Combined CT and serum CA19-9 for stratifying risk for progression in patients with locally advanced pancreatic cancer receiving intraoperative radiotherapy

Background and purpose The aim of this study was to evaluate the significance of baseline computed tomography (CT) imaging features and carbohydrate antigen 19-9 (CA19-9) in predicting prognosis of locally advanced pancreatic cancer (LAPC) receiving intraoperative radiotherapy (IORT) and to establish a progression risk nomogram that helps to identify the potential beneficiary of IORT. Methods A total of 88 LAPC patients with IORT as their initial treatment were enrolled retrospectively. Clinical data and CT imaging features were analyzed. Cox regression analyses were performed to identify the independent risk factors for progression-free survival (PFS) and to establish a nomogram. A risk-score was calculated by the coefficients of the regression model to stratify the risk of progression. Results Multivariate analyses revealed that relative enhanced value in portal-venous phase (REV-PVP), peripancreatic fat infiltration, necrosis, and CA19-9 were significantly associated with PFS (all p < 0.05). The nomogram was constructed according to the above variables and showed a good performance in predicting the risk of progression with a concordance index (C-index) of 0.779. Our nomogram stratified patients with LAPC into low- and high-risk groups with distinct differences in progression after IORT (p < 0.001). Conclusion The integrated nomogram would help clinicians to identify appropriate patients who might benefit from IORT before treatment and to adapt an individualized treatment strategy.

[1]  Axel Behrens,et al.  The roles of intratumour heterogeneity in the biology and treatment of pancreatic ductal adenocarcinoma , 2022, Oncogene.

[2]  Jeffrey E. Lee,et al.  Radiographic and Serologic Response to First-Line Chemotherapy in Unresected Localized Pancreatic Cancer. , 2022, Journal of the National Comprehensive Cancer Network : JNCCN.

[3]  Jin-Hyeok Hwang,et al.  Multi-Phase, Contrast-Enhanced Computed Tomography-Based Radiomic Prognostic Marker of Non-Metastatic Pancreatic Ductal Adenocarcinoma , 2022, Cancers.

[4]  Sang Min Lee,et al.  Systematic review and meta-analysis of MRI features for differentiating autoimmune pancreatitis from pancreatic adenocarcinoma , 2022, European Radiology.

[5]  Mi-Suk Park,et al.  Retrospective Evaluation of Treatment Response in Patients with Nonmetastatic Pancreatic Cancer Using CT and CA 19-9. , 2022, Radiology.

[6]  J. Ferlay,et al.  Pancreatic cancer: an increasing global public health concern , 2021, Gut.

[7]  Bohyun Kim,et al.  Identification of intratumoral fluid–containing area by magnetic resonance imaging to predict prognosis in patients with pancreatic ductal adenocarcinoma after curative resection , 2021, European Radiology.

[8]  E. O’Reilly,et al.  Pancreatic Cancer: A Review. , 2021, JAMA.

[9]  T. Luedde,et al.  Pre-Operative MDCT Staging Predicts Mesopancreatic Fat Infiltration—A Novel Marker for Neoadjuvant Treatment? , 2021, Cancers.

[10]  Kotaro Yoshida,et al.  CT-diagnosed extra-pancreatic extension of pancreatic ductal adenocarcinoma is a more reliable prognostic factor for survival than pathology-diagnosed extension , 2021, European Radiology.

[11]  T. Luedde,et al.  Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival. , 2021, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[12]  M. V. van Leeuwen,et al.  The Role of CT in Assessment of Extraregional Lymph Node Involvement in Pancreatic and Periampullary Cancer: A Diagnostic Accuracy Study. , 2021, Radiology. Imaging cancer.

[13]  Lianfang Zheng,et al.  Targeting hypoxic tumor microenvironment in pancreatic cancer , 2021, Journal of Hematology & Oncology.

[14]  Xianjun Yu,et al.  Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. , 2020, Biochimica et biophysica acta. Reviews on cancer.

