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UberDx Chapter 6

Harding PPThe latest salvo in the mammography overdiagnosis debate, from Harding et al at

JAMA Intern Med. Published online July 06, 2015. doi:10.1001/jamainternmed.2015.3043

A classic overdiagnosis curve, showing a dramatic increase in breast cancer diagnosis, as related to proportion of women getting mammograms, without a commensurate change in 10 year mortality.

If we can’t stop the mammography juggernaut, we should at least inform our patients of the risks of overdiagnosis.


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The Natural History of Benign Thyroid Nodules

Friday, we discussed the UBER sexy topic of thyroid nodules:

Durante et al, “The Natural History of Benign Thyroid Nodules,” JAMA. 2015; 313(9):926-935

Why do we care?

We all have “that patient” who has to get repeat thyroid ultrasounds and aspirations for either a nodule or multinodular disease. More than 90% of detected nodules are clinically insignificant benign lesions, but we are picking up more thyroid nodules everyday with our non-evidence-based annual physicals and incidentalomas on CT/MRI.

Currently, established guidelines for initial biopsy include:

– nodule size: > 1 cm

– sonographic characteristics: hypoechogenicity, irregular margins, taller-than-wide shape, intranodular vascular spots, microcalcifications

Furthermore, current guidelines recommend serial ultrasound exams for benign thyroid nodules and repeat needle biopsy if a nodule grows by 20%. The problem is that not much is known about the correlation between nodule growth and actual cancer.

This was a prospective study that followed some middle-aged Italian folks over five years with benign nodules, confirmed via laboratory testing and needle aspiration at the baseline evaluation. They received serial ultrasounds and a needle aspiration if they experienced nodule growth of 20% or if the ultrasound met the above-mentioned criteria for biopsy.

P: About a thousand Italian people, with a mean age of 52 years, 82% of whom were female. After loss to follow up and people who no longer met criteria (developed thyroid dysfunction), they were left with 992 patients.

I: This study wasn’t really about an “intervention,” rather it followed growth of nodules over time, so the groups were split into those who experienced growth vs…

C: Those who experienced no growth.

O: In 69% of patients, the thyroid nodules remained stable. 18% shrank spontaneously. In 2%, the nodules *disappeared.* 15% grew, most of which were in patients who had multiple nodules at baseline. 9% developed new nodules. “Over the course of the 5 years, 37% met re-aspiration criteria (growth or concerning features on ultrasound).” (growth or concerning features on ultrasound). Of these, 98.9% confirmed the baseline benign diagnosis.  Thyroid cancer was detected in 0.3% of the 1567 original nodules. 

Limitations:

– 1k patients in the grand scheme of things isn’t a whole lot, but it helps that this study underlines what we already suspected about thyroid nodules

– This doesn’t help us with younger people, in whom thyroid cancer is more prevalent

– 5 years of follow up is a drop in the bucket compared to the usual length of time our patients get follow up (eons) — additional studies should have a longer follow up time

– This was the most boring article EVER. Seriously. OMG.

Bottom Line: Don’t freak out about thyroid nodules! And the guidelines should probably space out ultrasounds because most of them won’t grow, anyway.


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Lung-Cancer Screening with Low-Dose Computed Tomography

Bonjou, zanmi!  Today, in Journal Club, we discussed:

Lung-Cancer Screening with Low-Dose Computed Tomography

Gould, MK. NEJM 6 Nov 2014 pp1813-1820

The issue:

Lung CA is the leading cause of death from cancer in both men and women in the US. Despite the advances of modern medicine, only 18% of patients with lung CA are still alive 5 years after diagnosis. Early trials of chest x-rays and sputum screening don’t decrease lung cancer mortality. This engendered studies worldwide that demonstrated the sensitivity of CT scanning, particularly the low dose varieties that reduce radiation by 75-80% (but are still 10-15 times higher than plain films). The pitfalls of these studies are that they were vulnerable to lead-time bias (read: same mortality, earlier diagnosis) and overdiagnosis.

The data:

The National Lung Screening Trial enrolled 50,000 people at 33 US centers who were:

  • 55-74 years of age
  • At least 30 pack year hx
  • If a former smoker, had to have quit within previous 15 years

Randomly assigned to three rounds of annual screening with low-dose CT vs chest radiography. 20% reduction in lung cancer mortality was shown (247 vs 309 deaths per 100,000 patient-years) which translated into 3 fewer deaths from lung CA per 1000 high risk patients who underwent low-dose CT screening. This magnitude of benefit is at least as great as that reported for breast cancer mortality with annual (not biennial) mammo screening among women 50-59 years of age. Which is to say, more lead-time bias.

Of course: 39% of the participants had at least one positive result, and more than 95% of these findings were falsely positive. 10% of participants underwent tissue sampling. This adds to the data that show the reduction in lung-cancer mortality observed in the NLST is not as clear as the author is purporting.

Funky stuff:

  • USPSTF jumped on the bandwagon in Dec 2013 and released a grade B recommendation in favor of annual low-dose CT screening for high risk patients (55-80 w/ 30py smoking hx who are either currently smoking or quit within the last 15 years).
  • Conflicting committee opinions on how to apply the NLST data have resulted in how Medicare will cover this.
  • The greatest benefits of screening are found in those at highest risk for death from lung cancer, who, really, have the least to gain from screening than those at low risk!

Conclusions we drew from the conclusions

  • Annual lung cancer screening of high risk and former smokers with low dose CT mirrors annual breast cancer screening in 50-59 year old women with mammography. i.e. increases lead time bias without making a real impact on our patients’ qualities of life.
  • Though the article’s recs say that screening with low-dose CT prevents one in five deaths from lung cancer, we can’t fiddle with the numbers to make this work. Fellows: could you help us with this?
  • Lung cancer screening is NOT a single test, it is ANNUAL testing and the article makes no judgment about cost-effectiveness.
  • False positives Each examination is approximately 20 times as likely to yield a false positive as it is to reveal lung cancer.
    • Of those false positives, 5% will require invasive evaluation.
  • No surprise here: screening for lung CA with low dose CT is not a substitute for smoking cessation.

EBM points:

Always look for the NNT on these things. Per The NNT (http://www.thennt.com/nnt/ct-scans-to-screen-for-lung-cancer/)

1 in 217 are helped (prevented death)
1 in 4 were harmed by false positive
1 in 30 were harmed by unnecessary surgery
1 in 161 were harmed by surgical complication

Per the NNT: “…Despite these caveats the significant and surprisingly large reduction in mortality using CT screening in this trial is promising. Because this is the first high quality randomized trial of CT screening it will take multiple further trials to confirm the benefit, and it will be critical to apply these data only to people at very high risk unless future trials expand to include others.”.

I dunno, y’all, our discussion made me more negative about it than The NNT seems to think.

Danielle (PGY-3)


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How many women have HPV?

Through the biostats information gleaned from the “ARTISTIC” trial and the U.K.’s NHS data, in addition to the wonderfully powerful tool of Bayesian Calculation, here’s a cool chart showing the estimated prevalence of HPV by age for women.  It uses an elegant model to extract likelihoods based on known probabilities.

You can easily see why patients between the ages of 21-24 are treated differently than at older ages (by the ASCCP guidelines) for pap smears of ASC-US and LSIL.  (Interpretation: the bump is biggest in the teenage years to the mid 20s.  Any guesses why?)

Projected HPV-16 rate in Women

(Don’t bother reading this article unless you’re a part of the Bayesian conspiracy.)

[edit: here is Raj’s picture since imgur is blocked on CHA work computers]

 

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