Radiotherapy For Pancreatic Cancer Research Articles

Dosimetry impact of distinct gating strategies in cine MR image-guided breath-hold pancreatic cancer radiotherapy.

To investigate the dosimetry effects of different gating strategies in cine magnetic resonance imaging (MRI)-guided breath-hold pancreatic cancer radiotherapy. Two cine MRI-based gating strategies were investigated： a tumor contour-based gating strategy at a gating threshold of 0-5% and a tumor displacement-based gating strategy at a gating threshold of 3-5 mm. The cine MRI videos were obtained from 17 pancreatic cancer patients who received MRI-guided radiation therapy. We calculated the tumor displacement in each cine MR frame that satisfied the gating threshold and obtained the proportion of frames with different displacements. We generated IMRT and VMAT plans using a 33 Gy prescription, and motion plans were generated by adding up all isocenter-shift plans corresponding to different tumor displacements. The dose parameters of GTV, PTV, and organs at risk (OAR) were compared between the original and motion plans. In both gating strategies, the difference was significant in PTV coverage but not in GTV coverage between the original and motion plans. OAR dose parameters deteriorate with increasing gating threshold. The beam duty cycle increased from 19.5±14.3% (median 18.0%) to 60.8±15.6% (61.1%) for gating thresholds from 0% to 5% in tumor contour-based gating and from 51.7±11.5% (49.7%) to 67.3±12.4% (67.1%) for gating thresholds from 3 to 5 mm in tumor displacement-based gating. In tumor contour-based gating strategy, the dose delivery accuracy deteriorates while the dose delivery efficiency improves with increasing gating thresholds. To ensure treatment efficiency, the gating threshold might be no less than 3%. A threshold up to 5% may be acceptable in terms of the GTV coverage. The displacement-based gating strategy may serve as a potential alternative to the tumor contour based gating strategy, in which the gating threshold of approximately 4 mm might be a good choice for reasonably balancing the dose delivery accuracy and efficiency.

Neoadjuvant Treatment versus Upfront Surgery for Primary Resectable Pancreatic Cancer: An Update Meta-Analysis of Comparative Studies

Abstract Background The role of neoadjuvant chemotherapy with or without radiotherapy in resectable pancreatic cancer has yet to be defined. Aims This meta-analysis aims to explore the benefit of a neoadjuvant treatment in resectable pancreatic cancer compared with upfront surgery in terms of overall survival. Methods MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with primary resectable pancreatic cancer treated with or without neoadjuvant treatment from January 2000 to December 2022. The quality assessment of the included studies was based on the Newcastle–Ottawa quality scale. Secondary outcomes included disease free survival, pathological lymph-node rate, overall and R0 resection rate. Results A total of eleven studies (seven randomized controlled trials and four cohort studies) with 9774 patients were included. Neoadjuvant treatment was found to be significantly associated to increased overall survival (p<0.001; OR: 0.82; 95% CI: 0.73–0.92) and disease-free survival (p<0.001; OR: 0.73; 95% CI: 0.59–0.89). The association of radiotherapy showed no additional benefit to chemotherapy alone in terms of overall survival in the subgroup analysis. Patients undergoing neo-adjuvant treatment were also found to be significantly associated with a higher R0 resection rate (p<0.001; OR: 1.67; 95% CI: 1.31–2.15) and negative lymph-node status (p<0.001; OR: 0.41; 95% CI: 0.26–0.64). Conclusions Neoadjuvant treatment seems to offer an advantage in terms of overall and disease-free survival in comparison to patients undergoing up-front surgery for primary resectable pancreatic cancer. Further RCTs should confirm these findings to generalize the indication of neoadjuvant treatment in this setting.

Intraoperative radiotherapy for resectable pancreatic cancer using a low-energy X-ray source: Follow-up outcomes

Intraoperative radiotherapy for resectable pancreatic cancer using a low-energy X-ray source: Follow-up outcomes

DeepPERFECT: Novel Deep Learning CT Synthesis Method for Expeditious Pancreatic Cancer Radiotherapy.

