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1.
Calcif Tissue Int ; 114(4): 444-449, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38252285

RESUMEN

Ameloblastoma is a rare odontogenic tumor which may be complicated by hypercalcemia in advanced disease. Tumoral parathyroid hormone-related peptide (PTHrP) production and local osteolysis from paracrine factors have been proposed as mechanisms. Mitogen-activated protein kinase (MAPK) inhibitors have been successfully used in ameloblastomas with BRAF V600E mutation to reduce symptoms and decrease tumor burden. Serum calcium has been observed to normalize following treatment with MAPK inhibitors; however, the response of PTHrP and markers of bone turnover has not been reported. We describe a case of a 55-year-old female with PTHrP-mediated hypercalcemia secondary to BRAF V600E-positive ameloblastoma with pulmonary metastases. Following treatment with dabrafenib and trametinib, the patient experienced the regression of pulmonary lesions and normalization of serum calcium, PTHrP, and markers of bone turnover. Tissue samples of ameloblastoma carrying BRAF V600E mutation are more likely to express PTHrP than tissue samples carrying wild-type BRAF. In our case, resolution of PTHrP-mediated hypercalcemia following initiation of BRAF/MEK inhibition provides additional evidence that the MAPK pathway contributes to PTHrP synthesis. It also raises the question of whether MAPK inhibitors would be effective in treating PTHrP-mediated hypercalcemia associated with other malignancies harboring BRAF V600E mutation.


Asunto(s)
Ameloblastoma , Hipercalcemia , Femenino , Humanos , Persona de Mediana Edad , Proteína Relacionada con la Hormona Paratiroidea , Hipercalcemia/tratamiento farmacológico , Ameloblastoma/tratamiento farmacológico , Ameloblastoma/genética , Ameloblastoma/patología , Proteínas Proto-Oncogénicas B-raf/genética , Calcio , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación
2.
Invest New Drugs ; 34(6): 771-776, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27565809

RESUMEN

Background Docetaxel is a standard first-line treatment option for men with metastatic castration resistant prostate cancer (mCRPC). Sunitinib is attractive as a maintenance therapy due to its mechanism of action, oral route of administration, and acceptable toxicity profile. We designed a phase II study of sunitinib in patients with mCRPC who responded to docetaxel. Methods Patients with responding or stable disease at the completion of docetaxel treatment received 50 mg of sunitinib on 4 week on 2 week off cycles. Treatment continued until disease progression (either by RECIST 1.1 criteria or by cancer related symptomatic progression), intolerable toxicity, start of new cancer therapy, withdrawal of consent, or death. The primary endpoint was progression free survival. Secondary endpoints included PSA response rate and safety. Results Twenty-three patients were enrolled and treated. The mean number of prior cycles of docetaxel given was 8.6 (range 4-12). The median number of cycles of sunitinib administered was 4 (range 1-11). Adverse events were generally grade 1-2 with 12 % grade ≥ 3 which were of a type and severity expected for sunitinib. Median PFS was 4.4 months (95 % CI: 1.6-5.1). Most patients had immediate PSA increases without other evidence of disease progression, with the mean increases in PSA over baseline being 197 %, 342 %, and 1437 % in Cycles 1, 2, and 3, respectively. Conclusion Sunitinib was tolerable as maintenance therapy but median PFS was significantly lower than the predefined threshold of 6 months.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Neoplasias Óseas/secundario , Manejo de la Enfermedad , Docetaxel , Estudios de Seguimiento , Humanos , Indoles/administración & dosificación , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/patología , Pirroles/administración & dosificación , Sunitinib , Tasa de Supervivencia , Taxoides/administración & dosificación
3.
Artículo en Inglés | MEDLINE | ID: mdl-38377684

