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Purpose: To investigate whether the dose planned for cardiac structures is associated with the risk of heart disease (HD) in patients with breast cancer treated with radiation therapy, and whether this association is modified by the presence of coronary artery calcification (CAC).Methods and Materials: Radiation therapy planning computed tomographic (CT) scans and corresponding dose distribution maps of 5561 patients were collected, 5300 patients remained after the exclusion of ineligible patients and duplicates; 1899 patients received their CT scan before 2011, allowing long follow-up. CAC was detected automatically. Using an artificial intelligence-based method, the cardiac structures (heart, cardiac chambers, large arteries, 3 main coronary arteries) were segmented. The planned radiation dose to each structure separately and to the whole heart were determined. Patients were assigned to a low-, medium-, or high-dose group based on the dose to the respective heart structure. Information on HD hospitalization and mortality was obtained for each patient. The association of planned radiation dose to cardiac structures with risk of HD was investigated in patients with and without CAC using Cox proportional hazard analysis in the long follow-up population. Tests for interaction were performed.Results: After a median follow-up of 96.0 months (interquartile range, 84.2-110.4 months) in the long follow-up group, 135 patients were hospitalized for HD or died of HD. If the dose to a structure increased 1 Gy, the relative HD risk increased by 3% to 11%. The absolute increase in HD risk was substantially higher in patients with CAC (event-ratelow-dose = 14-15 vs event-ratehigh-dose = 15-34 per 1000 person-years) than in patients without CAC (event-ratelow-dose = 6-8 vs event-ratehigh-dose = 5-17 per 1000 person-years). No interaction between CAC and radiation dose was found.Conclusions: Radiation exposure of cardiac structures is associated with increased risk of HD. Automatic segmentation of cardiac structures enables spatially localized dose estimation, which can aid in the prevention of radiation therapy-induced cardiac damage. This could be especially valuable in patients with breast cancer and CAC.

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.

Purpose To evaluate perceived access to health care and preferences for health care provision among patients (being) treated for breast cancer during the COVID-19 pandemic. Methods Longitudinal study within the prospective, multicenter UMBRELLA cohort of patients (being) treated for breast cancer. All cohort participants enrolled in UMBRELLA between October 2013 and November 2020 were sent a COVID-19-specific survey during the first and second wave of the COVID-19 pandemic, i.e., April 2020 and November 2020, respectively. Results In total, 1106 (69.3%) and 822 (50.9%) cohort participants completed the survey in the first and second wave, respectively. The proportion of patients experiencing that their treatment or follow-up care was affected due to COVID-19 decreased from 28.4% (n = 198) in April 2020 to 14.8% (n = 103) in November 2020. Throughout the pandemic, one or more hospital consultations were postponed in 10.0% (n = 82) of all patients and changed into a teleconsultation in 23.1% (n = 190). The proportion of patients who experienced a higher threshold to contact their general practitioner due to COVID-19 decreased from 29.9% (n = 204) in the first wave to 20.8% (n = 145) in the second wave. In-person consultations remained most preferred in 35.2% (n = 289) of all patients. Nearly half of all patients (48.3%, n = 396) indicated that telehealth would be a useful alternative for in-person consultations in future. Conclusion Perceived access to health care has improved substantially throughout the pandemic. Digital care is well received by patients (being) treated for breast cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s10549-021-06458-3.

Background and purpose: Accelerated partial breast irradiation (APBI) may benefit from the MR-Linac for target definition, patient setup, and motion monitoring. In this planning study, we investigated whether prone or supine position is dosimetrically beneficial for APBI on an MR-Linac and we evaluated patient comfort. Materials and methods: Twenty-patients (9 postoperative, 11 preoperative) with a DCIS or breast tumor

