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IMPORTANCE: Collecting patient-reported outcomes (PROs) in routine cancer care improves patient-clinician communication, decision making, and overall patient satisfaction. Recommendations exist regarding standardized ways to collect, store, and interpret PRO data. However, evidence on incorporating PROs into cancer process of care, especially the type of HIs that are warranted after observing a concerning PRO and the effectiveness of these HIs are lacking. OBJECTIVE: This study summarizes HIs triggered after PRO completion and their effectiveness in improving patient outcomes for adults being treated for cancer types that are resource intensive and associated with high symptom burden [i.e., gastrointestinal (GI), lung, and head and neck cancer (HNC)]. Secondary outcomes included factors associated with poor implementation of PROs. EVIDENCE REVIEW: A literature search of peer-reviewed publications on MEDLINE, CINAHL Plus, APA PsycInfo, Scopus, and Cochrane was conducted following PRISMA guidelines from 1 January 2012, to 31 July 2022. Trial and real-world studies describing HIs after PRO completion for adult patients being treated for GI, lung, and HNC were included. Sixteen studies involving 144,496 patients were included. The Joanna Briggs Institute critical appraisal checklist was used to assess risk of bias. FINDINGS: Of the 16 included studies, 5 included patients with HNC. Commonly used PRO measurement tools were the PRO-CTCAE and ESAS. Only three studies reported specific HIs delivered in response to concerning PROs and measured their effectiveness on patient outcomes. In all three studies, these HIs significantly improved cancer-related care. The most common HIs undertaken in response to concerning PROs were referrals to other specialists/allied healthcare professionals, medication changes, or self-management advice. Provider-related barriers to PRO measurement and delivery included the overwhelming number of alerts, the time required to address each PRO and the unclear role of healthcare providers in response to these alerts. Patient-related barriers included lower digital literacy and socioeconomic status, older age, rural living, and patients suffering from GI and HNC. CONCLUSIONS AND RELEVANCE: This review highlights that PRO-triggered HIs are heterogenous and can improve patient quality of life. Further studies are necessary to determine the types of interventions with the greatest impact on patient care and outcomes.
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Neoplasias , Qualidade de Vida , Adulto , Humanos , Neoplasias/terapia , Medidas de Resultados Relatados pelo PacienteRESUMO
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.
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Antígenos de Neoplasias/imunologia , Proteínas de Bactérias/imunologia , Sobreviventes de Câncer , Reações Cruzadas/imunologia , Neoplasias Pancreáticas/imunologia , Linfócitos T Citotóxicos/imunologia , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Antígenos de Neoplasias/genética , Proteínas de Bactérias/sangue , Proteínas de Bactérias/genética , Antígeno Ca-125/genética , Antígeno Ca-125/imunologia , Simulação por Computador , Reações Cruzadas/genética , Humanos , Imunoterapia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Prognóstico , Análise de Sobrevida , Linfócitos T Citotóxicos/citologia , Sequenciamento do ExomaRESUMO
Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response. Inhibiting CXCR4 in an experimental cancer medicine study by 1-wk continuous infusion of the small-molecule inhibitor AMD3100 (plerixafor) induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immune-mediated damage to noninfected tissues: Rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human pancreatic ductal adenocarcinoma and colorectal cancer by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells.