RESUMEN

Summary: Carcinoid heart disease is a rare complication of carcinoid syndrome, resulting in right-sided valvular heart disease and subsequent heart failure due to long-term exposure to vasoactive substances. The management of this condition is complex, often requiring surgical intervention. Current perioperative regimens entail the use of prophylactic somatostatin analogs to prevent carcinoid crisis; however, regimens vary widely among practitioners and evidence supporting their efficacy in this clinical setting is mixed. This case report describes the perioperative management of a 65-year-old man with carcinoid heart disease requiring tricuspid and pulmonary valve replacement surgery. As an adjunct to somatostatin analog therapy, the novel tyrosine hydroxylase inhibitor, telotristat, was initiated preoperatively. This combination resulted in normalization of preoperative urinary 5-HIAA levels. The patient successfully underwent tricuspid and pulmonic valve replacement without evidence of carcinoid crisis. This clinical case is the first published documenting the use of telotristat in the perioperative period in a patient with carcinoid syndrome and carcinoid heart disease and was associated with a good long-term outcome despite the high-risk nature of the case. Learning points: Carcinoid crisis is a life-threatening complication of carcinoid syndrome, resulting in hemodynamic instability, bronchospasm, and arrhythmia. Cardiac surgical patients with carcinoid syndrome present a unique challenge as they are subject to physiologic conditions and medications which can potentiate intraoperative carcinoid crisis. Perioperative management of patients with carcinoid syndrome currently entails the use of prophylactic somatostatin analogs; however, these agents do not prevent carcinoid crisis in all cases. Telotristat, a tryptophan hydroxylase inhibitor, shows promise as an adjunctive therapy to somatostatin analogs to reduce the risk of intraoperative carcinoid crisis.

4.
Cancers (Basel) ; 16(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38275868

RESUMEN

BACKGROUND: Neuroendocrine tumors (NET) are neoplasms that secrete peptides and neuroamines. For gastroenteropancreatic (GEP) NET, surgical resection represents the only curative option. Ten-year imaging surveillance programs are recommended due to long time-to-recurrence following resection. We performed retrospective chart review evaluating radiation exposure and practice patterns from surveillance of completely resected GEP NET. METHODS: We performed a retrospective cohort study of cases with well-differentiated GEP NET from January 2005 to July 2020. Location of primary, modality of imaging, and duration of follow-up were collected. Dosimetry data was collected to calculate effective dose. RESULTS: 62 cases were included with 422 surveillance scans performed. Cross-sectional imaging was used in 82% and functional imaging was used in 18% of scans. Mean number of scans per year was 1.25 (0.42-3). Mean total effective dose was 56.05 mSv (SD 45.56; 0 to 198 mSv) while mean total effective dose per year was 10.62 mSv (SD 9.35; 0 to 45 mSv). Over the recommended ten years of surveillance the estimated total effective dose was 106 mSv. CONCLUSIONS: Surveillance of completely resected GEP NET results in cumulative radiation doses in the range associated with secondary malignancy development. Strategies to minimize radiation exposure in surveillance should be considered in future guideline development.

5.
JCO Oncol Pract ; 19(7): 456-464, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37186890

RESUMEN

PURPOSE: Opioids are often necessary for patients experiencing high-intensity pain. However, side effects exist and some patients may misuse opioids. To better understand how opioids are prescribed to patients with early-stage cancer and how to enhance opioid safety, clinicians' views of opioid prescribing were explored. METHODS: This was a qualitative inquiry including any Alberta clinician prescribing opioids to patients with early-stage cancer. Semistructured interviews were conducted with nurse practitioners (NP), medical oncologists (MO), radiation oncologists (RO), surgeons (S), primary care physicians (PCP), and palliative care physicians (PC) between June 2021 and March 2022. Interpretive description was used to analyze the data using two coders (C.C. and T.W.). Debriefing sessions were used to resolve and discrepancies. RESULTS: Twenty-four clinicians were interviewed (NP [n = 5], MO [n = 4], RO [n = 4], S [n = 5], PCP [n = 3], and PC [n = 3]). The majority had been in practice at least 10 years. Prescribing practices were related to disciplinary perspective, goals of care, patient condition, and resource availability. Most clinicians did not see opioid misuse as a problem but were aware that specific patient risk factors are present and that long-term use can be problematic. Most clinicians undertake safe prescribing approaches tacitly (eg, screening for past opioid misuse and reviewing number of prescribers) and not all agreed they should be universally applied. Barriers (eg, procedural and time) and facilitators (eg, education) to safe prescribing approaches were identified. CONCLUSION: To enhance uptake and cross-disciplinary consistency of safe prescribing approaches, clinician education regarding opioid misuse and benefits of safe prescribing practices, and addressing procedural barriers are necessary.