Major sources of delay in the standard of care RT workflow are the need for multiple appointments and separate image acquisition. In this work, we addressed the question of how we can expedite the workflow by synthesizing planning CT from diagnostic CT. This idea is based on the theory that diagnostic CT can be used for RT planning, but in practice, due to the differences in patient setup and acquisition techniques, separate planning CT is required. We developed a generative deep learning model, deepPERFECT, that is trained to capture these differences and generate deformation vector fields to transform diagnostic CT into preliminary planning CT. We performed detailed analysis both from an image quality and a dosimetric point of view, and showed that deepPERFECT enabled the preliminary RT planning to be used for preliminary and early plan dosimetric assessment and evaluation.

The Role of MRI and PET/CT in Radiotherapy Target Volume Determination in Gastrointestinal Cancers-Review of the Literature.

Positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI) could improve accuracy in target volume determination for gastrointestinal cancers. A systematic search of the PubMed database was performed, focusing on studies published within the last 20 years. Articles were considered eligible for the review if they included patients with anal canal, esophageal, rectal or pancreatic cancer, as well as PET/CT or MRI for radiotherapy treatment planning, and if they reported interobserver variability or changes in treatment planning volume due to different imaging modalities or correlation between the imaging modality and histopathologic specimen. The search of the literature retrieved 1396 articles. We retrieved six articles from an additional search of the reference lists of related articles. Forty-one studies were included in the final review. PET/CT seems indispensable for target volume determination of pathological lymph nodes in esophageal and anal canal cancer. MRI seems appropriate for the delineation of primary tumors in the pelvis as rectal and anal canal cancer. Delineation of the target volumes for radiotherapy of pancreatic cancer remains challenging, and additional studies are needed.

Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer

Radiation therapy induces immunogenic cell death in cancer cells, whereby released endogenous adjuvants are sensed by immune cells to direct adaptive immune responses. TLRs expressed on several immune subtypes recognize innate adjuvants to direct downstream inflammatory responses in part via the adapter protein MyD88. We generated Myd88 conditional knockout mice to interrogate its contribution to the immune response to radiation therapy in distinct immune populations in pancreatic cancer. Surprisingly, Myd88 deletion in Itgax (CD11c)-expressing dendritic cells had little discernable effects on response to RT in pancreatic cancer and elicited normal T cell responses using a prime/boost vaccination strategy. Myd88 deletion in Lck-expressing T cells resulted in similar or worsened responses to radiation therapy compared to wild-type mice and lacked antigen-specific CD8+ T cell responses from vaccination, similar to observations in Myd88−/− mice. Lyz2-specific loss of Myd88 in myeloid populations rendered tumors more susceptible to radiation therapy and elicited normal CD8+ T cell responses to vaccination. scRNAseq in Lyz2-Cre/Myd88fl/fl mice revealed gene signatures in macrophages and monocytes indicative of enhanced type I and II interferon responses, and improved responses to RT were dependent on CD8+ T cells and IFNAR1. Together, these data implicate MyD88 signaling in myeloid cells as a critical source of immunosuppression that hinders adaptive immune tumor control following radiation therapy.

Sonocatalytic In Situ Induced Oxygen Storm Precision Enhanced Reactive Oxygen Therapy for Pancreatic Cancer

