Estimation of secondary cancer projected risk after partial breast irradiation at the 1.5 T MR-linac.

PURPOSE: For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air-tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL. METHODS: Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t­test with Bonferroni correction was used for comparison. RESULTS: The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected. CONCLUSION: Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM.

Acceptance of physical activity monitoring in cancer patients during radiotherapy, the GIROfit phase 2 pilot trial.

Background: In radiotherapy the timely identification of patients needing intervention and supportive care due to side effects is an important task especially in the outpatient setting. Activity trackers as an increasingly used lifestyle device may enable physicians to monitor patient's physical activity (PA) and to intervene early during the course of radiotherapy. Objective: The primary aim of this trial was to assess patient acceptance of PA monitoring in an outpatient setting and to correlate changes in PA with toxicity and changes in quality of life. Methods: Patients undergoing radio(chemo-)therapy with a curative intent were eligible to participate in this prospective pilot phase II trial. Patients were instructed to wear a commercially available activity tracker during the course of radiotherapy and four weeks afterwards. Quality of life (QoL) and fatigue was scored using the Functional assessment of Chronic Illness Therapy questionnaire. A linear regression was performed to determine baseline activity and changes in step counts during radiotherapy. Results: We included 23 patients in this trial. Two withdrew consent before the start of treatment, two patients were excluded after prophylactic feeding tube placement and prolonged recovery. Compliance in the remaining 19 patients was high, with availability of step-counts on 92% of the days. Baseline step counts were 6274 for breast cancer patients and 3621 for patients with other entities. Decreasing activity during radiotherapy coincided with the development of side effects and declines in quality of life. Conclusions: Activity trackers as tool to monitor PA during and after radiotherapy were accepted by a majority of the patients included in the current trial. Observed changes in PA correlated with patient reported side effects and QoL in some of the patients.

Analysis of the electron-stream effect in patients treated with partial breast irradiation using the 1.5 T MR-linear accelerator.

INTRODUCTION: The hybrid magnetic resonance linear accelerator (MRL) has the potential to test novel concepts in breast cancer patients such as daily MR-guided real-time plan adaptation. Before starting clinical trials, preparatory studies for example of the MR-dependent electron stream effect (ESE) are necessary. MATERIAL AND METHODS: To prospectively investigate the ESE, data from 11 patients treated with partial breast irradiation (PBI) at the 1.5 T MRL were evaluated. A bolus was placed on the chin and in vivo dosimetry results were compared with the dose simulated by the treatment planning system (TPS). The same measurements were carried out for three patients treated at a conventional linac. Toxicity and cosmesis were evaluated. RESULTS: Median doses measured and simulated on top/ underneath the bolus were 1.91 / 0.62 Gy and 2.82 / 0.63 Gy, respectively. Median differences between calculations and measurements were 0.8 Gy and 0.1 Gy. At the conventional linac, median measured doses on top/ underneath the bolus were 0.98 and 1.37 Gy. No acute toxicity exceeding grade 2 was recorded. Cosmesis was good or excellent and patient reported outcome measures were mostly scored as none or mild. CONCLUSION: The dose due to the ESE is low, correctly predicted by the TPS and effectively minimized by a bolus.

