RESUMEN
The anterior and lateral thalamus (ALT) contains head direction cells that signal the directional orientation of an individual within the environment. ALT has direct and indirect connections with the parietal cortex (PC), an area hypothesized to play a role in coordinating viewer-dependent and viewer-independent spatial reference frames. This coordination between reference frames would allow an individual to translate movements toward a desired location from memory. Thus, ALT-PC functional connectivity would be critical for moving toward remembered allocentric locations. This hypothesis was tested in rats with a place-action task that requires associating an appropriate action (left or right turn) with a spatial location. There are four arms, each offset by 90°, positioned around a central starting point. A trial begins in the central starting point. After exiting a pseudorandomly selected arm, the rat had to displace the correct object covering one of two (left versus right) feeding stations to receive a reward. For a pair of arms facing opposite directions, the reward was located on the left, and for the other pair, the reward was located on the right. Thus, each reward location had a different combination of allocentric location and egocentric action. Removal of an object was scored as correct or incorrect. Trials in which the rat did not displace any objects were scored as "no selection" trials. After an object was removed, the rat returned to the center starting position and the maze was reset for the next trial. To investigate the role of the ALT-PC network, muscimol inactivation infusions targeted bilateral PC, bilateral ALT, or the ALT-PC network. Muscimol sessions were counterbalanced and compared to saline sessions within the same animal. All inactivations resulted in decreased accuracy, but only bilateral PC inactivations resulted in increased non selecting, increased errors, and longer latency responses on the remaining trials. Thus, the ALT-PC circuit is critical for linking an action with a spatial location for successful navigation.
Asunto(s)
Lóbulo Parietal , Percepción Espacial , Ratas , Animales , Muscimol/farmacología , Lóbulo Parietal/fisiología , Tiempo de Reacción/fisiología , Percepción Espacial/fisiologíaRESUMEN
PURPOSE: About one-fifth of newly diagnosed cancer patients are parents to young children. These patients are at higher risk of psychosocial stress and inability to attend treatment due to having to balance their own healthcare needs with childcare duties. This study aims to explore the impact of childcare on cancer parents and elicit their perspectives on potential supports. The results could help inform the implementation of suitable childcare programs to remove this barrier in accessing care. METHODS: Patients at a large Canadian cancer treatment center were screened by oncologists for having minor children at home. Secure electronic surveys were then distributed to consenting participants. Domains surveyed included patient demographics, childcare burden, impact on treatment, and preference for childcare supports. RESULTS: The mean age of correspondents was 43.9 (range 33-54), 46 patients (92%) were female, and breast cancer was the most common primary tumor. The median number of children per correspondent was two, and their mean age was 8.4. Balancing childcare with cancer treatment had a significant impact on self-reported stress levels for most correspondents. Twenty (40%) participants had to reschedule and 7 (14%) participants missed at least one appointment due to childcare conflicts. During the COVID-19 pandemic, access to childcare resources decreased while childcare responsibilities increased. Three-quarters of correspondents reported that a flexible childcare would make it easier for them to adhere to appointment schedules. CONCLUSION: Childcare is a significant psychosocial barrier for patients accessing cancer care. Our results indicate that most parents undergoing treatment may benefit from hospital-based childcare services.
Asunto(s)
Neoplasias de la Mama , COVID-19 , Niño , Humanos , Femenino , Preescolar , Masculino , Cuidado del Niño/métodos , Pandemias , CanadáRESUMEN
Cancer patients may face difficulty evaluating web-based COVID-19 resources in context with their cancer diagnosis. The purpose of this study is to systematically evaluate educational resources available for cancer patients seeking online information on COVID-19 and cancer. The term "COVID-19 and Cancer" was searched in Google and metasearch engines Yippy and Dogpile. After applying inclusion and exclusion criteria, the results from the 3 lists were systematically combined for a final ranked list. This list was analyzed using a validated structured rating tool with respect to accountability, interactivity, organization, readability, and content coverage and accuracy. Three hundred ninety-eight websites were identified, and 37 websites were included for analysis. Only 43% of sites disclosed authorship, 24% cited sources, and 32% were updated within 3 months of the search date. Fifty-four percent of websites had high school readability (8.0-12.0), 43% were at university level or above, and no websites demonstrated the recommended reading level for health information for the public (< 6.0). Topics most discussed were special considerations for cancer patients during COVID-19 (84%) and COVID-19 risk factors (73%). Topics least covered were COVID-19 incidence/prevalence (5%) and prognosis (8%). There is some COVID-19 information for cancer patients available online, but quality is variable. Healthcare professionals may direct cancer patients to the most reliable COVID-19 and cancer websites shown in this study and results may be helpful when designing future online health information resources.
