Assessing the effect of hyperbaric oxygen therapy in breast cancer patients with late radiation toxicity (HONEY trial): a trial protocol using a trial within a cohort design

BACKGROUND: Breast cancer treatment with radiotherapy can induce late radiation toxicity, characterized by pain, fibrosis, edema, impaired arm mobility, and poor cosmetic outcome. Hyperbaric oxygen therapy (HBOT) has been proposed as treatment for late radiation toxicity; however, high-level evidence of effectiveness is lacking. As HBOT is standard treatment and reimbursed by insurers, performing classic randomized controlled trials is difficult. The "Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicity" (HONEY) trial aims to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the trial within cohorts (TwiCs) design. METHODS: The HONEY trial will be conducted within the Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Within UMBRELLA, breast cancer patients referred for radiotherapy to the University Medical Centre Utrecht are eligible for inclusion. Patients consent to collection of clinical data and patient-reported outcomes and provide broad consent for randomization into future intervention studies. Patients who meet the HONEY in- and exclusion criteria (participation ≥ 12 months in UMBRELLA, moderate/severe breast or chest wall pain, completed primary breast cancer treatment except hormonal treatment, no prior treatment with HBOT, no contraindications for HBOT, no clinical signs of metastatic or recurrent disease) will be randomized to HBOT or control group on a 2:1 ratio (n = 120). Patients in the control group will not be informed about participation in the trial. Patients in the intervention arm will undergo 30-40 HBOT treatment sessions in a high pressure chamber (2.4 atmospheres absolute) where they inhale 100% oxygen through a mask. Cohort outcome measures (i.e., physical outcomes, quality of life, fatigue, and cosmetic satisfaction) of the HBOT group will be compared to the control group at 3 months follow-up. DISCUSSION: This pragmatic trial within the UMBELLA cohort was designed to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the TwiCs design. Use of the TwiCs design is expected to address issues encountered in classic randomized controlled trials, such as contamination (i.e., HBOT in the control group) and disappointment bias, and generate information about acceptability of HBOT. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04193722 . Registered on 10 December 2019

Axillary reverse mapping in axillary surgery for breast cancer: an update of the current status

Abstract Axillary reverse mapping (ARM) is a technique by which the lymphatic drainage of the upper extremity that traverses the axillary region can be differentiated from the lymphatic drainage of the breast during axillary lymph node dissection (ALND). Adding this procedure to ALND may reduce upper extremity lymphedema by preserving upper extremity drainage. This review of the current literature on the ARM procedure discusses the feasibility, safety and relevance of this technique. A PubMed literature search was performed until 12 August 2015. A total of 31 studies were included in this review. The studies indicated that the ARM procedure adequately identifies the upper extremity lymph nodes and lymphatics in the axillary basin using blue dye or fluorescence. Preservation of ARM lymph nodes and corresponding lymphatics was proven to be oncologically safe in clinically node-negative breast cancer patients with metastatic lymph node involvement in the sentinel lymph node (SLN) who are advised to undergo a completion ALND. The ARM procedure is technically feasible with a high visualisation rate using blue dye or fluorescence. ALND combined with ARM can be regarded as a promising surgical refinement in order to reduce the incidence of upper extremity lymphedema in selected groups of patients.<br/

Timing of surgical intervention in necrotizing pancreatitis

Objective: To determine the effect of timing of surgical intervention for necrotizing pancreatitis. Design: Retrospective study of 53 patients and a systematic review. Setting: A tertiary referral center. Main Outcome Measure: Mortality. Results: Median timing of the intervention was 28 days. Eighty-three percent of patients had infected necrosis and 55% had preoperative organ failure. The mortality rate was 36%. Sixteen patients were operated on within 14 days of initial admission, 11 patients from day 15 to 29, and 26 patients on day 30 or later. This latter group received preoperative antibiotics for a longer period (P <.001), and Candida species and antibiotic-resistant organisms were more often cultured from the pancreatic or peripancreatic necrosis in these patients (P = .02). The 30-day group also had the lowest mortality (8% vs 75% in the 1 to 14-days group and 45% in the 15 to 29 days group, P <.001); this difference persisted when outcome was stratified for preoperative organ failure. During the second half of the study, necrosectomy was further postponed (43 vs 20 days, P = .06) and mortality decreased (22% vs 47%, P = .09). We also reviewed 11 studies with a total of 1136 patients. Median surgical patient volume was 8.3 patients per year (range, 5.3-15.6), median timing of surgical intervention was 26 days (range, 3-31), and median mortality was 25% (range, 6%-56%). We observed a significant correlation between timing of intervention and mortality (R = -0.603; 95% confidence interval, -2.10 to -0.02; P = .05). Conclusion: Postponing necrosectomy until 30 days after initial hospital admission is associated with decreased mortality, prolonged use of antibiotics, and increased incidence of Candida species and antibiotic-resistant organisms

Self-reported work ability in breast cancer survivors; a prospective cohort study in the Netherlands