Asunto(s)
Neoplasias , Trastornos Relacionados con Opioides , Cirujanos , Humanos , Analgésicos Opioides/efectos adversos , Pautas de la Práctica en Medicina , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/prevención & control , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico
6.
Am J Clin Oncol ; 45(5): 208-214, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35383575

RESUMEN

BACKGROUND: The past 2 decades have observed a number of advances in therapeutic approaches to patients with neuroendocrine neoplasms (NENs). This study aims to assess whether survival outcomes have changed among patients with NENs over the past 15 years, in a real-world, population-based study. MATERIALS AND METHODS: We accessed administrative databases within the province of Alberta, Canada, and we reviewed patients with invasive NENs diagnosed 2004 to 2019. Patients were classified according to the year of diagnosis into 3 groups: 2004 to 2008; 2009 to 2013; and 2014 to 2019. Kaplan-Meier survival estimates were used to compare overall survival (OS) according to different baseline characteristics (including the year of diagnosis). Multivariable Cox regression modeling was used to examine factors associated with the risk of death in this cohort. RESULTS: We included a total of 3431 patients in the study cohort. Using multivariable Cox regression analysis, the following factors were associated with worse survival: older age at diagnosis (hazard ratio [HR]: 3.45; 95% CI [confidence interval]: 2.74-4.35), male sex (HR: 1.38; 95% CI: 1.21-1.56), lung primary site (HR for lung vs. appendicular primary: 1.39; 95% CI: 1.01-1.92), Stage 4 disease (HR: 2.80; 95% CI: 2.38-3.30), South zone of the province (HR for South zone vs. Calgary zone: 1.85; 95% CI: 1.49-2.30), and higher comorbidity index (HR for ≥3 vs. 0: 2.66; 95% CI: 2.19-3.24). Although Kaplan-Meier method showed significant difference in OS according to diagnosis period, multivariable regression model showed that the period of diagnosis did not appear to impact OS (HR for diagnosis period 2004 to 2009 vs. 2014 to 2019: 1.04; 95% CI: 0.89-1.22). CONCLUSIONS: Over the study period (2004 to 2019), patients diagnosed during later periods did not appear to experience better OS compared with patients diagnosed at an earlier time.


Asunto(s)
Tumores Neuroendocrinos , Alberta/epidemiología , Estudios de Cohortes , Humanos , Estimación de Kaplan-Meier , Masculino , Tumores Neuroendocrinos/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
7.
Eur Thyroid J ; 11(1)2022 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-34981751

RESUMEN

Objective: The aim of the study was to identify patients with NTRK fusion-positive or RET fusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors. Methods: Patients were identified in the Calgary prospective thyroid cancer database (N= 482). Patients were 'pre-screened' with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were 'screened' for NTRK fusions and RET fusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3). Results: A total of 86 patients were included in 1 of 2 separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20 BRAF and RAS mutation-negative patients underwent OCAv3 screening, resulting in the detection of 4 patients with NTRKfusions and 4 patients with RET fusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and 2 with medullary thyroid carcinoma. During pre-screening, 1 patient with an NTRK fusion, 1 patient with a RET fusion, and 30 patients with BRAF mutations were identified. The remaining 9 patients received OCAv3 screening, resulting in detection of 1 patient with an NTRKfusion and 1 with a RET fusion (4/11, 36% of analyzed patients). Conclusions: Our findings indicate a higher rate of NTRK fusions and RETfusions in patients with thyroid cancer with RAI-resistant distant metastases and ATA high or intermediate risk of recurrence. This highlights the importance of early screening to enable intervention with a NTRK or RET inhibitor.