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Neoplasias Colorretais/metabolismo , Imunidade/imunologia , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptores CXCR4/efeitos dos fármacos , Receptores CXCR4/metabolismo , Idoso , Benzilaminas , Carcinoma Ductal Pancreático , Quimiocina CXCL12 , Neoplasias Colorretais/patologia , Ciclamos , Feminino , Compostos Heterocíclicos/antagonistas & inibidores , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Receptores CCR2/metabolismo , Receptores CXCR3/metabolismo , Receptores CXCR5/metabolismo , Receptores CXCR6/metabolismo , Receptores de Interleucina-8A/metabolismo , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/imunologia , Neoplasias PancreáticasRESUMO
BACKGROUND: Complementary medicines (CM) are frequently used by patients with cancer. Controversy exists over the effectiveness and risk that CM may add to conventional cancer therapy. The incidence of CM use among patients enrolled in phase III clinical trials is unknown. METHODS: Medication lists from 6 international phase III clinical trials were retrospectively reviewed to identify patients using CM. Patients had metastatic breast, colorectal, or lung cancers. Quality of life, adverse events, overall survival, and progression-free survival were compared between CM users and non-users. Baseline differences between groups were adjusted with propensity score matching groups. RESULTS: Seven hundred and six of 3446 patients (20.5%) used at least one CM. CM use was highest among patients with breast cancer (35.6%). CM users had more favorable baseline prognostic factors (ECOG 0-1, non-smoking status, younger age, and fewer metastases). CM use was associated with lower rates of adverse events (50% vs. 62%, P = .002) and quality of life was similar between both groups. After adjustment with propensity score matching, CM use was also associated with longer overall survival in patients with lung cancer (adjusted hazard ratio 0.80, 95%CI, 0.68-0.94, P =.0054). However, several key control variables like EGFR status were not available. CONCLUSION: One in 5 patients in phase III clinical trials report using CM. CM was not associated with worse cancer-specific outcomes. However, CM users had more favorable baseline prognostic factors, and likely other confounders that may have contributed to improved outcomes observed in the lung cohort. Physicians should monitor for CM use and potential interactions with clinical trial drugs.
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Ensaios Clínicos Fase III como Assunto , Terapias Complementares , Metástase Neoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Terapias Complementares/efeitos adversos , Terapias Complementares/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Metástase Neoplásica/terapia , Qualidade de Vida , Estudos RetrospectivosRESUMO
The PI3K/AKT/mTOR pathway activation plays a central role in glioblastoma multiforme (GBM) development and progression, and in resistance to anti-cancer therapies. Inhibition of the PI3K pathway has been shown to sensitize cultured glioma cells and tumor xenografts to the effects of temozolomide (TMZ) and radiation. Vistusertib is an oral inhibitor of mTORC1/2 complexes. The primary objective of this Canadian Cancer Trials Group phase I study was to determine the recommended phase II dose (RP2D) of vistusertib in patients with GBM receiving TMZ at first progression following primary treatment. Vistusertib was administered at a starting dose of 100 mg bid 2 days on/5 days off weekly with TMZ 150 mg/m2 daily for 5 days/28-days cycle. Dose escalation was according to a 3 + 3 design. Secondary objectives included assessment of vistusertib safety and toxicity profile, and preliminary efficacy. 15 patients were enrolled in the study (median age 66 (range 51-77), females 8). Vistusertib 125 mg BID in combination with TMZ 150 mg/m2 daily for 5 days was well tolerated. Vistusertib treatment-related adverse events were generally grade 1-2, with the most frequently reported being fatigue, gastrointestinal symptoms, and rash. Of 13 response evaluable patients, 1 patient (8%) had a partial response ongoing at 7.6 months of follow-up, and 5 patients had stable disease (38%) as best response (median duration 9.6 months, range 3.7-not yet reached). Six-month progression-free survival (PFS) rate was 26.6%. Combination of vistusertib with TMZ in GBM patients at first recurrence demonstrated a favorable safety profile at the tested dose levels.
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Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Morfolinas/administração & dosagem , Pirimidinas/administração & dosagem , Temozolomida/administração & dosagem , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/efeitos adversos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Pirimidinas/efeitos adversos , Temozolomida/efeitos adversosRESUMO
BACKGROUND: Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODS: The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTS: Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m(2) , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONS: In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice.
