Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8517-8517
Author(s):  
Davina Gale ◽  
Katrin Heider ◽  
Malcolm Perry ◽  
Giovanni Marsico ◽  
Andrea Ruiz-Valdepeñas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Sequencing ◽  
Early Stage ◽  
Post Treatment ◽  
Disease Stage ◽  
Analytical Sensitivity ◽  
Disease Relapse ◽  
Clinical Progression ◽  
Liquid Biopsies ◽  
Early Stage Disease

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to > 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value < 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.

scholarly journals Lung Cancer in Homeless People: Clinical Outcomes and Cost Analysis in a Single Institute

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Koung Jin Suh ◽  
Ki Hwan Kim ◽  
Jin Lim ◽  
Jin Hyun Park ◽  
Jin-Soo Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Medical Center ◽  
Homeless People ◽  
Stage Iv ◽  
Disease Stage ◽  
Curative Surgery ◽  
Early Stage Disease ◽  
Outpatient Visits

Introduction. To characterize the demographic and clinical features, outcomes, and treatment costs of lung cancer in homeless people. Methods. Medical records of 22 homeless patients with lung cancer at Seoul National University Boramae Medical Center in Seoul, South Korea, were retrospectively analyzed. Results. All patients were men (median age, 62 years). Most patients (78%) had advanced disease (stage IIIB, n=2; stage IV, n=15). Seven died during initial hospitalization (median survival, 1.5 months). Six were lost to follow-up after initial outpatient visits or discharges from initial admission (median follow-up, 13 days). Only 4 received appropriate treatment for their disease and survived for 1, 15, 19, and 28 months, respectively. Conversely, 4 of 5 patients with early stage disease (stage I, n=4; stage IIA, n=1) received curative surgery (median follow-up 25.5 months). The median treatment cost based on 29 days of hospitalization and 2 outpatient visits was $12,513, constituting 47.3% of the 2013 per capita income. Inpatient treatment accounted for 90% of the total costs. The National Health Insurance Service paid 82% of the costs. Conclusion. Among the homeless, lung cancer seems to be associated with poor prognosis and substantial costs during a relatively short follow-up and survival period.

Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3056-3056
Author(s):  
B.E. Shaw ◽  
N.P. Mayor ◽  
A.-M. Little ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
...  
Keyword(s):  
Late Stage ◽  
Early Stage ◽  
Disease Stage ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Early Stage Disease ◽  
Hla Alleles ◽  
Graft Versus Host ◽  
Multiple Loci ◽  
Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

scholarly journals Clinical features and overall survival among elderly cancer patients in a tertiary cancer center

2015 ◽  
Vol 13 (4) ◽  
pp. 487-491 ◽  
Author(s):  
Yuri Philippe Pimentel Vieira Antunes ◽  
Diogo Diniz Gomes Bugano ◽  
Auro del Giglio ◽  
Rafael Aliosha Kaliks ◽  
Theodora Karnakis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Solid Tumors ◽  
Early Stage ◽  
Large Population ◽  
Disease Stage ◽  
Cancer Center ◽  
Early Stage Disease ◽  
Number Of Patients

ABSTRACT Objective To evaluate the epidemiological profile and overall survival of a large population of elderly individuals diagnosed with solid tumors in a tertiary hospital. Methods This retrospective study included patients aged >65 years, diagnosed with solid tumors between January 2007 and December 2011, at Hospital Israelita Albert Einstein, São Paulo, Brazil. The medical records were reviewed to obtain information about clinical variables and overall survival. Results A total of 806 patients were identified, and 58.4% were male. Mean age was 74 years (65 to 99 years). The most common types were prostate (22%), colorectal (21%), breast (19%), and lung cancer (13%), followed by bladder (8%), pancreas (6%), and other types (11%). The majority of patients were diagnosed at early stage disease. After a median follow-up of 27 months (15 to 45 months), 29% of the patients (234/806) died, predominantly in the group older than 70 years. For the entire cohort, the median 2-year survival rate was 71%. Median overall survival was not reached within the study period. In a multivariate analysis, age (HR: 1.35; 95%CI: 1.25-1.45; p<0.001) and disease stage (HR: 1.93; 95%CI: 1.75-2.14; p<0.001) were independent negative predictors of poor survival. Conclusion The most prevalent tumors were prostate, colorectal, breast, and lung cancer, with the larger proportion diagnosed at initial stages, reflecting the great number of patients alive at last follow-up.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals A population-based analysis of spirometry use and the prevalence of chronic obstructive pulmonary disease in lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sophie Corriveau ◽  
Gregory R. Pond ◽  
Grace H. Tang ◽  
John R. Goffin
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Early Stage ◽  
Advanced Lung Cancer ◽  
Public Healthcare ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Early Stage Disease ◽  
Morbidity Score

