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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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Inmunoterapia/métodos , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
BACKGROUND: The integration of immune checkpoint inhibitors (ICI) for the treatment of melanoma has resulted in remarkable and durable responses. Given the potential role of immunosenescence, age may contribute to differential ICI efficacy and toxicity. While older patients have been studied in detail, outcomes from ICI in young patients (≤40 years) are not well characterised. METHODS: We performed a multi-institutional, retrospective study of patients with advanced melanoma treated with anti-PD-1 monotherapy or ICI combination (ipilimumab and anti-PD-1). Response rates, survival, and toxicities were examined based on age comparing those under 40 years of age with older patients (age 41-70 and ≥ 71 years). RESULTS: A total of 676 patients were included: 190 patients (28%) aged ≤40 years, 313 (46%) between ages 41-70, and 173 patients (26%) aged ≥71. Patients ≤40 years had higher response rates (53% vs 38%, p = 0.035) and improved progression-free survival (median 13.7 vs 4.0 months, p = 0.032) with combination ICI compared to monotherapy. Progression-free survival was similar among groups while overall survival was inferior in patients >70 years, who had low response rates to combination therapy (28%). ICIs had a similar incidence of severe toxicities, though hepatotoxicity was particularly common in younger patients vs. patients >40 with monotherapy (9% vs. 2%, p = 0.007) or combination ICI (37% vs. 10%, p < 0.001). CONCLUSIONS: ICIs had comparable efficacy between younger and older patients, although outcomes were superior with combination ICI compared to monotherapy in patients aged ≤40 years. Toxicity incidence was similar across age groups, though organs affected were substantially different.
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Antineoplásicos Inmunológicos , Melanoma , Neoplasias Primarias Secundarias , Humanos , Adulto Joven , Adulto , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Antineoplásicos Inmunológicos/efectos adversos , Melanoma/patología , Ipilimumab/uso terapéutico , Neoplasias Primarias Secundarias/inducido químicamenteRESUMEN
PURPOSE: Limited English-proficient (LEP) patients with non-small-cell lung cancer (NSCLC) may receive less palliative care services and more likely to receive aggressive end-of-life (EoL) care. Goals of this retrospective cohort study are to compare access to community palliative home care (CPHC), do not resuscitate (DNR) form completion, place of death, and health resource utilization at EoL between English-proficient (EP) and LEP patients with NSCLC in Vancouver, Canada. METHODS: All patients with advanced NSCLC referred in 2016 and received medical care were included. Patients were classified as LEP if seen with a medical interpreter. Descriptive statistics and univariate and multivariate analyses were used to compare the outcomes between the two groups. RESULTS: One hundred eighty-six patients were referred, 66% EP. Rates of CPHC referral and DNR form completion were the same for both groups (84% and 92%, P = 1.00). LEP patients received earlier access to CPHC (15 v 10 weeks before death, P = .039). Rates of ER visits within 6 months and 30 days of death were 0.89 for EP patients and 0.7 for LEP patients, P = .374, and 0.1 for EP patients and 0.13 for LEP patients, P = .244. Hospitalization rates within 6 months and 30 days of death were 1.4 for EP patients and 1.59 for LEP patients, P = .640, and 0.67 for EP patients and 0.81 for LEP patients, P = .091. EP patients were more likely to have a home death (26% v 14%), whereas LEP patients died in acute care (23% v 14%) or a tertiary palliative care unit (24% v 19%). This was not statistically significant (P = .335). LEP patients had better median overall survival (8.5 v 5.4 months, P < .001), but when controlled by age, mutation, and EP status, only receipt of palliative-intent systemic therapy was statistically significant. CONCLUSION: EP and LEP patients with NSCLC have similar referral rates to CPHC, DNR form completion, and EoL health resource utilization. The measured EoL variables did not demonstrate significant disparities between EP and LEP patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/terapia , Barreras de Comunicación , Muerte , Recursos en Salud , Humanos , Neoplasias Pulmonares/terapia , Estudios RetrospectivosRESUMEN
INTRODUCTION: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. METHODS: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. RESULTS: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis. CONCLUSIONS: From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.