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Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Modelos Estatísticos , Terapia de Alvo Molecular/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/secundário , Bases de Dados Factuais , Diarreia/induzido quimicamente , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Síndrome Mão-Pé/etiologia , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Indóis/administração & dosagem , Indóis/efeitos adversos , Estimativa de Kaplan-Meier , Neoplasias Renais/sangue , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mucosite/induzido quimicamente , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Valor Preditivo dos Testes , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sorafenibe , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , SunitinibeRESUMO
BACKGROUND: Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy. METHODS: In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark. The primary endpoint was overall survival since the initiation of second-line therapy. We compared the prognostic performance of the IMDC model with the three-factor MSKCC model used for previously treated patients for overall survival since the start of second-line targeted therapy. FINDINGS: Between Jan 1, 2005, and Nov 30, 2012, we included 1021 patients treated with second-line targeted therapy. Median overall survival since the start of second-line targeted therapy was 12·5 months (95% CI 11·3-14·3). Five of six predefined factors in the IMDC model (anaemia, thrombocytosis, neutrophilia, Karnofsky performance status [KPS] <80, and <1 year from diagnosis to first-line targeted therapy) were independent predictors of poor overall survival on multivariable analysis. The concordance index using all six prognostic factors (ie, also including hypercalcaemia) was 0·70 (95% CI 0·67-0·72) with the IMDC model and was 0·66 (95% CI 0·64-0·68) with the three-factor MSKCC model. When patients were divided into three risk categories using IMDC criteria, median overall survival was 35·3 months (95% CI 28·3-47·8) in the favourable risk group (n=76), 16·6 months (14·9-17·9) in the intermediate risk group (n=529), and 5·4 months (4·7-6·8) in the poor risk group (n=261). INTERPRETATION: The IMDC prognostic model can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy. The IMDC prognostic model in the second-line targeted therapy setting has an improved prognostic performance and is applicable to a more contemporary patient cohort than that of the three-factor MSKCC model. FUNDING: DF/HCC Kidney Cancer SPORE P50 CA101942-01, Kidney Cancer Research Network of Canada, Canadian Institute for Health Research, Trust Family, Loker Pinard, Michael Brigham, and Gerald DeWulf.
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Carcinoma de Células Renais/tratamento farmacológico , Técnicas de Apoio para a Decisão , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular , Terapia de Salvação , Ásia , Canadá , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/mortalidade , Análise Multivariada , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terapia de Salvação/efeitos adversos , Terapia de Salvação/mortalidade , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. METHODS: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. RESULTS: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. CONCLUSIONS: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.
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BACKGROUND: An estimated 20% to 30% of men with advanced prostate cancer carry a mutation in DNA damage repair genes, of which half are estimated to be germline. Eligibility criteria for germline genetic testing expanded significantly for Ontario patients in May 2021 and many centers adopted a "mainstream" model, defined as oncologist-initiated genetic testing. METHODS: We conducted a retrospective chart review to report on the first-year mainstream experience of a large tertiary oncologic center, the Sunnybrook Odette Cancer Centre. All patients who underwent mainstream at the discretion of their treating physician were included. A subset underwent somatic profiling as part of clinical trial screening. Descriptive statistics were used to report baseline clinicopathologic characteristics and treatments received. RESULTS: Between May 1, 2021, and May 30, 2022, 174 patients with prostate cancer underwent mainstream germline genetic testing with a 19-gene panel. Median age was 75 (IQR 68-80), and 82% of patients were diagnosed with either de novo metastatic or high-risk localized prostate adenocarcinoma. Fourteen patients (8%; 95% CI 4%-12%) were found to have a deleterious germline mutation, including pathogenic or likely pathogenic variants in BRCA1/2, ATM, CHEK2, PMS2, RAD51C, HOXB13, and BRIP1. Forty-nine patients (28%; 95% CI 21%-35%) were found to have a variant of uncertain significance. Thirty-four patients also had next-generation sequencing (NGS) of their somatic tissue. Among this subset, 8 of 34 (23%) had an alteration in homologous recombination repair (HRR) genes. Of the 14 patients with a germline mutation, none had a prior personal history of malignancy and 6 (43%) did not have any first- or second-degree relatives with history of prostate, pancreatic, breast, or ovarian cancer. CONCLUSION: We report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.
