RESUMO
BACKGROUND: Over the past decade, there has been increasing availability of novel therapeutics with improved tolerability and efficacy for advanced non-small cell lung cancer (NSCLC). The study goals were: to compare the uptake of systemic therapy (ST) before and after the availability of targeted tyrosine kinase inhibitors (TKI) and immunotherapy and to examine the changes in overall survival (OS) over time between younger and older adults with advanced NSCLC. METHODS: All patients with advanced NSCLC referred to British Columbia (BC) Cancer in 2009, 2011, 2015 and 2017 were included. One-year time points were based on molecular testing implementation and funded drug availability: baseline (2009), epidermal growth factor receptor TKI (2011), anaplastic lymphoma kinase TKI (2015) and Programed Death-1 (PD-1) inhibitors (2017). Age groups were <70years and ≥70years. Baseline demographics, simplified comorbidity scores (SCS), disease characteristics, and ST details were collected retrospectively. Variables were compared using X2, Fisher's exact tests and logistic-regression analysis. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: 3325 patients were identified. Baseline characteristics were compared between ages < 70 years and ≥ 70 years for each time cohort with significant differences noted in baseline Eastern Cooperative Oncology Group (ECOG) performance status and SCS. The rate of ST delivery trended upwards over time with age <70 years: 2009 44%, 2011 53%, 2015 50% and 2017 52% and age ≥70 years: 22%, 25%, 28% and 29% respectively. Predictors for decreased use of ST for age <70 years: ECOG ≥2, SCS ≥9, year 2011, and smoking history; and age ≥70 years: ECOG ≥2, years 2011 and 2015, and smoking history. The median OS of patients who received ST improved from 2009 to 2017: age <70 years 9.1 m vs. 15.5 m and age ≥70 years 11.4 m vs. 15.0 m. CONCLUSIONS: There was an increased uptake of ST for both age groups with the introduction of novel therapeutics. Although a smaller proportion of older adults received ST, those who received treatment had comparable OS to their young counterpart. The benefit of ST in both age groups was seen across the different types of treatments. With careful assessment and selection of appropriate candidates, older adults with advanced NSCLC appear to benefit from ST.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Imunoterapia/métodos , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Advances in curative treatment for breast, colorectal, NSCLC and prostate cancer have led to improvements in cancer survival. Cancer treatment and recovery time can vary depending on the recommended modalities and intensity of therapy. Our objective was to determine the current real world duration of curative treatments for the four common cancers. METHODS: A retrospective review was completed of patients referred to BC Cancer from 2010 to 2016, ≤ 65 years old, newly diagnosed with stage I-III breast, colorectal, NSCLC or prostate cancer who received curative intent treatment. Information was collected on baseline characteristics, date of diagnosis, surgery, type, duration and intent of both radiotherapy and chemotherapy. RESULTS: In total, 22,275 patients were included: 55.7% breast, 22.4% colorectal, 9.2% NSCLC, 12.7% prostate cancer. Stage I/II/III at diagnosis: breast 47.2/38.7/14.1%, colorectal 26.5/30.1/43.5%, NSCLC 46.5/18.1/35.4%, prostate 7.7/62.9/29.4%. Patients treated with definitive surgery only: breast 35.9%, colorectal 58%, NSCLC 52.2%, prostate 40.1%. The median duration of multimodality treatment was breast 24.6 weeks, colorectal 26.7 weeks, NSCLC 9.1 weeks, and prostate 6.0 weeks. CONCLUSIONS: Approximately half of patients who undergo curative cancer treatment require definitive radiotherapy or multimodality treatment. The median duration of therapy for the most commonly treated cancers ranged from 6.0-26.7 weeks. Multimodality curative treatment can be prolonged for selected cancers when accounting for the duration of adjuvant chemotherapy and radiotherapy and recovery time between modalities.
