Association between initiation of adjuvant chemotherapy beyond 30 days after surgery and overall survival among patients with triple-negative breast cancer

Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22–2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84–1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors:results from the SURVAYA study

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. Methods: A population-based, cross-sectional study was performed among long-term (5–20 years) AYA cancer survivors (18–39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5–7.0) (n = 3668). Sixty-one percent adhered to “limit the consumption of sugar sweetened drinks,” 28% to “be a healthy weight,” 25% to “fruit and vegetable consumption,” and 31% to “limit alcohol consumption.” Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14–1.85, and ORhigh = 1.87, 95% CI = 1.46–2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30–1.83, and ORhigh = 1.87, 95% CI = 1.46–2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50–0.92, and ORhigh = 0.30, 95% CI = 0.21–0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39–0.86, and ORhigh = 0.45, 95% CI = 0.30–0.69). Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.</p

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors:results from the SURVAYA study

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. Methods: A population-based, cross-sectional study was performed among long-term (5–20 years) AYA cancer survivors (18–39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5–7.0) (n = 3668). Sixty-one percent adhered to “limit the consumption of sugar sweetened drinks,” 28% to “be a healthy weight,” 25% to “fruit and vegetable consumption,” and 31% to “limit alcohol consumption.” Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14–1.85, and ORhigh = 1.87, 95% CI = 1.46–2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30–1.83, and ORhigh = 1.87, 95% CI = 1.46–2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50–0.92, and ORhigh = 0.30, 95% CI = 0.21–0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39–0.86, and ORhigh = 0.45, 95% CI = 0.30–0.69). Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.</p

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer

Purpose: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18–39 years) cancer. Methods: This study included n = 1457 male and n = 2112 female long-term survivors (M age = 43–45 years; 5–22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.Results: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2–3.6]), not having children (OR = 5.0; 95%CI [3.2–7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to “others”), and more intense treatments (OR = 1.5; 95%CI [1.1–2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. Conclusions: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors’ well-being. Implications for Cancer Survivors: The extent to which cryopreservation positively affects survivors’ well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.</p

HUMeral Shaft Fractures: MEasuring Recovery after Operative versus Non-operative Treatment (HUMMER): A multicenter comparative observational study

Background: Fractures of the humeral shaft are associated with a profound temporary (and in the elderly sometimes even permanent) impairment of independence and quality of life. These fractures can be treated operatively or non-operatively, but the optimal tailored treatment is an unresolved problem. As no high-quality comparative randomized or observational studies are available, a recent Cochrane review concluded there is no evidence of sufficient scientific quality available to inform the decision to operate or not. Since randomized controlled trials for this injury have shown feasibility issues, this study is designed to provide the best achievable evidence to answer this unresolved problem. The primary aim of this study is to evaluate functional recovery after operative versus non-operative treatment in adult patients who sustained a humeral shaft fracture. Secondary aims include the effect of treatment on pain, complications, generic health-related quality of life, time to resumption of activities of daily living and work, and cost-effectiveness. The main hypothesis is that operative treatment will result in faster recovery. Methods/design. The design of the study will be a multicenter prospective observational study of 400 patients who have sustained a humeral shaft fracture, AO type 12A or 12B. Treatment decision (i.e., operative or non-operative) will be left to the discretion of the treating surgeon. Critical elements of treatment will be registered and outcome will be monitored at regular intervals over the subsequent 12 months. The primary outcome measure is the Disabilities of the Arm, Shoulder, and Hand score. Secondary outcome measures are the Constant score, pain level at both sides, range of motion of the elbow and shoulder joint at both sides, radiographic healing, rate of complications and (secondary) interventions, health-related quality of life (Short-Form 36 and EuroQol-5D), time to resumption of ADL/work, and cost-effectiveness. Data will be analyzed using univariate and multivariable analyses (including mixed effects regression analysis). The cost-effectiveness analysis will be performed from a societal perspective. Discussion. Successful completion of this trial will provide evidence on the effectiveness of operative versus non-operative treatment of patients with a humeral shaft fracture. Trial registration. The trial is registered at the Netherlands Trial Register (NTR3617)

Erratum to: High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients: Results of the REACT-2 trial

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: K. Treskes1, S.A. Bos1, L.F.M. Beenen2, J.C. Sierink1, M.J.R. Edwards3, B.J

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Reliability and Reproducibility of the OTA/AO Classification for Humeral Shaft Fractures

Objectives: This study aimed to determine interobserver reliability and intraobserver reproducibility of the OTA/AO classification for humeral shaft fractures, and to evaluate differences between fracture types, fracture groups, and surgical specializations. Methods: Thirty observers (25 orthopaedic trauma surgeons and 5 general orthopaedic surgeons) independently classified 90 humeral shaft fractures according to the OTA/AO classification. Patients of 16 years and older were included. Periprosthetic, recurrent, and pathological fractures were excluded. Radiographs were provided in random order, and observers were blinded to clinical information. To determine intraobserver agreement, radiographs were reviewed again after 2 months in a different random order. Agreement was assessed using kappa statistics. Results: Interobserver agreement for the 3 fracture types was moderate (κ = 0.60; 0.59-0.61). It was substantial for type A (κ = 0.77; 0.70-0.84) and moderate for type B (κ = 0.52; 0.46-0.58) and type C fractures (κ = 0.46; 0.42-0.50). Interobserver agreement for the 9 fracture groups was moderate (κ = 0.48; 95% CI, 0.48-0.48). Orthopaedic trauma surgeons had better overall agreement for fracture types, and general orthopaedic surgeons had better overall agreement for fracture groups. Observers classified 64% of fractures identically in both rounds. Intraobserver agreement was substantial for the 3 types (κ = 0.80; 0.77-0.81) and 9 groups (κ = 0.80; 0.77-0.82). Intraobserver agreement showed no differences between surgical disciplines. Conclusions: The OTA/AO classification for humeral shaft fractures has a moderate interobserver and substantial intraobserver agreement for fracture types and groups

Sexual quality of life of adolescents and young adult breast cancer survivors

Background: With increasing survival rates of adolescents and young adults (AYAs) with breast cancer, health-related quality of life (HRQoL) becomes more important. An important aspect of HRQoL is sexual QoL. This study examined long-term sexual QoL of AYA breast cancer survivors, compared sexual QoL scores with that of other AYA cancer survivors, and identified factors associated with long-term sexual QoL of AYA breast cancer survivors. Materials and methods: Data of the SURVAYA study were utilized for secondary analyses. Sexual QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). Descriptive statistics were used to describe sexual QoL of AYA cancer survivors. Linear regression models were constructed to examine the effect of cancer type on sexual QoL and to identify factors associated with sexual QoL. Results: Of the 4010 AYA cancer survivors, 944 had breast cancer. Mean sexual QoL scores of AYA breast cancer survivors ranged from 34.5 to 60.0 for functional domains and from 25.2 to 41.5 for symptom-orientated domains. AYA breast cancer survivors reported significantly lower sexual QoL compared to AYA survivors of other cancer types on all domains. Age, time since diagnosis, relationship status, educational level, chemotherapy, hormonal therapy, breast surgery, body image, and coping were associated with sexual QoL of AYA breast cancer survivors. Conclusions: AYA breast cancer survivors experience decreased sexual QoL in the long term (5-20 years) after diagnosis and worse score compared to AYA survivors of other cancer types, indicating a clear need to invest in supportive care interventions for those at risk, to enhance sexual well-being.</p