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2.
Breast Cancer Res Treat ; 205(3): 619-631, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38526687

RESUMO

PURPOSE: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. METHODS: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20-39, 40-64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. RESULTS: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45-49 years than 40-44 years, despite the recommended starting screening age is 45 years in Taiwan. CONCLUSION: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis.


Assuntos
Neoplasias da Mama , Estilo de Vida , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Adulto , Prognóstico , Taiwan/epidemiologia , Idoso , Adulto Jovem , Sistema de Registros , Fatores Etários , Fatores de Risco , Índice de Massa Corporal
3.
Cancers (Basel) ; 16(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38473388

RESUMO

PURPOSE: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. METHODS: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". DISCUSSION: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. CONCLUSIONS: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38349208

RESUMO

CONTEXT: Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined. OBJECTIVE: To examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4cm in diameter. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all consecutive patients who underwent non-operative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001-2021. We included patients with an initial US-FNA confirming either: a) Bethesda 5 or 6 cytology or, b) a "suspicious" AFIRMA molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth. RESULTS: Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules ≥ 2 cm. No patients were found to develop new incident occurrence of lymph node or distant metastasis. One patient however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start non-operative selection. 21% of patients had an increase in maximum diameter more than 3 mm, and volume increase ≥50% was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth. CONCLUSIONS: These data expand consideration of active surveillance of papillary thyroid carcinoma in select patients with intrathyroidal suspected malignancy >1cm in diameter. Rescue surgery, if required at a later timepoint, appears effective.

5.
Photodermatol Photoimmunol Photomed ; 40(1): e12933, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288776

RESUMO

BACKGROUND: Skin cancer survivors are more vulnerable to subsequent skin cancers and other malignancies, but previous studies have not examined in detail their sun protection behavior prevalence by sociodemographic factors. We aimed to understand the sociodemographic disparities in the prevalence of three important types of sun protection behaviors: using sunscreen, seeking shade, and wearing protective clothing, among skin cancer survivors and those without skin cancer history. METHODS: We used the 2015 U.S. National Health Interview Survey to analyze 29,523 participants, of which 772 were skin cancer survivors and 28,751 were those without skin cancer history. We assessed overall and specific sun protection behavior prevalence based on using sunscreen, seeking shade, and wearing protective clothing. Weighted Poisson regression was used to estimate prevalence ratios. RESULTS: Melanoma and nonmelanoma skin cancer survivors had similar overall sun protection behavior (p > .05). Among all skin cancer survivors, 36.0% infrequently used sunscreen, 50.2% infrequently wore protective clothing, 47.8% infrequently sought shade, and 30.0% lacked frequent overall sun protection, which significantly differed from those without skin cancer history (p < .0001). The prevalence of frequent overall sun protection behavior was lower for those who were younger at survey, males, less educated, single or never married, or lived in poverty, regardless of their skin cancer history (p < .01). CONCLUSIONS: By identifying subpopulations with higher prevalence of infrequent sun protection among those with or without skin cancer history, our findings may encourage efforts to reduce sociodemographic disparities in sun protection behaviors and promote primary and tertiary skin cancer prevention.


Assuntos
Sobreviventes de Câncer , Neoplasias Cutâneas , Queimadura Solar , Masculino , Humanos , Estados Unidos/epidemiologia , Protetores Solares/uso terapêutico , Queimadura Solar/prevenção & controle , Comportamentos Relacionados com a Saúde , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/tratamento farmacológico , Roupa de Proteção
7.
Subst Use Misuse ; 59(4): 486-493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37970728

