Prognostic Value of [18F]-FDG PET/CT Radiomics Combined with Sarcopenia Status among Patients with Advanced Gastroesophageal Cancer.

We investigated, whether 18[18F]-FDG PET/CT-derived radiomics combined with sarcopenia measurements improves survival prognostication among patients with advanced, metastatic gastroesophageal cancer. In our study, 128 consecutive patients with advanced, metastatic esophageal and gastroesophageal cancer (n = 128; 26 females; 102 males; mean age 63.5 ± 11.7 years; age range: 29−91 years) undergoing 18[18F]-FDG PET/CT for staging between November 2008 and December 2019 were included. Segmentation of the primary tumor and radiomics analysis derived from PET and CT images was performed semi-automatically with a commonly used open-source software platform (LIFEX, Version 6.30, lifexsoft.org). Patients' nutritional status was determined by measuring the skeletal muscle index (SMI) at the level of L3 on the CT component. Univariable and multivariable analyses were performed to establish a survival prediction model including radiomics, clinical data, and SMI score. Univariable Cox proportional hazards model revealed ECOG (<0.001) and bone metastasis (p = 0.028) to be significant clinical parameters for overall survival (OS) and progression free survival (PFS). Age (p = 0.017) was an additional prognostic factor for OS. Multivariable analysis showed improved prognostication for overall and progression free survival when adding sarcopenic status, PET and CT radiomics to the model with clinical parameters only. PET and CT radiomics derived from hybrid 18[18F]-FDG PET/CT combined with sarcopenia measurements and clinical parameters may improve survival prediction among patients with advanced, metastatic gastroesophageal cancer.

Impact of pharmacodynamic biomarkers in immuno-oncology phase 1 clinical trials.

BACKGROUND: Phase 1 immuno-oncology (IO) trials frequently involve pharmacodynamic (PD) biomarker assessments involving tumour biopsies and/or blood collection, with increasing use of molecular imaging. PD biomarkers are set to play a fundamental role in early drug development of immuno-oncology (IO) agents. In the IO era, the impact of PD biomarkers for confirmation of biologic activity and their role in subsequent drug development have not been investigated. METHODS: Phase 1 studies published between January 2014 and December 2020 were reviewed. Studies that reported on-treatment PD biomarkers [tissue-derived (tissue-PD), blood-based (blood-PD) and imaging-based (imaging-PD)] were analysed. PD biomarker results and their correlation with clinical activity endpoints were evaluated. Authors' statements on the influence of PD biomarkers on further drug development decisions, and subsequent citations of PD biomarker study results were recorded. RESULTS: Among 386 trials, the most frequent IO agent classes evaluated were vaccines (32%) and PD-(L)1 inhibitors (25%). No PD biomarker assessments were reported in 100 trials (26%). Of the remaining 286, blood-PD, tissue-PD, and imaging-PD data were reported in 270 (94%), 94 (33%), and 12 (4%) trials, respectively. Assessments of more than one PD biomarker type were reported in 82 studies (29%). Similar proportions of blood-PD (9%), tissue-PD (7%), and imaging-PD studies (8%) had positive results that correlated with clinical activity. Results of 22 PD biomarker studies (8%) were referenced in subsequent clinical trials. CONCLUSIONS: Most phase 1 IO studies performed PD biomarker assessments. Overall, positive PD biomarker results were infrequently correlated with clinical activity or cited in subsequent trials, suggesting a limited impact on subsequent drug development. With emerging health regulatory emphasis on optimal dose selection based on PD activity, more informative and integrative multiplexed assays that capture the complexity of tumour-host immunity interactions are warranted to improve phase 1 IO trial methodology.

Nasopharyngeal Carcinoma Radiomic Evaluation with Serial PET/CT: Exploring Features Predictive of Survival in Patients with Long-Term Follow-Up.

PURPOSE: We aim determine the value of PET and CT radiomic parameters on survival with serial follow-up PET/CT in patients with nasopharyngeal carcinoma (NPC) for which curative intent therapy is undertaken. METHODS: Patients with NPC and available pre-treatment as well as follow up PET/CT were included from 2005 to 2006 and were followed to 2021. Baseline demographic, radiological and outcome data were collected. Univariable Cox proportional hazard models were used to evaluate features from baseline and follow-up time points, and landmark analyses were performed for each time point. RESULTS: Sixty patients were enrolled, and two-hundred and seventy-eight (278) PET/CT were at baseline and during follow-up. Thirty-eight percent (38%) were female, and sixty-two patients were male. All patients underwent curative radiation or chemoradiation therapy. The median follow-up was 11.72 years (1.26-14.86). Five-year and ten-year overall survivals (OSs) were 80.0% and 66.2%, and progression-free survival (PFS) was 90.0% and 74.4%. Time-dependent modelling suggested that, among others, PET gray-level zone length matrix (GLZLM) gray-level non-uniformity (GLNU) (HR 2.74 95% CI 1.06, 7.05) was significantly associated with OS. Landmark analyses suggested that CT parameters were most predictive at 15 month, whereas PET parameters were most predictive at time points 3, 6, 9 and 15 month. CONCLUSIONS: This study with long-term follow up data on NPC suggests that mainly PET-derived radiomic features are predictive for OS but not PFS in a time-dependent evaluation. Furthermore, CT radiomic measures may predict OS and PFS best at initial and long-term follow-up time points and PET measures may be more predictive in the interval. These modalities are commonly used in NPC surveillance, and prospective validation should be considered.

Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21): 15-Year Evaluation of an Innovative Research Training Program.

PURPOSE: To evaluate the 15-year impact of a transdisciplinary research training program for graduate students, postdoctoral fellows, and clinical trainees focused on radiation science, entitled Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) with a primary objective to build capacity in radiation research. METHODS AND MATERIALS: Alumni (n = 128) and mentors (n = 41) who participated in STARS21 between 2003 and 2018 were sent an anonymized online survey designed to evaluate the program. Twelve alumni and 7 mentors also volunteered to participate in semistructured interviews. The transcribed interviews were coded and analyzed using NVivo12-Pro software. Alumni employment and publications were assessed from program records and by web-based search queries. RESULTS: Alumni are located in 11 countries, and nearly 90% are employed in a research-oriented career and continue to publish in radiation medicine- or cancer-related fields. Of those invited, 46 alumni (36%) and 12 mentors (29%) completed the online survey. Approximately 87% of alumni valued interdisciplinary collaboration, and 80% indicated that STARS21 had encouraged them to pursue such collaborations. Alumni emphasized that STARS21 assisted their career development, and the majority of alumni and mentors would recommend STARS21 to other trainees (4.48 and 4.58, respectively; 5 = strongly agree). The time invested in the program was perceived by mentors as worthwhile for the knowledge and skills gained by trainees (4.67; 5 = strongly agree), and 64% of mentors indicated that these benefits were associated with improved trainee research productivity. From the alumni and mentor perspectives, the valuable skills acquired from STARS21 included scientific communication (85% and 83%, respectively) and networking (83% and 92%, respectively). CONCLUSIONS: STARS21 is an innovative research training program that promotes interdisciplinary collaboration in radiation medicine research, which is valued by alumni and mentor respondents. Alumni can acquire important skill sets for career development, with a large proportion of alumni currently engaged in radiation research around the world.

Radiological tumor response and histopathological correlation of hepatocellular carcinoma treated with stereotactic body radiation therapy as a bridge to liver transplantation.

PURPOSE: To assess the imaging findings of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) as a bridging therapy prior to liver transplantation (LT), with histopathological correlation at liver explant. METHODS: Our institutional review board approved this retrospective study. The study subjects included 25 HCC lesions in 23 patients (20 males; median age, 60 years; range 41-68 years) who underwent LT after SBRT for HCC as a bridge to LT in a single tertiary referral institution over a 12-year period. Target HCC lesions were assessed for imaging biomarkers on contrast-enhanced CT or MRI including change in HCC diameter and assessment of percentage necrosis. The radiologic response at pre-LT imaging was compared to explant pathology. RESULTS: There was a positive correlation between the tumor size (Spearman's ρ = 0.86; p < 0.001) and percentage necrosis (p < 0.001) on Pre-LT imaging and those on pathology. Partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST 1.1 were seen in 8 (32%), 15 (60%), and 2 (8%) lesions on pre-LT imaging, respectively. Of the 15 lesions with radiologic SD, 5/15 (33%) showed necrosis of more than 50% on post-SBRT imaging, while 9/15 (60%) showed necrosis of more than 50% at explant pathologic analysis, showing a tendency to underestimate the degree of tumor necrosis compared to pathology. CONCLUSION: RECIST 1.1 radiologic response criteria may underestimate the response to treatment with SBRT, and radiologic estimation of percent tumor necrosis was more closely correlated with pathologic percent tumor necrosis.

Rapid Adaptation of Breast Radiation Therapy Use During the Coronavirus Disease 2019 Pandemic at a Large Academic Cancer Center in Canada.

PURPOSE: Mitigation strategies to balance the risk of coronavirus disease 2019 (COVID-19) infection against oncologic risk in patients with breast cancer undergoing radiation therapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiation therapy by oncologic risk and omission or deferral of radiation therapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers and preserves resources. Herein, we present our early response and adaptation of breast radiation therapy utilization during the COVID-19 pandemic at a large academic cancer center in Canada. METHODS AND MATERIALS: A state of emergency was announced in Ontario on March 17, 2020, owing to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast radiation therapy starts, type of breast radiation therapy, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. RESULTS: After the declaration of emergency in Ontario, there was a decrease of 39% in radiation therapy starts in 2020 compared with 2019 (79 vs 129, P < .001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared with 2019 (46% vs 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiation therapy were aged >50 years in 2020, 66% (78 of 118) versus 83% (132 of 160) in 2019, P = .0027. CONCLUSIONS: A significant reduction in breast radiation therapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiation therapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical and is of particular importance for higher volume cancer sites where the potential effect on resources is greater.