Assuntos
Neoplasias da Mama/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Colorretais/terapia , Neoplasias Pulmonares/terapia , Neoplasias da Próstata/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de TempoRESUMO
PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to treatment with PD-1 and PD-L1 inhibitors. Different inhibitors have been developed with different PD-L1 assays, which use different PD-1 antibody clones on different immunohistochemistry platforms. Depending on instrument and reagent availability, laboratory-developed tests with cross-platform use of PD-L1 antibodies may have practical benefits over commercial assays. The 22C3 pharmDx Assay (referred to as 22C3 DAKO), the VENTANA PD-L1 SP263 Assay (referred to as SP263 VENTANA) and a lab-developed test using the 22C3 antibody on the VENTANA BenchMark ULTRA IHC/ISH system (referred to as 22C3 VENTANA) were performed on whole sections of 85 NSCLC surgical resections. All sections were independently scored by three pathologists using tumor proportion scores. Correlation coefficients for continuous scores in pairwise comparisons between assays ranged from 0.976 to 0.978. When using a 1% positivity threshold (dichotomous scores), the 22C3 DAKO assay and 22C3 VENTANA assays showed the greatest agreement (93% agreement, κ = 0.86, 95% CI 0.75-0.97), and the 22C3 DAKO and SP263 VENTANA assays tended to show slightly less agreement (84% agreement, κ = 0.66, 95% CI 0.50-0.82). When using a 50% positivity threshold (dichotomous scores), all pairwise comparisons showed similar agreement (96-99% agreement, κ = 0.89-0.97). Overall, there was no significant difference between assays at 1% or 50% thresholds (P = .77). These data are consistent with potential interchangeability of these assays, which may widen the scope of PD-L1 assays available to laboratories and reduce logistical barriers to testing.
Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Laboratórios/estatística & dados numéricos , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imuno-Histoquímica/métodos , Indicadores e Reagentes/provisão & distribuição , Laboratórios/provisão & distribuição , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Patologistas , Valor Preditivo dos TestesRESUMO
PURPOSE: The optimal time interval from neoadjuvant chemotherapy (NAC) to surgery in patients with breast cancer has not been established. We investigated whether different time intervals impact the rate of pathologic complete response (pCR), disease free survival (DFS), overall survival (OS), surgical complications, and rates of conversion from mastectomy to breast conserving surgery (BCS) in this population. METHODS: We identified patients who received NAC at the BC Cancer Agency followed by surgery from May 2012 to April 2018. Patients were grouped based on time interval between NAC and surgery: < 4 weeks, 4-8 weeks, and > 8 weeks. Kaplan Meier method was used to estimate DFS and OS. Rates of pCR between the time intervals were also compared. RESULTS: Of the 343 patients, 78 (22.8%) received surgery < 4 weeks, 233 (67.9%) received surgery between 4-8 weeks, and 32 (9.3%) received surgery > 8 weeks after NAC, with a median time to surgery (TTS) of 5.0 weeks. pCR was observed in 32.1%, 32.2%, and 28.1%, respectively (p = 0.90). Median follow-up time was 3.3 years. The 5-year DFS was 76%, 78%, and 70% (p = 0.89), respectively. The 5-year OS was 83%, 82%, and 78% (p = 0.33), respectively. No statistically significant differences were seen in surgical complications (p = 0.90), or rates of conversion from mastectomy to BCS (p = 0.19). CONCLUSIONS: There were no statistically significant differences in pCR, DFS, OS, surgical complications, and rates of conversion from mastectomy to BCS, among breast cancer patients receiving surgery < 4 weeks, 4-8 weeks, or > 8 weeks after the last dose of NAC.
Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Mastectomia , Estadiamento de Neoplasias , Listas de EsperaRESUMO
INTRODUCTION: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.3 months. Based on these results, the objective of this study was to characterize real-world NSCLC patients who received second-line therapy after single-agent pembrolizumab. METHODS: This was a retrospective cohort study considering stage IV NSCLC patients diagnosed with BC Cancer between 2018 and 2021 with PD-L1 ≥ 50% who received first-line single agent pembrolizumab. Patient demographics, cancer history, treatment administered, and survival were collected retrospectively. Descriptive statistics were produced. OS was calculated using Kaplan-Meier curves and compared using the log rank test. A multivariate model evaluated characteristics associated with the receipt of second-line therapy. RESULTS: A total of 718 patients were diagnosed with Stage IV NSCLC and received at least one cycle of pembrolizumab. The median duration of treatment was 4.4 months, and the follow-up duration was 16.0 months. There were 567 (79%) patients who had disease progression, of whom 21% received second-line systemic therapy. Within the subset of patients with disease progression, the median duration of treatment was 3.0 months. It would be found that patients who received second-line therapy had better baseline ECOG performance status, were younger at diagnosis, and had a longer duration of pembrolizumab. Within the full population, the OS from the treatment initiation date was 14.0 months. OS was 5.6 months in patients who did not receive additional therapy after progression and 22.2 months in patients who received subsequent therapy. Baseline ECOG performance status was associated with improved OS in multivariate analysis. CONCLUSION: Based on this real-world Canadian population, 21% of patients received second-line systemic therapy, despite second-line therapy being associated with prolonged survival. In this real-world population, we found that 60% fewer patients received second-line systemic therapy when compared to KEYNOTE-024. Although differences always exist when comparing a clinical and non-clinical trial population, our findings suggest undertreating stage IV NSCLC patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Antígeno B7-H1/metabolismo , Canadá , Progressão da DoençaRESUMO
Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42-0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34-0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44-1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Prospectivos , Neoplasias Pulmonares/tratamento farmacológico , Colúmbia BritânicaRESUMO
The evolution of diagnosis and treatment of advanced nonsmall-cell lung cancer (NSCLC) has led to increasing the use of targeted therapy and immune checkpoint inhibitors. The study goal was to assess the effect of molecular testing and the introduction of new therapies on overall survival (OS). All patients with stage IV NSCLC referred to BC Cancer were included in the study. Four 1-year time cohorts were created based on molecular testing implementation and funded drug availability: C1 baseline (2009), C2 EGFR TKI access (2011), C3 ALK inhibitor access (2015), C4 immunotherapy availability (2017). Baseline demographics, disease characteristics, and systemic therapy details were collected retrospectively. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. There were 3421 patients identified with stage IV NSCLC and 1319 (39%) received systemic therapy. In the four 1-year time cohorts C1/C2/C3/C4: driver mutation-targeted treatment increased 1/17/27/34% (of total systemic therapy), as did treatment with any line immunotherapy <1/1/9/38%. Median OS with best supportive care (BSC) was 3.4/3.1/3.2/2.9 m (p = 0.16) and with systemic treatment 9.9/10.9/13.9/15.0 m (p < 0.001). Median OS by treatment exposure was BSC 3.1 m, chemotherapy only 7.3 m, targeted therapy 17.5 m, and immunotherapy 20.7 m. In our real-world study, following the introduction of targeted therapy and immune checkpoint inhibitors, there was a significant improvement in OS in each successive time cohort concordant with advancements in therapeutic options.