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1.
Nat Commun ; 15(1): 3152, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605064

RESUMEN

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fluorodesoxiglucosa F18 , Radiofármacos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Estudios Retrospectivos
2.
Ann Surg ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38568206

RESUMEN

OBJECTIVES: Our objective was to investigate overall survival (OS) and length of stay (LOS) associated with differing management for high output (>1 liter over 24 h) leaks (HOCL) following cancer related esophagectomy. SUMMARY BACKGROUND: Although infrequent, chyle leak following esophagectomy is an event that can lead to significant perioperative sequelae. Low volume leaks appear to respond to non-operative measures, while HOCL often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001-2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital length of stay and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received non-operative management, 15 patients received prompt (<72 h from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer length of stay compared to early intervention (Slope=9.849, 95% Confidence Interval [CI] 3.431 to 16.267). Late intervention (Hazard Ratio (HR) 4.772, CI: 1.384 to 16.460) and non-operative management (HR 4.731, CI: 1.294 to 17.305) were associated with increased mortality compared to early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention in order to possibly reverse the prognostic implications of this potentially detrimental complication.

3.
Front Oncol ; 14: 1324057, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590653

RESUMEN

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of "adenocarcinoma with aberrant expression of ß-hCG" and finally pathologists at our hospital, who gave the diagnosis of "poorly differentiated carcinoma with choriocarcinoma features". Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 16 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features.

4.
Cancers (Basel) ; 16(5)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38473297

RESUMEN

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

5.
Cell Rep Med ; 5(3): 101463, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38471502

RESUMEN

[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478). Synthetic PET images are validated across imaging, biological, and clinical aspects. Radiologists confirm comparable imaging quality and tumor contrast between synthetic and actual PET scans. Radiogenomics analysis further proves that the dysregulated cancer hallmark pathways of synthetic PET are consistent with actual PET. We also demonstrate the clinical values of synthetic PET in improving lung cancer diagnosis, staging, risk prediction, and prognosis. Taken together, this proof-of-concept study testifies to the feasibility of applying deep learning to obtain high-fidelity PET translated from CT.


Asunto(s)
Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Tomografía Computarizada por Rayos X , Pronóstico
6.
JTO Clin Res Rep ; 5(2): 100623, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38357092

RESUMEN

Introduction: NSCLC transformation to SCLC has been best characterized with EGFR-mutant NSCLC, with emerging case reports seen in ALK, RET, and KRAS-altered NSCLC. Previous reports revealed transformed SCLC from EGFR-mutant NSCLC portends very poor prognosis and lack effective treatment. Genomic analyses revealed TP53 and RB1 loss of function increase the risk of SCLC transformation. Little has been reported on the detailed clinicogenomic characteristics and potential therapeutic targets for this patient population. Methods: In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with EGFR-mutant NSCLC transformed to SCLC. Demographic data, treatment course, and clinical molecular testing reports were extracted from electronic medical records. Kaplan-Meier analyses were used to estimate survival outcomes. Next generation sequencing-based assays was used to identify EGFR and co-occurring genetic alterations in tissue or plasma before and after SCLC transformation. Single-cell RNA sequencing (scRNA-seq) was performed on a patient-derived-xenograft model generated from a patient with EGFR-NSCLC transformed SCLC tumor. Results: A total of 34 patients were identified in our study. Median age at initial diagnosis was 58, and median time to SCLC transformation was 24.2 months. 68% were female and 82% were never smokers. 79% of patients were diagnosed as stage IV disease, and over half had brain metastases at baseline. Median overall survival of the entire cohort was 38.3 months from initial diagnoses and 12.4 months from time of SCLC transformation. Most patients harbored EGFR exon19 deletions as opposed to exon21 L858R alteration. Continuing EGFR tyrosine kinase inhibitor post-transformation did not improve overall survival compared with those patients where tyrosine kinase inhibitor was stopped in our cohort. In the 20 paired pretransformed and post-transformed patient samples, statistically significant enrichment was seen with PIK3CA alterations (p = 0.04) post-transformation. Profiling of longitudinal liquid biopsy samples suggest emergence of SCLC genetic alterations before biopsy-proven SCLC, as shown by increasing variant allele frequency of TP53, RB1, PIK3CA alterations. ScRNA-seq revealed potential therapeutic targets including DLL3, CD276 (B7-H3) and PTK7 were widely expressed in transformed SCLC. Conclusions: SCLC transformation is a potential treatment resistance mechanism in driver-mutant NSCLC. In our cohort of 34 EGFR-mutant NSCLC, poor prognosis was observed after SCLC transformation. Clinicogenomic analyses of paired and longitudinal samples identified genomic alterations emerging post-transformation and scRNA-seq reveal potential therapeutic targets in this population. Further studies are needed to rigorously validate biomarkers and therapeutic targets for this patient population.

