Overall and chemotherapy-free survival following stereotactic body radiation therapy for abdominopelvic oligometastases.

INTRODUCTION: Limited data establish the efficacy and safety of SBRT in the abdominopelvic (AP) space, where SBRT delivery is challenging due to the proximity of radiosensitive luminal gastrointestinal (GI) organs. The aim of this study was to assess clinical outcomes in patients with AP OM treated with SBRT. METHODS: Eligible patients were those with OM (defined as metastases in ≤3 total sites) in the AP space (excluding liver) treated with SBRT. Descriptive statistics and Kaplan-Meier estimates of (LC), progression-free survival (PFS), overall survival (OS) and chemotherapy-free survival (CFS) were performed. RESULTS: Fifty-one patients with 58 AP OM received SBRT between 2011 and 2015. Median follow-up was 21.9 months. All SBRT treatments were delivered in 5 fractions with a median dose of 35 Gy (25-40 Gy). Progression post-SBRT occurred in 38/51 patients (75%), with a median PFS of 4.9 months (95% CI: 2.5-7.5), and 2-year PFS of 29%. Rates of 2-and 4-year LC were 74% and 69%, respectively. Median OS was 42.6 months (95% CI: 31-55). Oligometastatic progression occurred in 21/38 patients, and of those, 48% (10/21) received further SBRT. Resulting 2- and 4-year CFS were 47% and 37%, respectively (median 15.1 months). Nineteen patients (37%) experienced a grade 1 or 2 acute toxicity. One grade 3 (acute) toxicity was observed. No grade 4 or 5 toxicities were detected. CONCLUSIONS: SBRT to AP OM was associated with sustained LC, excellent OS and minimal toxicity. The use of SBRT allowed for prolonged CFS and the salvage of limited-burden distant failures.

Differentiating platinum coated brachytherapy seeds and gold fiducial markers with varying off-resonant frequency offsets.

PURPOSE: To develop an off-resonant frequency filtered method to selectively differentiate between implanted gold fiducial markers and platinum coated brachytherapy seeds. MATERIALS AND METHODS: The magnetic susceptibilities for gold fiducial markers and brachytherapy seeds differ in magnitude and also in their signs, resulting in B0-field inhomogeneity patterns with opposite main lobes. A pulse sequence used to localize brachytherapy seeds with positive contrast, centre-out radial sampling with off-resonance reception (co-RASOR), was used to reconstruct images with a range of off-resonant frequency offsets. The proposed method utilizes two frequency filters to selectively reconstruct maximum intensity projections through band-pass regions where each seed has its maximal localized hyperintensity. Seeds were simulated and then placed in gel and tissue phantoms to validate the technique using orthogonal 2D slices with seeds both parallel and perpendicular to the B0-field. RESULTS: Dual-plane 2D co-RASOR sequences were reconstructed off-resonance with applied frequency filters to create two projections displaying each seed, which were then colour-coded to negative and positive frequencies. Phantom validation showed that each seed contains its maximal CNR in opposing frequency regions as predicted. Local maxima can also appear in both negative and positive frequency regions. The relative difference between the signal of each seed and these local maxima ranged from 1.19 to 3.73, and an image threshold was determined in all cases. Tissue validation showed the technique differentiates seeds correctly and is limited by the hyperintensity patterns observed in the co-RASOR method. CONCLUSIONS: Dual-plane co-RASOR offers sub-millimetre positive contrast from implanted seeds that contain unique off-resonant frequency maxima, which frequency filters can selectively differentiate.

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial.

IMPORTANCE: Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important. OBJECTIVE: To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with "good prognosis" rectal tumors for primary surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion. INTERVENTIONS: Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%. RESULTS: Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%). CONCLUSIONS AND RELEVANCE: The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer. TRIAL REGISTRATION: ISRCTN.com identifier: ISRCTN05107772.

