Claus Chunli Yang

Head and neck squamous cell carcinoma (HNSCC) accounts for ~3% of U.S. cancer diagnoses, and many patients present with locally or regionally advanced disease. Despite multimodal standard-of-care (SOC) treatment, the median overall survival for recurrent or metastatic disease remains ~12 months. Acquired resistance to cisplatin (CDDP) and radiotherapy (RT) remains a central barrier to durable response, motivating neoadjuvant strategies to improve efficacy in resistant tumors. Benzyl isothiocyanate (BITC) is a dietary phytochemical with selective anticancer activity. Across four patient-matched HNSCC cell lines spanning a range of intrinsic sensitivities to CDDP or RT, pretreatment with BITC before RT and CDDP significantly increased HNSCC cell death as measured by caspase-3/7 activity, regardless of each cell line’s single-agent sensitivity. Within 24 h, BITC elevated cytoplasmic ROS across all lines: BITC-resistant cell lines countered this with a more robust increase in the GSH/GSSG ratio and retained viability, whereas the BITC-sensitive lines mounted a weaker glutathione (GSH) response and required rescue with exogenous GSH or N-acetylcysteine (NAC), indicating redox-sensitive cytotoxicity. Transcriptomic time-course analysis suggested that BITC induces a coordinated stress response, including proteotoxic HSF1 activation, and suppresses DNA replication and homologous recombination repair, thereby supporting a transcriptional basis for the observed sensitization to DNA-damaging therapy. By enhancing the efficacy of RT and CDDP in HPV-negative HNSCC, BITC may be a promising neoadjuvant strategy to improve the therapeutic index of chemotherapy and radiation in these patients, warranting further investigation.

Positron emission tomography (PET) integrated with computed tomography (CT) has brought revolutionary changes in improving cancer care (CC) for patients. These include improved detection of previously unrecognizable disease, ability to identify oligometastatic status enabling more aggressive treatment strategies when the disease burden is lower, its use in better defining treatment targets in radiotherapy (RT), ability to monitor treatment responses early and thus improve the ability for early interventions of non-responding tumors, and as a prognosticating tool as well as outcome predicting tool. PET/CT has enabled the emergence of new concepts such as radiobiotherapy (RBT), radioimmunotherapy, theranostics, and pharmaco-radiotherapy. This is a rapidly evolving field, and this primer is to help summarize the current status and to give an impetus to developing new ideas, clinical trials, and CC outcome improvements.

The objective is to explore the possibility of optimal/rational application of setup margin during treatment planning for frameless stereotactic Gamma Knife radiosurgery/therapy. Uncertainty measurements for frameless Gamma Knife Icon treatment were used to calculate the necessary setup margin via four different published recipes and these margins were subsequently applied to treatment plans of 30 previously treated patients and replans were generated meeting comparable plan quality metrics. All plans were then analyzed based on the ability to maintain normal tissue dose tolerances and the relative increase in target dose coverage probability using a pass/fail scoring system based on published normal tissue dose constraints and an in-house developed optimal scoring method. Gross tumor volume/planning target volume (GTV/PTV) size strongly correlated with both meeting normal tissue tolerances and optimal scores for single fraction plans corroborating published clinical outcomes. The Van Herk Margin Formula (VHMF) and Parker margin formulae were indicated as good candidates for high probabilities of both meeting normal tissue goals and high optimal scores which generally translated to just over 1 mm in GTV to PTV margin. For single fraction treatment, GTV size is highly significant in predicting failure to meet normal tissue goals whereas whether setup margin was used was not a significant predictor. Setup margin can rationally be applied when fraction number is dictated by clinically indicated metrics regarding GTV size of greater or less than 4 cc. 1 mm is a reasonable practical application of margin added to GTV to ensure physical prescription dose target coverage for most cases when clinically desired based on disease type and intended outcome.