The purpose of this study is to evaluate the influence of the extent of surgery and radiation therapy (RT) on the rates and sites of local (LR) and regional recurrences (RR) in the EORTC 22922/10925 trial. Patients and methods: All data were extracted from the trial's individual patients’ case report forms (CRF) and analysed with a median follow-up of 15.7 years. Cumulative incidence curves were produced for LR and RR accounting for competing risks: an exploratory analysis of the effect of the extent of surgical and radiation treatments on LR rate was conducted using the Fine & Gray model accounting for competing risks and adjusted for baseline patient and disease characteristics. The significance level was set at 5%, 2-sided. Frequency tables were used to describe the spatial location of LR and RR. Results: Out of 4004 patients included in the trial, 282 (7%) patients experienced LR and 165 (4.1%) RR, respectively. Cumulative incidence rate of LR at 15 years was lower after mastectomy (3.1%) compared to BCS + RT (7.3%) (F&G: HR (Hazard Ratio) = 0.421, 95%CI = 0.282–0.628, p-value < 0.0001). LR were similar up to 3 years for both mastectomy and BCS but continued to occur at a steady rate for BCS + RT, only. The spatial location of the recurrence was related to the locoregional therapy applied and the absolute gain of RT correlated to stage of disease and extent of surgery. Conclusions: The extent of locoregional therapies impacts significantly on LR and RR rates and spatial location.

Contains fulltext : 235298.pdf (Publisher’s version ) (Open Access) Importance: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. Objective: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. Design, Setting, and Participants: In this multicenter cohort study of 15915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. Exposures: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Main Outcomes and Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). Conclusions and Relevance: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03206333.

Purpose: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the "Young Boost Trial". Material & methods: In the "Young Boost Trial" 2421 patients

Purpose We aimed to study radiation-induced gene expression changes and to identify differences in gene expression between patients with and without response to radiation therapy (RT) for invasive breast cancer with the purpose of exploring whether a predictive signature could be developed. Such a signature could assist in optimizing individualized locoregional treatment. Methods and Materials RNA-seq using next-generation sequencing was performed on fresh frozen samples from pretreatment biopsies and post-RT surgery specimens from patients with low-risk breast cancer treated within the multicenter preoperative accelerated partial breast irradiation trial. Patients were treated with preoperative RT (10 × 4 Gy in 10 days or 5 × 6 Gy in 5 days) and a lumpectomy 6 weeks thereafter. The response of the tumor to RT was evaluated by pathologic assessment. To analyze the gene expression data, unsupervised and supervised clustering was performed. Gene expression profiles were compared between biopsies of responders and nonresponders and between samples before and after RT. Results Ninety-four samples from 77 patients were analyzed: 68 pretreatment biopsies and 26 post-RT surgery specimens. Six patients had a (near) complete pathologic response, 3 patients had a good response, 32 patients had a partial response, and 22 patients had no or very limited response. Comparing patients with and without response to RT, 25 genes were significantly differentially expressed and were not linked to a pathway. Comparison of samples before and after RT identified significant changes in gene expression. Genes involved in p53 signaling, TNFA1 signaling, apoptosis, epithelial mesenchymal transition, and inflammatory response were upregulated. Genes involved in mitotic spindle, G2M checkpoint, and E2F targets were downregulated. Conclusions Radiation-induced gene expression changes mainly involved p53 signaling, cell cycle regulation, DNA repair, and inflammatory response. No clinically significant differences could be identified in gene expression between patients with and without response to RT.

Prior research underlined the importance of timely oncological care as longer waiting times from diagnosis to treatment may result in poorer survival outcomes. The aim of this study was to determine the impact of waiting time from diagnosis to treatment on overall survival (OS) in patients with cervical cancer treated with curative intent.Patients from a nationwide population-based cohort with newly diagnosed cervical cancer between 2010 and 2019 were studied. Patients who underwent surgery or (chemo)radiotherapy with curative intent were selected. Waiting time (i.e. interval between first pathologic confirmation and treatment) was modelled as continuous (i.e. linear per week), dichotomized (i.e. ≤8 versus8 weeks), and polynomial (i.e. restricted cubic splines). The association with OS was examined using Cox regression analyses.Among 6895 patients with cervical cancer, 2755 treated with primary surgery and 1898 who received primary (chemo)radiotherapy were included. Mean waiting time was 8.5 (±4.2) weeks to surgery and 7.7 (±2.9) weeks to (chemo)radiotherapy. Adjusted for confounders, waiting time to surgery was not significantly associated with OS (continuous HR 0.97 [95%CI: 0.93-1.01], dichotomized HR 0.93 [95%CI: 0.68-1.27], polynomial HR not significant). Similarly, a longer waiting time to (chemo)radiotherapy was not significantly associated with poorer OS (continuous HR 0.97 [95%CI: 0.93-1.00], dichotomized HR 0.91 [95%CI: 0.75-1.09], polynomial HR not significant).This large population-based study demonstrates that a longer waiting time (of up to 12 weeks) from diagnosis to treatment in patients with cervical cancer treated with curatively intended surgery or (chemo)radiotherapy does not negatively impact survival.