7.
Dis Esophagus ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38391198

RESUMEN

The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.

9.
Ann Thorac Surg ; 117(2): 320-326, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37080372

RESUMEN

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Peritoneales/terapia , Gastrectomía , Adenocarcinoma/cirugía , Neoplasias Gástricas/cirugía , Unión Esofagogástrica/cirugía , Neoplasias Esofágicas/cirugía , Estadificación de Neoplasias
10.
J Thorac Cardiovasc Surg ; 167(4): 1444-1453.e4, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37816395

RESUMEN

OBJECTIVE: Chemotherapy plus nivolumab is the standard of care neoadjuvant treatment for patients with resectable stage IB to IIIA non-small cell lung cancer. The influence of dual checkpoint blockade with chemotherapy on surgical outcomes remains unknown. We aimed to determine operative complexity and perioperative outcomes associated with neoadjuvant chemotherapy and nivolumab with or without ipilimumab. METHODS: A total of 44 patients with stage IB (≥4 cm) to IIIA non-small cell lung cancer were treated on sequential platform arms of the NEOSTAR trial. A total of 22 patients were treated with nivolumab + chemotherapy, and 22 patients were treated with ipilimumab + nivolumab + chemotherapy. The safety of surgical resection after neoadjuvant therapy was estimated using 30-day complication rates. Operative reports and surgeons' narratives were evaluated to determine procedural complexity and operative conduct. RESULTS: All 22 of 22 patients (100%) treated with nivolumab + chemotherapy underwent surgical resection: 20 R0 (90.9%), 17 (77.3%) lobectomies, 1 wedge resection, 2 segmentectomies, and 2 pneumonectomies. The majority, 21 of 22 (95%), were performed by thoracotomy. A total of 13 of 22 (59.1%) were rated as challenging resections. A total of 4 of 22 patients (18.2%) experienced grade 3 or greater Clavien-Dindo complication. A total of 20 of 22 patients (90.9%) treated with ipilimumab + nivolumab + chemotherapy underwent surgical resection: 19 R0 (95%), 18 (90%) lobectomies, 1 pneumonectomy, and 1 segmentectomy. A total of 16 of 20 (80%) resections were performed via thoracotomy, 3 of 20 (15%) via robotics, and 1 of 20 (5%) via thoracoscopy. A total of 9 of 20 (45%) resections were considered challenging. A total of 4 of 20 patients (20%) experienced grade 3 or greater Clavien-Dindo complication. CONCLUSIONS: Surgical resections are feasible and safe, with high rates of R0 after neoadjuvant chemotherapy and nivolumab with or without ipilimumab. Overall, approximately half of cases (22/42, 52.3%) were considered to be more challenging than a standard lobectomy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Nivolumab , Ipilimumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estadificación de Neoplasias , Terapia Neoadyuvante/efectos adversos , Resultado del Tratamiento
11.
J Thorac Cardiovasc Surg ; 167(2): 478-487.e2, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37356476

RESUMEN

OBJECTIVE: We evaluated self-reported financial burden (FB) after lung cancer surgery and sought to assess patient perspectives, risk factors, and coping mechanisms within this population. METHODS: Patients with lung cancer resected at our institution between January 1, 2016, and December 31, 2021, were surveyed. Descriptive and multivariable analyses were performed to evaluate the association between clinical and financial characteristics with patient-reported major ("significant" or "catastrophic") FB. RESULTS: Of 1477 patients contacted, 31.3% (n = 463) completed the survey. Major FB was reported by 62 (13.4%) patients. multivariable analyses demonstrated increasing age (odds ratio [OR], 0.92; 95% CI, 0.88-0.96), credit score >740 (OR, 0.29; 95% CI, 0.14-0.60), and employer-based insurance (OR, 0.24; 95% CI, 0.07-0.80) were protective factors. In contrast, an out of pocket cost greater than expected (OR, 3.63; 95% CI, 1.67-7.88), decrease in work hours (OR, 4.42; 95% CI, 1.59-12.25), or cessation of work (OR, 5.13; 95% CI, 2.06-12.78), chronic obstructive pulmonary disease diagnosis (OR, 5.39, 95% CI, 1.87-15.50), and hospital readmission (OR, 4.87; 95% CI, 1.11-21.42) were risk factors for FB. To pay for care, some patients reported "often" or "always" decreasing food (n = 102 [23.4%]) or leisure spending (n = 179 [40.7%]). Additionally, use of savings (n = 246 [62.9%]), borrowing funds (n = 72 [16.6%]), and skipping clinic visits (n = 36 [8.3%]) at least once were also reported. Coping mechanisms occurred more often in patients with major FB compared with those without (P < .001). CONCLUSIONS: Patients with resected lung cancer may experience major FB related to treatment with several identifiable risk factors. Targeted interventions are needed to limit the adoption of detrimental coping mechanisms and potentially affect survivorship.


