Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. METHODS: A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. RESULTS: In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. CONCLUSION: Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Adjuvant treatment decisions among adults aged 65 years and older with early-stage hormone receptor positive breast cancer seen in a simple multidisciplinary clinic versus standard consultation.

INTRODUCTION: Randomized studies support de-escalation of adjuvant therapy for a target population of older adults ≥65 years with stage I, estrogen-receptor (ER) positive breast cancer after breast conserving surgery. We sought to evaluate the impact of a simplified multidisciplinary clinic (s-MDC) in this population by comparing treatment patterns and patient perceptions of adjuvant radiation therapy (RT) and hormone therapy (HT) between patients seen in s-MDC vs. standard consultations. MATERIALS AND METHODS: Medical records were retrospectively reviewed for patients in the above target population who underwent surgery between August 2020 and May 2022 at our institution. Two cohorts were included: (1) patients seen in s-MDC, and (2) patients seen in standard clinic separately by medical and radiation oncology (non-s-MDC cohort). The non-s-MDC patients declined, could not attend, and/or were not referred to the s-MDC. Patients in the s-MDC cohort were prospectively administered validated questionnaires to evaluate patient reported data including the Decision Autonomy Preference Scale (DAPS), e-Prognosis, and Medical Maximizing-Minimizing Scale (MMS). Chi square, t-tests, and non-parametric equivalents compared demographics, and logistic regression evaluated RT and HT use and survey score outcomes between cohorts. RESULTS: A total of 127 patients met inclusion criteria, with 33 s-MDC and 94 non-s-MDC patients. There was no difference between the cohorts in age, margin status, histology, grade, or focality. In the s-MDC cohort there were significantly more patients without sentinel lymph node biopsy (71.3% vs 42.4%, p = 0.003) and mean tumor size was smaller (0.69 vs. 0.96 cm, p < 0.003), and Charlson comborbidity index (CCI) was higher (5.21 vs 4.96, p = 0.038). There was no significant difference in receipt of RT (65% s-MDC vs 77% standard; odds ratio [OR] = 0.55, p = 0.189), HT (78% ss-MDC vs 72% standard; OR = 1.36, p = 0.513), or both (50% s-MDC vs 59% standard; OR = 0.7, p = 0.429). The s-MDC cohort was significantly more likely to undergo accelerated (vs. standard hypofractionated) RT (70% vs 39%; OR = 3.59, p = 0.020). In s-MDC patients with completed questionnaires (n = 33), all whose selected "mostly patient (n=6)" based decision making by DAPS chose RT while all "mostly doctor (n=1)" chose no RT. Based on e-Prognosis, there were lower odds of RT for increasing Schonberg score/ higher 10 yr mortality risk (OR 0.600, p = 0.048). MMS score ≥ 40 ("maximizer") was strongly linked with the use of RT (OR 18.57, p = 0.011). DISCUSSION: For adults ≥65 years with early stage, ER positive breast cancer, s-MDC participation was not significantly associated with lower use of adjuvant RT or HT versus standard consultation but was significantly associated with shorter RT courses. DAPS and MMS results indicate that patient treatment preference may be predictable, highlighting an opportunity to tailor consultation discussions and recommendations based on intrinsic patient preferences and individual goals.

Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations.

The KEYNOTE-522 study is a practice-changing phase III randomized study that demonstrated that the addition of pembrolizumab to polychemotherapy improves outcomes in patients with high-risk early-stage triple-negative breast cancer (TNBC). This regimen is highly efficacious with unprecedented pathologic complete response (pCR) rates, and clinically meaningful improvements in event-free survival (EFS). However, the combination is also associated with significant high-grade treatment-related toxicity. The backbone regimen deviated from common practice, including the addition of carboplatin, lack of dose dense anthracyclines, and adjuvant capecitabine for residual disease, thus brining important questions regarding real-world translation of these results. This brief report practically addresses some of the most relevant questions physicians and patients face in optimizing care using the best available evidence.

Development of the Tiers of Service framework to support system and operational planning for children's healthcare services.