Contains fulltext : 245666.pdf (Publisher’s version ) (Open Access) Background: Coronary artery calcifications (CAC) is a strong predictor of cardiovascular disease (CVD), which can be automatically quantified on routine breast radiotherapy planning computed tomography (CT) scans. Around 8% of patients have (very) high CAC scores and corresponding increased risks of CVD. Aim: This study explores whether, how, and under what conditions women with breast cancer want to be informed about their CAC-based CVD risk. Methods: A cross-sectional survey study was conducted in a random sample of UMBRELLA, a prospective breast cancer cohort. Participants (n = 79) filled out a questionnaire about their knowledge on the CVD risk following breast cancer, their interest in being informed about their CVD risk based on CAC score, and preferences on how they would want to receive this information. Results: Most participants (66%) were not aware that the presence of CAC indicates an increased CVD risk. Participants indicated that they were not or only slightly aware of the risk of treatment-induced cardiotoxicity (48%), and that the risk of cardiotoxicity was higher in patients with pre-existing CVD risk factors (82%). The vast majority (90%) indicated that they want to be informed about in increased CAC-based CVD risk. Conclusions: The majority of patients with breast cancer wants to be informed about their CAC-based CVD risk. With the majority of patients with breast cancer undergoing radiotherapy, and with low cost and automated options for accurate CAC measurement in planning CT scans, it is important to develop strategies to manage patients with an increased CAC-based risk of CVD.

Accurate staging of para-aortic nodal status in cervical cancer is of great importance for individualizing treatment and impacting outcomes. Three-dimensional imaging (i.e. PET, CT, MRI) may miss para-aortic lymph node (PALN) metastases. The aim of this study was to systematically review and meta-analyze the proportion of upstaging by PALN dissection in patients with locally advanced cervical cancer without suspicious PALNs on imaging.PubMed/MEDLINE and Embase were systematically searched. The analysis included diagnostic studies that reported on 3D imaging and pre-therapeutic surgical assessment of PALN status in patients with cervical cancer. An overall pooled upstaging rate was calculated using a random-effects model.The search identified 16 eligible studies including 18 cohorts with a total of 1530 patients. Pooling of 12 cohorts demonstrated an upstaging rate of 12% (95% confidence interval [CI] 10-15%) by PALN dissection after negative PET or PET-CT. Pooling of 6 cohorts demonstrated a pooled upstaging rate of 11% (95% CI: 8-16%) by PALN dissection after negative MRI or CT. No significant heterogeneity in upstaging proportions across cohorts was observed (IThis meta-analysis demonstrates that in case of no suspicious PALN on PET-CT or MRI, PALN dissection still identifies lymph node metastases in a considerable amount of patients with locally advanced cervical cancer and especially in those patients with confirmed pelvic nodal metastases.

Purpose To evaluate symptoms of late radiation toxicity, side effects, and quality of life in breast cancer patients treated with hyperbaric oxygen therapy (HBOT). Methods For this cohort study breast cancer patients treated with HBOT in 5 Dutch facilities were eligible for inclusion. Breast cancer patients with late radiation toxicity treated with ≥ 20 HBOT sessions from 2015 to 2019 were included. Breast and arm symptoms, pain, and quality of life were assessed by means of the EORTC QLQ-C30 and -BR23 before, immediately after, and 3 months after HBOT on a scale of 0–100. Determinants associated with persistent breast pain after HBOT were assessed. Results 1005/1280 patients were included for analysis. Pain scores decreased significantly from 43.4 before HBOT to 29.7 after 3 months (p p p n = 576, 57.3%) and mild barotrauma (n = 179, 17.8%). Moderate/severe side effects were reported in 3.2% (n = 32) of the patients. Active smoking during HBOT and shorter time (i.e., median 17.5 vs. 22.0 months) since radiotherapy were associated with persistent breast pain after HBOT. Conclusion Breast cancer patients with late radiation toxicity reported reduced pain, breast and arm symptoms, and improved quality of life following treatment with HBOT.