Asunto(s)
Neoplasias Pulmonares , Humanos , Autoinforme , Neoplasias Pulmonares/cirugía , Costo de Enfermedad , Estrés Financiero , Factores de Riesgo , Adaptación Psicológica
12.
J Thorac Cardiovasc Surg ; 167(3): 814-819.e2, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37495170

RESUMEN

BACKGROUND: Appropriately selected patients clearly benefit from resection of colorectal cancer (CRC) pulmonary metastases (PMs). However, there remains equipoise surrounding optimal chest surveillance strategies following pulmonary metastasectomy. We aimed to identify risk factors that may inform chest surveillance in this population. METHODS: Patients who underwent CRC pulmonary metastasectomy were identified from a single institution's prospectively maintained surgical database. Clinicopathologic and genomic characteristics were collected. Patients were stratified by diagnosis of subsequent PM within 6 months of the index lung resection. Multivariate modeling was used to evaluate risk factors. RESULTS: A total of 197 patients met the study's inclusion criteria, of whom 52.3% (n = 103) developed subsequent PM, at a median of 9.51 months following the index metastasectomy. Patients with KRAS alterations (odds ratio [OR], 3.073; 95% confidence interval [CI], 1.363-6.926; P = .007), TP53 alterations (OR, 3.109; 95% CI, 1.318-7.341; P = .010) were found to be at risk of PM diagnosis within 6 months of the index metastasectomy, while those with an APC alteration (OR, .218; 95% CI, 0.080-0.598; P = .003) were protected. Moreover, patients who received systemic therapy within 3 months of the initial PM diagnosis also were more likely to develop early lung recurrence (OR, 2.105; 95% CI, 0.971-4.563; P = .059). CONCLUSIONS: Patients with KRAS alterations, TP53 alterations, and no APC alterations developed early recurrence in the lung following pulmonary metastasectomy, as did those who received chemotherapy after their initial PM diagnosis. As such, these groups benefit from early lung imaging after metastasectomy, as chest surveillance protocols should be based on patient-centered clinicopathologic and genomic risk factors.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Pulmonares , Metastasectomía , Humanos , Metastasectomía/efectos adversos , Metastasectomía/métodos , Proteínas Proto-Oncogénicas p21(ras)/genética , Neumonectomía/efectos adversos , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/secundario , Factores de Riesgo , Neoplasias Colorrectales/patología , Pronóstico , Tasa de Supervivencia , Estudios Retrospectivos
13.
J Thorac Cardiovasc Surg ; 167(5): 1617-1627, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37696428

RESUMEN

OBJECTIVE: We have previously demonstrated the negative impact of travel distance on adherence to surveillance imaging guidelines for resected non-small cell lung cancer (NSCLC). The influence of patient residential location on adherence to recommended postoperative treatment plans remains unclear. We sought to characterize the impact of travel distance on receipt of indicated adjuvant therapy in resected NSCLC. METHODS: We performed a single-institution, retrospective review of patients with stage II-III NSCLC who underwent upfront pulmonary resection, 2012-2016. Clinicopathologic and operative/perioperative details of treatment were collected. Travel distance was measured from patients' homes to the operative hospital. Our primary outcome was receipt of adjuvant systemic or radiotherapy. Travel distance was stratified as <100 or >100 miles. Multivariable logistic regression was performed. RESULTS: In total, 391 patients met inclusion criteria, with mean age of 65.9 years and fairly even sex distribution (182 women, 49.2%). Most patients were Non-Hispanic White (n = 309, 83.5%), and most frequent clinical stage was II (n = 254, 64.9%). Indicated adjuvant therapy was received by 266 (71.9%), and median distance traveled was 209 miles (interquartile range, 50.7-617). Multivariate analysis revealed that longer travel distance was inversely associated with receipt of indicated adjuvant therapy (odds ratio, 0.13; 95% confidence interval, 0.06-0.26; P < .001). In addition, Black patients were less likely to receive appropriate treatment (odds ratio, 0.05; 95% confidence interval, 0.02-0.15; P < .001). CONCLUSIONS: Travel distance >100 miles negatively impacts the likelihood of receiving indicated adjuvant therapy in NSCLC. Indications for systemic therapy in earlier staged disease are rapidly expanding, and these findings bear heightened relevance as we aim to provide equitable access to all patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Femenino , Anciano , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estadificación de Neoplasias , Neoplasias Pulmonares/cirugía , Terapia Combinada , Análisis Multivariante , Estudios Retrospectivos , Viaje
14.
J Thorac Oncol ; 19(3): 500-506, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38012986