Purpose: To evaluate patient-reported work ability of breast cancer patients, to compare scores with the Dutch general population, and to identify determinants of reduced work ability in breast cancer patients. Methods: In a prospective cohort study, we identified 939 patients <67 years. Employed patients filled out the Work Ability Index (WAI) questionnaire before the start of radiotherapy treatment (baseline) and at 6, 18, and 30 months. Work ability was compared with a matched Dutch cancer-free population (n=3,641). The association between (clinical) characteristics and work ability over time was assessed using mixed-effects models. Results: At baseline, 68% (n=641) of the respondents were employed and 64% (n=203) were employed at 30 months. Moderate or poor work ability was reported by 71% of patients at baseline, by 24% of the patients at 30 months and by 14% of the general population. Axillary lymph node dissection, (neo)adjuvant chemotherapy and locoregional radiotherapy were associated with reduced work ability. After 30 months, 18% of employed patients reported to have reduced their working hours, made substantial modifications to their work or were unable to work. Conclusion: Patient-reported work ability is strongly reduced during breast cancer treatment. Thirty months after treatment the proportion of women reporting poor or moderate work ability remains higher compared to the general population. Even though the proportion of women with paid employment is rather stable over time, substantial amendments in work are needed in 18% of patients. These findings emphasize the importance of informing patients on potential changes in work ability to allow shared decision making

Self-reported work ability in breast cancer survivors; a prospective cohort study in the Netherlands

Purpose: To evaluate patient-reported work ability of breast cancer patients, to compare scores with the Dutch general population, and to identify determinants of reduced work ability in breast cancer patients. Methods: In a prospective cohort study, we identified 939 patients <67 years. Employed patients filled out the Work Ability Index (WAI) questionnaire before the start of radiotherapy treatment (baseline) and at 6, 18, and 30 months. Work ability was compared with a matched Dutch cancer-free population (n=3,641). The association between (clinical) characteristics and work ability over time was assessed using mixed-effects models. Results: At baseline, 68% (n=641) of the respondents were employed and 64% (n=203) were employed at 30 months. Moderate or poor work ability was reported by 71% of patients at baseline, by 24% of the patients at 30 months and by 14% of the general population. Axillary lymph node dissection, (neo)adjuvant chemotherapy and locoregional radiotherapy were associated with reduced work ability. After 30 months, 18% of employed patients reported to have reduced their working hours, made substantial modifications to their work or were unable to work. Conclusion: Patient-reported work ability is strongly reduced during breast cancer treatment. Thirty months after treatment the proportion of women reporting poor or moderate work ability remains higher compared to the general population. Even though the proportion of women with paid employment is rather stable over time, substantial amendments in work are needed in 18% of patients. These findings emphasize the importance of informing patients on potential changes in work ability to allow shared decision making

Physical and mental health of breast cancer patients and survivors before and during successive SARS-CoV-2-infection waves

Purpose: During the first SARS-CoV-2-infection wave, a deterioration in emotional well-being and increased need for mental health care were observed among patients treated or being treated for breast cancer. In this follow-up study, we assessed patient-reported quality of life (QoL), physical functioning, and psychosocial well-being during the second SARS-CoV-2-infection wave in a large, representative cohort. Methods: This longitudinal cohort study was conducted within the prospective, multicenter UMBRELLA breast cancer cohort. To assess patient-reported QoL, physical functioning and psychosocial well-being, COVID-19-specific surveys were completed by patients during the first and second SARS-CoV-2-infection waves (April and November 2020, respectively). An identical survey was completed by a comparable reference population during the second SARS-CoV-2-infection waves. All surveys included the validated EORTC-QLQ-C30/BR23, HADS and “De Jong-Gierveld Loneliness” questionnaires. Pre-COVID-19 EORTC-QLQ-C30/BR23 and HADS outcomes were available from UMBRELLA. Response rates were 69.3% (n = 1106/1595) during the first SARS-CoV-2-infection wave and 50.9% (n = 822/1614) during the second wave. A total of 696 patients responded during both SARS-CoV-2-infection waves and were included in the analysis comparing patient-reported outcomes (PROs) during the second SARS-CoV-2-infection wave to PROs during the first wave. Moreover, PROs reported by all patients during the second SARS-CoV-2-infection wave (n = 822) were compared to PROs of a similar non-cancer reference population (n = 241) and to their pre-COVID-19 PROs. Results: Patient-reported QoL, physical functioning, and psychosocial well-being of patients treated or being treated for breast cancer remained stable or improved from the first to the second SARS-CoV-2-infection wave. The proportion of emotional loneliness reduced from 37.6 to 29.9% of patients. Compared to a similar non-cancer reference population, physical, emotional, and cognitive functioning, future perspectives and symptoms of dyspnea and insomnia were worse in patients treated or being treated for breast cancer during the second SARS-CoV-2-infection wave. PROs in the second wave were similar to pre-COVID-19 PROs. Conclusion: Although patients scored overall worse than individuals without breast cancer, QoL, physical functioning, and psychosocial well-being did not deteriorate between the first and second wave. During the second wave, PROs were similar to pre-COVID-19 values. Overall, current findings are cautiously reassuring for future mental health of patients treated or being treated for breast cancer