Radiation therapy (RT) is increasingly being used in gynecological cancer management. RT delivered with curative or palliative intent can be administered alone or combined with chemotherapy or surgery. Advanced treatment planning and delivery techniques such as intensity-modulated radiation therapy, including volumetric modulated arc therapy, and image-guided adaptive brachytherapy allow for highly conformal radiation dose delivery leading to improved tumor control rates and less treatment toxicity. Quality on-board imaging that provides accurate visualization of target and surrounding organs at risk is a critical feature of these advanced techniques. As soft tissue contrast resolution is superior with magnetic resonance imaging (MRI) compared to other imaging modalities, MRI has been used increasingly to delineate tumor from adjacent soft tissues and organs at risk from initial diagnosis to tumor response evaluation. Gynecological cancers often have poor contrast resolution compared to the surrounding tissues on computed tomography scan, and consequently the benefit of MRI is high. One example is in management of locally advanced cervix cancer where adaptive MRI guidance has been broadly implemented for adaptive brachytherapy. The role of MRI for external beam RT is also steadily increasing. MRI information is being used for treatment planning, predicting, and monitoring position shifts and accounting for tissue deformation and target regression during treatment. The recent clinical introduction of online MRI-guided radiation therapy (oMRgRT) could be the next step in high-precision RT. This technology provides a tool to take full advantage of MRI not only at the time of initial treatment planning but as well as for daily position verification and online plan adaptation. Cervical, endometrial, vaginal, and oligometastatic ovarian cancers are being treated on MRI linear accelerator systems throughout the world. This review summarizes the current state, early experience, ongoing trials, and future directions of oMRgRT in the management of gynecological cancers.

Purpose This study aimed to find indicators for early response to radiation therapy in breast cancer. These would be of help in tailoring treatment for individual patients. Methods and Materials We analyzed 66 patients with low-risk breast cancer (≥60 years; cT1-2pN0) treated within the Preoperative Accelerated Partial Breast Irradiation (PAPBI) trial. Patients received radiation therapy (RT; 10 x 4 Gray or 5 x 6 Gray), followed by a wide local excision after 6 weeks. Patients underwent magnetic resonance imaging (MRI) and 18F-fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) before RT and 5 weeks after RT, before surgery. We assessed the response to PAPBI using a histopathologic assessment and correlated this with responses on MRI and FDG PET/CT. We calculated the positive predictive values (PPVs) of MRI and PET/CT as the number of true positives (complete response on MRI/normalized at visual evaluation on PET/CT and pathologic complete response) divided by the number of patients with a complete response on MRI/normalized at visual evaluation on PET/CT. Similarly, the negative predictive values (NPVs) of MRI and PET/CT were calculated. Results The pathologic response was (nearly) complete in 15 (23%) of the 66 patients and partially complete in 28 (42%). The remaining 23 patients (35%) were nonresponders. The PPV of MRI (Response evaluation criteria in solid tumors [RECIST]) was 87.5% and the NPV was 85%. The PPV and NPV of PET/CT were 25% and 92%, respectively. Conclusions The most accurate method to predict a response and residual disease after preoperative RT in low-risk breast cancer was MRI, using RECIST.

Background The coronavirus disease 2019 (COVID-19) pandemic (officially declared on the March 11, 2020), and the resulting measures, are impacting daily life and medical management of breast cancer patients and survivors. We evaluated to what extent these changes have affected quality of life, physical, and psychosocial well-being of patients previously or currently being treated for breast cancer. Methods This study was conducted within a prospective, multicenter cohort of breast cancer patients and survivors (Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion). Shortly after the implementation of COVID-19 measures, an extra survey was sent to 1595 participants, including the validated European Organization for Research and Treatment of Cancer (EORTC) core (C30) and breast cancer- specific (BR23) Quality of Life Questionnaire (EORTC QLQ-C30/BR23) and Hospital Anxiety and Depression Scale (HADS) questionnaire. Patient-reported outcomes (PROs) were compared with the most recent PROs collected within UMBRELLA pre–COVID-19. The impact of COVID-19 on PROs was assessed using mixed model analysis, adjusting for potential confounders. Results 1051 patients and survivors (65.9%) completed the survey; 31.1% (n = 327) reported a higher threshold to contact their general practitioner amid the COVID-19 pandemic. A statistically significant deterioration in emotional functioning was observed (mean = 82.6 [SD = 18.7] to 77.9 [SD = 17.3]; P Conclusion During the COVID-19 pandemic, breast cancer patients and survivors were less likely to contact physicians and experienced a deterioration in their emotional functioning. Patients undergoing active treatment reported a substantial drop in social functioning. One in 2 reported loneliness that was moderate or severe. Online interventions supporting mental health and social interaction are needed during times of social distancing and lockdowns.