Role of the status of the mesorectal fascia in the selection of patients with rectal cancer for preoperative radiation therapy: a retrospective cohort study

Background: Patients with rectal cancer in whom the mesorectal fascia is threatened by tumour are more likely than all patients with stage II/III disease to benefit from preoperative radiotherapy (RT). The objective of this study was to assess whether the status of the mesorectal fascia versus a stage II/III designation can best inform the use of preoperative RT in patients undergoing major rectal cancer resection. Methods: We reviewed the charts of consecutive patients with primary rectal cancer treated by a single surgeon at McMaster University, Hamilton, Ontario, between March 2006 and December 2012. The status of the mesorectal fascia was assessed by digital rectal examination, pelvic computed tomography and, when needed, pelvic magnetic resonance imaging (MRI). Patients whose mesorectal fascia was threatened or involved by tumour received preoperative RT. The study outcomes were rates of positive circumferential radial margin (CRM) and local tumour recurrence. Results: A total of 153 patients were included, of whom 76 (49.7%) received preoperative RT because of concerns of a compromised mesorectal fascia. The median length of follow-up was 4.5 years. The number of CRM-positive cases in the RT and no-RT groups was 16 (22%) and 1 (1%), respectively (p < 0.01), and the number of cases of local tumour recurrence was 5 (7%) and 2 (3%), respectively (p = 0.2). Rates were similar when only patients with stage II/III tumours were included. Overall, 26 patients (17.0%) received MRI. Conclusion: The status of the mesorectal fascia, not tumour stage, may best identify patients for preoperative RT.

Contexte: Plus que tous les patients présentant une maladie de stade II/III, les patients atteints d'un cancer du rectum dont le fascia mésorectal est menacé par la tumeur sont de bons candidats à la radiothérapie (RT) préopératoire. L'objectif de cette étude était d'évaluer ce qui, entre l'état du fascia mésorectal et une désignation de stade II/III, permet le mieux de confirmer le bien-fondé d'une RT préopératoire chez les patients qui doivent subir une résection majeure pour cancer du rectum. Méthodes: Nous avons passé en revue les dossiers de patients consécutifs atteints d'un cancer rectal primaire traités par un seul chirurgien à l'Université McMaster, à Hamilton, en Ontario, entre mars 2006 et décembre 2012. L'état du fascia mésorectal a été évalué par toucher rectal, tomodensitométrie pelvienne et, au besoin, imagerie par résonnance magnétique (IRM) pelvienne. Les patients dont le fascia mésorectal était menacé ou affecté par la tumeur ont reçu une RT préopératoire. Les paramètres de l'étude étaient : taux de positivité de la marge radiale circonférentielle (MRC) et récurrence de la tumeur locale. Résultats: En tout, 153 patients ont été inclus, dont 76 (49,7 %) ont reçu une RT préopératoire en raison d'une atteinte du fascia mésorectal. La durée moyenne du suivi a été de 4,5 ans. Dans les groupes soumis et non soumis à la RT, les nombres de cas MRC-positifs ont été respectivement de 16 (22 %) et de 1 (1 %), (p < 0,01), et les nombres de cas de récurrence de la tumeur locale ont été respectivement de 5 (7 %) et de 2 (3 %) (p = 0,2). Les taux étaient similaires lorsque seuls les patients présentant des tumeurs de stade II/III étaient inclus. Globalement, 26 patients (17,0 %) ont subi l'IRM. Conclusion: C'est l'état du fascia mésorectal et non le stade de la tumeur qui peut le mieux permettre d'identifier les candidats à une RT préopératoire.

Resolution and registration in dual-plane co-RASOR MR.

Magnetic resonance imaging (MRI) has superior soft tissue contrast and lower interobserver variability compared to computed tomography and advances in equipment and pseudo-CT estimation have allowed for MR-only radiation therapy planning. Dedicated MR sequences have been used to localize paramagnetic structures with positive contrast, and most implanted seeds are gold fiducial markers (GFMs). We used a fast, dual-plane co-RASOR sequence to localize implanted GFMs with positive contrast in phantom and tissue to assess their resolution and registration accuracy of registration to CT. Off-resonant reconstructions of co-RASOR images were able to resolve GFMs down to 5 mm apart at 12 cm FOV. No systematic biases were observed by comparing registration of co-RASOR and bSSFP to CT images in an MR-compatible Lego phantom with a set of highly visible known points. The standard deviations of the MR to CT distance errors were <0.5 mm in all directions. We separated the component due to registration by comparing the two MR sequences, which had a maximum standard deviation of 0.36 mm in the SI-direction. Registration using the positive contrast points in a porcine sample phantom showed increased errors, but co-RASOR still performs acceptably with a target registration error of <0.75 mm. The dual-plane co-RASOR sequence could then be used for both registration and image tracking when performing MR-only radiation therapy planning.

