Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer.

Background: TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). Methods: In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat. Results: At 12 years median follow-up, overall and disease-free survivals between randomized arms were comparable, while survival time free from alteration significantly improved with H-IGRT which showed a gain of restricted mean survival time of 1.46 years over CRT, P=0.041. Discussion: The finding establishes TomoBreast as a proof-of-concept that hypofractionated image-guided radiation-therapy can improve the sparing of lung-heart function in breast cancer adjuvant therapy without loss in disease-free survival. Hypofractionation is advantageous, conditional on using an advanced radiation technique. Multicenter validation may be warranted. Trial registration: https://clinicaltrials.gov/ct2/show/NCT00459628. Registered 12 April 2007.

Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients.

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6-4.6 to 4.3-4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.

Lymphoscintigraphic Investigations for Axillary Web Syndromes.

Background: Axillary web syndrome (AWS) is a frequent complication after surgery for breast cancer, but its lymphatic involvement is not definitively established. Here we report the results of lymphoscintigraphic investigations in patients with AWS. Methods and Results: We conducted a retrospective, single-center review of lymphoscintigraphic investigations performed in 46 patients with AWS that was either clinically obvious or suspected. Of this group, 23 patients had two investigations with a mean interval of 19 weeks between them (range, 6-98 weeks). Results of the lymphoscintigraphic investigations, which were performed according to a well-standardized protocol, were classified into four patterns: normal; functional lymphatic insufficiency only (no lymphatic vascular morphologic abnormality); lymphovascular blockade without collateralization; and vascular collateralization and/or dermal backflow. Of the 46 patients, on the first lymphoscintigraphic investigation, four (8.6%) had a normal pattern, seven (15.2%) had functional lymphatic insufficiency only, four (8.6%) had lymphovascular blockade without collateralization, and 31 (67.3%) had vascular collateralization and/or dermal backflow. Among patients who underwent two investigations, four of the five who had only functional lymphatic insufficiency at the first investigation had developed vascular collateralization and/or dermal backflow by the second. The three patients who had lymphovascular blockade without collateralization at the first examination had also progressed to collateralization and/or dermal backflow at the second. None of the 15 patients who initially had vascular collateralization and/or dermal backflow showed any reversal at the second examination. Conclusions: Our analysis confirms the lymphatic nature of AWS and shows the lymphoscintigraphic patterns and evolutions of the lymphatic lesions with potential therapeutic implications. The retrospective review of our database is approved by the institutional ethics committee under number 2048.

Cardiopulmonary-related patient-reported outcomes in a randomized clinical trial of radiation therapy for breast cancer.

BACKGROUND: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity. METHODS: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain. RESULTS: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029. CONCLUSION: Modern radiation therapy can significantly improve long-term PRO. TRIAL REGISTRATION: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively.

Effectiveness of an Interprofessional Education Model to Influence Students' Perceptions on Interdisciplinary Work.

BACKGROUND: To prepare students adequately for the workplace, training on interprofessional practice should be included in the curricula of future health professionals. This study evaluated the effect of an interprofessional education session on undergraduate students' attitudes toward interprofessional collaboration. METHODS: A total of 225 medicine, nursing, physiotherapy, and nutrition and dietetics students were randomized to either an intervention (working together interprofessionally, n = 111) or control group (working together with their own profession, n = 114). Pre- and posttest assessment was performed with an adapted version of the Interdisciplinary Education Perception Scale. RESULTS: A statistically significant improvement in attitude for Perception of Competence Own Profession (0.82, p = .008) and Perception of Actual Cooperation (1.10, p = .004) was found for students in the intervention group compared with students in the control group. CONCLUSION: Interprofessional education sessions were likely to be effective on undergraduate students' attitudes toward interprofessional collaboration. [J Nurs Educ. 2021;60(9):494-499.].

The mediating effect of pain catastrophizing and perceived injustice in the relationship of pain on health-related quality of life in breast cancer survivors.

BACKGROUND: The importance of cognitive appraisals in the effectiveness of pain coping is well established. Two key variables in these appraisal processes are pain catastrophizing (PC) and perceived injustice (PI), which are known to increase the risk of long-term disability and aggravate the pain-related distress through maladaptive behavioral responses. However, to date, the mediating effects of these appraisals have not been examined concurrently in the breast cancer survivor (BCS) population, nor have they been related to health-related quality of life (HRQoL). METHODS: Using cross-sectional data from 110 BCS, structural path analyses were used to examine the mediating effects of PC and PI in the relationship of pain on the HRQoL in BCS. RESULTS: Results demonstrated a significant direct effect of pain and PI on HRQoL combined with a significant indirect effect through PI, but not through PC. An increase in pain is suggested to result in a decrease in quality of life. On the other hand, an increase in pain also is suggested to increase the PI. A similar relation with PC was not retained as significant. CONCLUSION: The relative salience of PI as a mediator of HRQoL underscores the fact that PI is not only understudied but also underappreciated and undertreated in the BCS population. The results of our study warrant replication across longitudinal studies but continue to expand upon the evidence of the multifactorial nature of pain coping in BCS.

