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1.
JAMA Oncol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917424

RESUMO

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain. Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone. Design, Setting, and Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019. Main Outcomes and Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models. Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051). Conclusions and Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.

2.
Radiother Oncol ; 142: 180-185, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31431385

RESUMO

PURPOSE: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. RESULTS: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). CONCLUSIONS: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

3.
Lancet ; 394(10215): 2165-2172, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31813635

RESUMO

BACKGROUND: Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. METHODS: We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. FINDINGS: Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). INTERPRETATION: External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. FUNDING: Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Carcinoma in Situ/radioterapia , Carcinoma Ductal de Mama/radioterapia , Idoso , Austrália , Neoplasias da Mama/cirurgia , Canadá , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/prevenção & controle , Nova Zelândia , Prognóstico , Taxa de Sobrevida
4.
Breast Cancer Res Treat ; 178(1): 221-230, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31368035

RESUMO

BACKGROUND: A better understanding underlying radiation (RT) response after breast-conserving surgery (BCS) is needed to mitigate over-treatment of DCIS. The hazard ratio (HR) measures the effect of RT but assumes the effect is constant over time. We examined the hazard function adjusted for adherence to surveillance mammography to examine variations in LR risk and the effect of RT over time. METHODS: Crude hazard estimates for the development of LR in a population cohort of DCIS treated by BCS ± RT were computed. Multivariable extended Cox models and hazard plots were used to examine the association between receipt of RT and risk of each outcome adjusted for baseline covariates and adherence to mammography. RESULTS: Population cohort includes 3262 women treated by BCS; 1635 received RT. Median follow-up was 13 years. LR developed in 364 women treated by BCS alone and 274 treated with RT. LR risk peaked at 2 years, declined until year 7, and then remained steady. The peak hazard of LR was associated with adverse features of DCIS. Early LR risk was attenuated in patients treated with RT but late annual risks of LR and invasive LR were similar among the two treatment groups. On multivariate analysis, RT was associated with a reduction in early LR risk (HR = 0.52, 95% CI 0.43-0.63, p < 0.0001) but did not reduce the risk of late LR (HR = 0.89, 95% CI: 0.67, 1.19, p = 0.44) (interaction, p = 0.002). CONCLUSIONS: The effect of RT is not uniform over time and greatest in the first 7 years after BCS for DCIS, which can guide future research to understand mechanisms underlying RT response and optimize future management of DCIS.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/terapia , Mastectomia Segmentar/métodos , Feminino , Humanos , Mamografia , Cooperação do Paciente , Vigilância da População , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
5.
N Engl J Med ; 380(25): 2395-2405, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31157962

RESUMO

BACKGROUND: The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS: We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS: The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS: Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Tamoxifeno/uso terapêutico , Adulto , Fatores Etários , Idoso , Algoritmos , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Pré-Menopausa , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptor ErbB-2 , Fatores de Risco
6.
Breast Cancer Res Treat ; 176(3): 657-667, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31076954

RESUMO

PURPOSE: Randomized trials studying endocrine therapy (ET) with and without radiation therapy (RT) following breast-conserving surgery (BCS) have detected differences in local recurrence (LR) but not survival among elderly women with hormone receptor positive stage I breast cancer (BC). We assembled a population-based cohort of such women to examine the use and outcomes associated with or without the administration of adjuvant radiotherapy (RT) or ET. METHODS: Women aged ≥ 65 years with stage I BC treated with BCS in Ontario between 2010 and 2016, their treatments and outcomes were ascertained using deterministic linkages of administrative databases. Multivariable Cox regression models were used to evaluate risks of ipsilateral LR and of any first in-breast event, categorizing women by their treatment. RESULTS: 5076 women were treated with BCS followed by RT + ET (n = 1964), RT alone (n = 1325), ET alone (n = 719), or no adjuvant treatment (n = 1068). Median follow-up was 5 years. LR occurred in 0.9% after adjuvant RT + ET, 1.4% after RT alone, 3.1% after ET alone, and 9.4% after BCS alone (p < 0.001). The adjusted risk of LR was increased in those who received no adjuvant therapy (HR = 13.43, CI: 7.89, 22.85), or ET alone (HR = 4.03, CI: 2.14, 7.59). The adjusted risk of any first in-breast event was greatest among those without any adjuvant therapy (HR = 7.61, 95%CI: 5.21, 11.11, p < 0.0001). Absolute and adjusted risks of any first in-breast event were comparable between those with ET alone (HR = 2.09, 95%CI: 1.27, 3.43, p = 0.0038) and those with RT alone (HR = 1.91, 95% CI: 1.25, 2.91, p = 0.0028). CONCLUSIONS: Older women with stage I BC who receive no adjuvant therapy have a significant absolute risk of LR and any first in-breast event, whereas the absolute risk of these events among those with either RT alone or ET alone is only slightly higher than among those treated with both.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Assistência ao Paciente , Cuidados Pós-Operatórios , Padrões de Prática Médica , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Feminino , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Assistência ao Paciente/métodos , Assistência ao Paciente/estatística & dados numéricos , Vigilância da População , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Prognóstico , Cooperação e Adesão ao Tratamento , Resultado do Tratamento
7.
Int J Radiat Oncol Biol Phys ; 105(1): 165-173, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31085285