Quality of preoperative pelvic computed tomography (CT) and magnetic resonance imaging (MRI) for rectal cancer in a region in Ontario: A retrospective population-based study.

BACKGROUND AND OBJECTIVES: Treatment decisions for rectal cancer rely on preoperative staging with CT and MRI scans. We assessed the quality of such scans in a region of Ontario. METHODS: We retrospectively collected data for patients undergoing rectal cancer surgery between July 2011 and December 2014. We measured three aspects of quality: use; comprehensiveness of reporting T-category, N-category, mesorectal fascia (MRF) status; and in non-radiated patients sensitivity and specificity of reports for relevant elements. RESULTS: A total of 559 patients underwent major rectal cancer surgery. Preoperative staging with CT and MRI was performed in 93% and 50% of patients. CT scan reports provided information on T-category, N-category, and MRF status in 41%, 92%, and 16% of cases. These same elements were reported on MRI in 88%, 93%, and 62% of cases. CT scan sensitivity and specificity was 80% and 80% for T-category, and 85% and 39% for N-category. MRI sensitivity and specificity was 75% and 81% for T-category, 79% and 37% for N-category, and 33% and 89% for MRF status. CONCLUSION: In this region of Ontario, pre-operative MRI was underutilized, CT reporting of MRF status was low, and when reported sensitivity and specificity of T- and N-category were similar for CT and MRI.

Pain Palliation Using Hypofractionated Radiotherapy for Unresectable Pancreatic Cancer.

BACKGROUND: Pain is a common symptom for patients with pancreatic cancer and is often treated using palliative radiation therapy. Standard palliative dose regimes typically consist of 2000 cGy to 3000 cGy in 5 to 10 fractions (fx). With the recent advancements in radiation dosimetric planning and delivery, the Juravinski Cancer Centre in Hamilton, Ontario, offers a hypofractionated dose of 2500 cGy in 5 fx for the improvement of pain and tumour control in selected pancreatic cancer patients. This project reviews the safety and efficacy of this prescription. METHODS: A retrospective analysis of 24 patients diagnosed with unresectable pancreatic cancer was conducted. Patient data were collected using in-house medical record systems including MOSAIQ, Meditech, and Centricity. Nonparametric data analysis tests were conducted using Minitab17. RESULTS: Nineteen of 24 patients (79%) reported a decrease in pain levels following radiation and 13 of 18 (72%) showed good local control of the tumour on a follow-up CT scan. Around 30% of patients reported nausea and vomiting and fatigue. Only 13% reported diarrhea and 8% reported constipation. Twenty-one percent reported pain flares. All patients were able to finish the entire treatment without pauses or delays. CONCLUSION: A palliative radiotherapy dose regime of 2500 cGy/5 fx demonstrates a potential for the effective control of pain with limited acute toxicities in patients with unresectable pancreatic cancer. This study aims to indicate the need for further prospective research comparing this regime to other standard treatments in order to determine which is most beneficial for the patient.

Localizing implanted fiducial markers using undersampled co-RASOR MR imaging.

The goal of this work was to use an undersampled, dual-plane centre-out radial sampling acquisition pulse sequence, with off-resonance reception, to localize fiducial markers with reduced acquisition time. Two iterative reconstruction techniques, conjugate gradient CG-SENSE and the variational penalty Total Generalized Variation (TGV), were investigated to minimize the undersampling artifacts in off-resonant radial imaging. Simulations of a field perturber were performed at sub-millimeter resolution and reconstructed to display signal pileups that can be radially compressed towards the geometric centre of the perturber for high contrast visualization, but contrast is non-recoverable as the echo time increases. A cylindrical platinum fiducial marker, placed in a phantom parallel and perpendicular to the B0-field was imaged with a short-TE half-echo readout. Contrast-to-Noise (CNR) between the signal of the fiducial its adjacent surrounding shell and half-maximum area were used to compare reconstruction methods and undersampling factors. For single slice acquisitions centred about the fiducial, each slice can be performed in as little as 2.8s. The total acquisition time to localize the fiducial marker in a phantom was reduced to 73s by undersampling (R=8) 37 axial and 15 coronal slices, effectively encoding 1.4s/slice. The noise present in undersampled images, for both scan planes and fiducial orientations, decreased significantly using TGV and CG-SENSE reconstructions, with TGV displaying better spatial resolution from reduced half-maximum area.

