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Ch 26 - Goodman K & Koong A: CyberKnife Radiosurgery for Pancreatic Cancer
Abstract and Figures
Pancreatic cancer remains one of the most lethal cancer diagnoses. The high mortality rate associated with this disease is primarily related to its advanced stage at diagnosis. Locally advanced carcinoma of the pancreas is uniformly fatal, and while chemoradiotherapy is the standard treatment, the results of conventional radiotherapy have been disappointing. Modern radiation therapy has increasingly used conformal fields and dose escalation to enhance tumor control. Extracranial stereotactic radiosurgery using CyberKnife® technology is a novel approach to administering tumoricidal radiation doses in a single outpatient treatment while minimizing the irradiation of surrounding healthy tissue. Phase I/II studies have demonstrated that CyberKnife radiosurgery is a safe and effective strategy for the management of patients with locally advanced and metastatic pancreatic cancer. It has been shown to provide palliation of local symptoms and is associated with a low incidence of local recurrence. The role of pre-operative radiosurgery in combination with gemcitabine chemotherapy is being investigated and has many theoretical advantages over conventional fractionation neoadjuvant chemoradiation.
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... For intracranial conditions, the CyberKnife system has been used to radiosurgically treat a variety of tumours such as residual small skull base menigiomas, small acoustic schwanomas (Sakamoto et al., 2005), small pituitary adenomas, and small metastases (Young et al., 2005) as well as other abnormalities such as small arteriovenous malformations (AVMs) and intractable pain such as in Trigeminal Neuralgia (Massaudi et al., 2005). With the Synchrony™ motion tracking system, tumours in organs moving with respiration such as the lung (Brown et al., 2005), the pancreas (Goodman & Koong, 2005), the liver and the kidney can be successfully targeted. Other tumours based in more rigid body anatomy, where minimal motion is expected, may be tracked via rigidly implanted markers including those in the spine and the prostate (Medbery et al., 2005). ...
... To date, more than 10,000 patients have benefited from the revolutionary concept of marrying robotics to image-guided radiosurgery. Scientific presentations and publications on the clinical applications of the CyberKnife are numerous – including intracranial (Young et al., 2005), spine (Gerszten et al., 2005), paediatric (Giller et al., 2005), prostate (Medbery et al., 2005), pancreas (Goodman & Koong, 2005), kidney and lung (Brown et al., 2005). @BULLET The RoboSim Neurosurgery Simulator (Radstzky A & Radolph M, 2001): This robotic neurosurgical simulator consists of a workstation and a robotic arm (NeuRobot). ...
Background:
For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors. and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head.
Methods:
Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence.
Results:
The overall median survival from the time of tissue diagnosis was 21 months (range 19-26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect.
Conclusion:
This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.
Background:For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors, and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. Methods:Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence. Results:The overall median survival from the time of tissue diagnosis was 21 months (range 19–26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect. Conclusion:This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.
A prospective study to determine the lymph node involvement in 33 pancreatectomy specimens (regional pancreatectomy 18, total pancreatectomy 7, Whipple partial pancreatectomy 8) was undertaken. There were 22 patients with pancreas duct adenocarcinoma, 6 with ampullary carcinoma, 3 with duodenal adenocarcinoma, 1 bile duct carcinoma and 1 of undetermined site of origin. Peripancreatic lymph nodes were divided into 5 main groups with subgroups. They are 1) Superior, Superior Head, Superior Body and Gastric; 2) Inferior: Inferior Head and Inferior Body, 3) Anterior: Anterior Pancreaticoduodenal, Pyloric and Mesenteric, 4) Posterior: Posterior Pancreaticoduodenal, Common Bile Duct, and 5) Splenic: lymph nodes at hilum of spleen and at the tail of pancreas. The average number of lymph nodes found in different types of surgical specimens was: regional pancreatectomy 70, total pancreatectomy 41, and Whipple procedure 33. The average number of lymph nodes involved with metastatic tumor in these specimens was, respectively, 5, 3 and 1. The most common sites of metastasis were in the Superior Head and in the Posterior Pancreaticoduodenal groups. Pancreatic duct adenocarcinoma tended to me-tastasize to multiple lymph nodes of the Superior Head, Superior Body and Posterior Pancreaticoduodenal lymph nodes (88% of patients). Ampullary adenocarcinoma metastasized less often (33%), usually to fewer nodes and to one adjacent periampullary group. Since in 33% of patients nodal metastases of duct adenocarcinoma of the head of the pancreas were present in groups not usually removed in the Whipple procedure, it would appear that this operation is inadequate for surgical eradication of pancreas duct adenocarcinoma of the head of the pancreas.
Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who undergo resection complete multimodality therapy, avoids resection in patients with rapidly progressive disease, and allows radiation therapy to be delivered to well-oxygenated cells before surgical devascularization. Twenty-eight patients with cytologic or histologic proof of localized adenocarcinoma of the pancreatic head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and 50.4 Gy) with the intent of proceeding to resection; all 28 completed this preoperative therapy. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. Our results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.
The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease.
One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.
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October 2005