Leonard Che Fru

BACKGROUND: Automation in radiotherapy presents a promising solution to the increasing cancer burden and workforce shortages. However, existing automated methods for breast radiotherapy lack a comprehensive, end-to-end solution that meets varying standards of care.

PURPOSE: This study aims to develop a complete portfolio of automated radiotherapy treatment planning for intact breasts, tailored to individual patient factors, clinical approaches, and available resources.

METHODS: We developed five automated conventional treatment approaches and utilized an established RapidPlan model for volumetric arc therapy. These approaches include conventional tangents for whole breast treatment, two variants for supraclavicular nodes (SCLV) treatment with/without axillary nodes, and two options for comprehensive regional lymph nodes treatment. The latter consists of wide tangents photon fields with a SCLV field, and a photon tangents field with a matched electron field to treat the internal mammary nodes (IMNs), and a SCLV field. Each approach offers the choice of a single or two isocenter setup (with couch rotation) to accommodate a wide range of patient sizes. All algorithms start by automatically generating contours for breast clinical target volume, regional lymph nodes, and organs at risk using an in-house nnU-net deep learning models. Gantry angles and field shapes are then automatically generated and optimized to ensure target coverage while limiting the dose to nearby organs. The dose is optimized using field weighting for the lymph nodes fields and an automated field-in-field approach for the tangents. These algorithms were integrated into the RayStation treatment planning system and tested for clinical acceptability on 15 internal whole breast patients (150 plans) and 40 external patients from four different institutions in Switzerland, Argentina, Iran, and the USA (360 plans). Evaluation criteria included ensuring adequate coverage of targets and adherence to dose constraints for normal structures. A breast radiation oncologist reviewed the single institution dataset for clinical acceptability (5-point scale) and a physicist evaluated the multi-institutional dataset (use as is or edit).

RESULTS: The dosimetric evaluation across all datasets (510 plans) showed that 100% of the automated plans met the dose coverage requirements for the breast, 99% for the SCLV, 98% for the axillary nodes, and 91% for the IMN. As expected, hot spots were more prevalent when multiple fields were combined. For the heart, ipsilateral lung, and contralateral breast, automated plans met constraints for 95%, 92%, and 95% of the plans, respectively. Physician evaluation of the 15 internal patients indicated that all automated plans were clinically acceptable with minor edits. Notably, the use of automated contours with the RapidPlan model resulted in plans that were immediately ready for use in 73% of cases (95% confidence interval, 95% CI [51- 96]) of patients, with the remaining cases requiring minor stylistic edits. Similarly, the physicist's review of the 40 multi-institution patients showed that the auto-plans were ready for use 79% (95% CI [73,85]) of the time (95% CI [73,85]), with edits needed for the remaining cases.

CONCLUSION: This study demonstrates the feasibility of a comprehensive automated treatment planning model for whole breast radiotherapy, effectively accommodating diverse treatment paradigms.

PMID:39699058 | DOI:10.1002/mp.17588

Understanding the dynamic nature of tumor hypoxia is vital for cancer therapy. The presence of oxygen within a tumor during radiation therapy increases the likelihood of local control. We used a novel interstitial diffuse optical probe to make real-time measurements of blood volume fraction and hemoglobin oxygen saturation within a tumor at a high temporal resolution. This device was initially characterized and benchmarked using a customized vessel designed to control hemoglobin oxygen saturation and blood volume in a solution of blood with different concentrations of an oxygen scavenger, tetrakis (hydroxymethyl) phosphonium chloride. The optical device was found to consistently monitor the changes in oxygen saturation and these changes correlated to the concentration of the oxygen scavenger added. In near-simultaneous measurements of blood volume and oxygen saturation in tumor-bearing mice, the changes in blood volume fraction and oxygen saturation measured with the interstitial diffuse optical probe were benchmarked against photoacoustic imaging system to track and compare temporal dynamics of oxygen saturation and blood volume in a patient-derived xenograft model of hypopharyngeal carcinoma. Positive correlations between our device and photoacoustic imaging in measuring blood volume and oxygen saturation were observed.

PMID:32095273 | PMC:PMC7039661 | DOI:10.1088/2057-1976/ab6e16

At the time of publication, our group had performed short tandem repeat (STR) testing on the SCC22B cell line and believed that had been correctly identified. As part of a recent comprehensive process to confirm the identity of cell lines in use in our lab, we repeated STR testing on all cell lines. These results were compared to the ExPASy Cellosaurus database (http://web.expasy.org/cellosaurus/). One cell line used in this manuscript was a near perfect match for T24 (CVCL_0554), a bladder carcinoma cell line commonly found as a cellular contaminant. Although we are unable to test the exact cells used in this manuscript, we believe that the cells labeled as SCC22B are most likely to actually be T24. The authors believe that neither the results nor the conclusions have been significantly changed on the basis of the specific cell line utilized.

PMID:29873307 | DOI:10.1088/1361-6560/aacaba

Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

PMID:26576743 | PMC:PMC4833657 | DOI:10.1088/0031-9155/60/24/9215