Protocol for the MATCH study (Mindfulness and Tai Chi for cancer health): A preference-based multi-site randomized comparative effectiveness trial (CET) of Mindfulness-Based Cancer Recovery (MBCR) vs. Tai Chi/Qigong (TCQ) for cancer survivors.

PURPOSE: A growing number of cancer survivors suffer high levels of distress, depression and stress, as well as sleep disturbance, pain and fatigue. Two different mind-body interventions helpful for treating these problems are Mindfulness-Based Cancer Recovery (MBCR) and Tai Chi/Qigong (TCQ). However, while both interventions show efficacy compared to usual care, they have never been evaluated in the same study or directly compared. This study will be the first to incorporate innovative design features including patient choice while evaluating two interventions to treat distressed cancer survivors. It will also allow for secondary analyses of which program best targets specific symptoms in particular groups of survivors, based on preferences and baseline characteristics. METHODS AND SIGNIFICANCE: The design is a preference-based multi-site randomized comparative effectiveness trial. Participants (N=600) with a preference for either MBCR or TCQ will receive their preferred intervention; while those without a preference will be randomized into either intervention. Further, within the preference and non-preference groups, participants will be randomized into immediate intervention or wait-list control. Total mood disturbance on the Profile of mood states (POMS) post-intervention is the primary outcome. Other measures taken pre- and post-intervention and at 6-month follow-up include quality of life, psychological functioning, cancer-related symptoms and physical functioning. Exploratory analyses investigate biomarkers (cortisol, cytokines, blood pressure/Heart Rate Variability, telomere length, gene expression), which may uncover potentially important effects on key biological regulatory and antineoplastic functions. Health economic measures will determine potential savings to the health system.

Fish-Derived Omega-3 Fatty Acids and Prostate Cancer: A Systematic Review.

BACKGROUND: The use of natural health products in prostate cancer (PrCa) is high despite a lack of evidence with respect to safety and efficacy. Fish-derived omega-3 fatty acids possess anti-inflammatory effects and preclinical data suggest a protective effect on PrCa incidence and progression; however, human studies have yielded conflicting results. METHODS: A search of OVID MEDLINE, Pre-MEDLINE, Embase, and the Allied and Complementary Medicine Database (AMED) was completed for human interventional or observational data assessing the safety and efficacy of fish-derived omega-3 fatty acids in the incidence and progression of PrCa. RESULTS: Of 1776 citations screened, 54 publications reporting on 44 studies were included for review and analysis: 4 reports of 3 randomized controlled trials, 1 nonrandomized clinical trial, 20 reports of 14 cohort studies, 26 reports of 23 case-control studies, and 3 case-cohort studies. The interventional studies using fish oil supplements in patients with PrCa showed no impact on prostate-specific antigen levels; however, 2 studies showed a decrease in inflammatory or other cancer markers. A small number of mild adverse events were reported and interactions with other interventions were not assessed. Cohort and case-control studies assessing the relationship between dietary fish intake and the risk of PrCa were equivocal. Cohort studies assessing the risk of PrCa mortality suggested an association between higher intake of fish and decreased risk of prostate cancer-related death. CONCLUSIONS: Current evidence is insufficient to suggest a relationship between fish-derived omega-3 fatty acid and risk of PrCa. An association between higher omega-3 intake and decreased PrCa mortality may be present but more research is needed. More intervention trials or observational studies with precisely measured exposure are needed to assess the impact of fish oil supplements and dietary fish-derived omega-3 fatty acid intake on safety, PrCa incidence, treatment, and progression.

Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines.

PURPOSE: To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure. MATERIALS AND METHODS: Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells. RESULTS: We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy. CONCLUSION: These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.

Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire-RTOG Modification.

CONTEXT: The 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537. OBJECTIVES: This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales. METHODS: EFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability. RESULTS: The 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ ≥ 0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ > 0.65). CONCLUSION: The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.

Phase 2 Study of Acupuncture-Like Transcutaneous Nerve Stimulation for Chemotherapy-Induced Peripheral Neuropathy.