Asunto(s)
COVID-19 , Información de Salud al Consumidor , Neoplasias , Humanos , COVID-19/epidemiología , Comprensión , InternetRESUMEN
PURPOSE: The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles. METHODS: An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data. RESULTS: Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus. CONCLUSIONS: Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Adyuvantes Inmunológicos , Neoplasias de la Mama/tratamiento farmacológico , Canadá , Consenso , Femenino , HumanosRESUMEN
PURPOSE: Approximately a quarter of cancer patients are parents to young children. One unique challenge faced by this patient group is the difficulty of accessing childcare support during medical appointments. Hospital-based childcare options could represent a solution to this problem, but to this point, no comprehensive scans have described existing on-site childcare centers. The purpose of this study is to identify and characterize on-site childcare services available to patients at selected North American hospitals. This information could inform the development of similar programs for cancer patients. METHODS: Using publicly available information, an environmental scan of the grey literature was conducted to investigate Canadian and American hospitals for the presence of childcare services. A standardized data collection tool was used to extract center characteristics. RESULTS: Twenty-six childcare centers were identified across 161 hospitals in both Canada and the USA, with 8/55 Canadian hospitals and 18/106 American hospitals having patient-accessible on-site services. The majority of the centers were associated with pediatric hospitals (77%). Only a single childcare center was associated with a cancer hospital. All centers accommodated children between the ages of 3 and 8. Most centers were open for over 30 h per week (77%) and were free of charge to users (89%). Other characteristics, including capacity and staffing, varied widely. CONCLUSIONS: These results represent an inventory of patient-accessible, on-site childcare services currently available at selected North American hospitals. Cancer patients who are also parents may especially benefit from this kind of support.
Asunto(s)
Cuidado del Niño , Neoplasias , Canadá , Niño , Guarderías Infantiles , Preescolar , Hospitales , Humanos , Neoplasias/terapiaRESUMEN
Malignant sarcomas are rare accounting for <1% of all adult solid malignancies and approximately 11% to 13% of all pediatric malignancies. TRK-inhibitors have demonstrated robust and long-lasting responses in patients with NTRK fusion-positive solid tumors, including sarcoma. Access to these agents in many jurisdictions such as Canada remains limited. We undertook a modified Delphi consensus to articulate and convey the clinical importance of these agents for the Canadian sarcoma community. A systematic search of published and presented literature was conducted to identify clinical trials reporting outcomes on the use of TRK-inhibitors in relapsed/refractory NTRK fusion-positive sarcoma. Three main consensus questions were identified: (a) is there currently an unmet clinical need for systemic therapy options in relapsed/refractory sarcoma? (b) do TRK-inhibitors confer a clinical benefit to patients with NTRK fusion-positive sarcoma? (c) do phase I/II basket trials provide sufficient evidence to justify funding of TRK-inhibitors in NTRK fusion-positive sarcoma? Response rates to the first and second surveys were 57% (n = 30) and 42% (n = 22), respectively. There was strong agreement among the Canadian sarcoma community that there was unmet clinical need for effective systemic therapy options in relapsed/refractory sarcoma, that TRK-inhibitors are a safe and effective treatment option for patients with NTRK fusion-positive sarcoma, and that available phase I/II basket trials provide sufficient evidence to support funding of these agents in relapsed/refractory NTRK fusion-positive sarcoma. TRK-inhibitors are a safe and effective systemic therapy option for patients with relapsed/refractory NTRK fusion-positive sarcoma.