Purpose To identify factors associated with (perceived) access to health care among (ex-)breast cancer patients during the COVID-19 pandemic. Methods Cross-sectional study within a large prospective, multicenter cohort of (ex-)breast cancer patients, i.e., UMBRELLA. All participants enrolled in the UMBRELLA cohort between October 2013 and April 2020 were sent a COVID-19-specific survey, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. Results In total, 1051 (66.0%) participants completed the survey. During COVID-19, 284 (27.0%) participants reported clinically relevant increased levels of anxiety and/or depression, i.e., total HADS score ≥ 12. Participants with anxiety and/or depression reported statistically significant higher barriers to contact their general practitioner (47.5% vs. 25.0%, resp.) and breast cancer physicians (26.8% vs. 11.2%, resp.) compared to participants without these symptoms. In addition, a higher proportion of participants with anxiety and/or depression reported that their current treatment or (after)care was affected by COVID-19 compared to those without these symptoms (32.7% vs. 20.5%, resp.). Factors independently associated with symptoms of anxiety and/or depression during COVID-19 were pre-existent anxiety (OR 6.1, 95% CI 4.1–9.2) or depression (OR 6.0, 95% CI 3.5–10.2). Conclusion During the COVID-19 pandemic, (ex-)breast cancer patients with symptoms of anxiety and/or depression experience higher barriers to contact health care providers. Also, they more often report that their health care was affected by COVID-19. Risk factors for anxiety and/or depression during COVID-19 are pre-existent symptoms of anxiety or depression. Extra attention—including mental health support—is needed for this group.

PurposeThe COVID-19 pandemic and the resulting social distancing and lockdown measures are having a substantial impact on daily life and medical management of people with breast cancer. We evaluated to what extent these changes have affected quality of life and physical, and psychosocial wellbeing of people (being) treated for breast cancer.MethodsThis study was conducted within the prospective Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Shortly after the implementation of COVID-19 measures, extra questionnaires were sent to 1595 cohort participants, including standard UMBRELLA quality of life (EORTC) questionnaires. Patient-reported outcomes (PROs) were compared to the most recent PROs collected within UMBRELLA before COVID-19. The impact of COVID-19 on PROs was evaluated using mixed models analysis.ResultsIn total, 1051 patients (66%) completed the questionnaires. One third (n = 327, 31%) reported a higher threshold to contact their general practitioner due to COVID-19. A significant deterioration in emotional functioning was observed (82·6 to 77·9, p < 0.001) and 505 (48%, 95% CI 45-51) patients reported moderate to severe loneliness. Small significant improvements were observed in QoL, physical-, social- and role functioning scores. In the subgroup of 51 patients under active treatment, there was a strong deterioration in social functioning (69·8 to 5·0, p = 0·03).ConclusionDue to COVID-19, patients (being) treated for breast cancer are less likely to contact physicians, and experience a deterioration in emotional functioning. Patients undergoing active treatment report a strong drop in social functioning. One in two patients reports (severe) loneliness. Online applications facilitating peer contact and e-mental health interventions could support mental health and social interaction times of total lockdown or social distancing.

Background: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation. Methods: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I–III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851. Findings: Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0–17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0–75·2) in the IM-MS irradiation group and 70·9% (68·6–72·9) in the control group (HR 0·95 [95% CI 0·84–1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5–26·6] vs 27·1% [25·1–29·2]; HR 0·87 [95% CI 0·77–0·98], p=0·024) and breast cancer mortality (16·0% [14·3–17·7] vs 19·8% [18·0–21·7]; 0·81 [0·70–0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4–63·2] vs 59·9% [57·5–62·2]; HR 0·93 [95% CI 0·84–1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7–72·2] vs 68·2% [65·9–70·3]; 0·93 [0·83–1·04], p=0·18). Causes of death between groups were similar. Interpretation: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I–III breast cancer. However, this is not converted to improved overall survival. Funding: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding.