Low-Energy Extracorporeal Shockwave Therapy as a Therapeutic Option for Patients with a Secondary Late-Stage Fibro-Lymphedema After Breast Cancer Therapy: A Pilot Study.

Background: Secondary lymphedema (LE) can occur after breast cancer (BC) therapy with axillary lymph node surgery and/or radiotherapy. Reported incidence varies around 20%. The aim of this study was to see whether low-energy extracorporeal shockwave therapy (ESWT) is a therapeutic option in end-stage secondary upper limb fibro-LE. Methods and Results: A pilot study was performed on 10 adult patients who presented with an end-stage LE after BC treatment. They were all treated with usual physical therapy and all had lymphatic surgery before. Eight sessions of ESWT were applied, 2600 shocks at 0.1 mJ/mm2, 2/week during 4 weeks. Upper limb volume decreased nonsignificantly, from 3086.4 ± 539.47 to 2909.1 ± 471.60 mL. Mean circumference of the upper limb was significantly decreased from 32.3 ± 3.01 to 31.4 ± 2.71 cm at the height of the upper arm, from 29.1 ± 2.89 to 28.1 ± 2.71 cm at the height of the elbow, and from 27.5 ± 4.08 to 26.8 ± 3.75 cm at the height of the forearm. Subjective measurements by visual analog scale showed significant decrease in both hardness from 57.3 ± 15.84 to 24.4 ± 21.89 mm and subjective feeling of edema from 44.2 ± 16.90 to 23.2 ± 21.16 mm. No adverse features were reported. Conclusion: We added some evidence that low-energy ESWT is well supported and has additional benefits also in longstanding fibro-lipo-LE on swelling of the arm leading to more subjective comfort for the patients.

Prevalence and risk factors of sleep disturbances in breast cancersurvivors: systematic review and meta-analyses.

BACKGROUND: Breast cancer remains the most frequently diagnosed malignancy among women worldwide, with rising incidence numbers. In Belgium, one out of eight women will be diagnosed with breast cancer. Fortunately, 80% of those breast cancer patients will still be alive 10 years after diagnosis due to improvements in screening and treatment strategies. However, an important portion of the breast cancer survivors (BCS) will face side effects, such as sleep disturbances, long after treatment ends. It has been demonstrated that untreated insomnia in BCS negatively impacts mood, physical symptoms, pain sensitivity, fatigue, and quality of life. Furthermore, insomnia is increasingly considered an independent risk factor for future depression in BCS. The importance of understanding sleep disturbances in cancer populations has been highlighted and recognized as warranting further research. Therefore, the purpose of this systematic review was to determine the prevalence and the risk factors for the development of sleep disturbances in BCS. METHODS: PubMed, Web of Science, and PEDro were systematically screened for studies encompassing data regarding the prevalence or risk factors of sleep disturbances in BCS. If possible, meta-analyses were performed. Subgroup analyses were undertaken based on the methodological quality, study design, type of sleep disturbance, and the use of a measurement tool with strong psychometric properties to investigate significant heterogeneity (I2 > 50%) across studies. RESULTS: A total of 27 studies were found eligible. The pooled estimate for sleep disturbances prevalence is 0.40 (95% confidence interval (CI) = [0.29-0.52], I2 = 100%, p < 0.00001) and ranged from 0.14 (95% CI = [0.04-0.24]) to 0.93 (95% CI = [0.91-0.95]). Subgroup analyses did not reduce the heterogeneity among studies. Meta-analyses were performed for seven risk factors. Significant differences for the odds of developing sleep disturbances were found for hot flashes (pooled OR (ORp) 2.25, 95% CI = [1.64-3.08], I2 = 0%, p = 0.90), race (ORp 2.31, 95% CI = [1.56-3.42], I2 = 0%, p = 0.47), and menopause (ORp 1.84, 95% CI = [1.11-3.06], I2 = 0%, p = 0.70). After withdrawing the studies that did not rely on the use of a measurement tool with strong psychometric properties, pain (ORp 2.31, 95% CI = [1.36-3.92], I2 = 27%, p = 0.25), depressive symptoms (ORp 3.20, 95% CI [2.32-4.42], I2 = 0%, p = 0.63), and fatigue (ORp 2.82, 95% CI = [1.98-4.02], I2 = 0%, p = 0.60) became significant as well, with a substantial decrease of heterogeneity. CONCLUSION: Prevalence for sleep disturbances ranged from 0.14 to 0.93 with the vast majority of the studies investigating insomnia and sleep-wake disturbances. High heterogeneity makes it difficult to draw firm conclusions. Pain, depressive symptoms, hot flashes, fatigue, non-Caucasian race, and menopausal status were significantly associated with increased odds for developing sleep disturbances.