Asunto(s)
Proteínas de Fusión Oncogénica/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor trkA/metabolismo , Receptor trkC/antagonistas & inhibidores , Sarcoma/tratamiento farmacológico , Encuestas y Cuestionarios/estadística & datos numéricos , Adolescente , Adulto , Anciano , Canadá , Consenso , Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Receptor trkA/genética , Receptor trkC/genética , Receptor trkC/metabolismo , Sarcoma/genética , Sarcoma/metabolismo , Análisis de Supervivencia , Adulto JovenRESUMEN
PURPOSE: To determine the efficacy and safety of cryoablation in patients with desmoid tumors (DTs) retrospectively over a 10-year period at a single institution. MATERIALS AND METHODS: Between February 25, 2010, and February 25, 2020, 25 patients (age, 12-80 years) with 26 lesions (mean preprocedural tumor volume was 237 cm3) were treated over 44 cryoablation procedures. Eleven patients were treated with first-line therapy. Fourteen patients had previous medical therapy, radiotherapy, and/or surgery. Subsequent clinical follow-up, imaging outcomes, and safety were analyzed for technical success, change in total lesion volume (TLV) and viable tumor volume (VTV), modified response evaluation criteria in solid tumors (mRECIST), progression-free survival (PFS) for tumor progression and symptom recurrence, symptom improvement, and procedure-related complications. Symptomatic improvement was defined as documentation of relief of pain (partial or complete) and/or functional impairment. RESULTS: All procedures were technically successful. At 7-12 months, median changes in TLV and VTV were -6.7% (P = .809) and -43.7% (P = .01), respectively. At 10-12 months, the mRECIST responses were complete response, 0%; partial response, 61.5% (8/13); stable disease, 30.8% (4/13); and progressive disease, 7.7% (1/13). The median PFS for tumor progression and symptom recurrence were not reached, with a median follow-up of 15.3 and 21.0 months, respectively. Symptomatic relief (partial or complete) was achieved in 96.9% (32/33) of patients. One major complication was noted (2.4%). CONCLUSIONS: In this retrospectively identified cohort, cryoablation was effective and safe for the local control of extra-abdominal DTs in short-term follow-up.
Asunto(s)
Criocirugía , Fibromatosis Agresiva , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Criocirugía/efectos adversos , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/cirugía , Humanos , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Patients with newly diagnosed breast cancer and high levels of anxiety often pursue more aggressive surgical interventions. The neoadjuvant treatment (NAT) setting could provide a window of opportunity to address patients' anxiety. However, the impact of anxiety on surgical decisions in the setting of NAT for breast cancer has not been previously studied. MATERIALS AND METHODS: A prospective database of patients with breast cancer treated with NAT at BC Cancer was used to identify patients treated with NAT and subsequent surgical resection. Patients with bilateral breast cancer or BRCA mutations or those referred to the hereditary cancer program were excluded. An anxiety score of 0-3 was assigned based on responses to the Edmonton Symptom Assessment System and Psychosocial Screen for Cancer. Clinicopathological information and treatment data were retrieved and cross-referenced between the low-anxiety (scores 0-1) and high-anxiety (scores 2-3) cohorts. RESULTS: From 2012 to 2016, 203 patients met eligibility criteria. Of these, 93 patients (45.8%) had low anxiety and 110 patients (54.2%) had high anxiety. Overall, 161 patients (79.3%) had locally advanced cancers; no differences in stage, grade, or biomarkers were found between the low- and high-anxiety cohorts. Patients with high self-reported anxiety at initial consultation were younger (mean 56 years vs. 60 years; p = .011) and more likely to undergo mastectomy for breast-conserving surgery-eligible disease and bilateral mastectomy for unilateral disease compared with those with low anxiety (37.3% vs. 18.3%; likelihood ratio 9.15; p = .002). No significant differences in treatment timelines were identified between the two cohorts. CONCLUSION: Patients with high anxiety at initial consultation were nine times more likely to undergo aggressive surgery compared with patients with low anxiety. These findings underscore the need for early identification of patients who may benefit from tailored supportive and educational services to address sources of anxiety and knowledge gaps. IMPLICATIONS FOR PRACTICE: The prevalence of anxiety among women with newly diagnosed breast cancer is being increasingly acknowledged. However, health care providers have not fully appreciated the impact of anxiety on the surgical management of patients with early-stage breast cancer. This study highlights the importance of self-reported anxiety on surgical management. The preoperative period provides a unique window of opportunity to address sources of anxiety and provide targeted educational materials over a period of 4-6 months, which may ultimately lead to less aggressive surgery when it is not needed.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Ansiedad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Mastectomía SegmentariaRESUMEN