RESUMEN

INTRODUCTION: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known. METHODS: We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups. RESULTS: A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib. CONCLUSIONS: Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.


Asunto(s)
Acrilamidas , Anticuerpos Biespecíficos , Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Femenino , Anciano , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inducido químicamente , Antineoplásicos/uso terapéutico , Receptores ErbB/genética , Receptores ErbB/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico
15.
J Surg Oncol ; 129(2): 331-337, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37876311

RESUMEN

BACKGROUND AND OBJECTIVES: For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging. METHODS: We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection. RESULTS: Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post-resection. CONCLUSIONS: We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Pulmonares , Humanos , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras) , Terapia Combinada , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía
16.
Ann Am Thorac Soc ; 21(1): 38-46, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37796618

RESUMEN

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC. Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative equations to generate race-specific and race-neutral normative equations to calculate percentage predicted forced expiratory volume in 1 second (FEV1%). The primary outcome of interest was the occurrence of postoperative pulmonary complications within 30 days of surgery. We used unadjusted and race-adjusted logistic regression models and least absolute shrinkage and selection operator analyses adjusted for relevant comorbidities to measure the association of race-specific and race-neutral FEV1% with pulmonary complications. Results: Thirty-one percent of patients who underwent surgery experienced pulmonary complications. Higher FEV1, whether measured with race-neutral (odds ratio [OR], 0.98 per 1% change in FEV1% [95% confidence interval (CI), 0.98-0.99]; P < 0.001) or race-specific (OR, 0.98 per 1% change in FEV1% [95% CI, 0.98-0.98]; P < 0.001) normative equations, was associated with fewer postoperative pulmonary complications. The area under the receiver operator curve for pulmonary complications was similar for race-adjusted race-neutral (0.60) and race-specific (0.60) models. Using least absolute shrinkage and selection operator regression, higher FEV1% was similarly associated with a lower rate of pulmonary complications in race-neutral (OR, 0.99 per 1% [95% CI, 0.98-0.99]) and race-specific (OR, 0.99 per 1%; 95% CI, 0.98-0.99) models. The marginal effect of race on pulmonary complications was attenuated in all race-specific models compared with all race-neutral models. Conclusions: The choice of race-specific or race-neutral normative PFT equations does not meaningfully affect the association of lung function with pulmonary complications after lobectomy for NSCLC, but the use of race-neutral equations unmasks additional effects of self-identified race on pulmonary complications.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Estudios Retrospectivos , Neumonectomía/efectos adversos , Pulmón/cirugía , Volumen Espiratorio Forzado , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía
17.
J Thorac Cardiovasc Surg ; 167(1): 329-337.e4, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37116780

RESUMEN

OBJECTIVES: Disparities in cancer care are omnipresent and originate from a multilevel set of barriers. Our objectives were to describe the likelihood of undergoing surgery for early-stage non-small cell lung cancer at minority-serving hospitals (MSHs), and evaluate the association of race/ethnicity with resection based on MSH status. METHODS: A retrospective study using the National Cancer Database (2008-2016) was conducted including patients with clinical stage I non-small cell lung cancer. MSHs were defined as hospitals in the top decile of providing care to Hispanic or African American patients. The primary outcome evaluated was receipt of definitive surgery at MSHs vs non-MSHs. Outcomes related to race/ethnicity stratified by hospital type were also investigated. RESULTS: A total of 142,580 patients were identified from 1192 hospitals (120 MSHs and 1072 non-MSHs). Most patients (85% [n = 121,240]) were non-Hispanic White, followed by African American (9% [n = 12,772]), and Hispanic (3%, [n= 3749]). MSHs cared for 7.4% (n = 10,491) of the patients included. In adjusted analyses, patients treated at MSHs were resected less often than those at non-MSHs (odds ratio, 0.87; 95% CI, 0.76-1.00; P = .0495). African American patients were less likely to receive surgery in the overall analysis (P < .01), and at MSHs specifically (P < .01), compared with non-Hispanic White patients. Hispanic patients had similar rates of resection in the overall analysis (P = .11); however, at MSHs, they underwent surgery more often compared with non-Hispanic White patients (P = .02). Resected patients at MSHs had similar overall survival (median, 91.7 months; 95% CI, 86.6-96.8 months) compared with those resected at non-MSHs (median, 85.7 months; 95% CI, 84.5-86.8 months). CONCLUSIONS: Patients with early-stage non-small cell lung cancer underwent resection less often at MSHs compared with non-MSHs. Disparities related to underutilization of surgery for African American patients continue to persist, regardless of hospital type.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Hospitales , Disparidades en Atención de Salud , Blanco
18.
Crit Care Nurse ; 43(6): 11-21, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38035619