RESUMO

PURPOSE: Regional nodal irradiation for women with breast cancer is known to be an important risk factor for the development of upper extremity lymphedema, but tools to accurately predict lymphedema risks for individual patients are lacking. This study sought to develop and validate a nomogram to predict lymphedema risk after axillary surgery and radiation therapy in women with breast cancer. METHODS AND MATERIALS: Data from 1832 women accrued on the MA.20 trial between March 2000 and February 2007 were used to create a prognostic model with National Cancer Institute Common Toxicity Criteria Version 2.0 grade 2 or higher lymphedema as the primary endpoint. Multivariable logistic regression estimated model performance. External validation was performed on data from a single large academic cancer center (N = 785). RESULTS: In the MA.20 trial cohort, 3 risk factors were predictive of lymphedema risk: body mass index (adjusted odds ratio, 1.05 per unit body mass index; 95% confidence interval [CI], 1.03-1.08, P < .001), extent of axillary surgery (adjusted odds radio for 8-11 lymph nodes removed, 3.28 [95% CI, 1.53-7.89] P = .004; 12-15 lymph nodes, 4.04 [95% CI, 1.76-10.26] P = .002; ≥16 nodes, 5.08 [95% CI, 2.26-12.70] P < .001), and extent of nodal irradiation (adjusted odds radio for limited, 1.66 [95% CI, 1.08-2.56] P = .02; for extensive, 2.31 [95% CI, 1.28-4.10] P = .004). A nomogram was created from these data that predicted lymphedema risk with reasonable accuracy confirmed by both internal (concordance index, 0.69; 95% CI, 0.64-0.74) and external validation (concordance index, 0.71; 95% CI, 0.66-0.76). CONCLUSIONS: The nomogram created from the MA.20 randomized trial data using clinical information may be useful for lymphedema screening and risk stratification for therapeutic intervention trials.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo/efeitos adversos , Irradiação Linfática/efeitos adversos , Linfedema/etiologia , Nomogramas , Complicações Pós-Operatórias/etiologia , Adulto , Axila , Índice de Massa Corporal , Canadá , Intervalos de Confiança , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco
8.
N Engl J Med ; 379(2): 111-121, 2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-29860917

RESUMO

BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180 .).


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Estudos Prospectivos , Receptor ErbB-2 , Receptores Estrogênicos , Receptores de Progesterona , Adulto Jovem
9.
Breast Cancer Res Treat ; 169(3): 537-548, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29455298

RESUMO

PURPOSE: Aromatase inhibitors are the most commonly prescribed adjuvant endocrine therapy for hormone-dependent early breast cancer in postmenopausal women. Among Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had comparable 5-year event-free survival. This companion study examined differences in patient-reported treatment-related symptoms (TRS) and health-related quality of life (HRQL) among postmenopausal women randomized to anastrozole or exemestane. METHODS: MA.27 participants (N = 686, of 7576) randomized to 5 years of anastrozole (1 mg/day, n = 371, Arm A) or exemestane (25 mg/day, n = 315, Arm E) completed the 56-item Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) questionnaire to assess TRS and HRQL. The FACT-ES was completed at baseline, 3, 6, 12, and 24 months. RESULTS: No significant differences in FACT-ES median scores measuring TRS and HRQL were observed between treatment arms at any time point. Change in TRS from baseline was statistically significant at 3, 6, 12, and 24 months. HRQL was stable over time in both arms. Greater TRS burden was associated with poorer HRQL (coefficient = 0.57, p < 0.001). Twenty percent of patients discontinued AI therapy by month 24 and 32% discontinued AIs at 4 years. In both arms, patients reporting more side effect bother prior to initiating study treatment had a higher risk of discontinuing treatment before completing protocol therapy (hazard ratio [HR] 1.29, 95% CI 1.08-1.55, p = 0.01). CONCLUSIONS: TRS and HRQL were comparable between anastrozole and exemestane. TRS negatively affect HRQL. Women who report being bothered by treatment side effects prior to initiating an AI are at increased risk for early treatment discontinuation.