PURPOSE: The optimal time interval from neoadjuvant chemotherapy (NAC) to surgery in patients with breast cancer has not been established. We investigated whether different time intervals impact the rate of pathologic complete response (pCR), disease free survival (DFS), overall survival (OS), surgical complications, and rates of conversion from mastectomy to breast conserving surgery (BCS) in this population. METHODS: We identified patients who received NAC at the BC Cancer Agency followed by surgery from May 2012 to April 2018. Patients were grouped based on time interval between NAC and surgery: < 4 weeks, 4-8 weeks, and > 8 weeks. Kaplan Meier method was used to estimate DFS and OS. Rates of pCR between the time intervals were also compared. RESULTS: Of the 343 patients, 78 (22.8%) received surgery < 4 weeks, 233 (67.9%) received surgery between 4-8 weeks, and 32 (9.3%) received surgery > 8 weeks after NAC, with a median time to surgery (TTS) of 5.0 weeks. pCR was observed in 32.1%, 32.2%, and 28.1%, respectively (p = 0.90). Median follow-up time was 3.3 years. The 5-year DFS was 76%, 78%, and 70% (p = 0.89), respectively. The 5-year OS was 83%, 82%, and 78% (p = 0.33), respectively. No statistically significant differences were seen in surgical complications (p = 0.90), or rates of conversion from mastectomy to BCS (p = 0.19). CONCLUSIONS: There were no statistically significant differences in pCR, DFS, OS, surgical complications, and rates of conversion from mastectomy to BCS, among breast cancer patients receiving surgery < 4 weeks, 4-8 weeks, or > 8 weeks after the last dose of NAC.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Mastectomía , Estadificación de Neoplasias , Listas de EsperaRESUMEN
BACKGROUND: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC. Aerobic exercise is associated with improved cognitive functioning in healthy older adults and adults with cognitive impairments. Accordingly, it holds promise as an intervention to prevent and/or manage CRCC. However, evidence from randomized controlled trials (RCTs) supporting a beneficial effect of aerobic exercise on CRCC is limited. The primary aim of the ACTIVATE trial is to evaluate the impact of supervised aerobic exercise on CRCC in women receiving chemotherapy for breast cancer. METHODS: The ACTIVATE trial is a two-arm, two-centre RCT. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy are recruited from hospitals in Ottawa (Ontario) and Vancouver (British Columbia), Canada. Recruits are randomized to the intervention group (aerobic exercise during chemotherapy) or the wait-list control group (usual care during chemotherapy and aerobic exercise post-chemotherapy). The primary outcome is cognitive functioning as measured by a composite cognitive summary score (COGSUM) of several neuropsychological tests. Secondary outcomes are self-reported cognitive functioning, quality of life, and brain structure and functioning (measured by magnetic resonance imaging (MRI)/functional MRI and electroencephalography). Assessments take place pre-chemotherapy (pre-intervention), mid-way through chemotherapy (mid-intervention/mid-wait period), end of chemotherapy (post-intervention/post-wait period; primary endpoint), 16-weeks post-chemotherapy, and at 1-year post-baseline. DISCUSSION: Aerobic exercise is a promising intervention for preventing and/or managing CRCC and enhancing quality of life among women diagnosed with breast cancer. The ACTIVATE trial tests several novel hypotheses, including that aerobic exercise can prevent and/or mitigate CRCC and that this effect is mediated by the timing of intervention delivery (i.e., during versus post-chemotherapy). Findings may support prescribing exercise during (or post-) chemotherapy for breast cancer and elucidate the potential role of aerobic exercise as a management strategy for CRCC in women with early-stage breast cancer. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov database ( NCT03277898 ) on September 11, 2017.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Trastornos del Conocimiento/terapia , Cognición/efectos de los fármacos , Ejercicio Físico/fisiología , Antineoplásicos/efectos adversos , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/prevención & control , Femenino , Humanos , Pruebas Neuropsicológicas , Selección de Paciente , Calidad de Vida , Tamaño de la Muestra , Autoinforme , Listas de EsperaRESUMEN
Breast cancer remains the most common cancer among women, and the second most common cause of cancer death. With advances in treatment, women are living longer, in some cases many years, with metastatic breast cancer (MBC). These advances are a direct result of research, however, many studies are primarily researcher or industry led, with minimal input from patients and caregivers. The James Lind Alliance (JLA) brings patients, caregivers, and clinicians together in priority setting partnerships (PSPs) to determine key priorities in research. In this study, we utilized the JLA approach to identify unanswered questions on MBC from patient and clinical perspectives and prioritized to reach a top 10. Following the established JLA approach, MBC patients, caregivers, and health care professionals (HCPs) were surveyed to elicit their questions regarding MBC. Research questions were generated from survey responses, and following literature review to ensure the questions were currently not completely answered, an interim prioritization survey was conducted to identify a shortlist of questions taken to a final consensus meeting. One thousand, one-hundred and ninety-four responses were collected from 668 individuals, which were refined into 62 unique unanswered questions. The interim prioritization survey was completed by 174 individuals, and the top 27 questions were taken to a final meeting to determine by consensus the top 10. The top 10 questions cover a wide range of research questions, identified by valuable stakeholders as being priorities. This list can be used to inform prioritization and funding of future MBC research.