RESUMEN

BACKGROUND: The aim of this evidence-based practice project was to determine if a digital air leak detection device could speed the identification of chest tube air leak cessation in patients after pulmonary lobectomy. Staff members assessing air leaks have varying levels of expertise, and the digital device is a limited resource in the study institution. A chest tube management algorithm is necessary to standardize care and determine which patients are most likely to benefit. IMPLEMENTATION: Twenty-five consecutive patients who underwent pulmonary lobectomy during the study period and continued to have a chest tube air leak on postoperative day 3 were monitored with digital air leak detection devices. The Mann-Whitney U test was used to compare chest tube duration and hospital length of stay between patients with digital devices and 259 patients who had traditional analog air leak detection devices (historical data from the departmental database over the previous 2 years). EVALUATION: Median chest tube duration and hospital stay were 1 day less in patients with digital devices than in those with traditional analog devices (P = .01 and P = .004, respectively), with a cost savings of $2659 per hospital day. Reductions in chest tube duration and length of stay aided in the development of a chest tube management algorithm. CONCLUSIONS: Critical care nurses are valued team members who treat patients after lung resections. Digital air leak detection devices can help them assess air leaks more accurately, benefiting the patients in their care.


Asunto(s)
Tubos Torácicos , Neumonectomía , Humanos , Tiempo de Internación , Algoritmos , Cuidados Críticos , Complicaciones Posoperatorias/terapia
19.
J Thorac Dis ; 15(10): 5507-5516, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37969292

RESUMEN

Background: Therapeutic decisions in non-small cell lung cancer (NSCLC) are stage-dependent, and, consequently, changes in an individual's stage carry potential for substantial alterations in management. Malignancy-related disturbances of the circulomic inflammatory environment may affect platelets quantitatively, ultimately leading to changes in tumor characteristics. Our objective was to identify circulomic characteristics associated with upstaging among chemotherapy-naïve patients with resected NSCLC and to assess the consequent impact on overall survival (OS). Methods: A retrospective review of a prospectively maintained thoracic surgery database was performed, identifying chemotherapy-naïve patients who underwent resection of clinical stage I-III NSCLC between 1998 and 2021. Clinicopathologic characteristics were gathered; circulomic variables comprised of platelet and lymphocyte count from the last blood draw prior to resection. Platelet-to-lymphocyte ratio (PLR) was calculated. A multivariate model evaluated variables that might affect upstaging. Kaplan-Meier analysis was performed to assess OS. Results: A total of 4,141 patients met inclusion criteria (median age: 67.0 years) among whom the sex distribution was fairly equal (2,189 female, 52.9%), and 1,016 (24.5%) individuals were upstaged. Patients with elevated PLR were found to have reduced risk of upstaging [odds ratio (OR): 0.757, 95% confidence interval (CI): 0.650-0.882]. Analyses revealed that median OS for patients who were upstaged was 80.0 months compared to 130.7 months among those who weren't upstaged (P<0.0001). Conclusions: PLR appears to predict upstaging in treatment-naïve patients with resected NSCLC. In addition to clinicopathologic characteristics, circulomic variables may provide insight relating to pathologic staging prior to resection. These findings may guide patient counseling regarding survival probability, as well as referral patterns for adjuvant therapy.

20.
Oncoscience ; 10: 44-53, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37736255

RESUMEN

Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma. In this case report, we discuss the case of a patient with a EWSR1-NFATC2 fusion positive bone sarcoma who had exceptional tumor control through using pazopanib and surgery for an overall duration exceeding 5 years. We also review the literature on EWSR1-NFATC2 translocation-associated sarcomas and use of pazopanib in bone sarcomas.

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