AbstractDeep‐buried tissue, extremely hypoxic blood supply, and complex tumor microenvironment are considered to be the hardest difficult barriers to the accurate treatment of pancreatic cancer. Herein, a novel Au@Co3O4 (AC)‐polyvinylpyrrolidone (AC‐PVP) sonocatalytic agent and radiation sensitizer with a multicore–shell structure are synthesized by a mild reduction method for reshaping the special physiological environment of pancreatic cancer. Oxygen storms can be generated under ultrasonic activation by in situ catalyzed H2O2 in tumor tissue. The oxygen storm improves the ability to produce superoxide anions by sonodynamic therapy as well as rapidly supplements the oxygen‐dependent on active oxygen such as auger electrons produced by high‐energy ray ionization during radiotherapy (RT), further enhancing the efficiency of RT. Interestingly, AC‐PVP can reduce the intracellular glutathione (GSH) level, thus preventing the generated reactive oxygen species from being consumed by GSH. More importantly, the glucose oxidase‐like of AC‐PVP can catalyze glucose in tumor tissue to produce H2O2, and continuously provide substrates for sonocatalytic to form self‐cycling oxygen production. This study offers a novel paradigm for achieving in situ precise self‐oxygenation to overcome the special physiological barrier of pancreatic cancer and efficient sonodynamic synergistic radiotherapy.

Stereotactic Radiotherapy for Critically Located Pancreatic and Biliary Targets: A Review on Simultaneous Integrated Protection and Other Dose-Painting Strategies to Minimize Dose to Critical Organs at Risk

Background: Stereotactic Radiotherapy (SRT) in pancreatic and biliary tract cancer (PBC) suffers from proximity to any organ(s) at risk (OARs). Some strategies to manage this issue have previously been proposed, such as Simultaneous Integrated Protection (SIP), with the aim of maintaining a biological effective dose prescription while reducing toxicities. We performed a systematic review of the literature about SRT techniques applied in patients with tumor in proximity to OARs, with the aim of testing safety and efficacy. Methods: using PRISMA guidelines, we selected studies from a pool of more than 25,000 articles published from 2010 to 30 January 2023 that explored the use of SRT to deliver targeted treatment for PBC. We then selected the ones referring to decreases in prescription doses (for SRT only) in the area of overlap between planning target volume (PTV) and OARs. Local control (LC) and toxicities being detailed were exclusion criteria for articles. Results: 9 studies were included in our review, considering 368 patients. One-year LC probability ranges between 67% and 98.3% were reported. Late G3 toxicities ranged between 0% and 5.3%, while G4-G5 late toxicities were both reported as 0.3%. Conclusion: prioritizing critical OAR constraints limits severe toxicities while preserving LC in PBC SRT. Improving in-study reporting is essential to confirm these promising results.

Robust Beam Selection Based on Water Equivalent Thickness Analysis in Passive Scattering Carbon-Ion Radiotherapy for Pancreatic Cancer.

Carbon-ion radiotherapy (CIRT) is one of the most effective radiotherapeutic modalities. This study aimed to select robust-beam configurations (BC) by water equivalent thickness (WET) analysis in passive CIRT for pancreatic cancer. The study analyzed 110 computed tomography (CT) images and 600 dose distributions of eight patients with pancreatic cancer. The robustness in the beam range was evaluated using both planning and daily CT images, and two robust BCs for the rotating gantry and fixed port were selected. The planned, daily, and accumulated doses were calculated and compared after bone matching (BM) and tumor matching (TM). The dose-volume parameters for the target and organs at risk (OARs) were evaluated. Posterior oblique beams (120-240°) in the supine position and anteroposterior beams (0° and 180°) in the prone position were the most robust to WET changes. The mean CTV V95% reductions with TM were -3.8% and -5.2% with the BC for gantry and the BC for fixed ports, respectively. Despite ensuring robustness, the dose to the OARs increased slightly with WET-based BCs but remained below the dose constraint. The robustness of dose distribution can be improved by BCs that are robust to ΔWET. Robust BC with TM improves the accuracy of passive CIRT for pancreatic cancer.

