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New treatment paradigms for resectable nonsmall cell lung cancer (NSCLC), with an emphasis on personalised care and a multidisciplinary approach, have significantly improved patient outcomes. The incorporation of immune checkpoint inhibitors into neoadjuvant, perioperative and adjuvant treatment algorithms is reshaping the standard of care for resectable NSCLC. Adjuvant targeted therapy trials have also paved the way for a much-needed personalised approach for patients with actionable genomic alterations. Innovative surgical techniques and judicious use of postoperative radiotherapy may mitigate the toxicity associated with a multimodality approach. Amid the many new treatment options, questions remain about the best approach to consider for each patient. Measurement of minimal residual disease and achievement of pathological complete response are emerging biomarkers of interest to help further refine treatment selection. This review summarises the current management of resectable NSCLC, focusing on ongoing and recent advances in surgical approaches, the role of postoperative radiotherapy and the rapidly changing field of systemic therapies.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/radioterapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Pneumonectomia/métodos , Terapia Neoadjuvante , Radioterapia Adjuvante , Terapia CombinadaRESUMO
BACKGROUND: Increasingly, survey researchers rely on hybrid samples to improve coverage and increase the number of respondents by combining independent samples. For instance, it is possible to combine 2 probability samples with one relying on telephone and another on mail. More commonly, however, researchers are now supplementing probability samples with those from online panels that are less costly. Setting aside ad hoc approaches that are void of rigor, traditionally, the method of composite estimation has been used to blend results from different sample surveys. This means individual point estimates from different surveys are pooled together, 1 estimate at a time. Given that for a typical study many estimates must be produced, this piecemeal approach is computationally burdensome and subject to the inferential limitations of the individual surveys that are used in this process. OBJECTIVE: In this paper, we will provide a comprehensive review of the traditional method of composite estimation. Subsequently, the method of composite weighting is introduced, which is significantly more efficient, both computationally and inferentially when pooling data from multiple surveys. With the growing interest in hybrid sampling alternatives, we hope to offer an accessible methodology for improving the efficiency of inferences from such sample surveys without sacrificing rigor. METHODS: Specifically, we will illustrate why the many ad hoc procedures for blending survey data from multiple surveys are void of scientific integrity and subject to misleading inferences. Moreover, we will demonstrate how the traditional approach of composite estimation fails to offer a pragmatic and scalable solution in practice. By relying on theoretical and empirical justifications, in contrast, we will show how our proposed methodology of composite weighting is both scientifically sound and inferentially and computationally superior to the old method of composite estimation. RESULTS: Using data from 3 large surveys that have relied on hybrid samples composed of probability-based and supplemental sample components from online panels, we illustrate that our proposed method of composite weighting is superior to the traditional method of composite estimation in 2 distinct ways. Computationally, it is vastly less demanding and hence more accessible for practitioners. Inferentially, it produces more efficient estimates with higher levels of external validity when pooling data from multiple surveys. CONCLUSIONS: The new realities of the digital age have brought about a number of resilient challenges for survey researchers, which in turn have exposed some of the inefficiencies associated with the traditional methods this community has relied upon for decades. The resilience of such challenges suggests that piecemeal approaches that may have limited applicability or restricted accessibility will prove to be inadequate and transient. It is from this perspective that our proposed method of composite weighting has aimed to introduce a durable and accessible solution for hybrid sample surveys.
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Pesquisadores , Humanos , ProbabilidadeRESUMO
BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.