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COVID-19 , Neoplasias Pulmonares , Neoplasias Torácicas , Proteína C-Reactiva , Prueba de COVID-19 , Humanos , Neoplasias Pulmonares/diagnóstico , Pronóstico , Sistema de Registros , Estudios Retrospectivos , SARS-CoV-2 , Neoplasias Torácicas/diagnósticoRESUMEN
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.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Molecular Dirigida , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Crizotinib/uso terapéutico , Análisis Mutacional de ADN , Femenino , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Despite successes in the development of innovative anticancer therapies, the fiscal and capacity restraints of the Canadian public healthcare system result in challenges with drug access. A meaningful proportion of systemic therapies ultimately do not receive public funding despite supporting clinical evidence. In this study, we assessed Canadian medical oncologists' current attitudes toward discussing publicly unfunded cancer treatments with patients and predictors of different practices. METHODS: A web-based survey consisting of multiple choice and case-based scenarios was distributed to medical oncologists identified through the Royal College of Physicians and Surgeons of Canada directory. RESULTS: A total of 116 responses were received. Almost all respondents reported discussing publicly unfunded treatments, including those who did so for Health Canada (HC) approved treatments (50%) and those who discussed off-label treatments (i.e., not HC approved) as guided by national guidelines (48%). Respondents in practice for over 15 years versus less than 5 years (OR 0.14, 95% CI 0.04-0.50, p = 0.002) and those who worked in a community practice versus comprehensive cancer center (OR 0.17, 95% CI 0.03-0.91, p = 0.04) were significantly less likely to discuss off-label treatment options with their patients. Almost half of respondents (47%) indicated that their institution did not permit the administration of unfunded treatments. CONCLUSIONS: There is variability in medical oncologists' practices when it comes to discussing unfunded therapies. Given the limitations within Canada's publicly funded healthcare system, physicians are faced with the challenge of navigating an increasingly complex balance between patient care and available resources. Engagement of relevant stakeholders and policy makers is crucial in the continued evaluation of Canada's drug funding process.
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Antineoplásicos , Actitud del Personal de Salud , Neoplasias , Oncólogos , Antineoplásicos/economía , Antineoplásicos/uso terapéutico , Actitud , Canadá , Encuestas de Atención de la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Internet , Neoplasias/tratamiento farmacológico , Sistema de Pago Simple/economía , Terapias en Investigación/economíaRESUMEN
The addition of immune checkpoint inhibitors (ICIs) to the therapeutic armamentarium for solid malignancies has resulted in unprecedented improvements in patient outcomes in many cancers. The landscape of ICIs continues to evolve with novel approaches such as dual immune checkpoint blockade and combination therapies with other anticancer agents including cytotoxic chemotherapies and/or antiangiogenics. However, there is significant heterogeneity seen in antitumor responses, with certain patients deriving durable benefit, others experiencing initial benefit followed by acquired resistance necessitating change in therapy, and still others who are primarily refractory to ICIs. While generally better tolerated than traditional cytotoxic chemotherapy, ICIs are associated with unique toxicities, termed immune-related adverse events (irAEs), which can be severe or even lethal. As a disease of aging, older individuals make up a large proportion of patients diagnosed with cancer, yet this population is often underrepresented in clinical trials. Because ICIs indirectly target malignant cells through T cell activation, it has been hypothesized that age-related changes to the immune system may impact the efficacy and toxicity of these drugs. In this review, we discuss differences in the clinical efficacy and toxicity of ICIs in patients at the extremes of age.