RESUMO

BACKGROUND: Cancer survivors are especially vulnerable to the carcinogenic effects of tobacco smoking, but there lacks a study comprehensively examining the sociodemographic disparities in current smoking prevalence in this population. In this study, we quantified the current cigarette smoking prevalence in cancer survivors and those without cancer history by sociodemographic factors, to identify subpopulations with high current smoking burden. METHODS: We conducted a cross-sectional study of 3,679 cancer survivors and 27,350 participants without cancer history who were 18 years of age or above in the 2019 National Health Interview Survey. Data for the study variables were obtained from computer-assisted personal or telephone interviews. Weighted Poisson regression was used to estimate prevalence ratios and 95% confidence intervals. RESULTS: Although the current smoking prevalence for cancer survivors was slightly lower than for those without cancer history, the prevalence exceeded 30% in cancer survivors in poverty or without health insurance. Individuals with significantly higher current smoking prevalence had lower education levels, were unmarried, did not have health insurance, or lived in poverty. The associations of age, sex, race, health insurance status, and poverty status with current smoking significantly differed between cancer survivors and those without cancer history. Sociodemographic disparities in current smoking prevalence were found in survivors of either smoking-related or nonsmoking-related cancers. CONCLUSION: High current smoking prevalence still exists in subpopulations of cancer survivors and those without cancer history. Our findings may strengthen efforts to reduce sociodemographic disparities in current smoking prevalence and to lower the overall smoking prevalence.


Assuntos
Sobreviventes de Câncer , Fumar Cigarros , Neoplasias , Humanos , Fumar Cigarros/epidemiologia , Prevalência , Estudos Transversais , Inquéritos e Questionários , Neoplasias/epidemiologia
8.
Surgery ; 175(1): 65-72, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37980200

RESUMO

BACKGROUND: Differences in presenting symptoms of primary hyperparathyroidism and outcomes of parathyroidectomy between sexes have been described, but whether these can be assessed by perioperative use of a validated tool, such as the Pasieka Parathyroidectomy Assessment Score, is unknown. METHOD: All patients with primary hyperparathyroidism were asked to complete symptom assessment at the preoperative and postoperative visits. The assessment included a query for 13 Pasieka Parathyroidectomy Assessment Score parameters evaluated using a visual analog scale as described by Pasieka (summative score 0-1,300), and general quality of life and wellness. A review of a prospectively maintained database of primary hyperparathyroidism patients (January 2016-December 2019) was performed, and those who had a 6-month cure after initial parathyroidectomy were included. RESULTS: The study cohort was mostly women (77%, 541/701). The median preoperative Pasieka Parathyroidectomy Assessment Score was higher in women (155, 0-1,190) than in men (80.5, 0-855, P < .001), although there were similar rates of asymptomatic primary hyperparathyroidism (Pasieka Parathyroidectomy Assessment Score = 0, 12.5% vs 7%, P = .042). After curative parathyroidectomy, women reported a substantial reduction in symptomatology, with Pasieka Parathyroidectomy Assessment Score declining by 35% at initial postoperative visit (median, 155 vs 100, P < .001), further decreasing to 48% by 6 months (155 vs 80, P < .001). The Pasieka Parathyroidectomy Assessment Score in men did change but to a much smaller degree at both the initial postoperative visit (80.5 vs 70; P = .036) and at 6 months (80.5 vs 57.5; P = .048). CONCLUSION: When assessed with the Pasieka Parathyroidectomy Assessment Score, improvement in symptoms was clearly demonstrated for women after curative parathyroidectomy. Whether symptom improvement also occurs in men is less apparent but may be due to disparities in the development and validation of outcomes tools in general.


Assuntos
Hiperparatireoidismo Primário , Humanos , Masculino , Feminino , Hiperparatireoidismo Primário/cirurgia , Qualidade de Vida , Caracteres Sexuais , Estudos Prospectivos , Paratireoidectomia
9.
Clin Lung Cancer ; 24(7): 651-659, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37714807