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Neoplasias , Radiocirurgia , Humanos , Neoplasias/mortalidade , Neoplasias/patologia , Neoplasias/radioterapia , Intervalo Livre de Progressão , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos de Equivalência como AsuntoRESUMO
Purpose: Moist desquamation (MD) is a concerning acute side effect of radiation therapy for breast cancer, often seen in skin folds for patients having large or pendulous breasts. In vivo skin dosimetry, clinical assessments, and patient-reported skin reactions were used to determine a relationship between dose-area metrics and the development of MD, to lend insight into skin tolerances and possibly guide future treatment planning dose constraints. Methods and Materials: Skin dose was measured using GafChromic film on the inner surface of an early prototype carbon-fiber accessory for breast support to remove the inframammary fold in 20 patients at high risk of developing MD undergoing adjuvant whole breast radiation therapy. Prescribed doses were 42.5 Gray (Gy) in 16 fractions or 50 Gy in 25 fractions using 6 to 15 MV x-rays. To account for fraction size differences, analysis was performed using the equivalent dose in 2 Gy fractions using α/ß = 11 (EQD211). MD was assessed out to 2 weeks post radiation therapy by trained therapists and by a patient-reported outcome questionnaire. Results: Statistically significant differences in areas receiving 30 to 48 Gy (EQD211) were observed between patients who did and did not develop MD in the inframammary area. Patients receiving EQD211 maximum dose ≤ 46 Gy and ≥ 38 Gy to ≤ 50 cm2 of their breast skin did not develop MD. Conclusions: The findings of this study offer insight into the relationship between skin toxicity and areas of skin irradiated to doses up to 50 Gy. Potential skin dose constraints to test in future studies to prevent MD are suggested.
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PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.
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Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Intervalo Livre de Progressão , Radiocirurgia/métodosRESUMO
BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS). METHODS: This single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated. RESULTS: 549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86-0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93-0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69-0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and 'other' (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS. CONCLUSION: PTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning.
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Neoplasias Pulmonares , Radiocirurgia , Humanos , Órgãos em Risco/patologia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversosRESUMO
Importance: After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases. Objective: To document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program. Design, Setting, and Participants: From November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series. Interventions: Stereotactic ablative body radiotherapy to up to 5 metastases. Main Outcomes and Measures: Rate of grade 2, 3, 4, and 5 toxic effects associated with SABR. Findings: Among 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%. Conclusions and Relevance: This single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02933242.
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Neoplasias Pulmonares , Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Neoplasias Pulmonares/patologia , Fracionamento da Dose de Radiação , Estimativa de Kaplan-MeierRESUMO
There has been an increasing interest in patient-reported outcome (PRO) measures in both the clinical and research settings to improve the quality of life among patients and to identify when clinical intervention may be needed. The primary purpose of this prospective study was to validate an acute breast skin toxicity PRO measure across a broad sample of patient body types undergoing radiation therapy. Between August 2018 and September 2019, 134 women undergoing adjuvant breast radiotherapy (RT) consented to completing serial PRO measures both during and post-RT treatment and to having their skin assessed by trained trial radiation therapists. There was high patient compliance, with 124 patients (92.5%) returning to the clinic post-RT for at least one staff skin assessment. Rates of moist desquamation (MD) in the infra-mammary fold (IMF) by PRO were compared with skin assessments completed by trial radiation therapists. There was high sensitivity (86.5%) and good specificity (79.4%) between PRO and staff-reported presence of MD in the IMF, and there was a moderate correlation between the peak severity of the MD reported by PRO and assessed by staff (rho = 0.61, p < 0.001). This prospective study validates a new PRO measure to monitor the presence of MD in the IMF among women receiving breast RT.