A prospective phase 2 study was conducted to evaluate the clinical utility of acupuncture-like transcutaneous nerve stimulation (ALTENS) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Eligible cancer patients had a < 2 ECOG performance score, received neurotoxic chemotherapy, and developed CIPN symptoms for > two months. Randomization was used to eliminate bias in patient selection for ALTENS and was not to compare the effectiveness between the two treatments.ALTENS treatments were delivered using Codetron units. Bilateral acupuncture points included LI4 and LIV3, plus LI11 or ST36 were stimulated. Acupuncture treatments were administered to CV6, SP6, ST6, LI11, Bafeng, Baxie and selective Jing points bilaterally. Twelve treatments were delivered twice weekly over 6 to 8 weeks. The Modified Total Neuropathy Score (mTNS), Numbness Score, and Edmonton Symptom Assessment Score (ESAS) were assessed at baseline, treatment completion, plus at 3 and 6 months follow-up. The primary study endpoint was mTNS score at 6 months. We planned to recruit 23 patients into each group. After 30 patients were recruited, 2 were lost to follow-up at 3 months in the ALTENS group and 3 in the acupuncture group. The research team decided to recruit all remaining consecutive patients only to the ALTENS group to ensure an adequate evaluation of ALTENS, the primary object of evaluation. There were 27 patients in the ALTENS group, with an average symptom duration of 10 months after chemotherapy. Twenty four and 23 patients completed the 3 and 6 month follow-up respectively. The median mTNS scores were 7.1, 4.0, 3.6 and 3.1 at baseline, treatment completion, 3 and 6 months follow-up, respectively. One-way ANOVA analysis showed a significant improvement in mTNS scores (p<0.001) at 6 months. Numbness scores were also significantly improved at 6 months. ESAS pain scores and perception of well-being scores analyses were inconclusive. There were no significant reported side effects of ALTENS. There were only 13 patients in the acupuncture group and the number was insufficient for either an independent or a comparative analysis. The results of this study suggests that ALTENS significantly reduces the mTNS scores and numbness in patients suffering from CIPN symptoms.

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PURPOSE: The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). METHODS: A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. RESULTS: There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. CONCLUSION: Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

Accuracy of Robotic Radiosurgical Liver Treatment Throughout the Respiratory Cycle.

PURPOSE: To quantify random uncertainties in robotic radiosurgical treatment of liver lesions with real-time respiratory motion management. METHODS AND MATERIALS: We conducted a retrospective analysis of 27 liver cancer patients treated with robotic radiosurgery over 118 fractions. The robotic radiosurgical system uses orthogonal x-ray images to determine internal target position and correlates this position with an external surrogate to provide robotic corrections of linear accelerator positioning. Verification and update of this internal-external correlation model was achieved using periodic x-ray images collected throughout treatment. To quantify random uncertainties in targeting, we analyzed logged tracking information and isolated x-ray images collected immediately before beam delivery. For translational correlation errors, we quantified the difference between correlation model-estimated target position and actual position determined by periodic x-ray imaging. To quantify prediction errors, we computed the mean absolute difference between the predicted coordinates and actual modeled position calculated 115 milliseconds later. We estimated overall random uncertainty by quadratically summing correlation, prediction, and end-to-end targeting errors. We also investigated relationships between tracking errors and motion amplitude using linear regression. RESULTS: The 95th percentile absolute correlation errors in each direction were 2.1 mm left-right, 1.8 mm anterior-posterior, 3.3 mm cranio-caudal, and 3.9 mm 3-dimensional radial, whereas 95th percentile absolute radial prediction errors were 0.5 mm. Overall 95th percentile random uncertainty was 4 mm in the radial direction. Prediction errors were strongly correlated with modeled target amplitude (r=0.53-0.66, P<.001), whereas only weak correlations existed for correlation errors. CONCLUSIONS: Study results demonstrate that model correlation errors are the primary random source of uncertainty in Cyberknife liver treatment and, unlike prediction errors, are not strongly correlated with target motion amplitude. Aggregate 3-dimensional radial position errors presented here suggest the target will be within 4 mm of the target volume for 95% of the beam delivery.

Assessing patient characteristics and radiation-induced non-targeted effects in vivo for high dose-rate (HDR) brachytherapy.