Marker-less online MR-guided stereotactic body radiotherapy of liver metastases at a 1.5 T MR-Linac - Feasibility, workflow data and patient acceptance.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is an established ablative treatment for liver tumors with excellent local control rates. Magnetic resonance imaging guided radiotherapy (MRgRT) provides superior soft tissue contrast and may therefore facilitate a marker-less liver SBRT workflow. The goal of the present study was to investigate feasibility, workflow parameters, toxicity and patient acceptance of MRgSBRT on a 1.5 T MR-Linac. METHODS: Ten consecutive patients with liver metastases treated on a 1.5 T MR-Linac were included in this prospective trial. Tumor delineation was performed on four-dimensional computed tomography scans and both exhale triggered and free-breathing T2 MRI scans from the MR-Linac. An internal target volume based approach was applied. Organ at risk constraints were based on the UKSABR guidelines (Version 6.1). Patient acceptance regarding device specific aspects was assessed and toxicity was scored according to the common toxicity criteria of adverse events, version 5. RESULTS: Nine of ten tumors were clearly visible on the 1.5 T MR-Linac. No patient had fiducial markers placed for treatment. All patients were treated with three or five fractions. Median dose to 98% of the gross tumor volume was 38.5 Gy. The median time from "patient identity check" until "beam-off" was 31 min. Median beam on time was 9.6 min. Online MRgRT was well accepted in general and no treatment had to be interrupted on patient request. No event of symptomatic radiation induced liver disease was observed after a median follow-up of ten month (range 3-17 months). CONCLUSION: Our early experience suggests that online 1.5 T MRgSBRT of liver metastases represents a promising new non-invasive marker-free treatment modality based on high image quality, clinically reasonable in-room times and high patient acceptance. Further studies are necessary to assess clinical outcome, to validate advanced motion management and to explore the benefit of online response adaptive liver SBRT.

Radiation Pneumonitis after Intensity-Modulated Radiotherapy for Esophageal Cancer: Institutional Data and a Systematic Review.

Radiation pneumonitis (RP) is a serious complication that can occur after thoracic radiotherapy. The goal of this study is to investigate the incidence of RP after radiochemotherapy with intensity modulated radiotherapy (IMRT) in patients with esophageal cancer and correlate this with dose volume histogram (DVH) related parameters. For this purpose, the clinical course of 73 patients was evaluated and irradiation doses to the lungs were extracted from radiotherapy treatment plans. Furthermore, a systematic review on this topic was conducted across PubMed. In our institutional cohort, Common Terminology Criteria for Adverse Events (CTCAE) grade II or higher RP occurred in four patients (5.5%). The systematic review identified 493 titles of which 19 studies reporting 874 patients qualified for the final analysis. No grade IV or V RP after radiochemotherapy with IMRT for esophageal cancer was reported in the screened literature. Grade II or higher RP is reported in 6.6% of the patients. A higher incidence can be seen with increasing values for lung V20. In conclusion, our institutional data and the literature consistently show a low incidence of symptomatic RP after radiochemotherapy in patients with esophageal cancer treated with IMRT. However, efforts should be made to keep the lung V20 below 23% and specific caution is warranted in patients with pre-existing lung conditions.

The influence of psychological variables on postoperative anxiety and physical complaints in patients undergoing lumbar surgery.

Previous research has indicated that postoperative distress is influenced by diverse biographic, medical and psychological variables, such as personality, coping behaviours and anxiety. The influence of state variables, apart from anxiety and coping behaviour, has received scant attention. Furthermore, the influence of coping behaviour has remained unclear. The present study investigated coping behaviour and indications of physical distress, i.e., preoperative fatigue, leg pain and back pain, besides preoperative anxiety, as predictors of postoperative anxiety and physical complaints in 126 patients undergoing lumbar surgery. Preoperative anxiety and leg pain independently predicted more postoperative anxiety beyond the influence of age, sex and medical variables. Preoperative anxiety and fatigue independently predicted more postoperative physical complaints. No associations were found between the coping behaviours and the postoperative variables. The implications of these results are discussed in relation to intervention strategies aimed at diminishing the stress of surgery.

Psychological variables as predictors of the length of post-operative hospitalization.

The extent to which measures of anxiety and personality characteristics, which had been assessed preoperatively, could predict the length of hospital stay following surgery, above and beyond what could be predicted on the basis of biographical, medical-status and post-operative anxiety variables, was examined in 58 patients with gall-bladder disease. Hierarchical multiple regression analysis revealed that gender, previous operations, complications and State Anxiety (A-State) measured on the third day post-operatively, jointly explained a significant proportion of the variance in the length of hospitalization. Neither preoperative anxiety measures nor personality characteristics had any significant incremental value in the prediction.