Knowledge-based adaptive planning quality assurance using dosimetric indicators for stereotactic adaptive radiotherapy for pancreatic cancer

IntroductionWe aimed to develop knowledge-based tools for robust adaptive radiotherapy (ART) planning to determine on-table adaptive DVH metric variations or planning process errors for stereotactic pancreatic ART. We developed volume-based dosimetric identifiers to identify deviations of ART plans from simulation plans. Materials and MethodsTwo patient cohorts who were treated on MR-Linac for pancreas cancer were included in this retrospective study; a training cohort and a validation cohort. All patients received 50 Gy in 5 fractions. PTV-OPT was generated by subtracting the critical organs plus a 5 mm-margin from PTV. Several metrics that potentially can identify failure-modes were calculated including PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5%. The difference between each DVH metric in each adaptive plan with the DVH metric in simulation plan was calculated. The 95% confidence interval (CI) of the variations in each DVH metric was calculated for the patient training cohort. Variations in DVH metrics that exceeded the 95% CI for all fractions in training and validation cohort were flagged for retrospective investigation for root-cause analysis to determine their predictive power for identifying failure-modes. ResultsThe CIs for the PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5% were ± 13%, ± 5%, ± 0.1, ± 0.03, respectively. We estimated the positive predictive value and negative predictive value of our method to be 77% and 89%, respectively, for the training cohort, and 80% for both in the validation cohort. DiscussionWe developed dosimetric indicators for ART planning QA to identify population-based deviations or planning errors during online adaptive process for stereotactic pancreatic ART. This technology may be useful as an ART clinical trial QA tool and improve overall ART quality at an institution.

A phase I dose escalation study of carbon-ion radiotherapy for pancreatic cancer.

TPS768 Background: Despite recent advances in chemotherapy and radiotherapy, the prognosis of unresectable locally pancreatic cancer (LAPC) patients remains poor. To improve the outcome, we have developed carbon ion radiotherapy (C-ion RT) for pancreatic cancer and have shown good results against conventional photon therapy. Compared to conventional photon therapy, C-ion RT can safely administer higher doses, and we find the possibility of long-term survival for some unresectable LAPC. Currently, C-ion RT is performed using 55.2 Gy (RBE) in 12 fractions. However local control is not satisfactory. Further dose escalation needs to be safely administered to further improve outcomes. We have developed a new treatment strategy: intensity-modulated ion therapy using the simultaneous integrated boost method and the linear transfer energy (LET) optimization method. We believe that these cutting-edge technologies will allow for a more intensive effect on pancreatic cancer. Thus, we started a clinical trial to evaluate the safety of dose escalation using these novel techniques. Methods: Eligibility included pathological or clinical confirmation of pancreatic cancer without distant metastasis. Carbon ion radiotherapy is given in 12 fractions over 3 weeks. The radiation doses are set in four steps, with increases ranging from 55.2 Gy (RBE) to 67.2 Gy (RBE). A minimum of three patients is enrolled in each cohort, and if there is no dose limiting toxicity (DLT), a dose escalation is performed. The primary endpoint is acute adverse events; the secondary outcomes are late adverse events, local control rate, and overall survival. We started this trial in September 2021. Cohort 1 has been completed without DLT. Cohort 2 is now starting enrollment. Clinical trial information: jRCTs032210292 .

Dose evaluations of organs at risk and predictions of gastrointestinal toxicity after re-irradiation with stereotactic body radiation therapy for pancreatic cancer by deformable image registration.

Re-irradiation of locally recurrent pancreatic cancer may be an optimal choice as a local ablative therapy. However, dose constraints of organs at risk (OARs) predictive of severe toxicity remain unknown. Therefore, we aim to calculate and identify accumulated dose distributions of OARs correlating with severe adverse effects and determine possible dose constraints regarding re-irradiation. Patients receiving two courses of stereotactic body radiation therapy (SBRT) for the same irradiated regions (the primary tumors) due to local recurrence were included. All doses of the first and second plans were recalculated to an equivalent dose of 2 Gy per fraction (EQD2). Deformable image registration with the workflow "Dose Accumulation-Deformable" of the MIM® System (version: 6.6.8) was performed for dose summations. Dose-volume parameters predictive of grade 2 or more toxicities were identified, and the receiver operating characteristic (ROC) curve was used to determine optimal thresholds of dose constraints. Forty patients were included in the analysis. Only the V 10 of the stomach [hazard ratio (HR): 1.02 (95% CI:1.00-1.04), P = 0.035] and D mean of the intestine [HR: 1.78 (95% CI: 1.00-3.18), P = 0.049] correlated with grade 2 or more gastrointestinal toxicity. Hence, the equation of probability of such toxicity was Additionally, the area under the ROC curve and threshold of dose constraints of V 10 of the stomach and D mean of the intestine were 0.779 and 77.575 cc, 0.769 and 4.22 Gy3 (α/β = 3), respectively. The area under the ROC curve of the equation was 0.821. The V 10 of the stomach and D mean of the intestine may be vital parameters to predict grade 2 or more gastrointestinal toxicity, of which the threshold of dose constraints may be beneficial for the practice of re-irradiation of locally relapsed pancreatic cancer.

