Background: Patients with pancreatic cancer often develop cancer cachexia, a complex multifactorial syndrome with weight loss, muscle wasting and adipose tissue depletion with systemic inflammation causing physical impairment. In patients with locally advanced pancreatic cancer (LAPC) neoadjuvant treatment is routinely performed to allow a subsequent resection. Herein, we assess body composition and laboratory markers for cancer cachexia both before and after neoadjuvant chemoradiation (CRT). Methods: Subcutaneous fat (SCF), visceral fat (VF), skeletal muscle (SM), weight and laboratory parameters were determined longitudinally in 141 LAPC patients treated with neoadjuvant CRT. Changes during CRT were statistically analyzed and correlated with outcome and Kaplan–Meier curves were plotted. Different prognostic factors linked to cachexia were assessed by uni- and multivariable cox proportional hazards models. Results: There was a significant decrease in weight as well as SCF, VF and SM during CRT. The laboratory parameter C-reactive protein (CRP) increased significantly, whereas there was a significant decrease in leukocyte count, hemoglobin, albumin and cholinesterase as well as in the tumor marker CA 19.9. Cachectic weight loss, sarcopenia, reductions in body compartments SCF, VF and SM, and changes in laboratory markers as well as resection affected survival in univariable analysis. In multivariable analysis, weight loss >5% (HR 2.8), reduction in SM >5% (HR 5.5), an increase in CRP (HR 2.2) or CA 19.9 (HR 1.9), and resection (HR 0.4) remained independently associated with survival, whereas classical cachexia and sarcopenia did not. Interestingly, the subgroup of patients with cachectic weight loss >5% or SM reduction >5% during CRT did not benefit from resection (median survival 12 vs. 27 months). Conclusions: Persistent weight loss and muscle depletion during CRT as well as systemic inflammation after CRT impacted survival more than cachexia or sarcopenia according classical definitions.

Background: Surgical resection offers the best chance of survival in patients with pancreatic cancer, but those with locally advanced disease (LAPC) are usually not surgical candidates. This cohort often receives either neoadjuvant chemotherapy or chemoradiation (CRT), but unintended weight loss coupled with muscle wasting (sarcopenia) can often be observed. Here, we report on the predictive value of changes in weight and muscle mass in 147 consecutive patients with LAPC treated with neoadjuvant CRT. Methods: Clinicopathologic data were obtained via a retrospective chart review. The abdominal skeletal muscle area (SMA) at the third lumbar vertebral body was determined via computer tomographic (CT) scans as a surrogate for the muscle mass and skeletal muscle index (SMI) calculated. Uni- and multi-variable statistical tests were performed to assess for impact on survival. Results: Weight loss (14.5 vs. 20.3 months; p = 0.04) and loss of muscle mass (15.1 vs. 22.2 months; p = 0.007) were associated with poor outcomes. The highest survival was observed in patients who had neither cachectic weight loss nor sarcopenia (27 months), with improved survival seen in those who ultimately received a resection (23 vs. 10 months; p < 0.001). Cox regression revealed that either continued weight loss or continued muscle wasting (SMA reduction) was predictive of poor outcomes, whereas a sarcopenic SMI was not. Conclusions: Loss of weight and lean muscle in patients with LAPC is prognostic when persistent. Therefore, both should be assessed longitudinally and considered before surgery.

(1) Background: A new radioactive positron emission tomography (PET) tracer uses inhibitors of fibroblast activation protein (FAPI) to visualize FAP-expressing cancer associated fibroblasts. Significant FAPI-uptake has recently been demonstrated in pancreatic cancer patients. Target volume delineation for radiation therapy still relies on often less precise conventional computed tomography (CT) imaging, especially in locally recurrent pancreatic cancer patients. The need for improvement in precise tumor detection and delineation led us to innovatively use the novel FAPI-PET/CT for radiation treatment planning. (2) Methods: Gross tumor volumes (GTVs) of seven locally recurrent pancreatic cancer cases were contoured by six radiation oncologists. In addition, FAPI-PET/CT was used to automatically delineate tumors. The interobserver variability in target definition was analyzed and FAPI-based automatic GTVs were compared to the manually defined GTVs. (3) Results: Target definition differed significantly between different radiation oncologists with mean dice similarity coefficients (DSCs) between 0.55 and 0.65. There was no significant difference between the volumes of automatic FAPI-GTVs based on the threshold of 2.0 and most of the manually contoured GTVs by radiation oncologists. (4) Conclusion: Due to its high tumor to background contrast, FAPI-PET/CT seems to be a superior imaging modality compared to the current gold standard contrast-enhanced CT in pancreatic cancer. For the first time, we demonstrate how FAPI-PET/CT could facilitate target definition and increases consistency in radiation oncology in pancreatic cancer.

Background: Reductions in tumor movement allow for more precise and accurate radiotherapy with decreased dose delivery to adjacent normal tissue that is crucial in stereotactic body radiotherapy (SBRT). Deep inspiration breath-hold (DIBH) is an established approach to mitigate respiratory motion during radiotherapy. We assessed the feasibility of combining modern optical surface-guided radiotherapy (SGRT) and image-guided radiotherapy (IGRT) to ensure and monitor reproducibility of DIBH and to ensure accurate tumor localization for SBRT as an imaging-guided precision medicine. Methods: We defined a new workflow for delivering SBRT in DIBH for lung and liver tumors incorporating SGRT and IGRT with cone beam computed tomography (CBCT) twice per treatment fraction. Daily position corrections were analyzed and for every patient two points retrospectively characterized: an anatomically stable landmark (predominately Schmorl’s nodes or spinal enostosis) and a respiratory-dependent landmark (predominately surgical clips or branching vessel). The spatial distance of these points was compared for each CBCT and used as surrogate for intra- and interfractional variability. Differences between the lung and liver targets were assessed using the Welch t-test. Finally, the planning target volumes were compared to those of free-breathing plans, prepared as a precautionary measure in case of technical or patient-related problems with DIBH. Results: Ten patients were treated with SBRT according this workflow (7 liver, 3 lung). Planning target volumes could be reduced significantly from an average of 148 ml in free breathing to 110 ml utilizing DIBH (p < 0.001, paired t-test). After SGRT-based patient set-up, subsequent IGRT in DIBH yielded significantly higher mean corrections for liver targets compared to lung targets (9 mm vs. 5 mm, p = 0.017). Analysis of spatial distance between the fixed and moveable landmarks confirmed higher interfractional variability (interquartile range (IQR) 6.8 mm) than intrafractional variability (IQR 2.8 mm). In contrast, lung target variability was low, indicating a better correlation of patients’ surface to lung targets (intrafractional IQR 2.5 mm and interfractional IQR 1.7 mm). Conclusion: SBRT in DIBH utilizing SGRT and IGRT is feasible and results in significantly lower irradiated volumes. Nevertheless, IGRT is of paramount importance given that interfractional variability was high, particularly for liver tumors.