[15]  Song-Cheol Kim,et al.  Estimating Recurrence after Upfront Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma by Using Pancreatic CT: Development and Validation of a Risk Score. , 2020, Radiology.

[16]  Yu Shi,et al.  Pancreatic adenocarcinoma: quantitative CT features are correlated with fibrous stromal fraction and help predict outcome after resection , 2020, European Radiology.

[17]  R. Krempien,et al.  ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in unresected pancreatic cancer. , 2020, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[18]  J. O’Sullivan,et al.  Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers , 2020, Nature Reviews Gastroenterology & Hepatology.

[19]  Jeffrey W. Clark,et al.  Intraoperative Radiation Therapy (IORT) for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma (BR/LA PDAC) in the Era of Modern Neoadjuvant Treatment: Short-Term and Long-Term Outcomes , 2019, Annals of Surgical Oncology.

[20]  M. Schipper,et al.  Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Jeffrey E. Lee,et al.  Radiographic and Serologic Predictors of Pathologic Major Response to Preoperative Therapy for Pancreatic Cancer. , 2019, Annals of surgery.

[22]  S. Shi,et al.  Experts' consensus on intraoperative radiotherapy for pancreatic cancer. , 2019, Cancer letters.

[23]  R. Pozzi Mucelli,et al.  Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection , 2018, European Radiology.

[24]  Jeong Ah Hwang,et al.  Pancreatic Ductal Adenocarcinoma: Rim Enhancement at MR Imaging Predicts Prognosis after Curative Resection. , 2018, Radiology.

[25]  Y. Cho,et al.  Risk Estimation for Biliary Atresia in Patients with Neonatal Cholestasis: Development and Validation of a Risk Score. , 2018, Radiology.

[26]  A. Biankin,et al.  Chemotherapy and radiotherapy for advanced pancreatic cancer. , 2018, The Cochrane database of systematic reviews.

[27]  R. Krempien,et al.  Intraoperative radiation therapy (IORT) in pancreatic cancer , 2017, Radiation Oncology.

[28]  T. Conroy,et al.  FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. , 2016, The Lancet. Oncology.

[29]  Elliot K Fishman,et al.  Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association. , 2014, Radiology.

[30]  K. Lillemoe,et al.  Long-Term Outcomes and Prognostic Factors for Patients With Unresectable Locally Advanced Pancreatic Cancer Treated With Intraoperative Radiotherapy at the Massachusetts General Hospital , 1978 to 2010 , 2013 .

[31]  D. Brizel,et al.  National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology , 2012 .

[32]  Jae Young Lee,et al.  Small (≤ 20 mm) pancreatic adenocarcinomas: analysis of enhancement patterns and secondary signs with multiphasic multidetector CT. , 2011, Radiology.

[33]  S. Park,et al.  Visually isoattenuating pancreatic adenocarcinoma at dynamic-enhanced CT: frequency, clinical and pathologic characteristics, and diagnosis at imaging examinations. , 2010, Radiology.

[34]  Y. Nishimura,et al.  Intraoperative radiotherapy for resected pancreatic cancer: a multi-institutional retrospective analysis of 210 patients. , 2010, International journal of radiation oncology, biology, physics.

[35]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[36]  W. Scheithauer,et al.  CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. , 2008, The Lancet. Oncology.

[37]  L. Ho,et al.  Survival in Pancreatic Carcinoma Based on Tumor Size , 2008, Pancreas.

[38]  D. Finkelstein,et al.  Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  Y. Nishimura,et al.  Evaluation of intraoperative radiation therapy for unresectable pancreatic cancer with FDG PET. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[40]  Y. Shibamoto,et al.  Tumor response and patterns of failure following intraoperative radiotherapy for unresectable pancreatic cancer--evaluation by computed tomography. , 1999, Acta oncologica.

[41]  Y. Nishimura,et al.  CT changes following IORT for unresectable pancreatic cancer. , 1997, Frontiers of radiation therapy and oncology.

[42]  Robert C. Wolpert,et al.  A Review of the , 1985 .