Cancer overdiagnosis: a biological challenge and clinical dilemma

Srivastava, Sudhir; Koay, Eugene J.; Borowsky, Alexander D.; Marzo, Angelo M. De; Ghosh, Sharmistha; Wagner, Paul D.; Kramer, Barnett S.

doi:10.1038/s41568-019-0142-8

Cited by 251 publications

(190 citation statements)

References 134 publications

Supporting

Mentioning

184

Contrasting

Unclassified

Order By: Relevance

“…In clinical practice, it is unjustified to follow-up a patient with preoperative diagnosis of PTC with LNM without surgery; thus, it is difficult to directly assess the unperturbed natural history of a given lesion [12]. Additionally, although radioguided occult localization technique could be used to localize the lesion site of cervical recurrences from DTC in a study [13], LNM status can still not be accurately assessed before surgery in clinical work.…”

Section: Discussionmentioning

confidence: 99%

Lymph node metastasis in young and middle-aged papillary thyroid carcinoma patients: a SEER-based cohort study

et al. 2020

View full text Add to dashboard Cite

Background: Lymph node metastasis (LNM) occurs frequently in young papillary thyroid carcinoma (PTC) patients, though the mortality rates are low. We aimed to analyze the relationship between age at diagnosis and LNM in PTC at a population level to elucidate the clinical behavior of PTC. Methods: Data of adult patients with surgically treated PTC and follicular thyroid carcinoma (FTC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) to investigate the relationship between age and clinical characteristics by curve estimation. The adjusted odds ratio of age and LNM rate were determined.Results: A total of 50,347 PTC (48,166) and FTC (2181) (median age: 45 and 50 years, respectively) patients met the inclusion criteria; 44.5% of those with PTC (21,428) had LNM. Rank-sum test analysis indicated differences in distribution of age in LNM-positive and LNM-negative PTC. The relationship between age, tumor size and LNM showed a quadratic curve in PTC. The mean tumor diameter and LNM rate correlated linearly with age in 18-59year-old patients. LNM rate decreased with age (R 2 = 0.932, P < .0001), especially women (R 2 = 0.951, P < .0001). Conclusion:In young and middle-aged PTC patients, LNM may resolve spontaneously with delayed diagnosis and management. Active surveillance of low-risk PTC is justified.

show abstract

Section: Discussionmentioning

confidence: 99%

Lymph node metastasis in young and middle-aged papillary thyroid carcinoma patients: a SEER-based cohort study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Pancreatic cancer (PC), with its low incidence but high mortality, is one of the most fatal malignant neoplasms globally. 1,2 The molecular mechanism and therapeutic strategies of PC have been continuously studied. 3,4 Therefore, it is of great significance for us to determine the molecular mechanism of PC and find more novel biomarkers for PC to contribute to the developmental, preventive and therapeutic strategies for PC.…”

Section: Introductionmentioning

confidence: 99%

<p>KRT17 Functions as a Tumor Promoter and Regulates Proliferation, Migration and Invasion in Pancreatic Cancer via mTOR/S6k1 Pathway</p>

Li¹,

Ni²,

Tang³

et al. 2020

CMAR

View full text Add to dashboard Cite

Background: Pancreatic cancer (PC) is one of the most well-known malignancies with high mortality, but the underlying mechanism of PC remains unknown. Keratin17 (KRT17) expression has been reported in many malignancies, but its functions in PC are not clear. The aim of our study was to evaluate KRT17 expression and its potential role in PC. Methods: The online databases GEPIA and THPA were used to identify KRT17 expression in tissues. Quantitative real-time PCR (qRT-PCR) was used to determine KRT17 expression in cell lines. Ki67 and ROS levels were detected by immunofluorescence assay and a 2ʹ,7ʹdichlorodihydrofluorescein diacetate (DCFH-DA) probe. KRT17 downregulation was induced by the small interfering RNA (siRNA) technique. Proliferation function was evaluated by colony formation assay and RTCA. Migration and invasion were evaluated by transwell migration assay. A Western blot assay was used to detect protein levels. Results: KRT17 was overexpressed in PC tissues compared to that in normal tissues. The results showed that Ki67 and ROS levels were decreased in pancreatic cancer cells after transfection with siKRT17. After KRT17 downregulation in PC cell lines, cell viability functions, including proliferation, migration and invasion, and mTOR/S6K1 phosphorylation levels were attenuated. Conclusion: KRT17 knockdown significantly inhibited proliferation, migration and invasion in pancreatic cancer cells.

show abstract

“…A major challenge of cancer early detection is the stochastic nature of cancer initiation and progression. While new technologies can detect smaller and smaller tumors, the optimal treatment of asymptomatic tumors is often unclear and needs to be balanced with the risk for overtreatment as well as undertreatment (Srivastava et al 2019;Mattox et al 2019). For example, in more than 20% of smokers suspicious lesions can be found by low-dose computed tomographic screening.…”

Section: Discussionmentioning

confidence: 99%

“…Early stage cancer patients are more likely to be cured than advanced stage cancer patients (Etzioni et al 2003;Song et al 2018;Srivastava et al 2019;Mattox et al 2019). For example, the five-year survival rate of lung cancer patients who are diagnosed at a localized stage is 57% while for those diagnosed with distant metastases is only 5% (Siegel, Miller, and Jemal 2020).…”

Section: Introductionmentioning

confidence: 99%

A mathematical model of ctDNA shedding predicts tumor detection size

Avanzini

Kurtz

Chabon

et al. 2020

Preprint

View full text Add to dashboard Cite

Early cancer detection aims to find tumors before they progress to an uncurable stage. Prospective studies with tens of thousands of healthy participants are ongoing to determine whether asymptomatic cancers can be accurately detected by analyzing circulating tumor DNA (ctDNA) from blood samples. We developed a stochastic mathematical model of tumor evolution and ctDNA shedding to investigate the potential and the limitations of ctDNA-based cancer early detection tests. We inferred ctDNA shedding rates of early stage lung cancers and calculated that a 15 mL blood sample contains on average only 1.5 genome equivalents of ctDNA for lung tumors with 1 billion cells (size of ~1 cm 3 ). We considered two clinically different scenarios: cancer screening and cancer relapse detection. For monthly relapse testing with a sequencing panel covering 20 tumor-specific mutations, we found a median detection size of 0.24 cm 3 corresponding to a lead time of 160 days compared to imaging-based relapse detection. For annual screening, we found a median detection size of 2.8-4.8 cm 3 depending on the sequencing panel size and on the mutation frequency. The expected detection sizes correspond to lead times of 390-520 days compared to current median lung tumor sizes at diagnosis. This quantitative framework provides a mechanistic interpretation of ctDNA-based cancer detection approaches and helps to optimize cancer early detection strategies.

show abstract

Cancer overdiagnosis: a biological challenge and clinical dilemma

Cited by 251 publications

References 134 publications

Lymph node metastasis in young and middle-aged papillary thyroid carcinoma patients: a SEER-based cohort study

Lymph node metastasis in young and middle-aged papillary thyroid carcinoma patients: a SEER-based cohort study

<p>KRT17 Functions as a Tumor Promoter and Regulates Proliferation, Migration and Invasion in Pancreatic Cancer via mTOR/S6k1 Pathway</p>

A mathematical model of ctDNA shedding predicts tumor detection size

Contact Info

Product

Resources

About