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Radiodermite , Feminino , Humanos , Mastectomia Segmentar , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Radiodermite/tratamento farmacológicoRESUMO
BACKGROUND: A novel device for supine positioning in breast radiotherapy for patients with large or pendulous breasts has been developed and tested in phase II studies. This trial is designed to assess the efficacy of the device to reduce skin toxicity and unwanted normal tissue dose in comparison to the current clinical standard for supine breast support during breast radiotherapy. METHODS: Patients at high risk for moist desquamation, having infra-mammary fold or lateral ptosis, will be randomized into two arms. Patients in the control arm will receive breast radiotherapy with supine positioning using current standard of care. Patients in the experimental arm will be positioned supine with the novel device. The primary endpoint is the incidence of moist desquamation in the infra-mammary fold. We hypothesize a 20% reduction (from 50 to 30%) in the rate of moist desquamation in the study arm versus the control arm. For 80% power, two-tailed α = 0.05 and 10% loss to follow up, 110 patients will be assigned to each arm. The proportion of patients experiencing moist desquamation in the two arms will be compared using logistic regression adjusting for brassiere cup size, skin fold size, body mass index, smoking status, and dose fractionation schedule. An unadjusted comparison will also be made using the chi-square test, or Fisher's exact test, if appropriate. Secondary endpoints include dose-volume statistics for the lung and heart, skin dose and clinical parameters including setup time, reproducibility, and staff experience with setup procedures. Patient-reported pain, skin condition interference with sleep and daily activities, and comfort during treatment are also secondary endpoints. DISCUSSION: Based on results from earlier phase II studies, it is expected that the device-enabled elimination of infra-mammary fold should reduce toxicity and improve quality of life for this patient population. Earlier studies showed reduction in dose to organs at risk including lung and heart, indicating potential for other long-term benefits for patients using the device. This study is limited to acute skin toxicity, patient-reported outcomes, and clinical factors to inform integration of the device into standard breast radiotherapy procedures. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04257396 . Registered February 6 2020.
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Neoplasias da Mama , Dermatopatias , Neoplasias da Mama/etiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Fibra de Carbono , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Mastectomia Segmentar/métodos , Estudos Multicêntricos como Assunto , Qualidade de Vida , Radioterapia Adjuvante/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos TestesRESUMO
Abscopal effect is a rare phenomenon in which treatment benefit from radiotherapy (RT) is seen outside the target field due to activation of the immune system inducing an anti-tumor effect. This phenomenon has been reported in cancer patients receiving immune checkpoint inhibitors (ICI). Here we report a case of presumed abscopal effect in malignant mesothelioma. The patient received second-line single-agent pembrolizumab however had disease progression after four cycles leading to palliative RT (20 Gray) to the right mainstem bronchus. Follow-up radiographic imaging confirmed benefit and pembrolizumab was continued. Follow-up computed tomography (CT) five months after RT, showed marked radiographic improvement of all measurable diseases with improvement in right-sided aerated lung volume. Because of the original disease progression on pembrolizumab, with marked improvements within and outside the RT field after RT, treatment response was presumed due to the abscopal effect.
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PURPOSE: Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR. METHODS AND MATERIALS: This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiation therapy without bolus or beam spoilers. The primary endpoint was the cumulative incidence of LR (CILR). Multivariable analysis (MVA) included mean beam energy, age, T-stage, nodal status, overall stage, lymphovascular invasion (LVI), grade, margin status, extensive intraductal component (EIC), breast cancer subtype, hormone therapy, and chemotherapy. In a subgroup with contoured surgical beds, another MVA included surgical bed-to-skin distance. RESULTS: The cohort consisted of 10,083 women treated from 2002 to 2011: 327 with 4 MV, 6006 with 6 MV, 2083 with >6 to 10 MV, and 1667 with >10 MV tangents. The median follow-up time was 11.1 years. The 10-year CILR was 3.1% (95% confidence interval [CI], 1.6-5.4) with 4 MV, 2.8% (2.4-3.3) with 6 MV, 4.2% (3.4-5.3) with >6 to 10 MV, and 2.6% (1.9-3.5) with >10 MV. On MVA of the entire cohort, LR risk was increased with positive margins, LVI, EIC, and lack of hormone therapy, but was not associated with beam energy (hazard ratio [HR], 1.01; 95% CI, 0.96-1.05; P = .8). On MVA of 3359 patients with contoured surgical beds, LR risk was not associated with surgical bed-to-skin distance (HR, 1.00; 95% CI, 0.99-1.02; P = .8). CONCLUSIONS: Use of higher breast tangent beam energies is not associated with increased risk of LR, including in cases with surgical beds that are close to the skin.
