Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma

Abstract

Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor-specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under-addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.

Keywords: cachexia; epidemiology; health outcomes; pancreatic neoplasms; screening and early detection.

Figure 1.

44-year-old woman with resectable PDAC arising from pancreatic body. A. Axial IV contrast-enhanced CT image shows a hypoenhancing pancreatic body mass (arrow) associated with pancreatic duct dilatation (white arrowhead). Tumor abuts splenic artery and splenic vein (black arrowhead). B. Coronal IV contrast-enhanced CT image with cinematic rendering improves conspicuity of pancreatic tumor (arrow) relatively to background pancreas and improves visualization of minimal tumor abutment of splenic artery (arrowhead).

Figure 2.

50-year-old man with locally advanced PDAC arising from head of pancreas. A, B. Axial IV contrast-enhanced CT images show (A) tumor (arrow) with SMA encasement (arrowhead), and (B) tumor (arrow) with encasement and near occlusion of portal vein (arrowhead). C. Coronal IV contrast-enhanced CT image with cinematic rendering improves visualization of tumor encasement (arrow) of SMA (white arrowhead) and portal vein (black arrowhead).

Figure 3.

70-year-old man with borderline resectable PDAC arising from pancreatic body. A. Axial IV contrast-enhanced CT image in maximum intensity projection shows tumor (arrow) encasement of celiac artery (arrowhead), common hepatic artery, and splenic artery. B. Sagittal IV contrast-enhanced CT image shows tumor encasement of the celiac artery (arrow) and sparing of the SMA (arrowhead), which allows for modified Appleby procedure.

Figure 4.

The Whipple procedure (pancreaticoduodenectomy) for resectable PDAC in the head of the gland. A. Normal anatomic relationship of the pancreas and surrounding structures. B. Diagram of a pancreatic head mass (white) to surround the pancreatic and bile ducts (shown in green). C. Standard resection for pancreaticoduodenectomy to include the head of the pancreas, duodenum, distal common bile duct, distal stomach, and gallbladder. D. Reconstruction to reconnect the pancreas, common bile duct, and stomach to the gastrointestinal tract.

Figure 5.

76 year-old woman with a large PDAC of the pancreatic tail underwent distal pancreatectomy and splenectomy revealing an 8.5 cm invasive carcinoma with a microscopically positive proximal pancreatic margin and 3 of 14 lymph nodes involved by carcinoma. She underwent 6 months of adjuvant FOLFIRINOX followed by adjuvant chemoradiation therapy to a dose of 45-to-50 Gy in 25 fractions using simultaneous integrated boost technique with concurrent capecitabine. Images show standard adjuvant radiation fields and dose distribution using IMRT in axial (A), coronal (B) and sagittal (C) planes. Scale: blue 17 Gy -> red 50 Gy.

Figure 6.

48 year-old man with a localized PDAC of the uncinate process encasing the SMA. He underwent 3 cycles of gemcitabine/abraxane, then SBRT guided by fiducial markers to 33 Gy in 5 fractions. He had 2 more cycles of chemotherapy, then underwent exploration revealing retraction from SMA and subsequent Whipple procedure. Images show (A) SBRT tumor volume (red) and duodenal planning organ at risk volume (PRV, purple). Dose distribution in axial (B) and coronal (C) planes. Scale: blue 11 Gy -> red 33 Gy.

Figure 7.

Examples of borderline resectable and unresectable PDAC. A. CT scan image (3D vascular reconstruction) of a borderline resectable PDAC with narrowing of the superior mesenteric vein (SMV, bright yellow arrows). Proximal and distal targets for reconstruction shown at orange arrows. B. Following neoadjuvant chemotherapy, the patient was taken to the operating room and the tumor was excised to include the involved SMV (left panel). The SMV was reconstructed using an interposition internal jugular vein graft (B, right panel, and C). D. Cross-sectional CT images of a locally advanced PDAC (middle panel, orange arrow). There is a proximal portal vein target (left panel, orange arrow), but only collaterals distally (right panel, blue arrows). With no distal target, reconstruction is not possible, making the tumor unresectable.

Figure 8.

63 year-old woman with locally advanced PDAC arising from the head of pancreas. After 6 months of mFOLFIRINOX, tumor continued to encase SMA and celiac artery. She was treated with hypofractionated, dose-escalated radiotherapy to an ablative dose of 67.5 Gy delivered in 15 daily fractions during breath hold. A. Target delineation shows integrated tumor volume (red), duodenum (blue), and stomach (pink). A 10mm planning organ at risk volume (PRV) around luminal bowel structures shown in cyan. Planning treatment volumes for 67.5 Gy (magenta) excluded from bowel PRV, whereas low dose 37.5 Gy PTV (green) overlaps both PRV and true bowel volume. B. Dose distribution for plan based on contours shown in (A). Scale: blue 20 Gy -> red 65 Gy.