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Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias da Próstata , Centros de Atenção Terciária , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Testes Genéticos/métodos , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Ontário , Proteína BRCA1/genética , Proteína BRCA2/genética , Predisposição Genética para Doença , Quinase do Ponto de Checagem 2/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteínas de Ligação a DNA/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas de Homeodomínio , RNA Helicases , Proteínas de Grupos de Complementação da Anemia de FanconiRESUMO
Importance: Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. Objective: To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. Design, Setting, and Participants: This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. Main Outcomes and Measures: The accuracy of algorithm cancer stages was compared with ground truth. Results: Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. Conclusion and Relevance: This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.
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BACKGROUND: Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery. METHODS: This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome. RESULTS: Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93). CONCLUSIONS: Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.
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Carcinoma de Células Escamosas , Metástase Linfática , Neoplasias Bucais , Esvaziamento Cervical , Recidiva Local de Neoplasia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Estudos Retrospectivos , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Doença , Linfonodos/patologia , Linfonodos/cirurgia , Estudos de Coortes , Prognóstico , Modelos de Riscos Proporcionais , Excisão de Linfonodo , AdultoRESUMO
Nivolumab, a PD-1 checkpoint inhibitor, was approved in Canada in 2017 for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on the phase 3 trial CHECKMATE-141. We aimed to examine the demographics and efficacy of nivolumab in a Canadian, real-world setting. A retrospective chart review was performed on patients who received nivolumab for R/M HNSCC from 2017 to 2020 at a high-volume cancer centre. Data were abstracted from 34 patients, based on physician notes and imaging reports. The median patient age at nivolumab initiation was 61, 24% were female, and 62% were current or former smokers. Prior to nivolumab, 44% of patients underwent surgery, 97% radiation, and 100% chemotherapy. Most (97%) therapies were for primary disease. Overall survival at 6 and 12 months following drug initiation was 38% and 23%, respectively. Progression-free survival at 6 and 12 months was 33% and 22%, respectively. Eighteen percent of patients experienced an immune-related adverse event, the most common of which was pneumonitis (3/8) and endocrine events (3/8). Seven out of eight of the immune adverse events were grade 1-2; 1/8 was grade 3. Nivolumab appears to have decreased survival rates in our single-centre Canadian population compared to CHECKMATE-141 and presented a manageable adverse event profile for R/M HNSCC.
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Neoplasias de Cabeça e Pescoço , Nivolumabe , Humanos , Feminino , Masculino , Nivolumabe/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Canadá , Neoplasias de Cabeça e Pescoço/tratamento farmacológicoRESUMO
INTRODUCTION: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. METHODS: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus ≥1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated therefrom. Intrapatient musculoskeletal changes were analyzed across various time points. RESULTS: TCA and PMI gradually declined over the study period (Pâ¯=â¯.002, Pâ¯=â¯.003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, Pâ¯=â¯.198). CONCLUSIONS: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients.