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Neoplasias da Mama , Recidiva Local de Neoplasia , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Margens de Excisão , Mastectomia Segmentar/métodos , Recidiva Local de Neoplasia/cirurgia , Estadiamento de NeoplasiasRESUMO
PURPOSE: Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population. METHODS AND MATERIALS: Patients aged 40 to 79 years with pT1-2 pN1 (node-positive) breast cancer diagnosed between 2005 and 2014 were identified. The inclusion criteria were modeled off of the TAILOR RT study, which is a randomized noninferiority clinical trial designed to assess the value of RNI in patients with low-risk N1 disease. Eligible patients had breast-conserving surgery or mastectomy and axillary lymph node dissection with 1 to 3 positive nodes, breast-conserving surgery and sentinel lymph node biopsy with 1 to 2 positive nodes, or mastectomy and sentinel lymph node biopsy with 1 positive node. Additionally, patients had luminal A breast cancers, as approximated by estrogen receptor positive (Allred 6-8/8), progesterone receptor (PR) positive (Allred 6-8/8), human epidermal growth factor receptor 2-negative, and grade 1 to 2 immunohistochemical testing. All patients were prescribed hormonal treatment. The primary endpoint of BCRFI, the time to any breast cancer recurrence or breast cancer-related death, was analyzed using a multivariate competing risks analysis. RESULTS: The cohort included 1169 women with a median follow-up of 9.2 years. Radiation treatments were not performed in 151 women treated with mastectomy alone, were delivered to the breast only in 133 women, and were delivered locoregionally in 885 women. Patients undergoing RNI were younger (median age: 58 vs 62 years), more likely to have 2 to 3 macroscopic lymph nodes involved, and more often received chemotherapy (all P < .05). The 10-year estimate of BCRFI was 90% without RNI versus 90% with RNI (P = .5). On multivariable analysis, RNI was not a significant predictor of BCRFI (hazard ratio: 1.0; P = .9). CONCLUSIONS: In this retrospective analysis, RNI was not associated with improved BCRFI for women with biologically low-risk N1 breast cancer. We advocate accrual to the ongoing TAILOR RT study.
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Neoplasias da Mama , Linfonodos , Recidiva Local de Neoplasia , Intervalo Livre de Progressão , Adulto , Idoso , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
PURPOSE: This pilot study (ClinicalTrials.gov NCT04543851) investigates a novel breast positioning device using a low density, high tensile carbon-fiber cradle to support the breast, remove the inframammary fold, and reduce dose to organs at risk for whole breast radiation therapy in the supine position. METHODS AND MATERIALS: Thirty patients with inframammary folds ≥1 cm or lateral ptosis in supine treatment position were planned with standard positioning and with a carbon-fiber Adjustable Reusable Accessory (CARA) breast support. Twenty patients received whole breast with or without regional nodal irradiation with 42.5 Gy in 16 fractions or 50 Gy in 25 fractions using CARA. Median body mass index was 32 in this study. RESULTS: CARA removed all inframammary folds and reduced V20Gyipsilateral lung, V105%breast, and V50% body, without compromising target coverage. Median (range) V20Gyipsilateral lung for whole breast radiation therapy was 12.3% (1.4%-28.7%) with standard of care versus 10.9% (1.2%-17.3%) with CARA (Wilcoxon P = .005). Median V105% breast was 8.0% (0.0%-29%) with standard of care versus 4.0% (0.0%-23%) with CARA (P = .006) and median V50% body was 3056 mL (1476-5285 mL) versus 2780 mL (1415-5123 mL) with CARA (P = .001). CARA was compatible with deep inspiration breath hold and achieved median V25Gyheart = 0.1% (range 0%-1.9%) for all patients with left breast cancer. Skin reactions with CARA were consistent with historical data and daily variation in treatment setup was consistent with standard supine positioning. CONCLUSIONS: CARA can reduce V105%breast, lung and normal tissue dose, and remove the inframammary fold for breast patients with large or pendulous breasts and high body mass index treated in the supine position, without compromising target coverage. CARA will undergo further study in a randomized controlled trial.
