[en] Surgically implanted electromagnetic transponders have been used in external beam radiotherapy for target localization and position monitoring in real time. The effect of transponders on proton therapy dose distributions has not been reported. A Monte Carlo implementation of the transponder geometry is validated against film measurements in a proton SOBP and subsequently used to generate dose distributions for transponders at different positions and orientations in the proton SOBP. The maximum dose deficit is extracted in each case. Dose shadows of up to 60% occur for transponders positioned very near the end of range of the Bragg peak. However, if transponders are positioned further than 5 mm from the end of range, and are not oriented parallel to the beam direction, then the dose deficit can be kept below 10%. (paper)

[en] We have used polished stainless steel as a mirror substrate to provide focusing of soft x rays in grazing-incidence reflection. The critical issue of the quality of the steel surface,polished and coated with gold, is discussed in detail. A comparison is made to a polished,gold-coated, electroless nickel surface, which provides a smoother finish. We used the surface height distributions, measured with an interferometric microscope and complemented by atomic-force microscope measurements, to compute power spectral densities and then to evaluate the surface roughness. The effects of roughness in reducing the specular reflectivity were verified by soft-x-ray measurements

[en] Small animal x-ray irradiation platforms are expanding the capabilities and future pathways for radiobiology research. Meanwhile, proton radiotherapy is transitioning to a standard treatment modality in the clinician’s precision radiotherapy toolbox, highlighting a gap between state-of-the-art clinical radiotherapy and small animal radiobiology research. Comparative research of the biological differences between proton and x-ray beams could benefit from an integrated small animal irradiation system for in vivo experiments and corresponding quality assurance (QA) protocols to ensure rigor and reproducibility. The objective of this study is to incorporate a proton beam into a small animal radiotherapy platform while implementing QA modelled after clinical protocols.

A 225 kV x-ray small animal radiation research platform (SARRP) was installed on rails to align with a modified proton experimental beamline from a 230 MeV cyclotron-based clinical system. Collimated spread out Bragg peaks (SOBP) were produced with beam parameters compatible with small animal irradiation. Proton beam characteristics were measured and alignment reproducibility with the x-ray system isocenter was evaluated. A QA protocol was designed to ensure consistent proton beam quality and alignment. As a preliminary study, cellular damage via γ-H2AX immunofluorescence staining in an irradiated mouse tumor model was used to verify the beam range in vivo.

The beam line was commissioned to deliver Bragg peaks with range 4–30 mm in water at 2 Gy min⁻¹. SOBPs were delivered with width up to 25 mm. Proton beam alignment with the x-ray system agreed within 0.5 mm. A QA phantom was created to ensure reproducible alignment of the platform and verify beam delivery. γ-H2AX staining verified expected proton range in vivo.

An image-guided small animal proton/x-ray research system was developed to enable in vivo investigations of radiobiological effects of proton beams, comparative studies between proton and x-ray beams, and investigations into novel proton treatment methods. (paper)

[en] Purpose: To examine the role of brachytherapy in the treatment of cholangiocarcinomas in a relatively large group of patients. Methods and Materials: Using the Surveillance, Epidemiology and End Results database, a total of 193 patients with cholangiocarcinoma treated with brachytherapy were identified for the period 1988-2003. The primary analysis compared patients treated with brachytherapy (with or without external-beam radiation) with those who did not receive radiation. To try to account for confounding variables, propensity score and sensitivity analyses were used. Results: There was a significant difference between patients who received radiation (n = 193) and those who did not (n = 6859) with regard to surgery (p < 0.0001), race (p < 0.0001), stage (p < 0.0001), and year of diagnosis (p <0.0001). Median survival for patients treated with brachytherapy was 11 months (95% confidence interval [CI] 9-13 months), compared with 4 months for patients who received no radiation (p < 0.0001). On multivariable analysis (hazard ratio [95% CI]) brachytherapy (0.79 [0.66-0.95]), surgery (0.50 [0.46-0.53]), year of diagnosis (1998-2003: 0.66 [0.60-0.73]; 1993-1997: (0.96 [0.89-1.03; NS], baseline 1988-1992), and extrahepatic disease (0.84 [0.79-0.89]) were associated with better overall survival. Conclusions: To the authors' knowledge, this is the largest dataset reported for the treatment of cholangiocarcinomas with brachytherapy. The results of this retrospective analysis suggest that brachytherapy may improve overall survival. However, because of the limitations of the Surveillance, Epidemiology and End Results database, these results should be interpreted cautiously, and future prospective studies are needed.

