Algorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial.

BACKGROUND: Chronic gastrointestinal symptoms after pelvic radiotherapy are common, multifactorial in cause, and affect patients' quality of life. We assessed whether such patients could be helped if a practitioner followed an investigative and management algorithm, and whether outcomes differed by whether a nurse or a gastroenterologist led this algorithm-based care. METHODS: For this three-arm randomised controlled trial we recruited patients (aged ≥18 years) from clinics in London, UK, with new-onset gastrointestinal symptoms persisting 6 months after pelvic radiotherapy. Using a computer-generated randomisation sequence, we randomly allocated patients to one of three groups (1:1:1; stratified by tumour site [urological, gynaecological, or gastrointestinal], and degree of bowel dysfunction [IBDQ-B score <60 vs 60-70]): usual care (a detailed self-help booklet), gastroenterologist-led algorithm-based treatment, or nurse-led algorithm-based treatment. The primary endpoint was change in Inflammatory Bowel Disease Questionnaire-Bowel subset score (IBDQ-B) at 6 months, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00737230. FINDINGS: Between Nov 26, 2007, and Dec 12, 2011, we enrolled and randomly allocated 218 patients to treatment: 80 to the nurse group, 70 to the gastroenterologist group, and 68 to the booklet group (figure). Most had a baseline IBDQ-B score indicating moderate-to-severe symptoms. We recorded the following pair-wise mean difference in change in IBDQ-B score between groups: nurse versus booklet 4·12 (95% CI 0·04-8·19; p=0·04), gastroenterologist versus booklet 5·47 (1·14-9·81; p=0·01). Outcomes in the nurse group were not inferior to outcomes in the gastroenterologist group (mean difference 1·36, one sided 95% CI -1·48). INTERPRETATION: Patients given targeted intervention following a detailed clinical algorithm had better improvements in radiotherapy-induced gastrointestinal symptoms than did patients given usual care. Our findings suggest that, for most patients, this algorithm-based care can be given by a trained nurse. FUNDING: The National Institute for Health Research.

Comparison of setup accuracy and intrafraction motion using stereotactic frame versus 3-point thermoplastic mask-based immobilization for fractionated cranial image guided radiation therapy.

PURPOSE: Prospectively compare patient setup accuracy and intrafraction motion of a standard 3-point thermoplastic mask with the Gill-Thomas-Cosman relocatable stereotactic frame, during fractionated cranial radiation therapy using the ExacTrac system (Brainlab AG Feldkirchen, Germany) for daily online correction. METHODS AND MATERIALS: The number of fractions with all postcorrection and post-treatment errors <2 mm was assessed in 21 patients undergoing fractionated stereotactic radiation therapy (13 frame setup, 8 mask setup) using daily online correction. Achievable patient setup accuracy and total intrafraction motion were evaluated. The relative contributions of movement during floor rotation and patient movement to intrafraction motion were calculated. RESULTS: With daily online correction, patient setup margins can be reduced from 1, 5, and 4 mm in the lateral, longitudinal, and vertical axes for mask setup and from 1-2, 2, and 1 mm, respectively, for frame setup to <1 mm isotropically for either immobilization system. Intrafraction movement was small for frame setup (mean [SD], -0.3 [0.3], -1.1[0.4], and -0.2 [0.6] in lateral, longitudinal and vertical axes, respectively; maximum, -2.7 mm [longitudinal axis]), and mask-setup (mean [SD], -0.4 [0.5], -0.8 [0.7], and 0.0 [0.3], respectively; maximum, -2.0 mm [longitudinal axis]) and is mainly due to floor rotation. Postcorrection and post-treatment errors were all <2 mm in 95% and 99% of fractions in the mask and frame, respectively, meeting the criteria for a 3-mm clinical target volume-planning target volume margin for either immobilization method. CONCLUSIONS: Daily online correction can compensate for less precise immobilization and permits stereotactic margins to be used for standard thermoplastic masks without the need for specialized mask systems.

Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial?

BACKGROUND: In rectal cancer, the standard of care after the completion of radiotherapy is surgery at 6 to 8 weeks. However, there is variation regarding the timing of surgery. OBJECTIVE: This investigation aimed to audit the timing of surgery following radiotherapy and to compare perioperative morbidity and tumor downstaging in patients operated on, before and after the 6- to 8-week window. DESIGN: A retrospective review of rectal cancers treated preoperatively in our cancer network over a 27-month period. The effect of "time till surgery" of 6 to 8 weeks, <6 weeks, and >8 weeks on T downstaging and nodal downstaging was calculated by univariate and multivariate logistic regression analyses. SETTING: This study was conducted in an oncology tertiary referral center in the Southwest London Cancer Network. PATIENTS: Patients receiving preoperative radiotherapy for primary locally advanced rectal cancer undergoing subsequent surgical resection were eligible. MAIN OUTCOME MEASURES: The primary outcome measurement was time to surgery following the completion of (chemo) radiotherapy. Thirty-day perioperative morbidity and mortality and tumor and nodal downstaging were examined according to the timing of surgery. LIMITATIONS: This study was limited by its nonrandomized retrospective design and the lack of standardization of preoperative chemotherapy. RESULTS: Thirty-two (34%) patients underwent surgery at 6 to 8 weeks, 45 (47%) at >8 weeks, and 18 (19%) at <6 weeks after radiotherapy. Delay was attributed to scheduling in 87% of cases and to comorbidities in the remainder. T downstaging occurred in 6 (33.3%) patients in the <6 weeks group, in 12 (37.5%) in the 6 to 8 weeks group, and in 28 (62.2%) in >8 weeks group with no significant differences in perioperative morbidity. On multivariate analysis, T downstaging was significantly greater for the >8 weeks group (OR, 3.79; 95% CI: 1.11-12.99; P = .03). More patients were staged ypT0-T2, 19 of 45 (42%) in the >8 weeks group vs other groups, 14 of 50 (28%, P < .05). CONCLUSIONS: Following radiotherapy, surgery frequently occurs at >8 weeks and is associated with increased downstaging. The consequences on survival and perioperative morbidity warrant further investigation.