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Crizotinibe/uso terapêutico , Análise Mutacional de DNA , Feminino , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: A fixed dose of 200 mg of pembrolizumab every 3 weeks (Q3W) is the standard of care for patients with stage IV non-small cell lung cancer (NSCLC) and PDL1 ≥50%. In April 2020, based on pharmacokinetic modeling without formal comparative studies, the FDA approved 400 mg every 6 weeks (Q6W). Pharmacokinetic studies also suggested comparable target engagement with weight-based and flat dosing for the respective schedules. The objective of this study was to determine if overall survival (OS) differs based on the Q3W vs. Q6W dosing schedule of pembrolizumab. METHODS: BC Cancer patients with stage IV NSCLC and PDL1 ≥50% treated with pembrolizumab were retrospectively reviewed. Patients were treated with weight-based dosing, per institution standard, of pembrolizumab 2 mg/kg Q3W or 4 mg/kg Q6W. Patient demographics, treatment and outcome were recorded. Patients were assigned to Q3W or Q6W according to the schedule that was used for the majority of treatment (greater than 50%). RESULTS: 718 patients with NSCLC and PDL1 ≥50% received first-line pembrolizumab between 2017 and2021, Q3W/Q6W dosing 677/41 patients. Baseline characteristics with respect to age, sex, smoking status, histology and performance status (PS) were similar between groups. In the multivariate model, including age, sex, PS and dosing schedule, the hazard ratio for death (HR) for OS Q3W vs. Q6W was 0.759 (p = 0.230). A 2:1 case-matched analysis for OS was performed, controlling for sex, age ± 5 years, PS and duration on pembrolizumab ± 2 months for Q3W vs. Q6W (n = 113) with a HR 0.834 (p = 0.500). CONCLUSIONS: There was no OS difference demonstrated with pembrolizumab dosing Q3W compared to Q6W in a multivariate analysis that included age, sex and PS. A case-matched analysis that controlled for these variables and for duration of treatment confirmed these findings. This study supports the use of Q6W pembrolizumab dosing, allowing for less frequent interactions with the medical system.
Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/administração & dosagemRESUMO
Introduction: Durvalumab 10 mg/kg every 2 weeks for 1 year after chemoradiation has improved overall survival (OS) in unresectable stage III NSCLC. Subsequently, a 20 mg/kg 4-weekly regimen was approved. The study goal was to compare the efficacy and toxicity of the two regimens. Methods: All patients with NSCLC treated with curative-intent chemoradiation followed by durvalumab from March 1, 2018 to December 31, 2020 at BC Cancer, British Columbia, Canada were included in this retrospective review. Durvalumab dosing schedule, toxicity, progression, and OS were collected. Comparisons between treatment groups were made using chi-square and independent t tests. Kaplan-Meier curves and log-rank test were used to analyze OS. Results: A total of 152 patients were included in the 2-weekly group and 53 patients in the 4-weekly group. The median follow-up was 19.7 months and 12.0 months, respectively. The median OS was not reached, but 12-month survival rates were 88.4% versus 85.2% (p = 0.55). Toxicity profiles were similar in terms of sites and severity. Conclusions: There was no significant difference in efficacy or toxicity between the 2-weekly and 4-weekly durvalumab in this cohort of patients with advanced NSCLC previously treated with curative-intent chemoradiation.
RESUMO
Background: Liquid biopsy (LB) can detect actionable genomic alterations in plasma circulating tumor circulating tumor DNA beyond tissue testing (TT) alone in advanced non-small cell lung cancer (NSCLC) patients. We estimated the cost-effectiveness of adding LB to TT in the Canadian healthcare system. Methods: A cost-effectiveness analysis was conducted using a decision analytic Markov model from the Canadian public payer (Ontario) perspective and a 2-year time horizon in patients with treatment-naïve stage IV non-squamous NSCLC and ⩽10 pack-year smoking history. LB was performed using the comprehensive genomic profiling Guardant360™ assay. Standard of care TT for each participating institution was performed. Costs and outcomes of molecular testing by LB + TT were compared to TT alone. Transition probabilities were calculated from the VALUE trial (NCT03576937). Sensitivity analyses were undertaken to assess uncertainty in the model. Results: Use of LB + TT identified actionable alterations in more patients, 68.5 versus 52.7% with TT alone. Use of the LB + TT strategy resulted in an incremental cost savings of $3065 CAD per patient (95% CI, 2195-3945) and a gain in quality-adjusted life-years of 0.02 (95% CI, 0.01-0.02) versus TT alone. More patients received chemo-immunotherapy based on TT with higher overall costs, whereas more patients received targeted therapy based on LB + TT with net cost savings. Major drivers of cost-effectiveness were drug acquisition costs and prevalence of actionable alterations. Conclusion: The addition of LB to TT as initial molecular testing of clinically selected patients with advanced NSCLC did not increase system costs and led to more patients receiving appropriate targeted therapy.
