Technological advances have ushered in a new era in advanced gastrointestinal endoscopy. With the incorporation of endoscopic ultrasound (EUS) into the diagnostic armamentarium, staging of esophageal, gastric, pancreatic, and rectal cancers now yields important information about primary tumor size and lymph node status at diagnosis. Since neoadjuvant therapies have an important role in the initial management of locally advanced tumors, having EUS available clarifies individualized treatment selection. At Moffitt Cancer Center, gastrointestinal endoscopic oncologists evaluate patients in multidisciplinary clinics with surgeons, medical oncologists and radiation oncologists, as well as participate in weekly tumor board. This close collaboration fosters consideration of all endoscopic modalities, both for diagnosis and treatment, early in the process.
One such area where EUS is critical to individualize patient selection is pancreatic cancer. In the past, patients presenting with a pancreatic mass would often be advised to undergo major exploratory surgery in order to determine whether a tumor was resectable. Now with EUS, a fine needle aspirate (FNA) can first be obtained to determine the histology. This is extremely helpful in confirming a pancreatic primary adenocarcinoma versus a neuroendocrine carcinoma versus a potentially benign lesion such as autoimmune pancreatitis, which would warrant medical management rather than surgical resection. Once a primary pancreas cancer is confirmed by needle aspirate in conjunction with a thin cut pancreas protocol cat scan (CT), EUS can then refine the relationship between the tumor and major blood vessels – a necessary step in determining resectability. Moffitt Cancer Center follows the National Comprehensive Cancer Network (NCCN) definition of resectable, borderline resectable and unresectable status. We have our own programmatic pathway of neoadjuvant multiagent chemotherapy followed by stereotactic body radiation therapy (SBRT) in the treatment of borderline resectable tumors to enhance conversion to margin negative surgery.
Prior to radiation, our group assists radiation oncologists with SBRT by endoscopically placing small radio-opaque markers (termed fiducial markers) into the pancreas tumor. SBRT relies on image-guided radiation therapy (IGRT), permitting escalation of radiation dose to tumors while minimizing dose to normal tissues. In fact, our radiation group uses them to guide respiratory-gated treatment so that the markers are viewed fluoroscopically on the treatment table. When the marker reaches the maximum exhalation position, the linear accelerator beams “on” to deliver a high dose fraction. This multidisciplinary team approach has not only led to the majority of borderline patients undergoing margin negative resection, but also has been associated with significant tumor and nodal downstaging. In fact, we have patients who have had pathologic complete responses as well as minimal microscopic disease remaining.
EUS also offers therapeutic intervention, including celiac plexus neurolysis for relief of chronic pain caused by unresectable pancreatic tumors – pain that is not readily relieved with narcotic medications. In the near future, EUS will likely offer other modalities for treatment and local control of unresectable tumors, including brachytherapy and cryoablation. Furthermore, EUS-guided fine-needle injection (EUS-FNI) is an attractive minimally invasive delivery system with potential applications in local and combination therapy against pancreatic cancers. Evidence of the feasibility of EUS-FNI of antitumor agents as well as brachytherapy and cryoablation has been growing with promising results.
Moffitt also uses endoscopically implanted fiducial markers to guide radiation therapy in other sites. Our group implants these markers at the superior and inferior aspect of the tumor in the esophagus and rectum. In the esophagus, there is significant respiratory-associated tumor motion that can be quantified with the markers, and appropriate shifts can be made to ensure the proper treatment alignment. Moreover, with the echoendoscope, we are also able to image the most medial extent of the liver, which is helpful when an FNA is necessary to confirm histology or when fiducial markers are needed to guide radiation therapy for primary tumors and oligo-metastasis.
Patients with Barrett esophagus with high-grade dysplasia, or with early esophageal cancers that do not invade the submucosa (uT1a), may also be candidates for minimally invasive therapeutic endoscopic procedures. These procedures consist of endoscopic mucosal resection (EMR) or endoscopic ablation including cryoablation, radiofrequency ablation (RFA) and photodynamic therapy (PDT). EMR is not only beneficial in obtaining a pathological stage of the tumor, as it can also be curative for T1a lesions. RFA has a proven track record of excellent results in the treatment of flat high grade dysplasia and even flat intramucosal carcinoma. Those patients with locally advanced esophageal cancer not deemed to be candidates for surgical resection may particularly benefit from cryoablation of the residual persistent dysplastic Barrett esophagus after definitive chemoradiation. Our GI group has previously reported an 88 percent rate of persistent Barrett esophagus in patients achieving a complete clinical response after definitive chemoradiation for invasive esophageal adenocarcinoma. Residual Barrett esophagus that is untreated may increase the risk of de novo adenocarcinoma. This has led to our approach of ensuring that patients who do not undergo surgery status post-chemoradiation are referred back for endoscopic evaluation. If residual Barrett esophagus persists, patients are offered cryoablation. We have previously shown that this modality is safe and effective in those patients who have received radiation as part of their treatment algorithm. Currently, the other ablative methods have not been evaluated in this patient population.
Finally, gastrointestinal therapeutic endoscopy offers patients with locally advanced esophageal cancer more options for palliation of dysphagia. Newer, more flexible and smaller caliber fully covered self-expanding metal stents are associated with better patient tolerability and less pain without increased risk for migration or tumor ingrowth and are also easily removable. These stents allow patients to maintain adequate nutrition by continuing regular per os intake while receiving therapy – an issue as important clinically as it is emotionally and mentally. They have been proven to be safe while patients receive radiation and most are deemed MRI compatible. All of these techniques are rapidly expanding options for cancer patients with involvement of the gastrointestinal tract. Optimal incorporation of these tools may allow us to better personalize treatment.
Adapted from Florida MD, January 2013