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias/tratamiento farmacológico , Factores de Edad , Anciano , Resistencia a Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/mortalidad , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Pancreatic adenocarcinoma carries a high risk of recurrence even after surgery and adjuvant chemotherapy. Current guidelines do not endorse routine surveillance imaging due to lack of evidence supporting a survival benefit. With current first-line palliative chemotherapy options, it is unclear whether surveillance allows for early detection of asymptomatic disease and therefore an improved opportunity to offer chemotherapy to fit patients. We sought to describe patterns of surveillance of resected pancreatic cancer at British Columbia (BC) Cancer and determine whether utilization of computerized tomography (CT) scans affected likelihood of receiving palliative chemotherapy at the time of recurrence. METHODS: A retrospective review was completed to identify patients treated at BC Cancer centres between 2010-2016 who had undergone curative intent resection and received at least one cycle of adjuvant chemotherapy. Information was collected on baseline characteristics, imaging scans done between adjuvant chemotherapy and recurrence, and receipt of palliative chemotherapy. Two cohorts were defined based on number of scans done between completion of adjuvant chemotherapy and recurrence: those with only 1 scan were defined as "symptomatic" recurrences and patients who had undergone more than 1 scan were considered "surveillance" recurrences. RESULTS: In total, 142 patients were included of which 115 (81%) patients developed recurrence. There were 22 patients (19%) in the "symptomatic" cohort and 93 patients (81%) in the "surveillance" cohort. Median time to recurrence 274 days (9.1 months) in the symptomatic cohort compared to 471 days (15.7 months) in the surveillance group. Patients who underwent surveillance scans were more likely to receive palliative chemotherapy at the time of recurrence, though statistical significance was not reached: 51% in surveillance group versus 27% in symptomatic group [odds ratio (OR) 2.11, 95% confidence interval (CI): 0.75-6.58, P=0.17]. CONCLUSIONS: Despite the absence of surveillance recommendations, the majority of patients underwent surveillance imaging. We demonstrated a non-significant increase in the likelihood of receiving palliative chemotherapy among patients who underwent surveillance scans. With more efficacious palliative chemotherapy options available, studies to determine whether receipt of chemotherapy in asymptomatic recurrences translates into improved survival and/or quality of life are warranted.
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Introduction: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) represent inhibitory immune checkpoints. Combination immune checkpoint inhibitor (ICI) therapy with anti-CTLA-4 plus anti-PD-1 antibodies in preclinical models demonstrated greater anti-tumor effect than therapy with either antibody alone. Based upon this anti-tumor effect, anti-CTLA-4 plus anti-PD-1 antibodies have since been tested in a patients, across tumor types, with advanced malignancies.Areas covered: Herein we describe the biologic rationale for combining anti-CTLA-4 plus anti-PD-1 antibodies, the early studies which established different treatment schedules of the ICI combination in melanoma, the definitive studies which established the role for anti-CTLA-4 plus anti-PD-1 antibodies in patients with advanced malignancies and the toxicity profiles of these agents. We also discuss several experimental disease settings where combined CTLA-4 and PD-1 blockade is being explored.Expert opinion: We anticipate that combination therapy with anti-CTLA-4 plus anti-PD-1 antibodies will become a treatment standard for patients with cancers both responsive and unresponsive to single agent ICI therapy. Given the toxicity profile, we expect that most patients will be treated with lower doses of anti-CTLA-4 and full doses of anti-PD-1 antibodies, however, there may be instances in which a higher dose of anti-CTLA-4 is preferred.