Assuntos
Neoplasias da Mama/epidemiologia , Adesão à Medicação , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol/administração & dosagem , Anastrozol/efeitos adversos , Anastrozol/uso terapêutico , Androstadienos/administração & dosagem , Androstadienos/efeitos adversos , Androstadienos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Medidas de Resultados Relatados pelo Paciente , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Clin Oncol ; 36(6): 563-571, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29328860

RESUMO

Purpose MA.17R was a Canadian Cancer Trials Group-led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor-positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Letrozol/uso terapêutico , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Feminino , Humanos , Pessoa de Meia-Idade
12.
JAMA Netw Open ; 1(5): e182081, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30646153

RESUMO

Importance: In women with locally advanced cancer of the cervix (LACC), staging defines disease extent and guides therapy. Currently, undetected disease outside the radiation field can result in undertreatment or, if disease is disseminated, overtreatment. Objective: To determine whether adding fludeoxyglucose F 18 positron emission tomography-computed tomography (PET-CT) to conventional staging with CT of the abdomen and pelvis affects therapy received in women with LACC. Design, Setting, and Participants: A randomized clinical trial was conducted. Women with newly diagnosed histologically confirmed International Federation of Gynecology and Obstetrics stage IB to IVA carcinoma of the cervix who were candidates for chemotherapy and radiation therapy (CRT) were allocated 2:1 to PET-CT plus CT of the abdomen and pelvis or CT alone. Enrollment occurred between April 2010 and June 2014 at 6 regional cancer centers in Ontario, Canada. The PET-CT scanners were at 6 associated academic institutions. The median follow-up at the time of the analysis was 3 years. The analysis was conducted on March 30, 2017. Interventions: Patients received either PET-CT plus CT of the abdomen and pelvis or CT of the abdomen and pelvis. Main Outcomes and Measures: Treatment delivered, defined as standard pelvic CRT vs more extensive CRT, ie, extended field radiotherapy or therapy with palliative intent. Results: One hundred seventy-one patients were allocated to PET-CT (n = 113) or CT (n = 58). The trial stopped early before the planned target of 288 was reached because of low recruitment. Mean (SD) age was 48.1 (11.2) years in the PET-CT group vs 48.9 (12.7) years in the CT group. In the 112 patients who received PET-CT, 68 (60.7%) received standard pelvic CRT, 38 (33.9%) more extensive CRT, and 6 (5.4%) palliative treatment. The corresponding data for the 56 patients who received CT alone were 42 (75.0%), 11 (19.6%), and 3 (5.4%). Overall, 44 patients (39.3%) in the PET-CT group received more extensive CRT or palliative treatment compared with 14 patients (25.0%) in the CT group (odds ratio, 2.05; 95% CI, 0.96-4.37; P = .06). Twenty-four patients in the PET-CT group (21.4%) received extended field radiotherapy to para-aortic nodes and 14 (12.5%) to common iliac nodes compared with 8 (14.3%) and 3 (5.4%), respectively, in the CT group (odds ratio, 1.64; 95% CI, 0.68-3.92; P = .27). Conclusions and Relevance: There was a trend for more extensive CRT with PET-CT, but the difference was not significant because the trial was underpowered. This trial provides information on the utility of PET-CT for staging in LACC. Trial Registration: ClinicalTrials.gov Identifier: NCT00895349.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Neoplasias do Colo do Útero/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/estatística & dados numéricos , Ontário/epidemiologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia
13.
Support Care Cancer ; 26(5): 1533-1541, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29189967

RESUMO

BACKGROUND: Better coordination of supportive services during the early phases of cancer care has been proposed to improve the care experience of patients. We conducted a randomized trial to test a community-based nurse-led coordination of care intervention in cancer patients. METHODS: Surgical practices were cluster randomized to a control group involving usual care practices or a standardized nursing intervention consisting of an in-person supportive care assessment with ongoing support to meet identified needs, including linkage to community services. Newly diagnosed breast and colorectal cancer patients within 7 days of cancer surgery were eligible. The primary outcome was the patient-reported outcome (PRO) of continuity of care (CCCQ) measured at 3 weeks. Secondary outcomes included unmet supportive care needs (SCNS), quality of life (EORTC QLQ-C30), health resource utilization, and level of uncertainty with care trajectory (MUIS) at 3 and/or 8 weeks. RESULTS: A total of 121 breast and 72 colorectal patients were randomized through 28 surgical practices. There was a small improvement in the informational domain of continuity of care (difference 0.29 p = 0.05) and a trend to less emergency room use (15.8 vs 7.1%) (p = 0.07). There were no significant differences between groups on unmet need, quality of life, or uncertainty. CONCLUSION: We did not find substantial gaps in the PROs measured immediately following surgery for breast and colorectal cancer patients. The results of this study support a more targeted approach based on need and inform future research focused on improving navigation during the initial phases of cancer treatment. ClinicalTrials.gov Identifier: NCT00182234. SONICS-Effectiveness of Specialist Oncology Nursing.