RESUMO

BACKGROUND AND PURPOSE: The role of stereotactic body radiation therapy (SBRT) in oligoprogressive non-small-cell lung cancer (NSCLC) is controversial. We evaluated whether SBRT in a subset of patients with oligoprogressive or oligorecurrent NSCLC offers a durable response, obviating the need to change systemic therapy. METHODS: A retrospective analysis of 168 NSCLC patients who underwent SBRT for oligoprogressive or oligorecurrent disease was performed. Oligoprogression was defined as progression in ≤5 lesions during or after systemic therapy following an initial complete or partial response. Oligorecurrence was defined as progression while off systemic therapy. Progression-free survival (PFS), overall survival (OS) and time to next treatment or death (TNT-D) were estimated. RESULTS: Median age was 68 years. Sixty-seven percent of patients were on systemic therapy at the time of progression. Progression at the primary site was present in 31% of the patients. The number of sites of metastatic progression was 0 to 2 in 76% and 3 to 5 in 24% of the patients. Two-year OS and PFS were 56% (95%CI 46%-64%) and 14% (95%CI 8%-21%), respectively. Median TNT-D was 9 months (95%CI 6-11). No grade 4 or 5 toxicity was seen. In multivariable analysis, patients with 3 to 5 sites of metastatic progression had worse OS (HR 2.6, 95%CI 1.5-4.3, P < .001) and shorter TNT-D (HR 1.7, 95%CI 1.1-2.5, P = .01) than those with 0 to 2 sites. CONCLUSION: SBRT is a safe and viable treatment option for oligoprogressive and oligorecurrent NSCLC. Patients with 0 to 2 sites had better OS and longer TNT-D compared to those with 3 to 5 lesions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Idoso , Neoplasias Pulmonares/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos
10.
JCO Precis Oncol ; 7: e2200445, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37656950

RESUMO

PURPOSE: With increased adoption of next-generation sequencing, tailored therapy on the basis of molecular status is being delivered for patients with early-stage resectable non-small-cell lung cancer (NSCLC). The purpose of this narrative review was to focus on recent developments of targeted therapies in the adjuvant and neoadjuvant/adjuvant setting for early-stage disease. METHODS: A systematic search of the MEDLINE/PubMed database was performed, focusing on studies published within the past 10 years. Our search queried "early-stage NSCLC (AND) tyrosine kinase inhibitor (TKI; OR) epidermal growth factor receptor (EGFR; OR) anaplastic lymphoma kinase (ALK)" and was limited only to prospective and ongoing studies. RESULTS: Most studies examining the benefit of targeted therapies in early-stage resectable NSCLC have been for EGFR-TKIs in the adjuvant setting. Currently, only one study, the ADAURA trial of adjuvant osimertinib, has demonstrated an overall survival benefit with the use of an EGFR-TKI in the adjuvant setting. Future work to build on the success of the ADAURA trial is focused on determining the optimal duration of targeted therapies and using biomarkers, such as circulating tumor DNA, to risk-stratify patients and guide maintenance targeted therapy duration. CONCLUSION: The results of several ongoing studies are eagerly awaited regarding the use of targeted therapies in the neoadjuvant/adjuvant setting and for more uncommon or rare mutations such as ALK, ROS proto-oncogene 1, rearranged during transfection, mesenchymal-epithelial transition factor, and B-Raf proto-oncogene V600E. The treatment landscape for early-stage NSCLC harboring actionable mutations is likely to shift dramatically in the upcoming decade.

11.
Circ Heart Fail ; 16(8): e010478, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37395128

RESUMO

BACKGROUND: Right heart failure (RHF) is associated with worse clinical outcomes. In addition to hemodynamic perturbations, the syndrome of RHF involves liver congestion and dysfunction. The mechanisms that underlie heart-liver interactions are poorly understood and may involve secreted factors. As a first step to understand the cardiohepatic axis, we sought to elucidate the circulating inflammatory milieu in patients with RHF. METHODS: Blood samples were collected from the inferior vena cava and hepatic veins during right heart catheterization from 3 groups of patients: (1) controls with normal cardiac function, (2) patients with heart failure who did not meet all criteria of RHF, and (3) patients who met prespecified criteria for RHF defined by hemodynamic and echocardiographic parameters. We performed a multiplex protein assay to survey levels of several circulating markers and analyzed their association with mortality and the need for a left ventricular assist device or heart transplant. Finally, we leveraged publicly available single-cell RNA sequencing data and performed tissue imaging to evaluate the expression of these factors in the liver. RESULTS: In this study, RHF was associated with elevated levels of a subset of cytokines/chemokines/growth factors compared with controls. In particular, soluble CD163 (cluster of differentiation 163) and CXCL12 (chemokine [C-X-C motif] ligand 12) were higher in RHF and predicted left ventricular assist device/transplant-free survival in an independent validation cohort. Furthermore, single-cell RNA sequencing and immunohistochemistry of human liver biopsies suggest that these factors are expressed by Kupffer cells and may be liver derived. CONCLUSIONS: RHF is associated with a distinct circulating inflammatory profile. Soluble CD163 and CXCL12 are novel biomarkers that can prognosticate patient outcomes. Future studies to define how these molecules influence heart failure phenotypes and disease progression may lead to new approaches to the management of patients with RHF.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Disfunção Ventricular Direita , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Estudos Retrospectivos , Progressão da Doença , Hemodinâmica , Biomarcadores
12.
Int J Radiat Oncol Biol Phys ; 117(5): 1287-1296, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37406826