RESUMO
OBJECTIVES: Little is known about how psychosocial factors and distress affect older patients with cancer and their survival. The study goals were to: 1) observe the prevalence of anxiety (ANX) and depression (DEP) symptoms at diagnosis in patients aged ≥65â¯years, 2) observe the association between social isolation (isolation) and distress, and 3) evaluate the impact on overall survival (OS). MATERIALS AND METHODS: A retrospective cohort study was completed for all patients ≥65â¯years (Nâ¯=â¯25,382) referred to the provincial cancer care program in British Columbia, Canada from 2011 to 2016. Patients who completed the Psychosocial Screen for Cancer within 6â¯months of diagnosis were included. Baseline and disease characteristics were collected retrospectively. RESULTS: Subclinical/clinical levels of ANX and DEP were found in 32% and 23%, respectively. Thirty-six percent of patients reported at least one indicator for isolation. Factors associated with distress at presentation included female, age 65-69, lung cancer, metastatic disease, and presence of any risk indicator for isolation (p-values <0.001). Patients with any risk indicator for isolation had higher rates of subclinical/clinical levels of ANX and DEP. On multivariate analysis including age, sex and stage, hazard ratio (HR) for death was increased with ANX (1.30), DEP (1.51) and isolation (1.12) (pâ¯<â¯0.001). CONCLUSIONS: Older adults with cancer with symptoms of distress are more likely to be female, aged 65-69, socially isolated, have metastatic disease or have lung cancer. ANX, DEP, and isolation are independent negative prognostic variables for OS. This vulnerable population should receive psychological support to improve outcomes.
Assuntos
Neoplasias Pulmonares , Angústia Psicológica , Idoso , Ansiedade/epidemiologia , Canadá , Depressão/epidemiologia , Feminino , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos , Estresse Psicológico/epidemiologiaRESUMO
PURPOSE: Regulatory agencies such as the US Food and Drug Administration and health technology assessment bodies are increasingly using real-world evidence (RWE). The ability of healthcare systems to reliably generate response rate and progression-free survival from real-world data is unknown. We examined the capacity of a single-payer system to provide RWE by evaluating the frequency of computed tomography (CT) imaging during standard first-line metastatic systemic treatment of breast, colorectal, and lung cancer. METHODS: A 1-year cohort of patients with metastatic-at-diagnosis breast, colorectal, and lung cancer treated with first-line systemic therapy (excluding hormone therapy) referred to BC Cancer in 2016 was retrospectively reviewed for first-line treatment and CT imaging. Duration of first-line treatment was calculated from the first to the last dose of therapy. CT imaging was counted from the start of therapy to 8 weeks after the last therapy dose. RESULTS: A cohort of 664 patients was identified from the BC Cancer Registry. Distribution of metastatic disease at diagnosis was breast (n = 82), colorectal (n = 214), and lung (n = 368) cancer. For breast, colorectal, and lung cancer, there was a baseline CT within 4 weeks of treatment initiation in 59%, 51%, and 48% of patients, with median duration of first-line treatment of 14.6, 25.3, and 11.9 weeks and median CT imaging interval of 9.1, 9.0, and 6.1 weeks. CONCLUSION: In our publicly funded healthcare system, availability of baseline CT imaging was 48% to 59% and the frequency of assessment ranged from 6.1 to 9.1 weeks, subject to patterns of practice and resource availability. Our system was not capable of providing RWE for image-based end points. Alternative end points should be considered to capitalize on the wealth of real-world data.
