). The median follow-up was 26 months. At the last follow-up, 34 of 44 (77%) of patients were alive, with 1- and 2-year OS of 90% and 79% and RFS of 88% and 71%, respectively. The most common grade 3+ toxicities observed were mucositis (31 patients [71%]) and nephrotoxicity (6 patients [13%]), both of which were deemed multifactorial in cause. Four patients (9%) in standard-dose cohort developed grade 3+ pneumonitis, with 3 cases in the setting of documented respiratory infection and only 1 (2%) deemed likely related to radiation alone. VMAT-TBI provides a safe alternative to cTBI. The dose modulation capability of VMAT-TBI may lead to new treatment strategies, such as simultaneous boost and further critical organ sparing, for better malignant cell eradication, immune suppression, and lower toxicities.

Benchmarking techniques for stereotactic body radiotherapy for early-stage glottic laryngeal cancer: LINAC-based non-coplanar VMAT vs. Cyberknife planning.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) was found effective in treating laryngeal cancer with only five treatment fractions by a recent clinical trial (NCT01984502, ClinicalTrials.gov). Nevertheless, this trial used the Cyberknife system, which is not widely accessible enough to benefit all patients affected by laryngeal cancer. Our study investigates the feasibility of larynx SBRT treatment planning on a conventional gantry-based LINAC and compares its plan quality with that from the Cyberknife. MATERIALS & METHODS: Ten larynx SBRT cases were originally treated by Cyberknife using fixed cones in our institution, with plans created and optimized using the Monte-Carlo algorithm in the MultiPlan treatment planning system. These cases were retrospectively planned in the Eclipse planning system for a LINAC with the same prescription dose. We used volumetric modulated arc therapy (VMAT) for larynx SBRT planning in Eclipse and incorporated non-coplanar arcs to approach the Cyberknife's large solid angle delivery space. We used both anisotropic analytical algorithm (AAA) and Acuros XB (AXB) algorithm for dose calculation and compared their accuracy by measurements on an in-house larynx phantom. We compared the LINAC VMAT plans (VMAT-AAA and VMAT-AXB) with the original Cyberknife plans using dosimetric endpoints such as the conformity index, gradient indices (R50, R20), OAR maximum/mean doses, and the monitor units. RESULTS: Phantom measurement showed that both the AAA and the AXB algorithms provided adequate dose calculation accuracy (94.7% gamma pass rate on 2%/2 mm criteria for AAA vs. 97.3% for AXB), though AXB provided better accuracy in the air cavity. The LINAC-based VMAT plans achieved similar dosimetric endpoints as the Cyberknife planning, and all plans met the larynx SBRT dosimetric constraints. Cyberknife plans achieved an average conformity index of 1.13, compared to 1.20 of VMAT-AXB and 1.19 of VMAT-AAA. The VMAT plans spared the thyroid gland better with average Dmean of 2.4 Gy (VMAT-AXB) and 2.7 Gy (VMAT-AAA), as compared to 4.3 Gy for Cyberknife plans. The VMAT-AAA plans had a slightly lower contralateral arytenoid Dmax (average: 15.2 Gy) than Cyberknife plans (average: 17.9 Gy) with statistical significance, while the contralateral arytenoid Dmax was similar between VMAT-AXB and Cyberknife plans with no statistically significant difference. Cyberknife plans offered slightly better R50 (average: 5.0) than VMAT-AXB (5.9) and VMAT-AAA (5.7) plans. The VMAT plans substantially reduced the plan MUs to less than 1/3 of the Cyberknife plans, and the differences were statistically significant. The other metrics were similar between VMAT and Cyberknife plans with no statistically significant differences. CONCLUSIONS: Gantry-based LINACs can achieve similar plan quality to Cyberknife systems. Treatment outcome with both methods remains to be investigated.

4D liver tumor localization using cone-beam projections and a biomechanical model.