8.
CMAJ Open ; 10(3): E633-E642, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35790231

RESUMEN

BACKGROUND: An absence of screening recommendations and the rapid progression of testicular germ cell tumours (TGCTs) offer a perspective on the potential impact of the COVID-19 pandemic on cancer presentations. We evaluated the presenting cancer stages of TGCTs in a real-world population before and during the pandemic to assess stage migration. METHODS: We performed a retrospective review of all new patients with TGCT diagnoses in Alberta, Canada, from Dec. 31, 2018, to Apr. 30, 2021, using the Alberta Cancer Registry. Because potential changes in staging should not occur instantaneously, we used a 6-month lag time from Apr. 1, 2020, for seminomas, and a 3-month lag time for nonseminomas, to compare initial cancer stages at presentation before and during the pandemic. We evaluated monthly rates of presentation by stage and histology. Exploratory outcomes included the largest tumour dimension, tumour markers and, for advanced disease, risk category and treatment setting. RESULTS: Of 335 patients with TGCTs, 231 were diagnosed before the pandemic and 104 during the pandemic (using a lag time). In total, 18 (7.8%) patients diagnosed before the pandemic presented with stage III disease, compared to 16 (15.4%) diagnosed during the pandemic (relative risk 1.97, 95% confidence interval [CI] 1.05-3.72). We observed no significant differences for secondary outcomes. Without a lag time, the rate ratio for a stage II presentation decreased significantly during the pandemic (0.40, 95% CI 0.21-0.72). INTERPRETATION: We observed signs of TGCT stage migration during the COVID-19 pandemic, driven by a decline in stage II disease and a potential rise in stage III disease. Management of TGCTs should remain a priority, even during a global pandemic.


Asunto(s)
COVID-19 , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Alberta/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/epidemiología , Pandemias , Estudios Retrospectivos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/patología
9.
Curr Oncol ; 28(1): 445-454, 2021 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33450906

RESUMEN

The expansion of cancer services closer to home has become a major focus of publicly funded healthcare, with cancer organizations attempting to invest in smaller centers by integrating radiotherapy into these facilities. In Canada this has resulted in Ontario, British Columbia and Alberta investing in 12 expanded regional centers over the past 20 years. Quebec, Manitoba and Nova Scotia have made similar investments. Alberta's three new centers opened in 2010, 2013 and 2021 (projected). This study examined improvements in wait times and patient throughput between 2010 and 2020, and highlighted strategies that will support the sustainability and growth of clinical activity through to 2030. Significant improvement in ready to treat wait times for radiotherapy have resulted from opening two centers, and the provincial throughput for patients requiring systemic or radiotherapy has gone up by 16%. A patient satisfaction survey demonstrated that rural patients are happy with their care and desire the provision of more of their cancer treatment closer to home. An expert panel provided recommendations on what needs to be done to stabilize recruitment and retention.