The course of anxiety and depression in patients undergoing coronary artery bypass graft surgery.

A semilongitudinal study was designed to follow-up the course of anxiety and depression in patients undergoing coronary artery bypass graft (CABG) surgery. The focus was on possible effects of gender and age on variations in both mean level and interindividual differences over time. At two timepoints before and two after surgery, 217 patients completed self-report questionnaires. Multivariate testing revealed an overall decrease in mean levels of anxiety and depression in the postoperative period but different trends for men and women. Compared with men, women reported more anxiety and depression, both pre- and postoperatively, but showed a relatively stronger decrease in the early postoperative period. Regarding variations in interindividual differences over time, multivariate testing revealed different trends of depression for men and women. Women appeared to be most homogeneous in the early days after surgery, whereas interindividual differences for men showed a stable trend.

A structural modeling analysis of anxiety and depression in patients undergoing coronary artery bypass graft surgery: a model generating approach.

The present study is a longitudinal study designed to explore structural relationships between anxiety, depression, personality, and background factors (e.g., gender, age, and complicated medical characteristics) in patients undergoing coronary artery bypass graft (CABG) surgery. At two timepoints before and two after CABG, 217 patients completed self-report questionnaires. To explore structural relationships, the structural equation modeling (SEM) method was applied. Using the model-generating approach, a model was developed, providing a good fit. The structural relationships revealed, in particular, the key position of neuroticism, which was related to both pre- and postoperative anxiety and depression. Relationships between anxiety and depression over time, both intra- and interrelationships, were relatively weak. Relationships between anxiety and depression at the same points in time were relatively strong, with preoperative depression leading to preoperative anxiety, and postoperative anxiety leading to postoperative depression. To provide a useful framework for development of intervention strategies, further research is needed to evaluate the plausibility of the final structural model.

The effect of carotid endarterectomy on mental functioning.

In order to ascertain the effect of carotid endarterectomy on mental functioning, carotid endarterectomy patients suffering from transient ischemic attacks (TIA) were compared preoperatively and postoperatively with cholecystectomy patients. Preoperatively, a tendency toward poorer verbal memory and greater well-being is found in carotid endarterectomy patients. Postoperatively, the overall mental functioning of the carotid endarterectomy patients is not significantly improved, though verbal fluency does show improvement. The well-being of both groups is significantly greater following operation. The complaints of the carotid endarterectomy patients during the (last) TIA had already diminished before operation and after operation remained practically on the same level. Preoperatively and postoperatively, no clear connection exists between mental functioning and age of patients in this experiment, not between mental functioning and the side of the operation. Finally, in the case of 5 patients, no long-term (4.5 months) effect of carotid endarterectomy could be indicated.

Pre-operative anxiety variables as possible predictors of post-operative stay in hospital.

The extent to which measures of pre-operative anxiety predict post-operative hospital stay, over and above what is predicted by biographical, medical status and post-operative anxiety variables, was examined in 81 cholecystectomy patients. Hierarchical multiple regression analysis revealed that patients who were older, had lower health status and suffered from wound infection, had a longer post-operative hospital stay than others. None of the pre-operative anxiety measures had a significant incremental value in the prediction of the post-operative hospital stay.

[Relationship between perioperative anxiety and postoperative recovery]. / Verband tussen peri-operatieve angst en postoperatief herstel.

One day before surgery and three days postoperatively, 118 cholecystectomy patients were investigated by means of several self-report anxiety-question(naire)s. On the basis of these, the patients were assigned to either the category more anxious postoperatively (A+) or the category less anxious postoperatively (A-). A+ patients rated preoperatively lower and postoperatively higher on the anxiety-question(naire)s than A- patients, and they stayed longer in hospital postoperatively.

Preoperative expectations of pain and recovery in relation to postoperative disappointment in patients undergoing lumbar surgery.