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Melanoma , Receptor de Muerte Celular Programada 1 , Antígeno CTLA-4 , Terapia Combinada , Humanos , InmunoterapiaRESUMEN
OBJECTIVES: MET exon 14 skipping is a potentially targetable molecular alteration. The goals of this study were to identify patients treated in British Columbia with MET exon 14 skipping to understand prevalence, biology and response to treatment, and to identify molecular signatures that may predict for response or resistance to targeted MET therapy in the setting of advanced disease. MATERIALS AND METHODS: A retrospective review was completed of patients found to have MET exon 14 skipping alterations between January 2016-September 2019. Information was collected on baseline characteristics, response to systemic treatments, and outcomes. RESULTS: Out of 1934 advanced, non-squamous and never-smoking squamous NSCLC patients tested, 41 patients were found to have MET exon 14 skipping (2.1 %). MET alteration types: 2% CBL binding-domain mutations, 34 % poly-pyrimidine tract deletions, 63 % splice donor mutations or deletions. The most common co-mutation was TP53 (22 %). Thirty-three patients received systemic therapy. Physician-assessed disease control was 68 % among 19 evaluable patients treated with crizotinib, 80 % among 10 evaluable patients treated with platinum-based chemotherapy, and 70 % among 10 evaluable patients treated with immunotherapy. Median time to treatment discontinuation was 3.0, 2.8, and 2.4 months, respectively. Median overall survival for metastatic patients treated with any systemic therapy was 15.4 months. In this small cohort, there were no clear correlations between molecular aberrations and response, time to treatment discontinuation, or survival for crizotinib, chemotherapy, and immunotherapy. CONCLUSION: The prevalence of MET exon 14 skipping in a North American population was 2.1 %. Unlike other targetable mutations, patients were older and more commonly current or former smokers. Patients with MET exon 14 skipping alteration demonstrate disease control with crizotinib, platinum-based chemotherapy and immunotherapy. Co-mutations with TP53 were commonly noted, but correlation between co-mutations and efficacy of therapy were not identified in this cohort.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Exones , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-met/genética , Estudios RetrospectivosRESUMEN
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.
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Neoplasias de la Mama/terapia , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Colorrectales/terapia , Neoplasias Pulmonares/terapia , Neoplasias de la Próstata/terapia , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de TiempoRESUMEN
After being stagnant for decades, there has finally been a paradigm shift in the treatment of small-cell lung cancer (SCLC) with the emergence and application of immune checkpoint inhibitors (ICIs). Multiple trials of first-line ICI-chemotherapy combinations have demonstrated survival benefit compared to chemotherapy alone in patients with extensive-stage SCLC, establishing this as the new standard of care. ICIs are now being applied in the potentially curative limited-stage setting, actively being investigated as concurrent treatment with chemoradiation and as adjuvant treatment following completion of chemoradiation. This review highlights the evidence behind the practice-changing addition of ICIs in the first-line setting of extensive-stage SCLC, the potentially practice-changing immunotherapy trials that are currently underway in the limited-stage setting, and alternate immunotherapeutic strategies being studied in the treatment of SCLC.
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Lung cancer is a leading cause of cancer-related mortality despite continued advances in diagnostic and therapeutic strategies. Although the development of immune checkpoint inhibitors has revolutionized the treatment landscape for advanced non-small cell lung cancer, many patients either have primary resistance to these agents or eventually develop secondary resistance necessitating a change to an alternate therapy. Understanding novel patterns of response to immunotherapy is crucial in determining appropriate selection and sequencing of treatment. Chemotherapy remains the standard of care in immunotherapy-refractory disease, but multiple trials are ongoing to explore the role of combination radioimmunotherapy and rechallenging with immunotherapy either alone or in combination with other antineoplastic agents.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
To understand the real impact of COVID-19 on cancer patients, an entirely new data collection effort was initiated within the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT). TERAVOLT reported high mortality related to COVID-19 infection in thoracic cancer patients and identified several negative prognostic factors. In this commentary, we discuss the importance and limits of patient registries to support decision-making in thoracic cancer during the SARS-CoV-2 pandemic.