Assuntos
Neoplasias da Mama/enfermagem , Neoplasias da Mama/cirurgia , Neoplasias Colorretais/enfermagem , Neoplasias Colorretais/cirurgia , Enfermagem Oncológica/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Qualidade de Vida
15.
Ann Surg Oncol ; 24(1): 38-51, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27646018

RESUMO

PURPOSE: A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). METHODS: A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. RECOMMENDATIONS: The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Tomada de Decisões , Feminino , Humanos , Mastectomia , Recidiva Local de Neoplasia/prevenção & controle , Estados Unidos
16.
Clin Lung Cancer ; 18(2): 250-254, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27876603

RESUMO

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia , Projetos de Pesquisa , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida
17.
Pract Radiat Oncol ; 6(6): e219-e234, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27659727

RESUMO

A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). METHODS: A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. RECOMMENDATIONS: The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.


Assuntos
Neoplasias da Mama/radioterapia , Mastectomia , Recidiva Local de Neoplasia/epidemiologia , Radioterapia Adjuvante/métodos , Axila , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Oncologia , Estadiamento de Neoplasias , Radioterapia (Especialidade) , Medição de Risco , Biópsia de Linfonodo Sentinela , Sociedades Médicas , Oncologia Cirúrgica , Estados Unidos
18.
Radiother Oncol ; 121(3): 414-419, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27637858

RESUMO

BACKGROUND AND PURPOSE: We report the long-term outcomes in patients enrolled in a multicenter randomized controlled trial comparing Intensity Modulated Radiation Therapy (IMRT) with standard wedge radiotherapy. MATERIALS AND METHODS: Trial participants were assessed to compare long-term side effects between treatment arms. The primary endpoint was chronic breast pain assessed by trained observers blinded to treatment allocation. Secondary endpoints included cosmesis and quality of life measures. RESULTS: Median follow-up time was 9.8years and 241 patients were available for assessment. There was no significant difference in chronic pain between treatment arms (OR=0.74, range 0.432-1.271). There were also no differences for the secondary endpoints. Univariate and multivariate analyses identified young age (p=0.013) and pain during RT (p<0.001) to be associated with chronic pain. Acute moist desquamation was associated with late subcutaneous fibrosis (p=0.003) and telangiectasia (p=0.039). Pain during RT was associated with a long-term poorer self-assessed cosmetic outcome (p<0.001) and quality of life (p<0.001). CONCLUSIONS: Breast IMRT cannot be recommended for all patients to reduce long-term side effects. However, late toxicities were significantly correlated with acute side effects, which are increased in patients having poor dose distribution. Breast IMRT may hence be useful for selected patients.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia de Intensidade Modulada/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/reabilitação , Dor Crônica/etiologia , Método Duplo-Cego , Estética , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Lesões por Radiação/etiologia , Radiometria/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Telangiectasia/etiologia
19.
J Clin Oncol ; 34(36): 4431-4442, 2016 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-27646947

RESUMO

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Guias de Prática Clínica como Assunto/normas , Relação Dose-Resposta à Radiação , Feminino , Humanos , Oncologia/normas , Radioterapia (Especialidade)/normas , Dosagem Radioterapêutica , Radioterapia Adjuvante/normas , Sociedades Médicas/normas , Oncologia Cirúrgica/normas , Estados Unidos
20.
Breast Cancer Res Treat ; 156(2): 343-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27006189

RESUMO

Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) < 70 years and 2159 (28 %) ≥ 70 years) were enrolled and followed for median 4.1 years. The 432 deaths comprised 187 (43 %) BC, 66 (15 %) cardiovascular, and 179 (41 %) OT. Five baseline factors were differentially associated with type of death. Older patients had greater BC (p = 0.03), cardiovascular (p < 0.001), and other types (p < 0.001) of mortality. Patients with pre-existing cardiovascular history had worse cardiovascular mortality (p < 0.001); those with worse ECOG performance status had worse OT mortality (p < 0.001). Patients with T1 tumors (p < 0.001) and progesterone receptor positive had less BC mortality (p < 0.001). Fewer BC deaths occurred with node-negative disease (p < 0.001), estrogen receptor-positive tumors (p = 0.001), and without adjuvant chemotherapy (p = 0.005); worse cardiovascular mortality (p = 0.01), with trastuzumab; worse OT mortality, for non-whites (p = 0.03) and without adjuvant radiotherapy (p = 0.003). Overall, 57 % of deaths in MA.27 AI-treated patients were non-breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Doenças Cardiovasculares/mortalidade , Quimioterapia Adjuvante/métodos , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Androstadienos/uso terapêutico , Neoplasias da Mama/patologia , Causas de Morte , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Nitrilos/uso terapêutico , Pós-Menopausa , Análise de Sobrevida , Resultado do Tratamento , Triazóis/uso terapêutico
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