The objective of the study is to discern any factors that may be predictive of patient-specific uncertainty related to residual error after cone-beam CT (CBCT) correction and motion measured by the high-definition motion management (HDMM) system. HDMM treatment logs were parsed via a Python 3 script and then analyzed for 30 patients. Additionally, CBCT registration and correction data was also collected and analyzed for the same 30 patients. Correlation analysis was then performed against various patient- and treatment-related factors to discern any potentially predictive factors. BMI was the only statistically significant predictor identified in this study with an r value of 0.393, p=0.032. Despite being identified as a predictor in other studies, treatment time, when treated as a continuous variable, did not show up as significant in this work. BMI may be predictive of patients who might require extra tactics to mitigate motion during frameless Gamma Knife® treatment.

Stereotactic body radiation therapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) patients who are either medically inoperable or who decline surgery. SBRT improves tumor control and overall survival (OS) in medically inoperable, early-stage, NSCLC patients. In this study, we investigated the effectiveness of two different SBRT doses commonly used and present our institutional experience. To determine the clinical outcomes between two treatment regiments (50 Gray [Gy] vs. 55 Gy in five fractions) among Stage I NSCLC patients treated with SBRT at a state academic medical center. We performed a retrospective analysis of 114 patients with Stage I (T1-2 N0 M0) NSCLC treated at a state academic medical center between October 2009 and April 2019. Survival analyses with treatment regimens of 50 Gy and 55 Gy in five fractions were conducted to detect any improvement in outcomes associated with the higher dose. The primary endpoints of this study included OS, local control (LC), and disease-free survival (DFS). Log-rank test and the Kaplan-Meier method were used to analyze the survival curves of the two treatment doses. The SPSS v.24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses. The 114 early-stage NSCLC patients (median age, 68 years; range 12 to 87 years) had a median follow-up of 25 months (range two to 86 months). The number of males (n = 72; 63.2 %) exceeded the number of females (n = 42; 36.8 %). The majority of patients in this study were Caucasians (n = 68; 59.6 %) and 46 patients were African Americans (40.4 %). Two-thirds of the patients (n = 76; 66.7 %) were treated with 50 Gy in five fractions, and 38 patients (33.3 %) with 55 Gy in five fractions. The one-, two-, and three-year OS and DFS rates were improved in the patients treated with 55 Gy [OS, 81.7 % vs. 72.8 %; 81.7 % vs. 58.9 %; 81.7 % vs. 46.7 % (p = 0.049)], [DFS, 69.7 % vs. 69.7 %; 61.9 % vs. 55.7 %; 61.9 % vs. 52.0 % (p = 0.842)], compared to those treated with 50 Gy. Adenocarcinoma was the most common histology in both groups (51.3 % and 68.4 %). Failure rates were elevated for the 50 Gy regimen [39 (34.2 %) vs. 12 (8.5 %)]. Three year control rates were (66.3 % vs. 96.6 %; p = 0.002) local control; (63.3 % vs. 94.4 %; p = 0.000) regional control; and (65.7 % vs. 97.1 %; p = 0.000) distant control, compared to those treated with 55 Gy. Early-stage NSCLC patients treated with SBRT 55 Gy in five fractions did better in terms of local control, overall survival, and disease-free survival rates compared to the 50 Gy in five fractions group.

Stereotactic radiosurgery (SRS) plans created using synthetic computed tomography (CT) images derived from magnetic resonance imaging (MRI) data may offer the advantage of inhomogeneity correction by convolution algorithms, as is done for CT-based plans. We sought to determine and validate the clinical significance and accuracy of synthetic CT images for inhomogeneity correction in MRI-only stereotactic radiosurgery plans for treatment of brain tumors. In this retrospective study, data from two patients with brain metastases and one with meningioma who underwent imaging with multiple modalities and received frameless SRS treatment were analyzed. The SRS plans were generated using a convolution algorithm to account for brain inhomogeneity using CT and synthetic CT images and compared with the original clinical TMR10 plans created using MRI images. Synthetic CT-derived SRS plans are comparable with CT-based plans using convolution algorithm, and for some targets, based on location, they provided better coverage and a lower maximum dose. The results suggest similar dose delivery results for CT and synthetic CT-based treatment plans. Synthetic CT plans offered a noticeable improvement in target dose coverage and a more gradual dose fall-off relative to TMR10 MRI-based plans. The major disadvantage is a slightly increased dose (by 0.37%) to nearby healthy tissue (brainstem) for synthetic CT-based plans relative to those created using clinical MRI images, which may be a problem for patients undergoing high-dose treatment.