RESUMO

PURPOSE: Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. METHODS AND MATERIALS: A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. RESULTS: The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P = .038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P = .043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P < .001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P = .014) were identified. No significant thresholds were identified for cardiac toxicity. CONCLUSIONS: In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inteligência Artificial , Teorema de Bayes , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Estudos Prospectivos , Dosagem Radioterapêutica
13.
Cancer Causes Control ; 34(12): 1073-1084, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37486400

RESUMO

PURPOSE: Cancer is the second leading cause of death globally and in the U.S., but screening can reduce cancer-related deaths. We analyzed data from a nationwide survey to compare how sociodemographic factors were associated with never or not timely screening for multiple types of cancer, and the use of different colorectal cancer screening procedures. METHODS: We analyzed data from the 2019 U.S. National Health Interview Survey. To understand breast, cervical, and colorectal cancer screening participation among those recommended to screen, we respectively analyzed 8,110 women 45 to 74 years of age, 9,583 women 21 to 65 years of age, and 13,497 individuals 50 to 75 years of age at survey. Weighted Poisson regression was used to estimate the unadjusted and confounding-adjusted prevalence ratio and 95% confidence intervals. RESULTS: In our analysis populations, 6.9% never had a mammogram, 14.6% never screened for cervical cancer, and 26.8% never screened for colorectal cancer; the prevalence respectively increased to 24.7%, 23.8%, and 32.3% for not timely screening according to national guidelines. The prevalence of never screening was 81.9% for non-invasive colorectal cancer tests, compared with 32.5% for colonoscopy or sigmoidoscopy. Individuals with lower education level, with no health insurance, or in poverty had higher prevalence of never screening for all three cancers. There was low sociodemographic disparity for the use of non-invasive colorectal cancer screening tests. CONCLUSION: Socioeconomically disadvantaged individuals have higher prevalence of never or not timely screening. The utilization of non-invasive colorectal cancer screening procedures remains low across sociodemographic groups.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Neoplasias do Colo do Útero , Humanos , Estados Unidos/epidemiologia , Feminino , Fatores Sociodemográficos , Detecção Precoce de Câncer/métodos , Colonoscopia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Programas de Rastreamento , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia
14.
Sci Adv ; 9(29): eadf4163, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37467337

RESUMO

Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro and tested on clinical tissues. This signature, termed CellDRIFT, increased with age across multiple tissues, distinguished tumor from normal tissue, was escalated in normal breast tissue from cancer patients, and was transiently reset upon reprogramming. In addition, within-person tissue differences were correlated with predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Our findings suggest that age-related replication may drive epigenetic changes in cells and could push them toward a more tumorigenic state.