Carbon Ion Radiotherapy Versus Perioperative Adjuvant Chemotherapy and Curative Surgery for Resectable Pancreatic Cancer.

The standard treatment for resectable pancreatic cancer is preoperative adjuvant chemotherapy (NAC) + curative surgery + adjuvant chemotherapy. Although excellent local control results of carbon ion radiotherapy (CIRT) for pancreatic cancer have been reported, no reports have compared CIRT with the standard treatment for resectable pancreatic cancer. In this study, we compared the results of CIRT for resectable pancreatic cancer with those of standard therapy and investigated the usefulness of CIRT. The subjects were 35 patients who underwent CIRT for clinical cT1-2, N0-1, and M0 cancers at Kanagawa Cancer Center, Yokohama, Japan, from September 2018 to September 2021, and 110 patients who underwent standard treatment (NAC + curative surgery + adjuvant). Overall survival (OS) and recurrence-free survival (PFS) were compared between the two groups using propensity score-matching (PSM). Twenty-three CIRT monotherapy patients were matched with NAC + curative surgery + adjuvant chemotherapy patients by PSM. Although there was no significant difference in RFS between the two groups, OS was significantly poorer in the CIRT monotherapy group than in the NAC + curative surgery + adjuvant chemotherapy group. This single-centre retrospective propensity score-matched comparison of CIRT and NAC + curative resection + adjuvant chemotherapy as the standard therapy for resectable pancreatic cancer showed an inferiority of CIRT in terms of OS, but no difference in PFS. Therefore, CIRT monotherapy may be a treatment strategy for patients with contraindications for standard treatment of curative surgery plus perioperative chemotherapy.

Evaluation of short-term gastrointestinal motion and its impact on dosimetric parameters in stereotactic body radiation therapy for pancreatic cancer

BackgroundThe aim of this study is to quantify the short-term motion of the gastrointestinal tract (GI-tract) and its impact on dosimetric parameters in stereotactic body radiation therapy (SBRT) for pancreatic cancer. MethodsThe analyzed patients were eleven pancreatic cancer patients treated with SBRT or proton beam therapy. To ensure a fair analysis, the simulation SBRT plan was generated on the planning CT in all patients with the dose prescription of 40 Gy in 5 fractions. The GI-tract motion (stomach, duodenum, small and large intestine) was evaluated using three CT images scanned at spontaneous expiration. After fiducial-based rigid image registration, the contours in each CT image were generated and transferred to the planning CT, then the organ motion was evaluated. Planning at risk volumes (PRV) of each GI-tract were generated by adding 5 mm margins, and the volume receiving at least 33 Gy (V33) < 0.5 cm3 was evaluated as the dose constraint. ResultsThe median interval between the first and last CT scans was 736 s (interquartile range, IQR:624–986). To compensate for the GI-tract motion based on the planning CT, the necessary median margin was 8.0 mm (IQR: 8.0–10.0) for the duodenum and 14.0 mm (12.0–16.0) for the small intestine. Compared to the planned V33 with the worst case, the median V33 in the PRV of the duodenum significantly increased from 0.20 cm3 (IQR: 0.02–0.26) to 0.33 cm3 (0.10–0.59) at Wilcoxon signed-rank test (p = 0.031). ConclusionThe short-term motions of the GI-tract lead to high dose differences.