Assuntos
Neoplasias Pulmonares , Atenção à Saúde , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The benefit of external beam radiation therapy (EBRT) in locally advanced, well- differentiated thyroid cancer (WDTC) is uncertain. The purpose of this study is to evaluate locoregional recurrence (LRR), progression-free survival, and cause-specific survival (CSS) of patients with pT4 well-differentiated thyroid carcinoma. METHODS AND MATERIALS: A population-based retrospective review was conducted of consecutive patients with pT4 WDTC (per the American Joint Committee on Cancer, 8th edition, criteria) treated provincially between 1985 and 2013. The primary endpoints were cumulative incidence of LRR and CSS. To account for the competing risks of death from other causes, a Fine-Gray's test was used. A Cox-proportional hazards model was used to analyze overall survival (OS). Multivariate models and propensity matching were used to account for the effects of covariates. RESULTS: A total of 405 patients were identified with a median follow-up time of 14.3 years for a total of 4209 person-years of follow up. The median age at the time of diagnosis was 53 years (range, 20-87). There were 211 patients (52%) who received EBRT. EBRT was associated with age ≥55 years (56% vs 35%; P < .001), airway involvement (42% vs 8%; P < .001), and R1/2 resection (81% vs 51%; P < .001). The 10-year outcomes for the non-EBRT and EBRT groups were 21.6% versus 11.4%, respectively, for LRR, 84.1% versus 93.1%, respectively, for CSS, and 85.7% versus 67.5%, respectively, for OS. On multivariate analysis, EBRT was associated with a lower rate of LRR (hazard ratio [HR]: 0.334; P < .001), but not associated with CSS (HR: 1.56; P = .142) nor OS (HR: 1.216; P = .335). After propensity score matching, the EBRT cohort had lower rates of LRR relative to the non-EBRT cohort (HR: 0.261; P = .0003), but there were no differences in CSS or OS. CONCLUSIONS: In this large, population-based analysis of patients with pT4 WDTC, EBRT was associated with lower rates of LRR, but no difference in CSS or OS.
Assuntos
Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pontuação de Propensão , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologiaRESUMO
INTRODUCTION: Management of recurrent differentiated thyroid cancer (DTC) may include surgery, radioactive iodine (RAI), and external beam radiotherapy (EBRT). Systemic therapy may also be offered for RAI-refractory DTC. The study objective was to review patterns of practice in British Columbia (BC) for treatment of recurrent DTC, assess rates of RAI-refractory disease, and evaluate outcomes. METHODS: BC Cancer provides cancer care to a population of 4.6 million. A retrospective review of all patients with DTC stage I-IVB disease referred to BC Cancer from 2009 to 2013 was conducted. Patient and DTC characteristics, locoregional and distant recurrence, surgical management, RAI, EBRT, and systemic therapy details were retrospectively collected. Relapse-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. RESULTS/DISCUSSION: Some 1062 DTC patients were identified. Median follow-up was 4.1 years. Baseline characteristics: female 74%, median age 50, papillary/follicular/Hurthle cell 92%/6%/2%. Stage at presentation: I 60%, II 8%, III 22%, IVA/IVB 10%. Locoregional and/or distant recurrence occurred in 136 patients (13%). Locoregional recurrence (n=118) was treated with surgery +/- RAI or EBRT 48%, RAI +/- EBRT 40%, EBRT alone 1%, 11% were observed without treatment. Some 27 patients had a second cancer recurrence. Some 37 patients (3%) developed distant metastatic disease and common sites of distant metastases were: lung 76%, bone 30%, and liver 8%. Some 27 cases (2%) were deemed RAI-refractory. Some six patients (0.6%) received systemic therapy with a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). Five-year RFS was calculated to be 82%, OS 95%, and DSS 98% for the study population. CONCLUSIONS: In our population-based study cohort, 87% of patients were rendered disease-free by primary disease management. Multi-modality treatment of locoregional recurrence facilitated disease-free status in the majority of patients (67%). RAI-refractory disease developed in 2% of patients and despite a significant number of metastatic recurrences, only a small number of patients received systemic therapy.