Chronic Pain in Breast Cancer Survivors: Nociceptive, Neuropathic, or Central Sensitization Pain?

INTRODUCTION: The differentiation between acute and chronic pain can be insufficient for appropriate pain management. The aim of this study was to evaluate the prevalence of the predominant pain type (nociceptive, neuropathic, or central sensitization [CS] pain) in breast cancer survivors (BCS) with chronic pain. The secondary aims were to examine (1) differences in health-related quality of life (HRQoL) between the different pain groups; and (2) the associations between patient-, disease-, and treatment-related factors and the different pain types. METHODS: To determine the prevalence of the predominant type of pain, a recently proposed classification system was used. BCS were asked to complete the VAS for pain, Douleur Neuropathique 4 Questionnaire, Margolis Pain Diagram, Central Sensitization Inventory, and Short Form 36 (SF-36). RESULTS: Ninety-one BCS participated, among whom 25.3% presented neuropathic pain, 18.7% nociceptive pain, and 15.4% CS pain. Mixed pain was found in 40.6%. A significant intergroup difference in HRQoL was found for SF-36 "general health" (P = 0.04). The odds for the presence of CS rather than nociceptive pain are 26 times higher in patients exposed to hormone therapy in comparison to the nonexposed (odds ratio 25.95, 95% confidence interval 1.33 to 504.37, P = 0.03). CONCLUSION: Neuropathic pain is most frequent in BCS. Strong associations were found between CS pain and hormone therapy.

Treatment of pain following cancer: applying neuro-immunology in rehabilitation practice.

AIM: Pain is the second most frequent persistent symptom following cancer treatment. This article aims at explaining how the implementation of contemporary pain neuroscience can benefit rehabilitation for adults following cancer treatment within an evidence-based perspective. MATERIALS AND METHODS: Narrative review. RESULTS: First, pain education is an effective but underused strategy for treating cancer related pain. Second, our neuro-immunological understanding of how stress can influence pain highlights the importance of integrating stress management into the rehabilitation approach for patients having cancer-related pain. The latter is supported by studies that have examined the effectiveness of various stress management programmes in this population. Third, poor sleep is common and linked to pain in patients following cancer treatment. Sleep deprivation results in a low-grade inflammatory response and consequent increased sensitivity to pain. Cognitive behavioural therapy for sleep difficulties, stress management and exercise therapy improves sleep in patients following cancer treatment. Finally, exercise therapy is effective for decreasing pain in patients following cancer treatment, and may even decrease pain-related side effects of hormone treatments commonly used in cancer survivors. CONCLUSIONS: Neuro-immunology has increased our understanding of pain and can benefit conservative pain treatment for adults following cancer treatment. Implications for Rehabilitation Pain education is effective for improving cancer pain; implementation of contemporary pain neuroscience into the educational programme seems warranted. Various types of stress management are effective for treating patients following cancer treatment. Poor sleep is common in patients following cancer treatment, and rehabilitation specialists can address this by providing exercise therapy, sleep hygiene, and/or cognitive behavioural therapy. Exercise therapy is effective for decreasing pain in patients following cancer treatment, including the treatment of pain as a common side effect of hormone treatments for breast cancer survivors.

Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Breast cancer remains the number 1 lethal malignancy in women. With rising incidence and decreased mortality, the number of breast cancer survivors has increased. Consequently, sequelae, such as pain, are becoming more important. PURPOSE: The purpose of this study was to identify risk factors for the development of pain in breast cancer survivors. METHODS: PubMed and Web of Science were systematically screened for studies encompassing risk factors for the development of pain in breast cancer survivors. Meta-analyses were carried out for risk factors described in more than one article. Moderator analysis was performed in case of high heterogeneity (I 2 > 50%) across studies. RESULTS: Seventeen studies were found eligible. Meta-analyses were performed for 17 factors. Significant differences for the odds of developing chronic pain were found for BMI (overall OR: 1.34, 95%CI 1.08-1.67, p = 0.008), education (overall OR: 1.23, 95%CI 1.07-1.42, p = 0.005), lymphedema (overall OR: 2.58, 95%CI 1.93-3.46, p < 0.00001), smoking status (overall OR: 0.75, 95%CI 0.62-0.92, p = 0.005), axillary lymph node dissection (overall OR: 1.25, 95%CI 1.04-1.52, p = 0.02), chemotherapy (overall OR: 1.44, 95%CI 1.24-1.68, p < 0.00001), and radiotherapy (overall OR: 1.32, 95%CI 1.17-1.48, p < 0.00001). After performing moderator analyses for age, comorbidities, hormone therapy, and breast surgery, hormone therapy became a significant risk factor as well (overall OR: 1.33, 95%CI 1.15-1.54, p = 0.0001). CONCLUSION: BMI > 30, education < 12-13 years, lymphedema, not smoking, axillary lymph node dissection, chemotherapy, hormone therapy, and radiotherapy were significantly associated with higher odds for the development of chronic pain, with lymphedema being the biggest risk factor. Lack of uniformity across the studies in defining pain, follow-up, measurement tools, and cut-off values for the diagnosis of pain was noted, resulting in greater inter-study variability.

Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Although aromatase inhibitors have proven to be an effective treatment of hormone receptor-positive breast cancer in postmenopausal women, aromatase inhibitor-induced arthralgia (AIA) is an adverse event associated with low compliance with treatment. The aim of this literature study is to assess the prevalence of AIA and to provide an overview of significant predictors for the development of AIA. METHODS: A systematic review was conducted using PubMed, Cochrane Library and Web of Science. A meta-analysis was performed and heterogeneity has been investigated by moderator analyses. The meta-analysis was repeated with studies that were considered as best evidence, i.e. studies with an above-average score on the STROBE checklist. RESULTS: Twenty-one studies (13,177 participants) were included. Prevalence rates ranged from 0.200 to 0.737. Meta-analysis resulted in a pooled estimate of 0.459 (95% CI = [0.397-0.520) with a high heterogeneity (I 2 = 98%). Moderator analysis showed no differences regarding heterogeneity. Predictors for the development of AIA included a body mass index of 25-30 kg/m2 (OR = 0.33), taxane-based chemotherapy (OR = 4.08), stage III cancer (OR = 0.32) and a duration of menopause of 5-10 years (OR = 1.10) or >10 years (OR = 0.44-3.29) (An OR <1 indicates a predictor of lower risk of AIA). DISCUSSION: Despite the established benefits of AI, an important portion of the patients experiences AIA. More research is needed to investigate the efficacy of treatments such as exercise therapy for AIA.

The Use of Noninvasive Imaging Techniques in the Assessment of Secondary Lymphedema Tissue Changes as Part of Staging Lymphedema.

Too often, in clinical settings, the diagnosis and evolution of lymphedema is determined by limb circumference measurements and/or volume calculations. Besides the unrecognition of small lymphedemas, these techniques provide little to no information concerning the stage of the lymphedema. This latter is important in choosing appropriate treatment modalities and making an accurate prognosis. Different imaging techniques are described in literature giving insights in tissue changes due to lymphedema. The aim of this article is giving an overview of possible texture changes linked to the different edema stages, visualized with noninvasive imaging procedures like ultrasonography, computed tomography, dual-energy x-ray absorptiometry, or magnetic resonance imaging.

Breast Cancer-Related Lymphedema: Quality of Life after Lymph Node Transfer.

BACKGROUND: Breast cancer-related lymphedema affects multiple aspects of patients' daily lives. The main aim of this study was to assess the impact of vascularized lymph node transfer on the quality of life in patients with lymphedema. METHODS: Between 2007 and 2012, 25 female patients with breast cancer-related lymphedema underwent vascularized lymph node transfer. In 22 cases, the patients underwent a simultaneous deep inferior epigastric artery perforator flap breast reconstruction based on the superficial circumflex iliac artery. The influence on quality of life was evaluated using the Upper Limb Lymphedema-27 questionnaire, which includes physical, psychological, and social dimensions. The authors also investigated risk factors for lymphedema, such as body mass index, smoking, age, and time between start of lymphedema and vascularized lymph node transfer, and their impact on quality of life. RESULTS: Twenty-one patients (84 percent) had an improvement of quality of life after vascularized lymph node transfer. The mean physical, psychological, and social scores were significantly improved postoperatively (p < 0.001). Risk factors for the development of lymphedema did not influence quality of life among patients with breast cancer-related lymphedema. Skin infections disappeared in 50 percent of the cases. Eleven patients (44 percent) discontinued compression therapy at a mean postoperative time interval of 29 months (range, 8 to 64 months). In the other patients (56 percent), the average frequency of compression therapy decreased from three sessions to one session per week. CONCLUSION: Vascularized lymph node transfer significantly improves quality of life among patients with breast cancer-related lymphedema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain.