Assuntos
Epigenoma , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patologia , Epigênese Genética , Envelhecimento/genética , Fatores de Risco
15.
Neoplasia ; 43: 100914, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37348427

RESUMO

BACKGROUND: With the recent success of immunotherapy, there is a growing interest in combining radiation with immunotherapy to boost abscopal response rates. Several challenges exist in determining how to synergize these two modalities in the treatment of metastatic NSCLC. METHODS: References for this review were identified through searches of MEDLINE/PubMed and Clinicaltrials.gov databases with the search terms "abscopal", "radiation OR radiotherapy," "NSCLC", and "lung" on the index date of July 2022 from 2000-2022. This systematic review focuses primarily on clinical papers. DISCUSSION: Early work combining radiotherapy with immunotherapy show promise in unlocking the abscopal effect. Preliminary evidence suggests that radiotherapy regimens with <5 fractions and smaller fields may be superior to regimens with 15 fractions and larger fields. There does not appear to be enough evidence to draw conclusions about the optimal timing of radiotherapy in relation to immunotherapy or the optimal anatomical location of radiation to induce the abscopal effect. Several studies suggest selecting patients with a higher absolute lymphocyte count (ALC) and lower neutrophil-to-lymphocyte ratio (NLR) may help to further boost abscopal response rates. Furthermore, selecting tumors with programmed death ligand-1 (PD-L1) expression, mismatch repair deficiency, and higher tumor mutational burden may similarly achieve this goal. Lastly, additional work is needed to minimize and predict for severe toxicity associated with combination therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Imunoterapia , Pulmão , Terapia Combinada , Neoplasias Pulmonares/radioterapia
16.
Clin Colon Rectal Surg ; 36(4): 259-264, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37223232

RESUMO

Delivering high-quality surgical care requires knowing how best to define and measure quality in surgery. Patient-reported outcomes (PROs) enable surgeons, health care systems, and payers to understand meaningful health outcomes from the patient's perspective and can be measured using patient-reported outcome measures (PROMs). As a result, there is much interest in using PROMs in routine surgical care, to guide quality improvement and to inform reimbursement pay structures. This chapter defines PROs and PROMs, differentiates PROMs from other quality measures such as patient-reported experience measures, describes PROMs in the context of routine clinical care, and provides an overview of interpreting PROM data. This chapter also describes how PROMs may be applied to quality improvement and value-based reimbursement in surgery.

17.
CRISPR J ; 6(3): 243-260, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37219969

RESUMO

Development of medicines using gene editing has been hampered by enzymological and immunological impediments. We described previously the discovery and characterization of improved, novel gene-editing systems from metagenomic data. In this study, we substantially advance this work with three such gene-editing systems, demonstrating their utility for cell therapy development. All three systems are capable of reproducible, high-frequency gene editing in primary immune cells. In human T cells, disruption of the T cell receptor (TCR) alpha-chain was induced in >95% of cells, both paralogs of the TCR beta-chain in >90% of cells, and >90% knockout of ß2-microglobulin, TIGIT, FAS, and PDCD1. Simultaneous double knockout of TRAC and TRBC was obtained at a frequency equal to that of the single edits. Gene editing with our systems had minimal effect on T cell viability. Furthermore, we integrate a chimeric antigen receptor (CAR) construct into TRAC (up to ∼60% of T cells), and demonstrate CAR expression and cytotoxicity. We next applied our novel gene-editing tools to natural killer (NK) cells, B cells, hematopoietic stem cells, and induced pluripotent stem cells, generating similarly efficient cell-engineering outcomes including the creation of active CAR-NK cells. Interrogation of our gene-editing systems' specificity reveals a profile comparable with or better than Cas9. Finally, our nucleases lack preexisting humoral and T cell-based immunity, consistent with their sourcing from nonhuman pathogens. In all, we show these new gene-editing systems have the activity, specificity, and translatability necessary for use in cell therapy development.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Humanos , Sistemas CRISPR-Cas/genética , Linfócitos T/metabolismo , Diferenciação Celular , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo
18.
Clin Colorectal Cancer ; 22(2): 167-174, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36878806