Asunto(s)
Investigación Biomédica , Neoplasias de la Mama , Neoplasias de la Mama/terapia , Cuidadores , Femenino , Personal de Salud , Humanos , Encuestas y CuestionariosRESUMEN
Mutations in ATP1A3 encoding the catalytic subunit of the Na/K-ATPase expressed in mammalian neurons cause alternating hemiplegia of childhood (AHC) as well as an expanding spectrum of other neurodevelopmental syndromes and neurological phenotypes. Most AHC cases are explained by de novo heterozygous ATP1A3 mutations, but the fundamental molecular and cellular consequences of these mutations in human neurons are not known. In this study, we investigated the electrophysiological properties of neurons generated from AHC patient-specific induced pluripotent stem cells (iPSCs) to ascertain functional disturbances underlying this neurological disease. Fibroblasts derived from two subjects with AHC, a male and a female, both heterozygous for the common ATP1A3 mutation G947R, were reprogrammed to iPSCs. Neuronal differentiation of iPSCs was initiated by neurogenin-2 (NGN2) induction followed by co-culture with mouse glial cells to promote maturation of cortical excitatory neurons. Whole-cell current clamp recording demonstrated that, compared with control iPSC-derived neurons, neurons differentiated from AHC iPSCs exhibited a significantly lower level of ouabain-sensitive outward current ('pump current'). This finding correlated with significantly depolarized potassium equilibrium potential and depolarized resting membrane potential in AHC neurons compared with control neurons. In this cellular model, we also observed a lower evoked action potential firing frequency when neurons were held at their resting potential. However, evoked action potential firing frequencies were not different between AHC and control neurons when the membrane potential was clamped to -80â¯mV. Impaired neuronal excitability could be explained by lower voltage-gated sodium channel availability at the depolarized membrane potential observed in AHC neurons. Our findings provide direct evidence of impaired neuronal Na/K-ATPase ion transport activity in human AHC neurons and demonstrate the potential impact of this genetic defect on cellular excitability.
Asunto(s)
Hemiplejía/diagnóstico , Hemiplejía/fisiopatología , Potenciales de la Membrana/fisiología , ATPasa Intercambiadora de Sodio-Potasio/fisiología , Adulto , Animales , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Técnicas de Cocultivo , Femenino , Hemiplejía/genética , Humanos , Lactante , Potenciales Postsinápticos Inhibidores/fisiología , Masculino , Ratones , Adulto JovenRESUMEN
Pulmonary artery sarcoma is a rare malignant neoplasm. Here, we describe a patient with a pulmonary artery sarcoma, which was only subtly visible and therefore not fully appreciated on initial transthoracic echocardiogram. Characterization of the tumor was aided by the use of multimodality imaging that included computed tomography, magnetic resonance imaging, and positron emission tomography. Familiarity with its appearance on multiple imaging modalities including echocardiography is important to ensure timely diagnosis, although the optimal treatment strategy is still unknown, and the prognosis remains poor.