Development of MRI sequences and processing methods for the production of images appropriate for direct use in stereotactic radiosurgery (SRS) treatment planning. MRI is useful in SRS treatment planning, especially for patients with brain lesions or anatomical targets that are poorly distinguished by CT, but its use requires further refinement. This methodology seeks to optimize MRI sequences to generate distortion-free and clinically relevant MR images for MRI-only SRS treatment planning. We used commercially available SRS MRI-guided radiotherapy phantoms and eight patients to optimize sequences for patient imaging. Workflow involved the choice of correct MRI sequence(s), optimization of the sequence parameters, evaluation of image quality (artifact free and clinically relevant), measurement of geometrical distortion, and evaluation of the accuracy of our offline correction algorithm. CT images showed a maximum deviation of 1.3 mm and minimum deviation of 0.4 mm from true fiducial position for SRS coordinate definition. Interestingly, uncorrected MR images showed maximum deviation of 1.2 mm and minimum of 0.4 mm, comparable to CT images used for SRS coordinate definition. After geometrical correction, we observed a maximum deviation of 1.1 mm and minimum deviation of only 0.3 mm. Our optimized MRI pulse sequences and image correction technique show promising results; MR images produced under these conditions are appropriate for direct use in SRS treatment planning.

Peer review systems within radiation oncology are important to ensure quality radiation care. Several individualized methods for radiation oncology peer review have been described. However, despite the importance of peer review in radiation oncology barriers may exist to its effective implementation in practice. The purpose of this study was to quantify the rate of plan changes based on our group peer review process as well as the quantify amount of time and resources needed for this process. Data on cases presented in our institutional group consensus peer review conference were prospectively collected. Cases were then retrospectively analyzed to determine the rate of major change (plan rejection) and any change in plans after presentation as well as the median time of presentation. Univariable logistic regression was used to determine factors associated with major change and any change. There were 73 cases reviewed over a period of 11 weeks. The rate of major change was 8.2% and the rate of any change was 23.3%. The majority of plans (53.4%) were presented in 6–10 min. Overall, the mean time of presentation was 8 min. On univariable logistic regression, volumetric modulated arc therapy plans were less likely to undergo a plan change but otherwise there were no factors significantly associated with major plan change or any type of change. Group consensus peer review allows for a large amount of informative clinical and technical data to be presented per case prior to the initiation of radiation treatment in a thorough yet efficient manner to ensure plan quality and patient safety.

Peer review, especially prospective peer review, has been supported by professional organizations as an important element in optimal Radiation Oncology practice based on its demonstration of efficacy at detecting and preventing errors prior to patient treatment. Implementation of peer review is not without barriers, but solutions do exist to mitigate or eliminate some of those barriers. Peer review practice at our institution involves three key elements: new patient conference, treatment planning conference, and chart rounds. The treatment planning conference is an adaptation of the group consensus peer review model from radiology which utilizes a group of peers reviewing each treatment plan prior to implementation. The peer group in radiation oncology includes Radiation Oncologists, Physician Residents, Medical Physicists, Dosimetrists, and Therapists. Thus, technical and clinical aspects of each plan are evaluated simultaneously. Though peer review is held in high regard in Radiation Oncology, many barriers commonly exist preventing optimal implementation such as time intensiveness, repetition, and distraction from clinic time with patients. Through the use of automated review tools and commitment by individuals and administration in regards to staffing, scheduling, and responsibilities, these barriers have been mitigated to implement this Group Consensus Peer Review model into a Radiation Oncology Clinic. A Group Consensus Peer Review model has been implemented with strategies to address common barriers to effective and efficient peer review.

Objective:To compare high-dose-rate (HDR) brachytherapy systems with 192Ir, 60Co and electronic brachytherapy source (EBS) for treatment of endometrial cancers.Methods:Two additional plans were gen...