PURPOSE: To improve the accuracy of liver tumor localization, this study tests a biomechanical modeling-guided liver cone-beam CT (CBCT) estimation (Bio-CBCT-est) technique, which generates new CBCTs by deforming a prior high-quality CT or CBCT image using deformation vector fields (DVFs). The DVFs can be used to propagate tumor contours from the prior image to new CBCTs for automatic 4D tumor localization. METHODS/MATERIALS: To solve the DVFs, the Bio-CBCT-est technique employs an iterative scheme that alternates between intensity-driven 2D-3D deformation and biomechanical modeling-guided DVF regularization and optimization. The 2D-3D deformation step solves DVFs by matching digitally reconstructed radiographs of the 3D deformed prior image to 2D phase-sorted on-board projections according to imaging intensities. This step's accuracy is limited at low-contrast intra-liver regions without sufficient intensity variations. To boost the DVF accuracy in these regions, we use the intensity-driven DVFs solved at higher-contrast liver boundaries to fine-tune the intra-liver DVFs by finite element analysis-based biomechanical modeling. We evaluated Bio-CBCT-est's accuracy with seven liver cancer patient cases. For each patient, we simulated 4D cone-beam projections from 4D-CT images, and used these projections for Bio-CBCT-est based image estimations. After Bio-CBCT-est, the DVF-propagated liver tumor/cyst contours were quantitatively compared with the manual contours on the original 4D-CT 'reference' images, using the DICE similarity index, the center-of-mass-error (COME), the Hausdorff distance (HD) and the voxel-wise cross-correlation (CC) metrics. In addition to simulation, we also performed a preliminary study to qualitatively evaluate the Bio-CBCT-est technique via clinically acquired cone beam projections. A quantitative study using an in-house deformable liver phantom was also performed. RESULTS: Using 20 projections for image estimation, the average (±s.d.) DICE index increased from 0.48 ±â€¯0.13 (by 2D-3D deformation) to 0.77 ±â€¯0.08 (by Bio-CBCT-est), the average COME decreased from 7.7 ±â€¯1.5 mm to 2.2 ±â€¯1.2 mm, the average HD decreased from 10.6 ±â€¯2.2 mm to 5.9 ±â€¯2.0 mm, and the average CC increased from -0.004 ±â€¯0.216 to 0.422 ±â€¯0.206. The tumor/cyst trajectory solved by Bio-CBCT-est matched well with that manually obtained from 4D-CT reference images. CONCLUSIONS: Bio-CBCT-est substantially improves the accuracy of 4D liver tumor localization via cone-beam projections and a biomechanical model.

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid Dmax (mean 20.6 Gy reduction, p <0.001), contralateral carotid Dmax (mean 28.1 Gy reduction, p <0.001), and thyroid Dmean (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord Dmax (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This "phantom-to-clinic" feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.

Wage theft as a neglected public health problem: an overview and case study from San Francisco's Chinatown District.

Wage theft, or nonpayment of wages to which workers are legally entitled, is a major contributor to low income, which in turn has adverse health effects. We describe a participatory research study of wage theft among immigrant Chinatown restaurant workers. We conducted surveys of 433 workers, and developed and used a health department observational tool in 106 restaurants. Close to 60% of workers reported 1 or more forms of wage theft (e.g., receiving less than minimum wage [50%], no overtime pay [> 65%], and pay deductions when sick [42%]). Almost two thirds of restaurants lacked required minimum wage law signage. We discuss the dissemination and use of findings to help secure and enforce a wage theft ordinance, along with implications for practice.

Adapting to context in community-based participatory research: "participatory starting points" in a Chinese immigrant worker community.

Community-based participatory research (CBPR) is increasingly being used to better understand and improve the health of diverse communities. A key strength of this research orientation is its adaptability to community contexts and characteristics. To date, however, few studies explicitly discuss adaptations made to CBPR principles and processes in response to community context and partners' needs. Using data from our CBPR study, the San Francisco Chinatown Restaurant Worker Health and Safety Project, and drawing from literature on immigrant political incorporation, we examine the links between the contexts of the Chinese immigrant worker community, adaptations made by our collaborative, and study outcomes. In particular, we explore the concepts of contexts of reception and participatory starting points, which may be especially relevant for partnerships with immigrant communities whose members have historically had lower rates of civic and political participation in the US. We discuss contextual findings such as worker partner accounts of language barriers, economic and social marginalization, and civic skills and participation, as well as subsequent adaptations made by the partnership. We also describe the relative effectiveness of these adaptations in yielding equitable participation and building partners' capacity. We conclude by sharing lessons learned and their implications for CBPR and partnerships with immigrant communities more broadly.

Promoting health and safety in San Francisco's Chinatown restaurants: findings and lessons learned from a pilot observational checklist.

Noncompliance with labor and occupational health and safety laws contributes to economic and health inequities. Environmental health agencies are well positioned to monitor workplace conditions in many industries and support enhanced enforcement by responsible regulatory agencies. In collaboration with university and community partners, the San Francisco Department of Public Health used an observational checklist to assess preventable occupational injury hazards and compliance with employee notification requirements in 106 restaurants in San Francisco's Chinatown. Sixty-five percent of restaurants had not posted required minimum wage, paid sick leave, or workers' compensation notifications; 82% of restaurants lacked fully stocked first-aid kits; 52% lacked antislip mats; 37% lacked adequate ventilation; and 28% lacked adequate lighting. Supported by a larger community-based participatory research process, this pilot project helped to spur additional innovative health department collaborations to promote healthier workplaces.

A study on the dosimetric accuracy of treatment planning for stereotactic body radiation therapy of lung cancer using average and maximum intensity projection images.