RESUMO
INTRODUCTION: Information on the psychosocial distress and needs of sarcoma patients at diagnosis is sparse. The Canadian Problem Checklist (CPC) and Psychosocial Screen for Cancer-Revised (PSSCAN-R) are validated tools to identify cancer patients' distress and are administered to all new patients referred to BC Cancer prior to their consultation. We used the CPC and PSSCAN-R to understand sarcoma patients' needs at the initial oncology consultation in British Columbia, Canada. MATERIALS AND METHODS: All sarcoma patients who completed the CPC and PSSCAN-R within 6 months of diagnosis between 2011 and 2016 were included. The retrospective chart review identified baseline demographics: age, performance status, disease location, resectability, and histology. Analysis was conducted using descriptive statistics, chi-squared test, Fisher's exact test, and Kaplan-Meier method. RESULTS: 413 sarcoma patients were identified. The majority of patients were over the age of 40 (83.3%) with ECOG performance status 0-1 (82.6%) and lower extremity tumors (55.4%). The most common diagnoses were liposarcoma 21.3%, undifferentiated pleomorphic sarcoma 12.1%, and myxofibrosarcoma 11.1%. At the initial consultation, 42.6% of patients were deemed resectable, 8.5% unresectable/metastatic, and 48.9% required further staging investigations. The top three patient-reported distress symptoms were feeling tense and unable to relax (50%), feeling nervous and shaky (48%), and experiencing repetitive and scary thoughts (42%). 38% of patients had subclinical/clinical anxiety symptoms, and 21% of patients had subclinical/clinical depression symptoms. 5% of patients expressed suicidal ideation. The top three concerns/needs were understanding of illness/treatment (45.5%), fear/worries (45.3%), and worry about family (23%). No differences in overall survival were identified for patients displaying symptoms of depression or anxiety versus no symptoms. DISCUSSION: Up to 45% of sarcoma patients experience some form of psychological distress at disease presentation. Patients desire information about their diagnosis and treatment. Tailored interventions to individual psychological comorbidity and improved patient education resources would be beneficial.
RESUMO
BACKGROUND: Methadone has been shown to be effective for cancer pain. Most published switching methods are complete in less than three days, requiring very close supervision, usually in an inpatient setting. This need for hospitalization is a barrier to access. We present a large retrospective study of slow outpatient methadone starts and describe our starting method. METHODS: Charts were reviewed of patients referred to the Pain and Symptom Management/Palliative Care clinics at the six BC Cancer Agency's regional centers that underwent initiation of methadone for analgesia over a 14-year period. Patient characteristics, method of start, and outcomes of methadone treatment were recorded. RESULTS: Of the 652 identified patients, we were able to determine outcomes of methadone initiation in 564 (86.5%). Among these, 422 (74.8%) were deemed successful initiations, as determined by whether or not the patient remained on methadone at follow-up with subjective improvement in pain control, on a stable dose of methadone. Of the unsuccessful trials, 97/142 were primarily due to adverse events, 16 of which were considered serious enough to require hospitalization, including two due to sudden cessation of opioid therapy leading to withdrawal. Some of the included adverse events were not necessarily causal from the initiation of methadone, for example, development of bowel obstruction or delirium. Only one death occurred from a deliberate overdose of multiple medications, including methadone. CONCLUSIONS: Initiation of methadone for analgesia in ambulatory cancer patients can be done safely in an outpatient setting using a start-low go-slow method, and can be expected to be helpful in â¼75% of patients. Discontinuation is more likely to be for side effects than for inadequate analgesia. Access to methadone therapy can safely be widened by slow initiation, avoiding more dangerous rapid switching protocols and reducing the need for hospitalization.