Comparative treatment planning between proton and X-ray therapy in pancreatic cancer.

With the utilization of new biologic agents and experimental chemotherapy in the treatment of pancreatic cancer, the issue of local-regional control will become increasingly important. This study was undertaken to determine the feasibility of dose escalation using proton therapy, as compared to conventional 3-dimensional conformal radiation, by minimizing the dose to normal tissues. The photon treatment plans of 4 patients with unresectable pancreatic cancer treated on a biologic therapy trial were utilized. Each patient was treated using a 3- or 4-field photon plan with 45 Gy to the clinical target volume (CTV), followed by a boost of 14.4 Gy to the gross target volume (GTV). Using a Helax treatment planning system, proton plans were generated to encompass the same CTV and GTV to the same prescribed dose. Dose-volume histograms (DVHs) were generated for the GTV, CTV, spinal cord, liver, and right and left kidneys. Each DVH was compared between the photon and proton plans. Proton plans utilized either a 2- or 3-field technique. Available energies included 130 or 180 MeV. Range modulators and bolus were used as needed to conform to the target volume. With the CTV and GTV receiving the same dose from the proton and photon plans, all individual proton plans were superior to the photon plans in reduction of normal tissue dose. For the 4 patients, the average dose reduction to 50% of the organ at risk was 78% to spinal cord (p = 0.003), 73% to left kidney (p = 0.025), 43% to right kidney (p = 0.059), and 55% to liver (p = 0.061). These comparative treatment plans show proton therapy results in significant reductions of dose to normal tissue compared to conventional photons while treating the same target volumes. This allows for the design of dose-escalation protocols using protons in combination with new biologic therapies and chemotherapy.     

Scaphoid fractures: evaluation with high-spatial-resolution US initial results.

PURPOSE: To evaluate the diagnostic accuracy of high-spatial-resolution ultrasonography (US) in the diagnosis of scaphoid fractures. MATERIALS AND METHODS: In 72 hours after acute wrist trauma, 15 consecutive patients were examined for possible scaphoid fractures clinically and with conventional radiographs, including scaphoid views. Thereafter, high-spatial-resolution US was performed by two experienced radiologists blinded to the results of the previously performed investigations. High-spatial-resolution US of the scaphoid bones was performed from the palmar, lateral, and dorsal directions in the longitudinal and transverse planes. US findings indicative of a scaphoid fracture were cortical discontinuity and/or periosteal elevation. Finally, magnetic resonance (MR) images (short inversion time inversion-recovery, T1- and T2*-weighted) (ie, the standard) of the affected wrist were obtained and evaluated for a possible scaphoid fracture by two radiologists in consensus. RESULTS: Nine of 15 patients had scaphoid fractures. Seven (78%) of nine patients had positive findings at high-spatial-resolution US and five (56%) had such findings at conventional radiography (ie, four occult scaphoid fractures), with an accuracy of 87% and 73%, respectively. Two (50%) of four radiographically occult scaphoid fractures were depicted with high-spatial-resolution US. Sonographic findings of scaphoid fractures were either cortical discontinuity (n = 4), periosteal elevation (n = 2), or a combination of these two findings (n = 1). CONCLUSION: High-spatial-resolution US is a reliable diagnostic tool for the evaluation of occult scaphoid fractures and should be considered an adequate alternative diagnostic tool prior to computed tomography or MR imaging.     

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self‐administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e‐mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1–0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low‐grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice‐daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low‐grade dysplasia, and 52% for high‐grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence‐based guidance is required to enhance clinical practice.     

Toxicity study of gemcitabine, oxaliplatin, and bevacizumab, followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy, in patients with locally advanced pancreatic cancer

Purpose

Platinum compounds or bevacizumab, in combination with gemcitabine, achieved good response rates in early studies in advanced pancreatic cancer. This prompted an evaluation of an aggressive approach to allow better local control and resectability in locally advanced disease.

Methods

We piloted a combination of gemcitabine/oxaliplatin/bevacizumab Q2w for four cycles, followed by oxaliplatin and bevacizumab added to infusional 5-FU and radiotherapy, in patients with locally advanced pancreatic cancer.

Results

Nineteen patients were treated, of whom 17 completed the protocol-specified treatment. Median age was 60 years. Fifteen had unresectable, and four had borderline resectable disease. Toxicity of chemotherapy was moderate: grade III neutropenia (5) and grade I/II nausea, vomiting, fatigue, and neuropathy. During chemoradiation, major grade III toxicities were nausea and vomiting (3 each). One patient had intractable pain early on, necessitating treatment cessation. Response rate for 18 evaluable patients was 11 % (by RECIST); five patients (4 inoperable, 1 borderline, 26 %) went on to have surgery. One-year overall survival was 58 % and progression-free survival was 37 %.

Conclusions

This combination, associated with higher response rates in metastatic disease, had a lower than expected response rate in primary tumors. Although tolerable, our approach failed to affect clinical outcomes meaningfully.