Objectives To guide decision making in preventing over- or under-treatment in older breast cancer patients who have undergone breast conserving surgery, we analyzed prognostic factors and risk of recurrence in a consecutive series of patients ≥ 65 years old with breast cancer and identified subgroups that may benefit or not from more intensive treatment. Methods Patients ≥65 years of age with breast cancer (pT1-2/pN0-2) treated with breast conserving surgery and postoperative radiation therapy at the Netherlands Cancer Institute (NKI) between 1980 and 2008 were identified. Endpoints were locoregional recurrence (LRR), distant metastasis (DM) and overall survival (OS). Multivariable analyses were performed using Cox proportional hazards models. Results 1922 patients with a median age of 70 years were analyzed. The 5- and 10- years LRR rates were 2% and 3% respectively. In multivariable analysis there was no significant factor influencing LRR risk. Patients with low risk tumors (node negative patients with T1 and ER positive, grade 1 or 2) had lower risk of DM (HR 0.26) and better OS (HR 0.65) compared to patients with higher risk tumors (grade 3 and/or node positive). Conclusion In elderly breast cancer patients the risk of LRR and DM is low. In patients with less favorable characteristics the risk of LRR is equally low, with a higher risk to develop DM and worse OS. Treatment in the low risk group may be minimized, while for the higher risk group adjuvant treatment could be intensified.

Purpose In this multicenter phase 2 feasibility study, we investigated the impact of preoperative accelerated partial breast irradiation (PAPBI) on local control, breast fibrosis, and cosmetic outcome. Methods and Materials Women aged >60 years with an invasive, unifocal (mammography and magnetic resonance imaging), nonlobular adenocarcinoma of the breast were treated with PAPBI. Six weeks after radiation therapy, a wide local excision was performed. Radiation therapy consisted of 10 × 4 Gy (2010-2013) or 5 × 6 Gy (after 2013) to the tumor (gross target volume) with a 25 mm margin (20 mm from gross target volume to clinical target volume, 5 mm planning target volume). Results One hundred thirty-three patients treated between 2010 and 2016 were analyzed with a median follow-up of 5.0 years (0.9-8.8 years). Seventy-eight (59%) patients were treated with 10 × 4 Gy in 2 weeks and 55 (41%) patients with 5 × 6 Gy in 1 week. Eighteen postoperative complications (14%) occurred in 15 patients (11%). The proportion of patients with no to mild fibrosis in the treated part of the breast at 2 years and later time points was around 90%. Cosmesis improved over time in several patients: excellent to good cosmetic score as rated by the physician was 68% at 6 months and 92% at 5 years. Seventy-seven percent (6 months) to 82% (5 years) of patients were “satisfied” or “very satisfied” with their cosmetic outcome. Three recurrences were detected in the biopsy track and 1 recurrence in the ipsilateral breast. Conclusions PAPBI is a feasible method with a low postoperative complication rate, limited fibrosis, and good to excellent cosmetic outcome. The local recurrence rate was 3% at 5 years; however, no local recurrences were observed since removal of the needle biopsy track.

Background and purpose The aim of this study is to assess the toxicity and cosmetic outcome of preoperative accelerated partial breast irradiation (PAPBI) for breast cancer patients with low risk on local recurrence. Material and methods Women aged ⩾60years with an invasive, unifocal ⩽3cm on MRI, (non-lobular) adenocarcinoma of the breast and a negative sentinel node received PAPBI (40Gray in 10 fractions over 2weeks). Six weeks after radiotherapy a wide local excision was performed. Results 70 patients with a median follow-up of 23months (3–44months) were evaluated. The overall postoperative infection rate was 11%. At 1, 2 and 3years of follow-up respectively 89%, 98% and 100% of patients had no or mild induration-fibrosis. Fibrosis was only found in a small volume of the breast. The global cosmetic outcome was good to excellent in 77% at 6months to 100% at 3years. Two patients developed a local recurrence. Conclusion Our first results show limited fibrosis in a small volume and good to excellent cosmetic outcome. In selected patients, preoperative radiotherapy appears to be a good option for breast conserving therapy.