PURPOSE: To assess the accuracy of current stereotactic body radiation therapy (SBRT) lung treatment planning methodologies on irregular breathing patterns, we have performed a systematic dosimetric evaluation in phantoms by utilizing maximum intensity projection (MIP) and average (AVG) images generated from four dimensional computed tomography (4DCT). METHODS: A custom built programmable lung phantom was used to simulate tumor motions due to various breathing patterns of patients. 4DCT scans were obtained in helical mode, and reconstructed AVG and MIP datasets were imported into the Pinnacle 8.0 h treatment planning system. SBRT plans were generated and executed, and delivered doses were measured by radiochromic film for analysis. RESULTS: For targets moving regularly or irregularly within a small range (7.0+/-1.8 mm, n=6), we observed good agreement between the measured and computed dose distributions. However, for targets moving irregularly with a larger range (20.8+/-2.6 mm, n=4), the measured isodose lines were found to be shifted relative to the planned distribution, resulting in an under-dosing (over 10%) in a portion of the PTV. We further observed that the discrepancy between planned and measured dose distribution is due to the inaccurate representation of irregular target motion in the MIP images generated from 4DCT. CONCLUSIONS: Caution should be used when planning from 4DCT images in the presence of large and irregular target motion. The inaccuracy inherent in 4DCT MIP and AVG images can be mitigated through the application of methodologies to reduce respiratory motion, such as abdominal compression, and through the use of volumetric image guidance (e.g., cone beam CT-CBCT) to assure precise targeting with minimal shifts.

Using community-based participatory research to design and initiate a study on immigrant worker health and safety in San Francisco's Chinatown restaurants.

BACKGROUND: Restaurant workers have among the highest rates of work-related illness and injury in the US, but little is known about the working conditions and occupational health status of Chinese immigrant restaurant workers. METHODS: Community-based participatory research (CBPR) was employed to study restaurant working conditions and worker health in San Francisco's Chinatown. A community/academic/health department collaborative was formed and 23 restaurant workers trained on research techniques and worker health and safety. A worker survey instrument and a restaurant observational checklist were collaboratively developed. The checklist was piloted in 71 Chinatown restaurants, and the questionnaire administered to 433 restaurant workers. RESULTS: Restaurant workers, together with other partners, made substantial contributions to construction of the survey and checklist tools and improved their cultural appropriateness. The utility of the checklist tool for restaurant-level data collection was demonstrated. CONCLUSIONS: CBPR holds promise for both studying worker health and safety among immigrant Chinese restaurant workers and developing culturally appropriate research tools. A new observational checklist also has potential for restaurant-level data collection on worker health and safety conditions.

Evaluation of chemopreventive agents for genotoxic activity.

We conducted genetic toxicity evaluations of 11 candidate chemopreventive agents with the potential for inhibiting carcinogenesis in humans at increased risk of cancer. The compounds were evaluated for bacterial mutagenesis in the Salmonella-E. coli assay, for mammalian mutagenesis in mouse lymphoma cells, for chromosome aberrations in Chinese Hamster Ovary (CHO) cells, and for micronucleus induction in mouse bone marrow. Tested agents were indole 3-carbinol (I3C), bowman-birk inhibitor concentrate (BBIC), black tea polyphenols (BTP), farnesol, geraniol, l-Se-methylselenocysteine (SeMC), 5,6-dihydro-4H-cyclopenta[1,2]-dithiol-3-thione(DC-D3T), 4'-bromoflavone, 2,5,7,8-tetramethyl-(2R-[4R,8R,12-trimethyltridecyl] chroman-6-yloxy) acetic acid (alpha-TEA), SR13668 (2,10-dicarbethoxy-6-methoxy-5,7-dihydro-indolo[2,3-b] carbazole and SR16157 (3-O-sulfamoyloxy-7alpha-methyl-21-(2-N,N-diethylaminoethoxy)-19-norpregna-1,3,5(10)-triene). All these agents, except I3C and BTP, were negative in the Salmonella-E. coli assay in the presence and absence of metabolic activation (S9). I3C and BTP induced a weak mutagenic response in the presence and absence of S9 with strains TA100 and TA98, respectively. Of the three compounds tested in the mouse lymphoma assay (I3C, BBIC, and BTP), only BTP was mutagenic in the presence of S9. In the chromosomal aberration assay, of the 8 compounds that were tested, 4'-bromoflavone elicited a positive response in the absence of S9 only, while SR16157 was positive in the presence of S9. The results with geraniol remain inconclusive. I3C, BBIC and BTP were not tested in the chromosomal aberration assay. None of the 11 agents induced micronuclei in mouse bone marrow erythrocytes.

The impact of a worker health study on working conditions.

A research partnership of representatives from labor, academia, and public health enabled unionized San Francisco hotel workers to achieve important policy changes in workplace health and safety. Known as the "Housekeeping Study," the project took sixteen months to complete. A unique aspect of the project was that it utilized participatory action research methods, involving workers themselves as full participants in the study. A core group of 25 hotel room cleaners was involved in each phase of the project. The study developed health data which enabled room cleaners and their union to formulate and justify a contract proposal calling for a significant reduction in housekeeping workloads. The employer association agreed to a contract which reduced the maximum required room assignment from 15 rooms to 14 rooms per day in 14 San Francisco hotels. By lowering the maximum work assignment, these workers set a new standard which can potentially protect the health of room cleaners across the country. The project can serve as a model for worker and union participation in academic research, as well as for the application of research to improving working conditions, particularly for low-wage immigrant workers.