Asunto(s)
Neoplasias , Alberta , Colombia Británica , Ciudades , Humanos , Neoplasias/radioterapia , Encuestas y Cuestionarios
10.
JCO Oncol Pract ; 17(9): e1354-e1361, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34351822

RESUMEN

PURPOSE: This study reports on a mixed methods evaluation conducted within a provincial cancer program in Alberta, Canada. The purpose was to capture key learnings from a rapid virtual care implementation because of the COVID-19 pandemic and to understand the impact on patient and staff experiences. METHODS: Administrative data were collected for 21,362 patients who had at least one virtual or in-person visit to any provincial cancer center from April 1, 2020, to June 10, 2020. Patient surveys were conducted with 397 randomly selected patients who had received a virtual visit. Surveys were also conducted with 396 Cancer Care Alberta staff. RESULTS: 14,906 virtual visits took place in this period, and about 40% of weekly visits were virtual. Significant differences were observed in both patient-reported symptom questionnaire completion rates and referrals to supportive care services between patients seen in-person and virtually. Patients receiving active treatments reported significantly lower levels of satisfaction with virtual visits than those seen for follow-up, but overall 90% of patients indicated interest in receiving virtual care in the future. Staff thought virtual visits increased patients' access to care but less than one third (31.5%) felt confident meeting patients' emotional needs and having conversations about disease progression and/or end of life virtually. CONCLUSION: The COVID-19 pandemic has driven the rapid implementation of virtual visits for cancer care delivery in health care settings. The findings from this mixed methods evaluation provide a concrete set of considerations for organizations looking to develop a large-scale, enduring virtual care strategy.


Asunto(s)
COVID-19 , Neoplasias , Telemedicina , Alberta/epidemiología , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias , SARS-CoV-2
11.
Artículo en Inglés | MEDLINE | ID: mdl-34444115

RESUMEN

An increasing incidence of cancer has led to high patient volumes and time challenges in ambulatory oncology clinics. By knowing how many patients are experiencing complex care needs in advance, clinic scheduling and staff allocation adjustments could be made to provide patients with longer or shorter timeslots to address symptom complexity. In this study, we used predictive analytics to forecast the percentage of patients with high symptom complexity in one clinic population in a given time period. Autoregressive integrated moving average (ARIMA) modelling was utilized with patient-reported outcome (PRO) data and patient demographic information collected over 24 weeks. Eight additional weeks of symptom complexity data were collected and compared to assess the accuracy of the forecasting model. The predicted symptom complexity levels were compared with observation data and a mean absolute predicting error of 5.9% was determined, indicating the model's satisfactory accuracy for forecasting symptom complexity levels among patients in this clinic population. By using a larger sample and additional predictors, this model could be applied to other clinics to allow for tailored scheduling and staff allocation based on symptom complexity forecasting and inform system level models of care to improve outcomes and provide higher quality patient care.


Asunto(s)
Instituciones de Atención Ambulatoria , Modelos Estadísticos , Predicción , Humanos , Incidencia , Medición de Resultados Informados por el Paciente
12.
Oral Oncol ; 121: 105477, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34388408

RESUMEN

Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.


Asunto(s)
Antineoplásicos , Radioisótopos de Yodo , Tolerancia a Radiación , Neoplasias de la Tiroides , Antineoplásicos/uso terapéutico , Canadá , Consenso , Humanos , Radioisótopos de Yodo/uso terapéutico , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/radioterapia
13.
Curr Oncol ; 28(1): 523-548, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467570

RESUMEN

The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an NTRK gene fusion, we also suggest a tumour-agnostic consensus for NTRK gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Biomarcadores , Canadá , Consenso , Humanos , Receptor trkA/genética
14.
BMJ Open ; 10(10): e037222, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-33067276