Abstract Background Chronic obstructive pulmonary disease (COPD) and lung cancer are associated diseases. COPD is underdiagnosed and thus undertreated, but there is limited data on COPD diagnosis in the setting of lung cancer. We assessed the diagnosis of COPD with lung cancer in a large public healthcare system. Methods Anonymous administrative data was acquired from ICES, which links demographics, hospital records, physician billing, and cancer registry data in Ontario, Canada. Individuals age 35 or older with COPD were identified through a validated, ICES-derived cohort and spirometry use was derived from physician billings. Statistical comparisons were made using Wilcoxon rank sum, Cochran-Armitage, and chi-square tests. Results From 2002 to 2014, 756,786 individuals were diagnosed with COPD, with a 2014 prevalence of 9.3%. Of these, 51.9% never underwent spirometry. During the same period, 105,304 individuals were diagnosed with lung cancer, among whom COPD was previously diagnosed in 34.9%. Having COPD prior to lung cancer was associated with lower income, a rural dwelling, a lower Charlson morbidity score, and less frequent stage IV disease (48 vs 54%, p < 0.001). Spirometry was more commonly undertaken in early stage disease (90.6% in stage I-II vs. 54.4% in stage III-IV). Conclusion Over a third of individuals with lung cancer had a prior diagnosis of COPD. Among individuals with advanced lung cancer, greater use of spirometry and diagnosis of COPD may help to mitigate respiratory symptoms.

scholarly journals Radiomics is feasible for prediction of spread through air spaces in patients with nonsmall cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuki Onozato ◽  
Takahiro Nakajima ◽  
Hajime Yokota ◽  
Jyunichi Morimoto ◽  
Akira Nishiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Predictive Model ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Characteristic Curve ◽  
Sublobar Resection ◽  
Tumor Spread ◽  
Early Stage Disease ◽  
Significant Difference ◽  
Spread Through Air Spaces

AbstractTumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (−) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p < 0.01). These results suggest that radiomics with machine-learning helped to develop a favorable model of STAS (+) NSCLC, which might be useful for the proper selection of candidates who should undergo sublobar resection.

The effects of season and devil facial tumour disease on the reproductive physiology of the male Tasmanian devil (Sarcophilus harrisii)

2012 ◽  
Vol 24 (7) ◽  
pp. 999 ◽  
Author(s):  
T. Keeley ◽  
P. D. McGreevy ◽  
J. K. O'Brien
Keyword(s):  
Early Stage ◽  
Reproductive Function ◽  
Serum Testosterone ◽  
Serum Cortisol ◽  
Disease Stage ◽  
Rapid Decline ◽  
Tasmanian Devil ◽  
Early Stage Disease ◽  
Devil Facial Tumour Disease ◽  
Disease Free

Devil facial tumour disease (DFTD) is the cause of the rapid decline of wild Tasmanian devils. Female devils are seasonal breeders with births peaking during autumn (i.e. March) but the degree of reproductive seasonality in male devils is unknown. The objective of this study was to examine the potential effects of season and DFTD on reproductive function in male devils (n = 55). Testicular (1.90 ± 0.23 g) and epididymal (0.90 ± 0.06 g) weights were maximal during autumn and spring (P < 0.05), whereas prostate (3.71 ± 0.74 g) and Cowper’s gland (0.68 ± 0.22; 0.52 ± 0.21 g) weights peaked during autumn (P < 0.001). The motility of spermatozoa from the cauda epididymides extracted post-mortem was similar (P > 0.05) across season and disease state (31.5 ± 13.1% total motility). Testicular and epididymal weights were no different between animals displaying late or early-stage DTFD signs or disease-free animals (P > 0.1). The accessory sex glands were larger in late-stage DFTD animals than in animals with early-stage disease signs or which were disease-free (P < 0.01) but effects of season on this result can’t be excluded. Serum testosterone concentrations peaked during summer (0.25 ± 0.18 ng mL–1) but values were not different from the preceding and subsequent seasons (P > 0.05), nor influenced by disease stage (P > 0.1). Seasonal and DFTD-related changes in serum cortisol concentrations were not evident (P > 0.1). Male devil reproduction does not appear to be restricted by season nor inhibited by DFTD.

scholarly journals International Study of Primary Mucinous Ovarian Carcinomas Managed at Tertiary Medical Centers

2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  
Keyword(s):  
Early Stage ◽  
Statistical Tests ◽  
Stage Iv ◽  
Stage I ◽  
Stage Iii ◽  
Oncologic Outcomes ◽  
Disease Stage ◽  
Ovarian Carcinomas ◽  
Early Stage Disease ◽  
Medical Centers

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

scholarly journals Implementation of targeted screening for lung cancer in a high-risk population within routine NHS practice using low-dose computed tomography

Thorax ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 348-350 ◽  
Author(s):  
Helen Grover ◽  
Thomas Ross ◽  
Elizabeth Fuller
Keyword(s):  
Lung Cancer ◽  
Low Dose ◽  
Screening Programme ◽  
Early Stage ◽  
High Risk Population ◽  
Curative Intent ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Targeted Screening ◽  
Low Dose Computed Tomography

We report a primary care-based lung cancer targeted screening programme using low-dose CT (LDCT) in South Tyneside and Sunderland. Ever smokers with ≥10 pack-years aged 55–74 years were identified at annual COPD review. 925 individuals attended for LDCT. 2% (n=19/925) had lung cancer diagnosed. 66.7% (n=14/21) had early stage disease and 78.9% (n=15/19) were offered treatment with curative intent. 79.3% of individuals attending for LDCT were ranked in the lowest deprivation quintiles. This approach has been successfully established in routine NHS practice; it is effective with improvements in stage of disease and engages individuals in deprived areas.

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