BACKGROUND: In addition to fatigue, pain is the most frequent persistent symptom in cancer survivors. Clear guidelines for both the diagnosis and treatment of pain in cancer survivors are lacking. Classification of pain is important as it may facilitate more specific targeting of treatment. In this paper we present an overview of nociceptive, neuropathic and central sensitization pain following cancer treatment, as well as the rationale, criteria and process for stratifying pain classification. MATERIAL AND METHODS: Recently, a clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain was developed, based on a large body of research evidence and international expert opinion. We, a team of 15 authors from 13 different centers, four countries and two continents have applied this classification algorithm to the cancer survivor population. RESULTS: The classification of pain following cancer treatment entails two steps: (1) examining the presence of neuropathic pain; and (2) using an algorithm for differentiating predominant nociceptive and central sensitization pain. Step 1 builds on the established criteria for neuropathic pain diagnosis, while Step 2 applies a recently developed clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain to the cancer survivor population. CONCLUSION: The classification criteria allow identifying central sensitization pain following cancer treatment. The recognition of central sensitization pain in practice is an important development in the integration of pain neuroscience into the clinic, and one that is relevant for people undergoing and following cancer treatment.

The effect of material modeling on finite element analysis of human breast biomechanics.

PURPOSE: Finite element analysis has been used extensively in the study of biomechanical modeling of the breast. However, issues regarding the complexity of material models and the influences of geometric boundary conditions on the accuracy of a breast Finite Element (FE) model are still under debate. This work demonstrates the importance of material modeling in FE models of the breast. METHODS: A simple hemispherical geometry is used to model the shape of a human breast. Different material models are being investigated to accurately model changes in terms of displacement, stress, and reaction forces distribution. RESULTS: The results obtained using nonlinear material models are compared with those obtained employing their linear approximation. Results have shown that differences, in terms of displacement, ranging between 20% and more than 80%, may occur and that large differences are present in terms of maximum principal stresses when the displacement is correctly approximated. CONCLUSIONS: This study clearly shows that, in a FE model, simulating large deformations material modeling strongly influences the accuracy of the solution.

Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy.

BACKGROUND: Health-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. METHODS: A total of 121 stage I-II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. RESULTS: On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA with the Bonferroni correction did not show any significant differences between groups in HRQOL scores. CONCLUSIONS: TT patients had a better improvement in global health status and role- and cognitive-functioning, and a faster recovery from fatigue, than CR patients. These results suggest that a shorter fractionation schedule may reduce the adverse effects of treatment.

Early contralateral shoulder-arm morbidity in breast cancer patients enrolled in a randomized trial of post-surgery radiation therapy.

INTRODUCTION: Shoulder/arm morbidity is a common complication of breast cancer surgery and radiotherapy (RT), but little is known about acute contralateral morbidity. METHODS: Patients were 118 women enrolled in a RT trial. Arm volume and shoulder mobility were assessed before and 1-3 months after RT. Correlations and linear regression were used to analyze changes affecting ipsilateral and contralateral arms, and changes affecting relative interlimb differences (RID). RESULTS: Changes affecting one limb correlated with changes affecting the other limb. Arm volume between the two limbs correlated (R = 0.57). Risk factors were weight increase and axillary dissection. Contralateral and ipsilateral loss of abduction strongly correlated (R = 0.78). Changes of combined RID exceeding 10% affected the ipsilateral limb in 25% of patients, and the contralateral limb in 18%. Aromatase inhibitor therapy was significantly associated with contralateral loss of abduction. CONCLUSIONS: High incidence of early contralateral arm morbidity warrants further investigations.

Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial.

BACKGROUND: TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. METHODS: The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. RESULTS: By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). CONCLUSIONS: There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer follow-up of patients. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT00459628.

Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy.

BACKGROUND: Scapula alata (SA) is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT). METHODS: The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. RESULTS: Of 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009), 6.1 (P = 0.016), and 6.1 (P = 0.005), respectively. Randomization group was not significant. At one to three months' post-RT, mean arm volume increased by 4.1% (P = 0.036) and abduction decreased by 8.6% (P = 0.046) among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. CONCLUSION: The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.