RESUMEN

PURPOSE: The Alberta Prostate Cancer Research Initiative (APCaRI) Registry and Biorepository was established in 2014 by the APCaRI to facilitate the collection of clinical and patient-reported data, biospecimen, to measure prostate cancer outcomes and to support the development and clinical translation of innovative technologies to better diagnose and predict outcomes for patients with prostate cancer. PARTICIPANTS: Men suspected with prostate cancer and referred to Urology centres in Alberta were enrolled in the APCaRI 01 study, while men with a prior prostate cancer diagnosis participated in the APCaRI 03 study from 1 July 2014 to 30 June 2019. The APCaRI Registry and Biorepository links biospecimens and data from a wide representation of patients drawn from an Alberta population of more than 4 million. FINDINGS TO DATE: From 1 July 2014 to 30 June 2019, total APCaRI 01 and 03 study recruitment was 3754 men; 142 (4%) of these men withdrew in full, 65 men (2%) withdrew biospecimens and 123 men (3%) died of any cause. Over this same time, 8677 patient-reported outcome measure (PROM) surveys and 7368 biospecimens were collected and are available from the registry and biorepository, respectively. The data entry error rate was 0.8% and 0.95% for critical and non-critical values, respectively, and 1.8% for patient-reported surveys. FUTURE PLANS: The APCaRI Registry and Biorepository will collect longitudinal data and PROM surveys until 2024, patient outcomes up to 25 years after recruitment and biospecimen storage for up to 25 years. The APCaRI cohorts will continue to provide data and samples to researchers conducting retrospective studies. The richness of the data and biospecimens will complement many different research questions, ultimately to improve the quality of care for men with prostate cancer.


Asunto(s)
Neoplasias de la Próstata , Alberta/epidemiología , Humanos , Masculino , Medición de Resultados Informados por el Paciente , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Sistema de Registros , Estudios Retrospectivos , Tecnología
15.
J Clin Oncol ; 38(10): 1041-1049, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32031899

RESUMEN

PURPOSE: To assess the safety/tolerability and antitumor activity of enfortumab vedotin (EV), a novel investigational antibody-drug conjugate that delivers the microtubule-disrupting agent, monomethyl auristatin E, to cells that express Nectin-4. METHODS: EV-101 is a phase I dose escalation/expansion study that enrolled patients with Nectin-4-expressing solid tumors (eg, metastatic urothelial carcinoma [mUC]) who progressed on ≥ 1 prior chemotherapy regimen and/or programmed death-1 receptor/programmed death ligand-1 [PD-(L)1] inhibitor, including a cohort of patients with mUC who received prior anti-PD-(L)1 therapy. Patients received escalating doses of EV up to 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle. Primary objectives were evaluation of safety/tolerability and pharmacokinetics; antitumor activity was a secondary objective. RESULTS: Enrolled patients with mUC (n = 155) were heavily pretreated, with 96% having prior platinum-based chemotherapy and 29% receiving ≥ 3 lines of prior treatment. Maximum tolerated dose of EV was not established; however, the recommended phase II dose was identified as 1.25 mg/kg. Rash, peripheral neuropathy, fatigue, alopecia, and nausea were the most common treatment-related adverse events (TRAEs); the most common TRAEs were grade 1-2 in severity. Among the 112 patients with mUC treated with single-agent EV 1.25 mg/kg, the investigator-assessed confirmed objective response rate (ORR) was 43%, and duration of response was 7.4 months. Median overall survival (OS) was 12.3 months, and the OS rate at 1 year was 51.8%. Similar ORR and estimated median OS were observed in patients ≥ 75 years of age with and without prior anti-PD-(L)1 treatment, liver metastases, or upper-tract disease. CONCLUSION: Single-agent EV was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging. A pivotal phase II and a confirmatory phase III study are ongoing.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Moléculas de Adhesión Celular/metabolismo , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Adulto Joven
16.
BJU Int ; 102(5): 551-5, 2008 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-18510661