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Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Sarcopenia , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/patologia , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Estudos RetrospectivosRESUMO
INTRODUCTION: Earlier application of oral androgen receptor-axis-targeted therapies in patients with metastatic castration-sensitive prostate cancer (mCSPC) has established improvements in overall survival, as compared to androgen deprivation therapy (ADT) alone. Recently, the use of apalutamide plus ADT has demonstrated improvement in mCSPC-related mortality vs. ADT alone, with an acceptable toxicity profile. However, the cost-effectiveness of this therapeutic option remains unknown. METHODS: We used a state-transition model with probabilistic analysis to compare apalutamide plus ADT, as compared to ADT alone, for mCSPC patients over a time horizon of 20 years. Primary outcomes included expected life-years (LY), quality-adjusted life-years (QALY), lifetime cost (2020 Canadian dollars), and incremental cost-effectiveness ratio (ICER). Parameter and model uncertainties were assessed through scenario analyses. Health outcomes and cost were discounted at 1.5%, as per Canadian guidelines. RESULTS: For the base-case analysis, expected LY for ADT and apalutamide plus ADT were 4.11 and 5.56, respectively (incremental LY 1.45). Expected QALYs were 3.51 for ADT and 4.84 for apalutamide plus ADT (incremental QALYs 1.33); expected lifetime cost was $36 582 and $255 633, respectively (incremental cost $219 051). ICER for apalutamide plus ADT, as compared to ADT alone, was $164 700/QALY. Through scenario analysis, price reductions ≥50% were required for apalutamide in combination with ADT to be considered cost-effective, at a cost-effectiveness threshold of $100 000/QALY. CONCLUSIONS: Apalutamide plus ADT is unlikely to be cost-effective from the Canadian healthcare perspective unless there are substantial reductions in the price of apalutamide treatment.
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Brain metastases (BM) are perceived as a rare complication of prostate cancer associated with poor outcome. Due to limited published data, we conducted a literature review regarding incidence, clinical characteristics, treatment options, and outcomes of patients with prostate cancer BM. A literature analysis of the PubMed, MEDLINE, and EMBASE databases was performed for full-text published articles on patients diagnosed with BM from prostate cancer. Eligible studies included four or more patients. Twenty-seven publications were selected and analyzed. The sources of published patient cohorts were retrospective chart reviews, administrative healthcare databases, autopsy records, and case series. BM are rare, with an incidence of 1.14% across publications that mainly focus on intraparenchymal metastases. Synchronous visceral metastasis and rare histological prostate cancer subtypes are associated with an increased rate of BM. Many patients do not receive brain metastasis-directed local therapy and the median survival after BM diagnosis is poor, notably in patients with multiple BM, dural-based metastases, or leptomeningeal dissemination. Overall, prostate cancer BM are rare and associated with poor prognosis. Future research is needed to study the impact of novel prostate cancer therapeutics on BM incidence, to identify patients at risk of BM, and to characterize molecular treatment targets.
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OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) placement is essential for the provision of enteral nutrition in select head and neck cancer (HNC) patients. Minimally invasive tube placement is facilitated through one of two techniques, push or pull, but there have been conflicting results regarding safety profiles of these procedures. The objectives of this study were to determine the association of PEG insertion technique with gastrostomy tube complications, including stomal metastases. METHODS: A multi-institutional retrospective cohort study of patients with HNC undergoing PEG insertion by either the pull (gastroscope assisted) or push (fluoroscopy assisted) technique was performed. Tube-related complications included infection, dislodgement, deterioration, leak, and other. Adjusted analysis was performed via a multivariable logistic regression model. RESULTS: 1,575 patients were included across three institutions. Tube-related complications occurred in 36% of patients, the most common being peristomal leak (13%) and infection (16%). The push technique (OR 2.66, 95% CI: 1.42-4.97), and the presence of T4 disease (OR 4.62, 95% CI: 1.58-13.51), were associated with a greater risk of developing any tube-related complication. Infection rates were similar between pull and push cohorts. All detected stoma metastases occurred with the pull technique, with an overall prevalence of 0.32% amongst the cohort. CONCLUSIONS: The push technique is associated with a greater risk of developing any tube-related complication, but the rate of stomal metastases may be higher with the pull technique. There is potential for quality improvement measures to improve tube-related complications associated with either technique.
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Gastrostomia , Neoplasias de Cabeça e Pescoço , Nutrição Enteral/métodos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Both Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT). METHODS: We conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints. RESULTS: After a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4-91.8%) of ABI versus 67.1% (57.5-78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3-100%) and 92.7% (85.0-100%) in the DOC and ABI groups (p = 0.97), respectively. CONCLUSIONS: In this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.