RESUMO

Total neoadjuvant therapy (TNT) has emerged as the preferred approach for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a greater likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016 and 2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, nonadenocarcinoma histology, received RT to a nonrectum site, or received a nondefinitive RT dose. Data were analyzed using linear regression, χ2 test, and binary logistic regression. Of the 26,375 patients included, most patients were treated at an academic facility (94.6%). Five thousand three (19.0%) patients received TNT, and 21,372 (81.0%) patients did not receive TNT. The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016 to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, P = .040). The most common TNT regimen was multiagent chemotherapy followed by long-course chemoradiation (73.2% of cases from 2016-2020). There was a significant increase in utilization of short-course RT as part of TNT from 2.8% in 2016 to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, P = .035). Factors associated with a lower likelihood of TNT usage included age >65, female gender, Black race, and T3 N0 disease. TNT use in the United States has increased significantly from 2016-2020, with approximately 34.6% of patients with LARC receiving TNT in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network guidelines recommending TNT as the preferred approach.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Feminino , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Reto/patologia , Neoplasias Retais/patologia , Quimiorradioterapia/métodos , Estadiamento de Neoplasias
19.
Am J Clin Oncol ; 46(5): 199-205, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36882926

RESUMO

BACKGROUND: This study evaluates population-based outcomes of patients with squamous cell carcinoma (SCC) of the nasal cavity treated in British Columbia. METHODS: A retrospective review of nasal cavity SCC treated from 1984 to 2014 was performed (n = 159). Locoregional recurrence (LRR) and overall survival (OS) were evaluated. RESULTS: The 3-year OS was 74.2% for radiation alone, 75.8% for surgery alone, and 78.4% for surgery and radiation ( P = 0.16). The 3-year LRR was 28.4% for radiation alone, 28.2% for surgery alone, and 22.6% for surgery and radiation ( P = 0.21). On multivariable analysis, surgery and postoperative radiation relative to surgery alone was associated with a lower risk of LRR (hazard ratio: 0.36, P = 0.03). Poor Eastern Cooperative Oncology Group status, node-positive, orbital invasion, smoking, and advanced age were associated with worse OS (all P <0.05). CONCLUSION: In this population-based analysis, multimodality treatment with surgery and adjuvant radiation were associated with improved locoregional control for SCC of the nasal cavity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resultado do Tratamento , Cavidade Nasal/patologia , Recidiva Local de Neoplasia/patologia , Carcinoma de Células Escamosas/patologia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias
20.
Thyroid ; 33(6): 705-714, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36974361

RESUMO

Background: Molecular testing (MT) is emerging as a potential prognostic factor that can be available before treatment of differentiated thyroid carcinoma begins. Among patients eligible for either lobectomy or total thyroidectomy as their initial therapy, our study aims were to assess (1) if conventionally available preoperative factors are associated with incomplete response to initial therapy, and (2) if MT results can be a surrogate for the ATA Risk Stratification System (RSS) to estimate risk of recurrence. Methods: The data of consecutive thyroid cancer patients without preoperative lateral neck disease or distant metastasis who underwent index thyroidectomy between November 1, 2017 and October 31, 2021 were reviewed. Logistic regression models including preoperative variables such as MT and/or the postoperatively available RSS were constructed to predict disease recurrence, either structural or biochemical. Model discrimination using the c-statistic and goodness-of-fit test were compared. Results: Among 945 patients studied, 50 (5.2%) recurred with 18-month median follow-up. Recurrences were detected in 17 (2.9%), 20 (6.7%), and 13 (22.8%) patients with RSS-low, -intermediate, and -high cancers, respectively (p < 0.001). In multivariable analysis, only tumor size was associated with recurrence (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.5). In a different model analyzing 440 (46.6%) patients with available MT results, recurrence was associated with both larger tumor size (OR 1.4 [95% CI 1.1-1.8]) and MT results (p < 0.001). Including MT improved the c-statistic by 27%, which was statistically no different than the model incorporating only the RSS (p = 0.15). Conclusions: Disease recurrence was observed across all ATA RSS categories in short-term follow-up, and tumor size was the only conventional preoperative factor associated with recurrence. When MT results were incorporated, they not only improved predictive ability beyond tumor size alone, but also yielded similar ability as the gold standard ATA RSS. Thus, MT results might aid the development of novel preoperative risk stratification algorithms.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Adenocarcinoma/cirurgia , Prognóstico , Medição de Risco
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