Asunto(s)
Imagen Multimodal/métodos , Arteria Pulmonar/diagnóstico por imagen , Sarcoma/diagnóstico por imagen , Neoplasias Vasculares/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Ecocardiografía , Resultado Fatal , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía de Emisión de Positrones , Arteria Pulmonar/cirugía , Sarcoma/cirugía , Tomografía Computarizada por Rayos X , Neoplasias Vasculares/cirugía , Adulto JovenRESUMEN
Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor-positive (HR+) tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR+/HER- advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients. Although the safety profiles of these combinations are generally predictable and manageable, both everolimus and palbociclib are associated with an increased risk of potentially serious or early-onset toxicities requiring individualized a priori adverse event risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Although each of these combinations improves progression-free survival, none with the exception of anastrazole plus fulvestrant have demonstrated improved overall survival. PI3K catalytic-α mutations assessed from circulating tumor DNA represent the first potentially viable serum biomarker for the selection of ET combinations, and new data demonstrate the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis. Therapeutic ratios of select ET combinations support their use in first- and second-line settings, but optimal sequencing has yet to be determined. THE ONCOLOGIST: 2017;22:12-24 IMPLICATIONS FOR PRACTICE: Emerging data show that new endocrine therapy (ET) combinations can improve progression-free and overall survival outcomes in patients with hormone receptor-positive, HER2-negative (HR+/HER-) advanced breast cancer. Level 1 evidence supports consideration of dual ET regimens, particularly in ET-naïve patients, or palbociclib plus letrozole as first-line therapy, as well as the addition of mTOR or CDK4/6 inhibitors to established ET in the second-line setting and in select first-line patients. Some combinations are associated with increased risk of class-specific toxicities that will require individualized risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Recent data on a noninvasive biomarker assay that predicts response to a phosphoinositide 3-kinase inhibitor demonstrates the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Nitrilos/administración & dosificación , Proteínas Nucleares/genética , Factores de Transcripción/genética , Triazoles/administración & dosificación , Anastrozol , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , ADN Tumoral Circulante/sangre , Supervivencia sin Enfermedad , Estradiol/administración & dosificación , Estradiol/efectos adversos , Estradiol/análogos & derivados , Femenino , Fulvestrant , Humanos , Letrozol , Mutación , Células Neoplásicas Circulantes/metabolismo , Nitrilos/efectos adversos , Proteínas Nucleares/sangre , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Posmenopausia/sangre , Piridinas/administración & dosificación , Piridinas/efectos adversos , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Factores de Transcripción/sangre , Triazoles/efectos adversosRESUMEN
BACKGROUND/AIMS: Understanding the influence or impact of epidemiological factors on cancer outcomes in clinical trials can broaden our knowledge of disease, trial populations and therapeutic effects thus leading to improved patient care. However, there is a lack of data on cancer patients' compliance with an epidemiology questionnaire in the context of a clinical trial. PATIENTS AND METHODS: Cancer patients were provided with a hypothetical scenario and surveyed regarding their willingness and preferences to complete an epidemiology questionnaire if incorporated into a cancer therapy trial. Patient compliance with completing a voluntary epidemiology questionnaire and trial coordinators perceptions therein were separately determined in the NCIC Clinical Trials Group HN.6 clinical trial, an ongoing randomized phase III trial comparing two first-line treatment regimens in patients with locoregionally advanced head and neck cancer. RESULTS: Of 617 cancer patients from community, academic and tertiary cancer centres, the majority were willing to complete an epidemiology questionnaire either unconditionally (45%), or provided it did not inconvenience them (31%); 4% would refuse. Patients preferred shorter questionnaires of 30-50 questions requiring 10-20 min to complete, administered over 1-3 sessions. Patients were less willing, but still compliant, to answer questions relating to sexual history (71%) and annual household income (66%) relative to other questions (>90%). Eighteen percent thought that the questionnaire should be mandatory, with 31% believing that they may benefit personally from such research. In the HN.6 trial, compliance averaged 94.8% per question. CONCLUSIONS: Cancer patients are very willing to complete epidemiology questions in clinical trials.