RESUMEN

OBJECTIVE: To investigate the use of docetaxel 75 mg/m(2) intravenously every 3 weeks plus prednisone 5 mg orally twice daily in men with metastatic hormone-refractory prostate cancer (HRPC) progressing after first-line mitoxantrone/prednisone (MP), the primary outcome being progression-free survival with prostatic-specific antigen (PSA) and pain response, toxicity and quality of life (QoL) also assessed. PATIENTS AND METHODS: Thirty patients from four centres were enrolled in the study; all had had previous MP for symptomatic, metastatic HRPC and all had castrate levels of testosterone maintained during therapy. RESULTS: At enrolment, the median age was 69 years, the mean PSA level was 324 ng/dL, and 86% of patients reported pain. There was a PSA response in 57% of the men and a reduction in pain in >60%; the overall QoL was maintained. There were four cases of febrile neutropenia and two treatment-related deaths. The median progression-free and overall survival were 5 and 15 months, respectively. CONCLUSION: Docetaxel was associated with high rates of PSA and pain response in this study. Non-haematological toxicity was similar to that during first-line treatment, but rates of febrile neutropenia and toxic death appeared to be slightly higher. In selected patients with progressive metastatic HRPC previously treated with mitoxantrone, docetaxel appears to be a beneficial therapeutic option.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Metástasis de la Neoplasia , Neoplasias Hormono-Dependientes/mortalidad , Dolor/etiología , Prednisona/administración & dosificación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Calidad de Vida , Análisis de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento
17.
J Adolesc Young Adult Oncol ; 7(1): 61-71, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28795857

RESUMEN

PURPOSE: Adult survivors of childhood cancers (ASCCs) are a unique and growing population. Because these individuals were diagnosed in childhood, their developmental stage at diagnosis may influence medical sequelae and perception of their cancer diagnosis and potentially result in long-term complications and challenges. Our aim was to determine how developmental stage, time since diagnosis, and cognitive impairment relate to Canadian ASCC distress and unmet needs. METHODS: Canadian ASCCs aged 19-77 years (N = 115) diagnosed between ages 0 and 5 (n = 25), 6 and 12 (n = 22), or 13 and 18 (n = 68) completed demographic, neurocognitive self-report, depression, and anxiety and unmet needs questionnaires. RESULTS: The developmental stage predicted distress, ß = -0.29, p = 0.01. Survivors diagnosed in middle childhood reported significantly more distress than those diagnosed in adolescence. Shorter time since diagnosis predicted greater psychosocial needs, ß = -0.24, p = 0.05, and greater distress, ß = -0.22, p = 0.05. Greater memory impairment predicted higher need across outcomes, ß = -0.36-0.61, p < 0.05. In adjusted analyses for unmet needs, endorsement of cancer affecting education and/or work importantly altered outcomes. CONCLUSION: Our results indicate that greater self-reported memory impairment increases childhood cancer survivors' care needs. We additionally suggest that supportive care interventions might best target those reporting work or education interruption due to cancer. Identification of ASCCs who report work/school interruptions may provide a quick screen for health providers to assess possible need for intervention. ASCCs still experience unmet needs long into survivorship.


Asunto(s)
Supervivientes de Cáncer/psicología , Neoplasias/diagnóstico , Neoplasias/psicología , Adulto , Anciano , Disfunción Cognitiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Estadificación de Neoplasias , Neoplasias/mortalidad , Tasa de Supervivencia , Factores de Tiempo , Adulto Joven
18.
Oncol Nurs Forum ; 44(4): 435-445, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28632242

RESUMEN

PURPOSE/OBJECTIVES: To document self-reported physical health and activity levels of older caregivers. Gender differences in physical health, physical activity levels, and predictors of physical activity were also examined.
. DESIGN: A cross-sectional study.
. SETTING: Tom Baker Cancer Centre in Calgary, Alberta, Canada.
. SAMPLE: 130 caregivers aged 60 years or older caring for individuals with breast, prostate, or colorectal cancer.
. METHODS: Self-report survey including validated questionnaires on physical and mental health and physical activity levels. Convenience sampling was used. Data were analyzed using descriptive statistics, correlations, and multiple regression.
. MAIN RESEARCH VARIABLES: The physical component score of the SF-36v2® was the main research variable. Other variables included the mental component score of the SF-36v2, sleep quality, depression, social support, physical activity levels, and anxiety.
. FINDINGS: The mean age of caregivers was 70 years. Physical health and physical activity levels were higher than population norms. A significant difference in physical health (p = 0.015) existed between men and women but not in physical activity levels (p = 0.079). Predictors of physical activity levels were age (ß = -0.291), physical health (ß = 0.307), and caregiving hours per week (ß = -0.221).
. CONCLUSIONS: The findings suggest that gender had a minimal effect on physical health and no effect on physical activity levels in older caregivers. Depression and poor sleep quality were high in some caregivers but did not predict physical activity levels. 
. IMPLICATIONS FOR NURSING: The negative effects of caregiving on physical health and physical activity levels in older caregivers are not universal. Nurses should be aware of the caregiving situation and promote health based on the individual.