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Betacoronavirus/aislamiento & purificación , Toma de Decisiones Clínicas , Infecciones por Coronavirus/complicaciones , Carga Global de Enfermedades/normas , Neumonía Viral/complicaciones , Guías de Práctica Clínica como Asunto/normas , Neoplasias Torácicas/terapia , COVID-19 , Infecciones por Coronavirus/virología , Humanos , Cooperación Internacional , Pandemias , Neumonía Viral/virología , Sistema de Registros , SARS-CoV-2 , Neoplasias Torácicas/epidemiología , Neoplasias Torácicas/virologíaRESUMEN
AIMS: Accurate assessment of programmed death-ligand 1 (PD-L1) levels in non-small cell lung carcinoma (NSCLC) samples is complicated by intratumoral heterogeneity. We aimed to: (i) establish whether intratumoral PD-L1 variation is associated with differences in local histotype; (ii) identify histotypes associated with a tendency for there to be higher or lower PD-L1 scores; and (iii) estimate the frequency of clinically significant discordance in PD-L1 levels between intratumoral histotype areas. METHODS AND RESULTS: We reviewed 166 NSCLC resection specimens clinically tested for PD-L1 with the 22C3 pharmDx assay. Multiple histotypes were present in 55% (68/123) of non-mucinous adenocarcinoma samples. Solid histotypes had significantly higher PD-L1 levels than other histotypes, both when samples were grouped by predominant histotype, and when histotype areas within a tumour were compared (P < 0.02). Lepidic areas had significantly lower PD-L1 levels than other histotype areas within the same tumour (P < 0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (PD-L1 tumour proportion score of 1% or 50%) was present in 32% (22/68) of non-mucinous adenocarcinoma specimens with multiple histotype areas. The lepidic histotype was most frequently involved in discordance. CONCLUSIONS: Intratumoral heterogeneity in PD-L1 is associated with variation in histotype. Over-representation of solid areas may increase the PD-L1 score assigned to a tumour, whereas over-representation of lepidic areas may decrease the PD-L1 score. Evaluation of how histotype representation impacts on the predictive value of PD-L1 testing is warranted.
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Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib. Another oral kinase inhibitor, regorafenib, is not considered standard of care treatment for differentiated thyroid cancer. The chemical structures of regorafenib and sorafenib differ by a single fluorine atom. Given the significant improvement in progression-free survival (PFS) of sorafenib compared to placebo demonstrated in the phase 3 DECISION trial, we report on a patient with iodine-refractory follicular thyroid cancer treated with regorafenib as part of a phase 1 clinical trial. A 75 year old woman was diagnosed with follicular thyroid carcinoma in 2006 and initiated on treatment with regorafenib in 2011. She has completed 76 cycles with stable disease and pulmonary metastases 34% smaller than baseline.
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The number of operative procedures involving the creation of an intestinal stoma is likely to increase as the population ages. Understanding the role of age on postoperative outcomes such as quality of life (QoL) and self-efficacy is critical to developing appropriate supportive strategies. A descriptive survey study was conducted among 18 patients (11 men seven women, age range 47 to 90 years) who had an intestinal ostomy created during a 3-year period at the University of Alberta Hospital in Edmonton, Alberta, Canada. The Stoma Quality of Life Survey and a self-efficacy survey examining self-care, activities of daily living, and instrumental activities of daily living were administered. Patient records were obtained through a retrospective chart review; of the 57 patients identified, 18 were still alive, had not undergone stoma reversal, were cognitively competent, and agreed to participate. Seven patients were <65 years old and 11 were ≥65 years old. Of those, four patients had their stoma since 2009, four patients since 2010, and 10 patients since 2011. Although older patients had more comorbidities and higher mortality following the surgery (46.1% for patients >65 versus 26.1%, for patients <65 years old), no statistically significant difference was found between the two groups for stoma-associated QoL and self-efficacy scores. In patients who had stoma surgery in 2011, older patients on average had higher QoL scores (65.21 versus 61.87, maximum score 100, P = 0.56), but lower self-efficacy scores (32.50 versus 35.25, maximum score 40, P = 0.50). These findings are similar to previously reported study results. However, the small study sample size limits analysis of the variables that may affect QoL in stoma patients. This study supports the need for additional prospective studies to help clinicians develop effective support strategies.