Asunto(s)
Neoplasias/epidemiología , Neoplasias/terapia , Sujetos de Investigación/psicología , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Effective communication in the operating room is crucial for patient safety and optimal outcomes. Structured debriefing communication tools can improve team coordination and address recurring safety concerns. During the unique circumstances of the COVID-19 pandemic, this study evaluated an approach to documentation and loop closure that functioned under constrained hospital resources, a loss of capacity for face-to-face provider training and loop closure, and periods of performing only urgent and emergent surgery for which some debriefing elements, like patient disposition and equipment needs, are more dynamic. METHODS: Employing a longitudinal repeated-measures design, this quality improvement study used a newly integrated module within the electronic health record system to document debriefings, which were linked to surveys assessing perceptions of the debriefing process. Data were collected from 56 operating rooms in 3 separate hospital towers during a 3-year period ending December 2023, encompassing 4 reiterative Plan-Do-Study-Act cycles. RESULTS: The study recorded 49,426 surgical debriefings. The overall incidence of debriefing increased 111% during the study period, reaching 88% during the third and final year of the project. Compared with 193 preintervention surveys, 129 postintervention surveys demonstrated increased incidence of perceiving debriefings as very or extremely effective (52% vs 38%, P = .02), greater frequency of discussing whether equipment issues occurred (87% vs 75%, P = .008), and greater frequency of loop closure (46% vs 34%, P = .03) and leadership (Chair or Program Director of Quality) involvement in loop closure activities (14% vs 3%, P = .008) addressing issues identified during debriefs. CONCLUSION: Despite challenges associated with implementation during a viral pandemic, the intervention was associated with increased incidence and perceived effectiveness of documented surgical debriefings, greater frequency of downstream loop closure, and positive impacts on team communication.
RESUMEN
Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.
RESUMEN
In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300× compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables plasma-only (non-tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune-checkpoint inhibition.
Asunto(s)
ADN Tumoral Circulante , Variaciones en el Número de Copia de ADN , Aprendizaje Automático , Neoplasia Residual , Carga Tumoral , Humanos , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Neoplasia Residual/genética , Secuenciación Completa del Genoma , Neoplasias/genética , Neoplasias/sangre , Neoplasias/terapia , Neoplasias/patología , Polimorfismo de Nucleótido Simple , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patologíaRESUMEN
Recent exciting advances in the diagnosis and management of breast cancer have improved outcomes for Canadians diagnosed and living with breast cancer. However, the reach of this progress has been uneven; disparities in accessing care across Canada are increasingly being recognized and are at risk of broadening. Members of racial minority groups, economically disadvantaged individuals, or those who live in rural or remote communities have consistently been shown to experience greater challenges in accessing 'state of the art' cancer care. The Canadian context also presents unique challenges-vast geography and provincial jurisdiction of the delivery of cancer care and drug funding create significant interprovincial differences in the patient experience. In this commentary, we review the core concepts of health equity, barriers to equitable delivery of breast cancer care, populations at risk, and recommendations for the advancement of health equity in the Canadian cancer system.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/terapia , Canadá , GeografíaRESUMEN
BACKGROUND: Breast angiosarcoma may arise spontaneously (primary breast angiosarcoma (PBA)) or may arise secondary to a biological insult, such as radiation therapy (secondary breast angiosarcoma (SBA)). We evaluated the imaging findings of patients diagnosed with PBA and SBA within the province of British Columbia, Canada. MATERIALS AND METHODS: This was a multi-center, retrospective study of patients diagnosed with PBA and SBA over a 25-year period. Patients were identified via a provincial database which registers all cases of sarcoma. Patients diagnosed with histologically proven PBA and SBA were eligible for inclusion. Multimodal breast imaging reviewed included mammography, ultrasound, magnetic resonance imaging, and computed tomography. RESULTS: Thirteen patients were diagnosed with PBA and 22 patients were diagnosed with SBA. The median (interquartile range (IQR)) age of patients diagnosed with PBA (45.5 years (19.7 years)) was less than that of patients diagnosed with SBA (75.8 years (13.8 years), P < .001). Patients diagnosed with PBA (90.9%) were more likely to present with a parenchymal mass clinically and radiographically than those with SBA (28.6%, P < .002). Patients diagnosed with SBA (71.4%) were more likely to present with cutaneous findings than patients diagnosed with PBA (0.0%, P < .05). Without specific clinical context, the imaging findings of PBA and SBA were observed to be non-specific. CONCLUSION: This is the only study which evaluated the imaging findings of patients diagnosed with PBA and SBA within a large, defined geographical area. Given non-specific imaging findings, awareness of the disease and clear and timely communication between radiologists and clinicians is required to ensure appropriate diagnosis and management.