BACKGROUND: Providing access to pediatric healthcare services in British Columbia, Canada, presents unique challenges given low population densities spread across large geographic distances combined with a lack of availability of specialist providers in remote areas, leading to quality of care shortcomings and inequalities in care delivery. The study objective was to develop a framework that provides a common language and methodology for defining and planning child and youth healthcare services across the province. METHODS: The framework was developed in two phases. In Phase 1, a literature and jurisdictional review was completed using the following inclusion criteria: (i) description of a framework focusing on organizing service delivery systems (ii) that supports health service planning, (iii) includes specialty or subspecialty services and (iv) has been published since 2008. In Phase 2, a series of meetings with key provincial stakeholders were held to receive feedback on the developed Tiers of Service framework versions that were based on the literature and jurisdictional review and adjusted to the British Columbian health care context. The final version was endorsed by the Child Health BC Steering Committee. RESULTS: Ten medical articles and thirteen jurisdictional papers met the established selection criteria and were included in this study. Most frameworks were developed by the Australian national or state jurisdictions and published in jurisdictional papers (n = 8). Frameworks identified in the medical literature were mainly developed in Canada (n = 3) and the US (n = 3) and focused on maternity, neonatal, critical care and oncology services. Based on feedback received from the expert group, the framework was expanded to include community-based services, prevention and health determinants. The final version of the Tiers of Service framework describes the specific services to be delivered at each tier, which are categorized as Tier 1 (community services) through Tier 6 (sub-specialized services). Two consecutive steps were identified to effectively use the framework for operational and system planning: (i) development of a 'module' outlining the responsibilities and requirements to be delivered at each tier; and (ii) assessment of services provided at the health care facility against those described in the module, alignment to a specific tier, identification of gaps at the local, regional and provincial level, and implementation of quality improvement initiatives to effectively address the gaps. CONCLUSIONS: The benefits of the Tiers of Service framework and accompanying modules for health service planning are being increasingly recognized. Planning and coordinating pediatric health services across the province will help to optimize flow and improve access to high-quality services for children living in British Columbia.

Developing a province-wide hip surveillance program for children with cerebral palsy: from evidence to consensus to program implementation: a mini-review.

Hip displacement is a common orthopedic problem in children with cerebral palsy (CP) that can result in significant morbidity. Hip surveillance has been shown to reduce the incidence of hip dislocations in children with CP and to reduce the need for salvage hip surgeries. Guidelines for hip surveillance have been developed and can be adapted to meet local needs. Implementation of surveillance guidelines for a population of children is complex and highly dependent upon the region, province/state, or country's system of care for children with CP. Recognizing that implementation of the evidence on hip surveillance was necessary in British Columbia, a Canadian province spanning 1 million square kilometers, a comprehensive, coordinated approach to hip surveillance was developed collaboratively by provincial stakeholders. Surveillance guidelines and a desired implementation plan were established based on the best available research evidence, current international practice, and service delivery in British Columbia. Staged implementation preceded full provincial roll out. Implementation was supported by detailed communication, knowledge translation, and evaluation plans. This province-wide hip surveillance program is the first of its kind in North America.

Improving value and access to specialty medical care for families: a pediatric surgery telehealth program

Background: In Canada, access to subspecialty surgical services for children imposes inconvenience and financial hardship on geographically remote families. The purpose of this study was to evaluate a recently implemented pediatric surgical telehealth pilot program from the family and provider perspectives. Methods: Enabled by an existing telehealth infrastructure for pediatric subspecialty medicine and mental health, a pilot telehealth program for surgical consultation was established by a single surgeon in British Columbia. Following establishment of eligibility criteria, patients from remote communities requiring new consultation or clinical follow-up were offered a telehealth alternative. At the end of the encounter, both the parent and patient (if appropriate) provided feedback via a questionnaire. Provider satisfaction was also assessed via a questionnaire. We estimated costs avoided and analyzed data on pediatric surgery consultation wait time. Results: Between September 2014 and November 2017, 80 patients were seen in 19 remote telehealth centres, 23 as new referrals and 57 in follow-up consultation. Among new referrals, the commonest diagnosis was chest wall deformity. The average travel distance avoided was 705 km, with an estimated direct cost avoidance of $585. Sixty-four families (80%) completed the questionnaire. Almost all (63 [98%]) indicated high overall satisfaction with the telehealth experience. Provider satisfaction was similarly high, in terms of both the technology user interface and clinical effectiveness. Overall pediatric surgical consultation wait times were unaffected. Conclusion: Implementation of telehealth technology in a pediatric surgical practice offered high value to patients/families and, from the provider's perspective, yielded an acceptable alternative to in-person assessment.