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Neoplasias da Mama , Órgãos em Risco , Neoplasias da Mama/radioterapia , Fibra de Carbono , Feminino , Coração , Humanos , Projetos Piloto , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement. METHODS AND MATERIALS: For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011. Eligible patients had newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with adjuvant or neoadjuvant radiation therapy. For the bolus and no-bolus groups, we compared the cumulative incidence of local recurrence (LR) and locoregional recurrence (LRR) with distant recurrence and death as competing risks and breast cancer mortality (BCM). Multivariable analysis of LR and BCM included stage, subtype, lymphovascular invasion, grade, margin status, beam energy, bolus use, hormone therapy, chemotherapy, and reconstruction. RESULTS: Systemic therapy was used for 98% of the 1887 patients. The bolus group had 1569 patients and the no-bolus group had 318 patients. Bolus was used in 51% (281/550) of patients treated with reconstruction and 96% (1288/1337) of patients treated without reconstruction. The 10-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: LR 1.9% (1.3-2.7) versus 0.9% (0.3-2.6), LRR 3.1% (2.3-4.0) versus 3.2% (1.6-5.5), and BCM 19.4% (17.3-21.6) versus 18.3% (13.9-23.2). On multivariable analysis, bolus use was not associated with better LR (hazard ratio = 1.4 [0.3-6.4]) or BCM (hazard ratio = 0.8 [0.5-1.2]). CONCLUSIONS: For patients treated with mastectomy, radiation therapy, and modern systemic therapy, the cumulative incidence of LR was low, with or without bolus. Because bolus use increases toxicity and does not reduce LR or BCM, it should no longer be used routinely for patients without skin involvement who receive systemic therapy.
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Neoplasias da Mama/radioterapia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Combinada/métodos , Intervalos de Confiança , Feminino , Humanos , Incidência , Mamoplastia/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Recidiva Local de Neoplasia/mortalidade , Cuidados Pós-Operatórios/métodos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Radioterapia Conformacional/métodos , Pele/efeitos da radiaçãoRESUMO
OBJECTIVE: To determine whether signed family physician reminder letters to women overdue for screening mammography prompts rescreening. METHODS: A randomized double-blind trial conducted in 2013 among women aged 51-73 and overdue for screening by 6-24 months. The study was carried out by the publicly funded British Columbia Cancer Agency Screening Mammography Program, which routinely sends standard reminder postcards to women who are due for mammography. Participating family physicians signed letters for the overdue women in their practices. The overdue women were mailed either the signed reminder letter and the standard reminder postcard, or the standard reminder postcard alone. The primary endpoint was the proportion of overdue women that attended a screening mammogram appointment within six months of mailing the study letters. The analysis was by intention to treat. RESULTS: In total, 822 family physicians participated and 5638 women were randomized. Mammography attendance by six months after mailing the reminders was 34.4% (947/2749) for women in the signed family physician letter arm, compared with 24.0% (660/2749) for women in the control arm (p < 0.0001). Adjusting for age, number of previous screening mammograms, and months overdue, women in the signed letter arm were significantly more likely to return for screening than women in the control arm (RR 1.41; 95% confidence interval: 1.30-1.54). CONCLUSION: A signed family physician reminder letter improved mammography attendance for women who were overdue for screening mammography.