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

PURPOSE: To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. METHODS: In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. RESULTS: On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. CONCLUSION: MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

Metastatic ovarian and primary peritoneal cancer: assessing chemotherapy response with diffusion-weighted MR imaging--value of histogram analysis of apparent diffusion coefficients.

PURPOSE: To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer. MATERIALS AND METHODS: Research ethics committee approval and patient written informed consent were obtained. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed through the abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4 [standard deviation]) with newly diagnosed or recurrent disease. Reproducibility and intra- and interobserver agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each time point from pixel ADCs from five or fewer target lesions. Mean ADC, percentiles (10th, 25th, 50th, 75th, 90th), skew, kurtosis, and their change were analyzed according to histologic grade, primary versus recurrent disease status, and response, determined with integrated biochemical and morphologic criteria, with a linear mixed model. Areas under receiver operating characteristic curve (AUCs) for combinations of parameters were calculated with linear discriminant analysis. RESULTS: Coefficients of variation for repeat measurements and for within and between observers were 4.8%, 11.4%, and 13.7%, respectively. Grade and disease status did not significantly affect histogram parameters. Pretreatment ADCs were not predictive of response. In responders, all ADCs increased after the first and third cycle (P < .001), while skew and kurtosis decreased after the third (P < .001 and P = .006, respectively); however, in nonresponders, no parameter changed significantly. Percentage change of the 25th percentile performed best in identifying response (AUC = 0.82 and 0.83 after first and third cycle, respectively), whereas combination of parameters did not improve accuracy. CONCLUSION: An early increase of ADCs and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW MR imaging can aid in early monitoring of treatment efficacy in patients with advanced ovarian cancer.

Masked hypertension in untreated normotensives: difference between a work day and a leisure day?

OBJECTIVE: To compare ambulatory blood pressure recorded during a work day with a leisure day regarding masked hypertension. DESIGN: A randomized crossover study in middle-aged normotensives. PARTICIPANTS: Thirty-seven untreated middle-aged normotensives (17 women), who had repeated office blood pressure less than 140/90 mmHg. MAIN OUTCOME MEASURE: Individual difference of masked hypertension between a work day and a leisure day. RESULTS: Office systolic/diastolic blood pressure mean (SD) was 0.3/0.6 (6.4/5.2) mmHg higher during the work day. The mean (SD) systolic/diastolic 24-h, day and night blood pressure was 2.8/3.1 (4.5/3.6), 2.2/2.5 (4.9/4.2) and 1.3/1.9 (4.6/4.0) mmHg higher during the work day than during the leisure day. Individual comparisons of occurrence of ambulatory blood pressure values above normal during day (systolic ≥135 or diastolic ≥85) showed a statistically significant difference between the work day and the leisure day, P=0.0412. The P values for the individual comparisons of occurrence of ambulatory blood pressure values above normal during 24 h (systolic ≥130 or diastolic ≥80), and during night (systolic ≥120 or diastolic ≥70 mmHg) were P=0.0771 and 0.6171, respectively. CONCLUSION: Ambulatory blood pressure was somewhat higher during the work day than during the leisure day, and there was statistically significant individual difference concerning masked hypertension during daytime. Thus, in normotensives such as in hypertensives, ambulatory blood pressure during a work day seems to give the best information. Diastolic blood pressure values above normal were more common than systolic. However, systolic blood pressure is considered of greater importance in this age group and no participant had extremely high values.

Does blood pressure differ between users and non-users of hormone replacement therapy? The Women's Health In the Lund Area (WHILA) Study.

OBJECTIVE: To examine whether blood pressure over 24 h differed between postmenopausal women receiving and not receiving hormone replacement therapy. METHODS: One group of hormone replacement postmenopausal women (n = 32) and one group of non-hormone replacement (n = 32) postmenopausal women underwent non-invasive 24-h ambulatory blood pressure monitoring. They were randomly selected among the 2000 firstly screened women in an ongoing project in Lund, Sweden. The study was designed to detect a difference of 5 mmHg in diastolic blood pressure over 24 h with a power of 80% and 5% significance (two-tailed test). RESULTS: The hormone replacement women had a mean (SD) office blood pressure of 128/76 (12/8) mmHg and the non-hormone replacement 126/78 (16/8) mmHg. Mean ambulatory blood pressure over 24 h, day and night, in the hormone replacement group was 121/72 (11/7), 126/76 (12/8), 111/64 (11/7) mmHg. The corresponding values in the non-hormone replacement group were 118/72 (12/7), 124/77 (12/7), and 107/64 (13/7) (p > 0.40 for diastolic blood pressure and p > 0.20 for systolic blood pressure). Mean heart rate over 24 h was 71 (7) and 73 (8) beats/min in the hormone and non-hormone replacement groups, respectively. CONCLUSION: There was no difference in blood pressure or heart rate between the hormone replacement and non-hormone replacement postmenopausal women, either over 24 h or during the day or night. Hormone replacement in postmenopausal women seems not to have an influence on blood pressure, but of course we are aware that this is a cross-sectional study, which has its limitations.