[en] Biological experiments of proton FLASH radiation have demonstrated reduced normal tissue toxicity while maintaining equipotent tumor killing effects in-vivo. Further experimental evidence will need to be developed to determine accurate irradiation parameters to optimize this effect for biomechanism discovery and clinical translation. Radiobiological assays have proven highly sensitive to variability in experimental conditions including irradiation parameters. At FLASH dose rates, dose delivery time structure can be expected to play a significant role. Therefore, robust irradiation and data collection techniques must be implemented to ensure accurate cross comparisons and reproducible biological effects. (author)

[en] Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC

[en] Purpose: Extrahepatic cholangiocarcinomas (EHC) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (RT) for EHC have not been performed. The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population. Methods and Materials: This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was overall survival. Results: Patients underwent surgery (28.8%), RT (10.0%), surgery and RT (14.7%), or no RT or surgery (46.4%). The median age of the patient population was 73 years (range, 23-104), 52.5% were men, and 80.7% were white. The median overall survival time was 16 months (95% confidence interval [CI] 15-17), 9 months (95% CI 9-11), 9 months (95% CI 9-10), and 4 months (95% CI 3-4) for surgery and RT, surgery, RT, and no RT or surgery, respectively. The overall survival was significantly different between the surgery and surgery and RT groups (p < .0001) and RT and no RT or surgery groups (p < .0001) on the log-rank test. The propensity score-adjusted analyses of surgery and RT vs. surgery (hazard ratio, 0.94; 95% CI, 0.84-1.05) were not significantly different, but that for RT vs. no RT or surgery (hazard ratio, 0.61; 95% CI, 0.54-0.70) was significantly different. Conclusion: These results suggest that palliative RT prolongs survival in patients with EHC. The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score. Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC.

[en] Purpose: Uncontrolled local growth is the cause of death in ∼30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. Methods: The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6–53.8 and 34.9–52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations

[en] Purpose: Over the past 30 years, much work in treatment of breast cancer has contributed to improvement of cosmetic and functional outcomes. The goal of breast-conservation treatment (BCT) is avoidance of mastectomy through use of lumpectomy and adjuvant radiation. Modern data demonstrate “excellent” or “good” cosmesis in >90% of patients treated with BCT. Methods and Materials: Patient-reported data were gathered via a convenience sample frame from breast cancer survivors using a publically available, free, Internet-based tool for creation of survivorship care plans. During use of the tool, breast cancer survivors are queried as to the cosmetic appearance of the treated breast, as well as perceived late effects. All data have been maintained anonymously with internal review board approval. Results: Three hundred fifty-four breast cancer survivors having undergone BCT and voluntarily using this tool were queried with regard to breast cosmesis and perceived late effects. Median diagnosis age was 48 years, and median current age 52 years. “Excellent” cosmesis was reported by 27% (n = 88), “Good” by 44% (n = 144), “Fair” by 24% (n = 81), and “Poor” by 5% (n = 18). Of the queries posted to survivors after BCT, late effects most commonly reported were cognitive changes (62%); sexual concerns (52%); changes in texture and color of irradiated skin (48%); chronic pain, numbness, or tingling (35%); and loss of flexibility in the irradiated area (30%). Survivors also described osteopenia/osteoporosis (35%), cardiopulmonary problems (12%), and lymphedema (19%). Conclusions: This anonymous tool uses a convenience sample frame to gather patient reported assessments of cosmesis and complications after breast cancer. Among the BCT population, cosmetic assessment by survivors appears less likely to be “excellent” or “good” than would be expected, with 30% of BCT survivors reporting “fair” or “poor” cosmesis. Patient reported incidence of chronic pain, as well as cognitive and sexual changes, also appears higher than expected.

[en] Purpose: Pain is a common symptom among cancer patients, yet many patients do not receive adequate pain management. Few data exist quantifying analgesic use by radiation oncology patients. This study evaluated the causes of pain in cancer patients and investigated the reasons patients fail to receive optimal analgesic therapy. Methods and Materials: An institutional review board-approved, Internet-based questionnaire assessing analgesic use and pain control was posted on the OncoLink (available at (www.oncolink.org)) Website. Between November 2005 and April 2006, 243 patients responded. They were predominantly women (73%), white (71%), and educated beyond high school (67%) and had breast (38%), lung (6%), or ovarian (6%) cancer. This analysis evaluated the 106 patients (44%) who underwent radiotherapy. Results: Of the 106 patients, 58% reported pain from their cancer treatment, and 46% reported pain directly from their cancer. The pain was chronic in 51% and intermittent in 33%. Most (80%) did not use medication to manage their pain. Analgesic use was significantly less in patients with greater education levels (11% vs. 36%, p = 0.002), with a trend toward lower use by whites (16% vs. 32%, p 0.082) and women (17% vs. 29%, p = 0.178). The reasons for not taking analgesics included healthcare provider not recommending medication (87%), fear of addiction or dependence (79%), and inability to pay (79%). Participants experiencing pain, but not taking analgesics, pursued alternative therapies for relief. Conclusions: Many radiation oncology patients experience pain from their disease and cancer treatment. Most study participants did not use analgesics because of concerns of addiction, cost, or failure of the radiation oncologist to recommend medication. Healthcare providers should have open discussions with their patients regarding pain symptoms and treatment