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Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Medicina de Família e Comunidade/organização & administração , Mamografia/métodos , Médicos de Família , Sistemas de Alerta , Idoso , Agendamento de Consultas , Colúmbia Britânica , Método Duplo-Cego , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Cooperação do Paciente , Relações Médico-PacienteRESUMO
PURPOSE: The Cancer and Leukemia Group B (CALGB) 9343 trial randomized elderly women with estrogen receptor-positive, stage 1 breast cancer to receive either hormone therapy (HT) or HT and radiation therapy (HT-RT) after lumpectomy and showed no difference in survival. After this publication, a practice guideline made HT alone a standard treatment option in British Columbia. The subsequent population-based pattern of practice was studied. METHODS AND MATERIALS: All women aged 70 to 79 years, referred after lumpectomy from 1999 to 2009, with stage 1, estrogen receptor-positive breast cancer were identified. The use of adjuvant HT or HT-RT was evaluated in 2 eras: before (1999-2003) and after (2005-2009) the CALGB publication. The proportion receiving each treatment in these eras was determined. Kaplan-Meier analyses with Cox regression were used for survival endpoints. The Fine and Gray method was used with non-breast cancer death as a competing risk for event-free survival. The Charlson score was used to quantify comorbidity. Adherence was defined as dispensation of 80% of prescribed HT. RESULTS: HT-RT was used in 91% of patients before (n=319) and 89% of patients after (n=403) the CALGB publication (P=.4). In the HT-alone group, the rate of HT adherence was 75% at 1 year and 55% at 4 years. The 10-year locoregional recurrence-free survival rate was 98% with HT-RT and 90% with HT alone (P=.01), whereas the 10-year breast cancer-specific survival rate was 96% with HT-RT and 95% with HT alone (P=.2). Patients with grade 3 histology or lymphovascular invasion were more likely to have low event-free survival. On multivariate analysis, treatment type did not predict overall survival (P=.3). CONCLUSIONS: Our patient outcomes closely matched those of the CALGB trial, suggesting that its results are generalizable to a population of elderly breast cancer patients with typical HT adherence. The CALGB trial results, as well as the resulting practice guideline, did not change the use of adjuvant HT-RT in our population-based cancer program.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Colúmbia Britânica , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia Segmentar/métodos , Mastectomia Segmentar/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
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 VidaRESUMO
OBJECTIVES: To evaluate the cosmetic effect of a tumor-bed boost after hypofractionated whole breast irradiation (HF-WBI+B) using a patient-reported questionnaire. MATERIALS AND METHODS: Between 2000 and 2005, 4392 women aged 75 years and younger with unilateral early-stage breast cancer received HF-WBI alone or HF-WBI+B. From each group, 800 randomly sampled surviving and nonrelapsed women were invited to complete the Breast Cancer Treatment Outcomes Scale questionnaire. RESULTS: A total of 312 women completed the questionnaire: 154 received HF-WBI alone and 158 received HF-WBI+B. Median ages of respondents were 57 years for HF-WBI alone and 52 years for HF-WBI+B (P<0.001). Women receiving HF-WBI+B had a shorter follow-up interval, higher T stage, higher grade, and were more likely to have had nodal radiotherapy and chemotherapy. There were similar responses comparing the overall appearance of the treated to untreated breast (42% stating no or slight difference for HF-WBI alone vs. 41% for HF-WBI+B, P=0.87). The HF-WBI+B group was: (a) slightly worse on the cosmetic subscale (2.3 vs. 2.1, P=0.02); (b) worse on the pain subscale (2.0 vs. 1.6, P<0.0001); but (c) better on the functional subscale (1.5 vs. 1.8, P<0.001). When the pain subscale was applied to the area around the scar (a surrogate for the tumor-bed), the 2 groups were similar (2.0 vs. 2.0, P=0.71). CONCLUSIONS: Similar to conventional fractionated whole breast radiotherapy with a tumor-bed boost, women who received short fractionation whole breast radiotherapy with boost self-report only slightly worse long-term cosmetic and pain outcomes compared with women who received short fractionation alone.
Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Medidas de Resultados Relatados pelo Paciente , Hipofracionamento da Dose de Radiação , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Estética , Feminino , Seguimentos , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor/etiologia , Radioterapia/efeitos adversos , Radioterapia/métodos , Inquéritos e Questionários , Fatores de TempoRESUMO
Although it has been argued that leader-member exchange (LMX) is a phenomenon that develops over time, the existing LMX literature is largely cross-sectional in nature. Yet, there is a great need for unraveling how LMX develops over time. To address this issue in the LMX literature, we examine the relationships of LMX with 2 variables known for changing over time: job performance and justice perceptions. On the basis of current empirical findings, a simulation deductively shows that LMX develops over time, but differently in early stages versus more mature stages. Our findings also indicate that performance and justice trends affect LMX. Implications for LMX theory and for longitudinal research on LMX, performance, and justice are discussed. (PsycINFO Database Record