Contexte: Au Canada, l'accès aux services chirurgicaux surspécialisés pour enfants est source d'inconvénients et de difficultés financières pour les familles vivant en région éloignée. L'objectif de cette étude était d'évaluer le point de vue des familles et des fournisseurs de services sur un programme pilote de télésanté pédiatrique récemment mis en oeuvre. Méthodes: Ce programme pilote de consultation chirurgicale à distance a été mis sur pied par un chirurgien de Colombie-Britannique, qui s'est servi d'une infrastructure de télésanté préexistante permettant la prestation de services surspécialisés de médecine et de santé mentale pour enfants. Une fois leur admissibilité établie, les patients vivant en région éloignée et ayant besoin d'une consultation ou d'un suivi clinique se sont vu offrir des services de télésanté. Après la consultation, les parents et le patient (lorsque c'était approprié) ont rempli un formulaire de rétroaction. La satisfaction des fournisseurs de soins a été également évaluée au moyen d'un questionnaire. Nous avons estimé les coûts évités et analysé les données sur le temps d'attente pour une consultation en chirurgie pédiatrique. Résultats: Entre septembre 2014 et novembre 2017, 80 patients ont consulté 19 centres de télésanté : 23 pour une nouvelle consultation et 57 pour un suivi. Parmi les nouveaux cas, le diagnostic le plus fréquent était une malformation de la paroi thoracique. En moyenne, 705 km de déplacements ont été évités, ce qui représente un coût estimé de 585 $. Soixante-quatre familles (80 %) ont rempli le questionnaire, et presque toutes (63 [98 %]) se sont dites globalement satisfaites de leur expérience de télésanté. La satisfaction des fournisseurs de soins était également élevée, tant en ce qui a trait à l'interface utilisateur des outils technologiques qu'à l'efficacité clinique. Le programme n'a eu aucun effet sur le temps d'attente général pour une consultation en chirurgie pédiatrique. Conclusion: L'utilisation de services de télésanté en chirurgie pédiatrique a été d'une grande valeur pour les patients et leur famille. Du point de vue des fournisseurs de soins, elle a constitué une solution de rechange acceptable aux consultations en personne.

Dose-dependent effect of mammographic breast density on the risk of contralateral breast cancer.

PURPOSE: Increased mammographic breast density is a significant risk factor for breast cancer. It is not clear if it is also a risk factor for the development of contralateral breast cancer. METHODS: The data were obtained from Breast Cancer Surveillance Consortium and included women diagnosed with invasive breast cancer or ductal carcinoma in situ between ages 18 and 88 and years 1995 and 2009. Each case of contralateral breast cancer was matched with three controls based on year of first breast cancer diagnosis, race, and length of follow-up. A total of 847 cases and 2541 controls were included. The risk factors included in the study were mammographic breast density, age of first breast cancer diagnosis, family history of breast cancer, anti-estrogen treatment, hormone replacement therapy, menopausal status, and estrogen receptor status, all from the time of first breast cancer diagnosis. Both univariate analysis and multivariate conditional logistic regression analysis were performed. RESULTS: In the final multivariate model, breast density, family history of breast cancer, and anti-estrogen treatment remained significant with p values less than 0.01. Increasing breast density had a dose-dependent effect on the risk of contralateral breast cancer. Relative to 'almost entirely fat' category of breast density, the adjusted odds ratios (and p values) in the multivariate analysis for 'scattered density,' 'heterogeneously dense,' and 'extremely dense' categories were 1.65 (0.036), 2.10 (0.002), and 2.32 (0.001), respectively. CONCLUSION: Breast density is an independent and significant risk factor for development of contralateral breast cancer. This risk factor should contribute to clinical decision making.

Prevention of hip displacement in children with cerebral palsy: a systematic review.

AIM: To conduct a systematic review and evaluate the quality of evidence for interventions to prevent hip displacement in children with cerebral palsy (CP). METHOD: A systematic review was performed using American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were completed in seven electronic databases. Studies were included if participants had CP and the effectiveness of the intervention was reported using a radiological measure. Results of orthopaedic surgical interventions were excluded. RESULTS: Twenty-four studies fulfilled the inclusion criteria (4 botulinum neurotoxin A; 2 botulinum neurotoxin A and bracing; 1 complementary and alternative medicine; 1 intrathecal baclofen; 1 obturator nerve block; 8 positioning; 7 selective dorsal rhizotomy). There was significant variability in treatment dosages, participant characteristics, and duration of follow-up among the studies. Overall, the level of evidence was low. No intervention in this review demonstrated a large treatment effect on hip displacement. INTERPRETATION: The level and quality of evidence for all interventions aimed at slowing or preventing hip displacement is low. There is currently insufficient evidence to support or refute the use of the identified interventions to prevent hip displacement or dislocation in children and young people with CP. WHAT THIS PAPER ADDS: High-quality evidence on prevention of hip displacement is lacking. No recommendations can be made for preventing hip displacement in children with cerebral palsy because of poor-quality evidence. High-quality, prospective, longitudinal studies investigating the impact of interventions on hip displacement are required.

Dependence of nanoparticle-cell recognition efficiency on the surface orientation of scFv targeting ligands.

The surface activation of multifunctional nanoparticles (MNPs) with peptide ligands directing their targeting to cancer cells is an emerging research area in nanobiotechnology. In this paper, water-soluble MNPs have been synthesized and functionalized with an scFv antibody variant specific toward the HER2 receptor overexpressed in several breast cancer cell lines. The scFv was genetically engineered to introduce a cysteine residue inside the loop sequence bridging the VH and VL lobes of the molecule and a histidine tag at the C-terminus in the VL fragment. The Cys and 6 × His functionalities were exploited as orthogonal reactive groups driving the scFv conjugation to MNPs. In this way, scFv positioning on the MNP surface was forced into two different orientations depending on the molecular binding site used for conjugation. The resulting scFv-functionalized MNP1 and MNP2, respectively, were assessed as to their labeling efficiency and selectivity to HER2-positive MCF7 cells. We demonstrate that, while both MNP1 and MNP2 were selective for HER2, there is a remarkable preference for scFv presentation with VH and VL lobes concurrently available for receptor recognition (MNP1) in terms of cell binding efficiency, suggesting that ligand orientation may strongly affect cell binding from MNPs.

