Dosimetric and radiobiological impact of abdominal compression on adjacent gastro-intestinal critical structures for patients treated with upper and mid-abdominal stereotactic body radiotherapy.

OBJECTIVES: We evaluated the dosimetric and radiobiological impact of abdominal compression (AC) on nearby gastrointestinal critical structures (GI-CS) and reported toxicities of patients treated with non-hepatic abdominal stereotactic body radiotherapy (SBRT). METHODS: Two sets of CT scans, planning scans with AC and pre-treatment diagnostic scans without AC (non-AC) were compared for patients treated with a prescription dose to planning target volume (PTV) ≥25 Gy/5-fractions at a single institution. Target volumes were delineated on both sets of scans and PTV was expanded isotropically by 2 cm (PTV+2) and 4 cm (PTV+4). All GI-CS were summated to create a composite CS (GI-lumen). Rigid registration of AC and non-AC scans was done using Velocity AI (Varian Medical Systems) to obtain dose distribution information. Lymann-Probit and logit models were used for radiobiological calculations. Toxicity scores were obtained from prospectively collected clinical data. RESULTS: A total of 12 patients were included. Mean PTV volumes were 190.3cc and 196.4cc with AC and non-AC (p=0.95). Significant improvement in V30 of GI-lumen was seen with AC (0.11cc vs. 4.97cc, p=0.04). There were no differences in the normal tissue complication probabilities of the individual GI-CS or the summary indices except a notable trend towards better NTCP for small bowel late effects with AC (0.21% vs. 2.45%; p=0.055). Three patients had acute grade-1 anorexia, one patient had acute grade-2 gastritis. There was no grade ≥3 GI toxicity. At a median follow-up of 2.6 years, total of 8/12 (66.7%) patients developed local recurrence of whom 4 (33.3%) had isolated local recurrence. CONCLUSION: Use of AC did not result in any dosimetric or radiobiological inferiority for GI-CS. The current cohort completed their treatment with minimal toxicity.

In vivo Portal Imaging Dosimetry Identifies Delivery Errors in Rectal Cancer Radiotherapy on the Belly Board Device.

PURPOSE: We recently developed a novel, open-source in vivo dosimetry that uses the electronic portal imaging device to detect dose delivery discrepancies. We applied our method on patients with rectal cancer treated on a belly board device. METHODS: In vivo dosimetry was performed on 10 patients with rectal cancer treated prone on the belly board with a 4-field box arrangement. Portal images were acquired approximately once per week from each treatment beam. Our dosimetry method used these images along with the planning CT to reconstruct patient planar dose at isocenter depth. RESULTS: Our algorithm proved sensitive to dose discrepancies and detected discordances in 7 patients. The majority of these were due to soft tissue differences between planning and treatment, present despite matching to bony anatomy. As a result of this work, quality assurance procedures have been implemented for our immobilization devices. CONCLUSION: In vivo dosimetry is a powerful quality assurance tool that can detect delivery discrepancies, including changes in patient setup and position. The added information on actual dose delivery may be used to evaluate equipment and process quality and to guide for adaptive radiotherapy.

Neoadjuvant therapy for downstaging of locally advanced hilar cholangiocarcinoma: a systematic review.

BACKGROUND: Hilar cholangiocarcinoma is a rare but highly lethal type of cancer. A minority of patients present with resectable disease. Surgery remains the only treatment modality offering a chance of long-term survival. Unresectable patients are typically offered palliative treatment. The aim of this systematic review was to summarize the evidence for neoadjuvant therapy followed by surgical resection in patients presenting with hilar cholangiocarcinoma. METHODS: Cochrane databases, Medline, PubMed and EMBASE were systematically searched to identify articles describing neoadjuvant therapy and surgical resection or re-assessment of resectability in patients with hilar cholangiocarcinoma. Included were all articles with original research. Study selection and data extraction were performed separately by two reviewers using a standardized protocol. RESULTS: From 732 articles 8 full text articles and 2 abstracts met the inclusion criteria. The 2 abstracts and 1 full text article were case reports, 3 articles were retrospective and 4 were prospective studies (2 phase I and 2 phase II studies). Photodynamic therapy, chemotherapy and radiation therapy were used in various indications in populations that included patients with hilar cholangiocarcinoma, some of which were primarily unresectable. Overall quality of articles was limited. CONCLUSION: Current evidence suggests that neoadjuvant therapy in patients with unresectable hilar cholangiocarcinoma can be performed safely and in a selected group of patients can lead to subsequent surgical R0 resection. Surgical resection of downstaged patients should be assessed in properly designed phase II studies.

Small bowel dose parameters predicting grade ≥ 3 acute toxicity in rectal cancer patients treated with neoadjuvant chemoradiation: an independent validation study comparing peritoneal space versus small bowel loop contouring techniques.

PURPOSE: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. METHODS AND MATERIALS: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. RESULTS: Grade ≥3 small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. CONCLUSION: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity.

Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer.

PURPOSE: As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2) -overexpressing breast cancer patients is not yet fully defined. We aimed to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancer patients in comparison with HER-2-negative patients. PATIENTS AND METHODS: To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis. RESULTS: Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. CONCLUSION: Our study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.