PubMed · 14520786
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Cole A Giller. 2003. What I learned while dying.. https://pubmed.ncbi.nlm.nih.gov/14520786/
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PURPOSE: Development and implementation of a strategy to use a stereotactic ultrasound (US)-based image-guided targeting device (BAT) to align intensity-modulated radiotherapy (IMRT) target volumes accurately in the upper abdomen. Because the outlines of such targets may be poorly visualized by US, we present a method that uses adjacent vascular guidance structures as surrogates for the target position. We assessed the potential for improvement of daily repositioning and the feasibility of daily application. METHODS AND MATERIALS: A total of 62 patients were treated by sequential tomotherapeutic IMRT between October 2000 and June 2003 for cholangiocarcinoma and gallbladder carcinoma (n = 10), hepatocellular carcinoma (n = 10), liver metastases (n = 11), pancreatic carcinoma (n = 20), neuroblastoma (n = 3), and other abdominal and retroperitoneal tumors (n = 8). The target volumes (TVs) and organs at risk were delineated in contrast-enhanced CT data sets. Additionally, vascular guidance structures in close anatomic relation to the TV, or within the TV, were delineated. Throughout the course of IMRT, US BAT images were acquired during daily treatment positioning. In addition to the anatomic structures typically used for US targeting (e.g., the TV and dose-limiting organs at risk), CT contours of guidance structures were superimposed onto the real-time acquired axial and sagittal US images, and target position adjustments, as indicated by the system, were performed accordingly. We report the BAT-derived distribution of shifts in the three principal room axes compared with a skin-mark-based setup, as well as the time required to perform BAT alignment. The capability of the presented method to improve target alignment was assessed in 15 patients by comparing the organ and fiducial position between the respective treatment simulation CT with a control CT study after US targeting in the CT suite. RESULTS: A total of 1,337 BAT alignments were attempted. US images were not useful in 56 setups (4.2%), mainly because of limited visibility due to daily variations in colonic and gastric air. US imaging was facilitated in intrahepatic tumors and asthenic patients. The mean +/- SD shift from the skin mark position was 4.9 +/- 4.35, 6.0 +/- 5.31, and 6.0 +/- 6.7 mm in the x, y, and z direction, respectively. The mean magnitude vector of three-dimensional alignment correction was 11.4 +/- 7.6 mm. The proportion of daily alignments corrected by a magnitude of >10, >15, and >20 mm was 48.9%, 25.1%, and 12.7%, respectively. The magnitude of shifts in the principal directions, as well as the three-dimensional vector of displacement, was statistically significant (test against the zero hypothesis) at p <0.0001. The guidance structures that were the most valuable for identification of the TV position were the branches of the portal vein, hepatic artery, and dilated bile ducts in intrahepatic lesions and the aorta, celiac trunk, superior mesenteric artery, and extrahepatic aspects of the portal vein system in retroperitoneal and extrahepatic lesions. The mean total setup time was 4.6 min. The correlation of BAT targeting with target setup error assessment in the control CT scans in 15 patients revealed setup error reduction in 14 of 15 alignments. The average setup error reduction, assessed as a reduction in the length of setup error three-dimensional magnitude vector, was 54.4% +/- 26.9%, with an observed mean magnitude of residual setup error of 4.6 +/- 3.4 mm. The sole worsening of an initial setup was by a magnitude of <2 mm. US targeting resulted in statistically significant improvements in patient setup (p = 0.03). CONCLUSION: Daily US-guided BAT targeting for patients with upper abdominal tumors was feasible in the vast majority of attempted setups. This method of US-based image-guided tumor targeting has been successfully implemented in clinical routine. The observed improved daily repositioning accuracy might allow for individualized reduction of safety margins and optional dose escalation. Compared with the established application of the BAT device for prostate radiotherapy, in which the target can be directly visualized, the TV in the present study was predominantly positioned relative to guidance vascular structures in close anatomic relation. We perceived an enormous potential in improved and individualized patient positioning for fractionated radiotherapy and also for stereotactic extracranial radiotherapy and radiosurgery, especially for tumors of the liver and pancreas.
BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) allows detailed imaging of both intramural and extramural structures of the gastrointestinal (GI) tract and also allows tissue samples to be obtained from masses and lesions in the GI tract. The objective of the current study was to determine the diagnostic utility of EUS-FNA in evaluating intramural and extramural GI tract lesions. METHODS: The authors evaluated all EUS-FNA specimens of GI tract lesions obtained over a 30-month period (from August 2000 to February 2003). Samples of pancreatic and intrabdominal/mediastinal lymph nodes were excluded from the study. A single endosonographer performed all procedures. An attending cytopathologist also was present on site to assess specimen adequacy. Cytologic diagnoses were analyzed for correlations with final diagnoses, which were based on histologic examination of biopsied/resected pathology materials and/or clinical follow-up findings. RESULTS: Sixty-two EUS-FNA specimens of intramural and extramural GI tract lesions were obtained from a total of 60 patients. The mean patient age was 58.8 years (standard deviation, 15.3 years). Thirty-six patients (60%) were male, and 24 (40%) were female. Twenty-eight patients had surgical pathologic evaluation of the corresponding lesions. The remaining 32 patients were followed clinically for a mean duration of 9.5 months (standard deviation, 7.7 months). The anatomic sites of the lesions were as follows: esophagus in 23 patients (37%), stomach in 13 patients (21%), duodenum in 15 patients (24%), and rectum/sigmoid in 11 patients (18%). It is noteworthy that 29 patients (43%) previously had experienced unsuccessful attempts at tissue diagnosis by endoscopic forceps biopsy. Of the 62 EUS-FNA specimens, 43, 4, and 15 were reported as being positive for a neoplasm, suspicious, and benign, respectively. Neoplastic lesions included carcinoma (n = 24), gastrointestinal stromal tumor (GIST; n = 18), neuroendocrine neoplasm (n = 2), and lymphoma (n = 1). There were two cases of endometriosis, three foregut duplication cysts, and one case of diverticulosis. There were two lesions that yielded false-negative findings (one gastric lymphoma and one GIST) secondary to sampling or interpretive error. There also were three cases that yielded false-positive findings (one case of endometriosis, one case of duodenal diverticula with smooth muscle hyperplasia, and one case of normal pancreas, which presented as a periduodenal mass). The sensitivity, specificity, and diagnostic accuracy of EUS-FNA in diagnosing GI tract neoplastic lesions were 89%, 88%, and 89%, respectively. CONCLUSIONS: EUS-FNA provides accurate tissue diagnosis in a wide variety of extraintestinal mass lesions and intramural GI tumors, particularly in patients for whom previous endoscopic forceps biopsy was unsuccessful in establishing a diagnosis.
Selective induction of vascular damage within a growing tumor is a potentially important approach in the search for potent anticancer therapeutics. Tubulin-binding (antimitotic) agents destabilize cellular microtubules, suppress tumor growth, and exert antivascular effects with varying degrees of tumor selectivity in preclinical models. The tumor-selective, antivascular effects of ABT-751, a novel, orally active antimitotic agent, currently in phase II clinical development, were characterized in vivo in the present study. We developed an in vivo rat model designed to quantify acute changes in regional vascular resistance (VR) in both tumor and non-tumor vascular beds simultaneously. Tissue-isolated tumors (1 g) with blood flow supplied by a single epigastric artery were grown in rats. Subsequently, tumor blood flow was measured under anesthesia in solid tumors and also in mesenteric, renal, and normal epigastric arteries. Phenylephrine-induced (1 micromol/kg) increases in VR were not different between tumor and non-tumor epigastric arteries, suggesting that tumor vessels possess relatively normal vasoconstrictive function. ABT-751 (3, 10, and 30 mg/kg; i.v.) produced modest transient increases in mean arterial pressure with no effect on heart rate. Tumor VR increased to 75+/-36, 732+/-172, and 727+/-125% above baseline, respectively (P<0.05 for the 10 and 30 mg/kg doses), whereas VR in normal epigastric arteries was not significantly affected. Administration of ABT-751 produced transient modest ( P<0.05) increases in mesenteric VR and no effect on renal VR. These results demonstrate that ABT-751 produces marked reductions in tumor blood flow in the intact rat at doses that exert negligible effects on normal vascular function.