PURPOSE: To test whether blood, urine, and tissue based colony-forming assays are a useful clinical detection tool for assessing fractionated treatment responses and non-targeted radiation effects in bystander cells. MATERIALS AND METHODS: To assess patients' responses to radiation treatments, blood serum, urine, and an esophagus explant-based in vivo colony-forming assay were used from oesophageal carcinoma patients. These patients underwent three fractions of high dose rate (HDR) intraluminal brachytherapy (ILBT). RESULTS: Human keratinocyte reporters exposed to blood sera taken after the third fraction of brachytherapy had a significant increase in cloning efficiency compared to baseline samples (p < 0.001). Such results may suggest an induced radioresistance response in bystander cells. The data also revealed a clear inverse dose-rate effect during late treatment fractions for the blood sera data only. Patient characteristics such as gender had no statistically significant effect (p > 0.05). Large variability was observed among the patients' tissue samples, these colony-forming assays showed no significant changes throughout fractionated brachytherapy (p > 0.05). CONCLUSION: Large inter-patient variability was found in the urine and tissue based assays, so these techniques were discontinued. However, the simple blood-based assay had much less variability. This technique may have future applications as a biological dosimeter to predict treatment outcome and assess non-targeted radiation effects.

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.

PURPOSE AND OBJECTIVES: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. METHODS AND MATERIALS: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. RESULTS: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were -0.53 and -0.27 (P=.45) and -0.6 and -0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. CONCLUSIONS: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint-the change in radiation-induced xerostomia symptom burden at 9 MFR-was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS.

Patient-centered care in cancer treatment programs: the future of integrative oncology through psychoeducation.

The reciprocal relationship between the mind and body has been a neglected process for improving the psychosocial care of cancer patients. Emotions form an important link between the mind and body. They play a fundamental role in the cognitive functions of decision-making and symptom control. Recognizing this relationship is important for integrative oncology. We define psychoeducation as the teaching of self-evaluation and self-regulation of the mind-body process. A gap exists between research evidence and implementation into clinical practice. The patients' search for self-empowerment through the pursuit of complementary therapies may be a surrogate for inadequate psychoeducation. Integrative oncology programs should implement psychoeducation that helps patients to improve both emotional and cognitive intelligence, enabling them to better negotiate cancer treatment systems.

Flax and Breast Cancer: A Systematic Review.

BACKGROUND: Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may possess phytogestrogenic, anti-inflammatory, and hormone modulating effects, respectively. We conducted a systematic review of flax for efficacy in improving menopausal symptoms in women living with breast cancer and for potential impact on risk of breast cancer incidence or recurrence. METHODS: We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to January 2013 for human interventional or observational data pertaining to flax and breast cancer. RESULTS: Of 1892 records, we included a total of 10 studies: 2 randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5 observational studies. Nonsignificant (NS) decreases in hot flash symptomatology were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic index (P< .05) and decreased HER2 expression (P< .05) and cell proliferation (Ki-67 index; NS) among newly diagnosed breast cancer patients when compared with placebo. Uncontrolled and biomarker studies suggest beneficial effects on hot flashes, cell proliferation, atypical cytomorphology, and mammographic density, as well as possible anti-angiogenic activity at doses of 25 g ground flax or 50 mg secoisolariciresinol diglycoside daily. Observational data suggests associations between flax and decreased risk of primary breast cancer (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients. CONCLUSIONS: Current evidence suggests that flax may be associated with decreased risk of breast cancer. Flax demonstrates antiproliferative effects in breast tissue of women at risk of breast cancer and may protect against primary breast cancer. Mortality risk may also be reduced among those living with breast cancer.

Black cohosh and breast cancer: a systematic review.

BACKGROUND: Many women use black cohosh as a natural treatment for menopausal symptoms. However, controversy exists around safety in breast cancer, because of its purported estrogenic activity. We conducted a systematic review of black cohosh use in women with or at risk of breast cancer. METHODS: We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to July 2012 and October 2012 for human interventional or observational data pertaining to the safety and efficacy of black cohosh in patients with or at risk of breast cancer, including an assessment of the effect of black cohosh on estrogen responsive tissues. RESULTS: Of 450 records, we included 26 articles: 14 randomized controlled trials, 7 uncontrolled trials, and 5 observational studies.The evidence on efficacy for ho t flashes is divided, with some benefits seen when compared with baseline, but not when compared with placebo. Two observational studies found no association between black cohosh and risk of breast cancer, whereas 2 studies reported significant reductions in risk of primary breast cancer among postmenopausal women (adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82), and risk of recurrence (adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89). Seventeen trials showed no significant impact on circulating hormone levels or proliferation in estrogen responsive tissues. CONCLUSIONS: Current evidence does not support an association between black cohosh and increased risk of breast cancer. There is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flashes in breast cancer patients. Given conflicting but promising results, and apparent safety, further research is warranted.