Parents of children with cancer: which factors explain differences in health-related quality of life.

Research with parents of children with cancer has identified factors related to their adjustment and coping, but it is not fully understood why some parents do well and others do not. Guided by a stress process model, we examined the interrelationships among a comprehensive set of factors to identify the most important determinants of health-related quality of life (HRQoL) in parents of children in active treatment for cancer. A cross-sectional survey of 411 parents (80% response rate) of children receiving cancer treatment in Canada was conducted between November 2004 and February 2007. The following constructs were measured: background and context factors, child characteristics, family-centered service delivery, caregiver strain, intrapsychic factors, coping/supportive factors and parental HRQoL. The model was evaluated using structural equation modeling. Analysis was stratified by time since diagnosis (i.e., <12 months and ≥12 months). For those within 12 months of their child's diagnosis, family-centred service provision, caregiver strain, and self-perception accounted for 58% of the variation in psychosocial health, whereas caregiver strain and social support explained 50% of the variation in physical health. For parents in the >12 month group, caregiving strain was the only factor with a direct relationship with parental psychosocial and physical health, accounting for 66% and 55% of the variance in these constructs, respectively. Our findings reinforce the need for health professionals to be particularly attuned to family caregivers in the early stages of treatment and identify potential areas for interventions to promote parental health.

Impact of caring for a child with cancer on parents' health-related quality of life.

PURPOSE: To compare the health-related quality of life (QOL) of parents of children who are undergoing treatment for cancer with that of Canadian population norms and to identify important parent and child predictors of parental QOL. PATIENTS AND METHODS: A total of 411 respondents of 513 eligible parents were recruited from five pediatric oncology centers in Canada between November 2004 and February 2007. Parents were asked to complete a questionnaire booklet that included a measure of adult QOL (SF-36), a measure of child health status (functional status IIR), and questions to assess health-promoting self-care actions (eg, sleep, diet, and exercise habits) and characteristics of the child with cancer (eg, relapse status, time since diagnosis, prognosis, treatment intensity). RESULTS: Compared with population norms, parents of children with cancer reported poorer physical and psychosocial QOL in all psychosocial domains (effect sizes range, -0.71 to -1.58) and in most physical health domains (effect sizes range, -0.08 to -0.63). Parent characteristics associated with better parental QOL included better eating, exercise and sleep habits, younger age, and higher income. Child characteristics associated with better parental QOL included better child health status (functional status IIR scores), lower treatment intensity, and longer time since diagnosis. CONCLUSION: Parents of children with cancer report poorer QOL compared with population norms. Interventions directed at parents should be included as part of the treatment plan for a child with cancer. Modifiable variables associated with poorer parental QOL, such as sleep quality and diet and exercise habits, indicate those parents most likely to experience poor QOL and may be potential areas for intervention.

Developing a literature base to understand the caregiving experience of parents of children with cancer: a systematic review of factors related to parental health and well-being.

GOAL OF WORK: This paper describes a literature review conducted to identify important factors that have been investigated as explanations of variability in the health and well-being of parents of children with cancer. Our purpose was to build a literature base that could be used to guide and direct future research. MATERIALS AND METHODS: Medline, Cinahl, EMBASE, PsycINFO, and Sociological Abstracts were searched from 1980 to 2005 using the keywords neoplasms; child(ren) aged 0-18 years; parent(s), caregiver(s), mother(s), or father(s). For papers that met the study inclusion criteria, sample characteristics and information about factors related to caregiver health, or the relationship between such factors, were extracted. The findings were organized according to the six main constructs that form the caregiving process and caregiver burden model: background/context variables; child characteristics; caregiver strain; self-perception; coping factors; and caregiver physical and psychological health. MAIN RESULTS: Articles meeting the inclusion criteria totaled 57. We found substantial research showing that certain child characteristics (e.g., child behavior; time since diagnosis) and indicators of coping (e.g., family cohesion, social support, stress management) are related to parental psychological health. Other aspects of the caregiving process (e.g., parental self-perception, family-centered care, and physical health) have received less research attention. CONCLUSION: Various limitations and gaps in the current literature were identified in our review. Future research to understand the complex interrelationships between factors involved in the caregiving process should examine hypotheses that are guided by a theoretical framework and tested using advanced statistical techniques.