Identification of Biomarkers Related to the Efficacy of Radiotherapy in Pancreatic Cancer.

Pancreatic cancer (PC) has one of the highest mortality rates, with an overall five-year survival rate of only 7%. When diagnosed, PC is limited to the pancreas in only 20% of patients, whereas in 50% it has already metastasized. This is due to its late diagnosis, which makes the treatments used, such as radiotherapy, difficult, and reduces survival rates. Therefore, the importance of this study in detecting genes that may become possible biomarkers for this type of tumor, especially regarding the human secretome, is highlighted. These genes participate in pathways that are responsible for tumor migration and resistance to therapies, along with other important factors. To achieve these goals, the following online tools and platforms have been expanded to discover and validate these biomarkers: The Human Protein Atlas database, the Xena Browser platform, Gene Expression Omnibus, the EnrichR platform and the Kaplan-Meier Plotter platform. Our study adopted a methodology that allows the identification of potential biomarkers related to the effectiveness of radiotherapy in PC. Inflammatory pathways were predominantly enriched, related to the regulation of biological processes, primarily in cytokine-derived proteins, which are responsible for tumor progression and other processes that contribute to the development of the disease. Radiotherapy treatment demonstrated greater efficacy when used in conjunction with other forms of therapy since it decreased the expression of essential genes involved in several inflammatory pathways linked to tumor progression.

Intraoperative Radiotherapy for Resectable Pancreatic Cancer Using a Low-energy X-ray Source: Follow-up Outcomes

Intraoperative Radiotherapy for Resectable Pancreatic Cancer Using a Low-energy X-ray Source: Follow-up Outcomes

Dosimetric evaluation of magnetic resonance imaging-guided adaptive radiation therapy in pancreatic cancer by extent of re-contouring of organs-at-risk.

The safety of online contouring and planning for adaptive radiotherapy is unknown. This study aimed to evaluate the dosimetric difference of the organ-at-risk (OAR) according to the extent of contouring in stereotactic magnetic resonance image-guided adaptive RT (SMART) for pancreatic cancer. We reviewed the treatment plan data used for SMART in patients with pancreatic cancer. For the online contouring and planning, OARs within 2 cm from the planning target volume (PTV) in the craniocaudal direction were re-controlled daily at the attending physician's discretion. The entire OARs were re-contoured retrospectively for data analysis. We termed the two contouring methods the Rough OAR and the Full OAR, respectively. The proportion of dose constraint violation and other dosimetric parameters was analyzed. Nineteen patients with 94 fractions of SMART were included in the analysis. The dose constraint was violated in 10.6% and 43.6% of the fractions in Rough OAR and Full OAR methods, respectively (p = 0.075). Patients with a large tumor, a short distance from gross tumor volume (GTV) to OAR, and a tumor in the body or tail were associated with more occult dose constraint violations-large tumor (p = 0.027), short distance from GTV to OAR (p = 0.061), tumor in body or tail (p = 0.054). No dose constraint violation occurred outside 2 cm from the PTV. More occult dose constraint violations can be found by the Full OAR method in patients with pancreatic cancer with some clinical factors in the online re-planning for SMART. Re-contouring all the OARs would be helpful to detect occult dose constraint violations in SMART planning. Since the dosimetric profile of SMART cannot be represented by a single fraction, patient selection for the Full OAR method should be weighted between the clinical usefulness and the time and workforce required.