Background. The aim of this study was to assess the accuracy of 18F-FDG PET/CT in T1 breast cancer regarding visualization of the primary tumor and the detection of locoregional and distant metastases. Methods. Sixty-two women with invasive T1 breast cancer underwent a PET/CT. Image acquisition of the thorax was done in prone position with hanging breasts, followed by whole-body scanning in supine position. Primary tumor FDG uptake was evaluated and compared with clinical and histopathological characteristics. Presence of locoregional and distant metastases was assessed and compared with conventional imaging procedures. Results. The primary tumor was visible with PET/CT in 54 (87%) of 62 patients, increasing from 59% (10/17) in tumors ≤ 10 mm to 98% (44/45) in tumors over 10 mm. All triple negative and HER2-positive tumors and 40/48 (83%) ER-positive/HER2-negative tumors were visualized. Sensitivity and specificity of PET/CT in the detection of axillary metastases were 73% and 100%, respectively. PET/CT depicted periclavicular nodes in two patients. Of 12 distant lesions, one was confirmed to be a lung metastasis, three were false positive, and eight were new primary proliferative lesions. Conclusion. Using optimal imaging acquisition, the majority of T1 breast carcinomas can be visualized with PET/CT. Specificity in the detection of axillary metastases is excellent, but sensitivity appears to be limited. Additional whole body imaging has a low yield in this specific patient group.

Risk factors for local recurrence in breast cancer after breast conserving therapy (BCT) differ from those for local recurrence after mastectomy. To better guide optimal treatment of individual patients, it is desirable to identify patients at high risk for local recurrence. Several clinical and histopathologic factors, such as young age and presence of ductal carcinoma in situ, are known to be predictors for local recurrence after BCT. After mastectomy, lymph node status and tumor size are dominant risk factors for local recurrence. The results of recent expression profiling studies have explained differences in prognosis and risk for local recurrence and also explained response to different therapies (adjuvant systemic therapy and radiotherapy). Because of the variation in different subtypes of breast cancer and the difference in amount of tumor burden remaining after surgery, finding robust predictive profiles is complex. In this review, we describe the predictive and prognostic factors for local recurrence after mastectomy and BCT and also describe the role of radiosensitivity in local recurrence. Semin Radiat Oncol 22:100-107 (c) 2012 Elsevier Inc. All rights reserved

Item does not contain fulltext The challenge of adequate target volume definition in external beam partial breast irradiation (PBI) could be overcome with preoperative irradiation, due to less inter-observer variation. We compared the target volume delineation for external beam PBI on preoperative versus postoperative CT scans of twenty-four breast cancer patients.

Premenstrual syndrome (PMS) is characterised by the occurrence of physical and psychological symptoms during the luteal phase of almost every menstrual cycle. These symptoms disappear at the beginning of menstruation, and a symptom-free period of at least a week ensues. Premenstrual dysphoric disorder (PMDD) is a variation of PMS, with predominantly psychological symptoms. The aetiology of PMD and PMDD is not known. A possible explanation however is an abnormal, stronger reaction to physiologically normal hormonal fluctuations. Diagnosing PMS and PMDD requires prospective daily monitoring of symptoms over at least two menstrual cycles. No effective medication for the treatment of PMS has been registered in the Netherlands. In randomized placebo-controlled trials selective serotonin reuptake inhibitors and oral contraceptives containing drosperinone have been found to have a positive effect on the physical and psychological symptoms of PMS and PMDD.

Contains fulltext : 57393.pdf (Publisher’s version ) (Closed access) PURPOSE: Recognition of hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial carcinoma from sporadic carcinoma by histologic features as compared with colonic cases. STUDY DESIGN: Case-control study. METHODS AND MATERIALS: From the files of the Nijmegen Hereditary Cancer Clinic, HNPCC-related (n = 6) endometrial and colorectal (n = 18) carcinomas were selected. For every HNPCC-related tumor, 2 sporadic control cases were included. The tumors were evaluated for the following 7 pathologic features: tumor differentiation, T-stage, growth pattern, presence of Crohn-like lymphoid reaction, mucinous differentiation, presence of lymphangioinvasive growth, and the amount of tumor-infiltrating lymphocytes. RESULTS: HNPCC-related endometrial carcinomas were significantly more often poorly differentiated (83% versus 27%), more often showed the presence of a Crohn-like lymphoid reaction (100% versus 13%) and lymphangioinvasive growth (67% versus 0%), and high number of tumor-infiltrating lymphocytes were more often present (100% versus 36%) compared with sporadic endometrial carcinomas. The differences between HNPCC and sporadic colorectal cancer specimens were less discriminating. CONCLUSIONS: HNPCC-related endometrial carcinomas are characterized by poor differentiation, more frequent Crohn-like lymphoid reaction, lymphangioinvasive growth and more tumor-infiltrating lymphocytes. These features therefore might form the basis for selecting patients for counseling in a hereditary cancer clinic or testing for microsatellite instability or mutation analysis of mismatch repair genes, especially when they are of relatively young age.