OBJECTIVES: In groups of lumbar surgery patients who had different expectations about postoperative pain and recovery, this study investigated disappointment three days and three months after surgery. Our hypothesis was that patients who did not expect any postoperative pain and who expected a fast rate of recovery were at risk of becoming disappointed. METHODS: One day before surgery, 120 patients who underwent lumbar surgery were interviewed about their expectations regarding postoperative pain, rate of recovery, and return to work. Levels of postoperative pain and disappointment were measured three days and three months postoperatively. RESULTS: Patients who did not expect to have any postoperative pain reported significantly less disappointment three days and three months after surgery than did patients who expected to have postoperative pain. No significant differences were found in postoperative disappointment between the groups with different expectations regarding the rate of recovery or the return to work. CONCLUSION: Contrary to our hypothesis, the results suggest that patients who do not expect to experience any postoperative pain will be less disappointed after surgery than patients who expect to be in pain. Implications for the theory of mental preparation and for preoperative intervention strategies aimed at diminishing the stress of surgery are discussed.

Effects of sounds presented during general anaesthesia on postoperative course.

In a double-blind, randomized study, patients undergoing cholecystectomy were administered one of four different sounds during general anaesthesia: positive suggestions, nonsense suggestions, seaside sounds or sounds from the operating theatre. The effect of these sounds on the postoperative course was examined to assess intraoperative auditory registration. No differences were found between the four groups in postoperative variables.

Prediction of quality of life after coronary artery bypass graft surgery: a review and evaluation of multiple, recent studies.

OBJECTIVE: To review studies predicting psychosocial outcome after coronary artery bypass graft surgery (CABG). METHODS: Seventeen prospective studies, appearing in the MEDLINE and PsycLIT data bases between 1986 and 1996, were reviewed regarding objectives, methodological issues, results, and clinical relevance. RESULTS: All studies reported that psychological factors bad predictive value. In particular, preoperative anxiety and depression predicted postoperative psychological maladjustment; social support, preoperative feelings of control, denial, and optimism contributed to psychological adjustment. CONCLUSIONS: Many specific psychological outcomes seem to be best predicted by preoperative assessment of functions in that specific area, especially in the case of anxiety and depression. Furthermore, personality factors including denial, optimism, control, and the need for support appear to be predictors of psychological outcome. Appropriate identification of predictive factors might improve the development of individually tailored interventions for patients at risk of postoperative psychological problems.

Methane oxidation and the competition for oxygen in the rice rhizosphere.

A mechanistic approach is presented to describe oxidation of the greenhouse gas methane in the rice rhizosphere of flooded paddies by obligate methanotrophic bacteria. In flooded rice paddies these methanotrophs compete for available O(2) with other types of bacteria. Soil incubation studies and most-probable-number (MPN) counts of oxygen consumers show that microbial oxygen consumption rates were dominated by heterotrophic and methanotrophic respiration. MPN counts of methanotrophs showed large spatial and temporal variability. The most abundant methanotrophs (a Methylocystis sp.) and heterotrophs (a Pseudomonas sp. and a Rhodococcus sp.) were isolated and characterized. Growth dynamics of these bacteria under carbon and oxygen limitations are presented. Theoretical calculations based on measured growth dynamics show that methanotrophs were only able to outcompete heterotrophs at low oxygen concentrations (frequently < 5 microM). The oxygen concentration at which methanotrophs won the competition from heterotrophs did not depend on methane concentration, but it was highly affected by organic carbon concentrations in the paddy soil. Methane oxidation was severely inhibited at high acetate concentrations. This is in accordance with competition experiments between Pseudomonas spp. and Methylocystis spp. carried out at different oxygen and carbon concentrations. Likely, methane oxidation mainly occurs at microaerophilic and low-acetate conditions and thus not directly at the root surface. Acetate and oxygen concentrations in the rice rhizosphere are in the critical range for methane oxidation, and a high variability in methane oxidation rates is thus expected.