Hypofractionated radiotherapy for pancreatic cancer

Category: Outcomes of treatment (including chemotherapy, chemo-RT and RT)

Improving Outcomes Prediction Using a Combination of MRI Wavelet Delta-Radiomic Textures and Clinical Biomarkers for MR-Guided Adaptive Radiation Therapy of Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> We have previously reported that wavelet delta radiomic features (WDRF) extracted from daily MRIs can predict treatment response of MRI-guided adaptive radiation therapy (MRgART) for pancreatic cancer. This study aims to investigate whether combining available clinical biomarkers with the WDRF would improve outcome prediction for pancreatic cancer treated with pre-operative MRgART. <h3>Materials/Methods</h3> This method was developed and demonstrated using 90 daily motion averaged MRI sets derived from 4D MRIs acquired during MRgART with concurrent chemotherapy for 18 pancreatic cancer patients treated in 5 SBRT fractions on a 1.5T MR-Linac, along with their CA19-9, CEA, metastatic status, and follow up data. For each daily MRI set, wavelet decompositions were applied a programming environment to provide a robust way for feature extraction and to overcome challenges with inter- and intra-patient MRI intensity variations. 438 WDRF were calculated from different decomposition levels. Good or bad response groups were defined based on pathological response or distant metastasis free progression, and 50% reduction in CA19-9. The time between the end of treatment and end points of death or presence of distant metastasis within 2 years were used to build progression free survival (PFS) model. Spearman correlations were applied to rule out redundant features. T-test and regression models were used to identify independent WDRFs with significant changes that correlate to response and to examine the effect of combining CA19-9, CEA, and WDRFs on response prediction. Concordance statistics was used to measure model effectiveness. A Cox analysis was performed to identify predictors of PFS and test the association of the combinations on PFS correlations. The effect of a decrease in CA19-9 or CEA levels during treatment versus failure of CA19-9 or CEA levels to normalize on PFS was examined. <h3>Results</h3> Spearman correlation showed that 67 WDRFs from different wavelet decomposition were not redundant and can be used for the analysis. 30 WDRF demonstrated opposite trends correlating to response. Of these, 8 WDRFs passed the t-test showing significant changes correlating to response by the 3rd or 4th fraction. CA199 and CEA were each correlated to 2 WDRFs. Increasing CA19-9, CEA levels during treatment were correlated to bad response. Incorporating CEA, CA19-9 with the significant WDRFs increased the concordance statistics from 0.65 to 0.96. The Cox multivariate analysis showed that a treatment related decrease in CA19-9 levels (p=0.0017), and 3 WDRFs (p=0.004-0.013) were independent predictors of PFS. The hazard ratio was reduced from 0.57, p=0.03 for using CA19-9 only to 0.163, p=0.004 for the combination of WDRFs and CA19-9. <h3>Conclusion</h3> Combining wavelet delta-radiomics features extracted from daily treatment MRIs with common clinical biomarkers improves outcome prediction for chemoradiation therapy of pancreatic cancer and may ultimately enable intensification of additional treatment to improve outcomes.

Expression of Ki67 and p53 and their Relationship with the Survival Time of High-Dose Hypofractionated Radiotherapy in Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> To analyze the expression of Ki67 and p53 in pancreatic cancer and their relationship with the survival time of high-dose hypofractionated radiotherapy. <h3>Materials/Methods</h3> The biopsies of 55 patients with pancreatic cancer were collected retrospectively before receiving high-dose hypofractionated radiotherapy. Immunohistochemical SP method was used to detect the expression of Ki67 and p53 in pancreatic cancer. Log-rank test was used to compare the difference of survival time between different expression levels. Cox model was analyzed by multivariate analysis. <h3>Results</h3> The expression rates of Ki67 and p53 protein in puncture tissues were 41.8% and 47.3%, respectively. Univariate survival analysis showed that the survival time of Ki67 and p53 negative expression group was significantly longer than that of positive group (P < 0.05). Multivariate analysis showed that Ki67, p53 and distant metastasis were independent prognostic factors of pancreatic cancer patients receiving high-dose hypofractionated radiotherapy. <h3>Conclusion</h3> The expression level of Ki67 and p53 protein in pathological tissue before treatment is an important index to predict the survival time of high-dose hypofractionated radiotherapy for pancreatic cancer.