Asunto(s)
Cuidadores/psicología , Ejercicio Físico/psicología , Estado de Salud , Calidad de Vida/psicología , Factores Sexuales , Anciano , Anciano de 80 o más Años , Alberta , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Encuestas y Cuestionarios
19.
J Phys Act Health ; 14(7): 578-595, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28290737

RESUMEN

BACKGROUND: Family caregivers are an important health care resource and represent a significant proportion of Canadian and US populations. Family caregivers suffer physical and psychological health problems because of being in the caregiver role. Interventions to support caregiver health, including physical activity (PA), are slow to be investigated and translated into practice. PURPOSE: To examine the evidence for PA interventions in caregivers and determine factors hampering the uptake of this evidence into practice. METHODS: A systematic review and evaluation of internal and external validity using the RE-AIM (Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance) framework was conducted. Randomized controlled trials or pretest/posttest studies of PA interventions were included. RESULTS: Fourteen studies were published between 1997 and 2015. Methodological quality of studies and risk of bias was variable. External validity criteria were often not reported. Mean reporting levels were 1) reach, 53%; 2) efficacy/effectiveness, 73%; 3) adoption, 18%; 4) implementation, 48%; and 5) maintenance, 2%. CONCLUSIONS: The lack of reporting of components of internal and external validity hinders the integration of caregiver PA interventions into clinical or community settings. Researchers should focus on standardized outcomes, accepted reporting criteria, and balancing factors of internal and external validity, to advance the state of the science.


Asunto(s)
Cuidadores/psicología , Ejercicio Físico/fisiología , Promoción de la Salud/métodos , Humanos
20.
Contemp Clin Trials ; 50: 273-83, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27530087

RESUMEN

BACKGROUND: Family caregivers (FCs) to cancer patients are at increased risk for physical and emotional health problems as a result of being in the caregiver role. Current research on interventions for FCs has focused on psychological support or educational interventions, with very little investigation of exercise in maintaining or improving health. Based on our preliminary survey, participation in regular exercise to improve health was noted as a priority for FCs. The purpose of the study described in this protocol is to examine the impact of a 12-week structured exercise program on physical functioning (primary outcome), physical activity levels and psychological well-being (secondary outcomes), in FCs caring for adult cancer patients. In addition, the trial described here will examine the outcomes from a 12-week maintenance program, immediately following the initial program. METHODS/DESIGN: A mixed methods design using a randomized control trial (RCT) with a 50/50 allocation ratio for the quantitative portion, followed by face to face interviews and qualitative data analysis. Approximately 86 participants will be enrolled over a 10 month period. The intervention will consist of a structured exercise program of aerobic and resistance training. An intention to treat principle using mixed effects modeling will guide data analysis. DISCUSSION: FCs will continue to play a pivotal role in the care of cancer patients as the incidence and chronicity of cancer increases. The research described in this protocol will provide information about the impact of an exercise program in supporting FC health. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02580461.


Asunto(s)
Cuidadores/psicología , Terapia por Ejercicio/métodos , Terapia por Ejercicio/psicología , Humanos , Salud Mental , Cooperación del Paciente , Aptitud Física , Calidad de Vida , Proyectos de Investigación , Sueño , Factores Socioeconómicos , Factores de Tiempo
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