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Medcity Converge 2018 Philadelphia: Live Coverage @pharma_BI
Stephen J. Williams: Reporter
3.3.3 Medcity Converge 2018 Philadelphia: Live Coverage @pharma_BI, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair
MedCity CONVERGE is a two-day executive summit that gathers innovative thought leaders from across all healthcare sectors to provide actionable insight on where oncology innovation is heading.
On July 11-12, 2018 in Philadelphia, MedCity CONVERGE will gather technology disruptors, payers, providers, life science companies, venture capitalists and more to discuss how AI, Big Data and Precision Medicine are changing the game in cancer. See agenda.
The conference highlights innovation and best practices across the continuum—from research to technological innovation to transformations of treatment and care delivery, and most importantly, patient empowerment—from some of the country’s most innovative healthcare organizations managing the disease.
Meaningful networking opportunities abound, with executives driving the innovation from diverse entities: leading hospital systems, medical device firms, biotech, pharma, emerging technology startups and health IT, as well as the investment community.
Day 1: Wednesday, July 11, 2018
7:30 AM
2nd Floor – Paris Foyer
Registration + Breakfast
8:15 AM–8:30 AM
Paris Ballroom
Welcome Remarks: Arundhati Parmar, VP and Editor-in-Chief, MedCity News
8:30 AM–9:15 AM
Paris Ballroom
Practical Applications of AI in Cancer
We are far from machine learning dictating clinical decision making, but AI has important niche applications in oncology. Hear from a panel of innovative startups and established life science players about how machine learning and AI can transform different aspects in healthcare, be it in patient recruitment, data analysis, drug discovery or care delivery.
Opening Keynote: Dr. Joshua Brody, Medical Oncologist, Mount Sinai Health System
The Promise and Hype of Immunotherapy
Immunotherapy is revolutionizing oncology care across various types of cancers, but it is also necessary to sort the hype from the reality. In his keynote, Dr. Brody will delve into the history of this new therapy mode and how it has transformed the treatment of lymphoma and other diseases. He will address the hype surrounding it, why so many still don’t respond to the treatment regimen and chart the way forward—one that can lead to more elegant immunotherapy combination paths and better outcomes for patients.
Startups from diagnostics, biopharma, medtech, digital health and emerging tech will have 8 minutes to articulate their visions on how they aim to tame the beast.
Breakout: Biopharma Gets Its Feet Wet in Digital Health
In the last few years, biotech and pharma companies have been leveraging digital health tools in everything from oncology trials, medication adherence to patient engagement. What are the lessons learned?
Moderator:Anthony Green, Ph.D., Vice President, Technology Commercialization Group, Ben Franklin Technology Partners Speakers: Derek Bowen, VP of Business Development & Strategy, Blackfynn, Inc. Gyan Kapur, Vice President, Activate Venture Partners Tom Kottler, Co-Founder & CEO, HealthPrize Technologies @HealthPrize
11:00 AM–11:45 AM
Paris Ballroom
Breakout: How to Scale Precision Medicine
The potential for precision medicine is real, but is limited by access to patient datasets. How are government entities, hospitals and startups bringing the promise of precision medicine to the masses of oncology patients
Building a Precision Medicine Business from the Ground Up: An Operating and Venture Perspective
Dr. Pellini has spent more than 20 years working on the operating side of four companies, each of which has pushed the boundaries of the standard of care. He will describe his most recent experience at Foundation Medicine, at the forefront of precision medicine, and how that experience can be leveraged on the venture side, where he now evaluates new healthcare technologies.
The randomized, controlled clinical trial is the gold standard, but it may be time for a new model. How can patient networks and new technology be leveraged to boost clinical trial recruitment and manage clinical trials more efficiently?
CONVERGEnce on Steroids: Why Comcast and Independence Blue Cross?
This year has seen a great deal of convergence in health care. One of the most innovative collaborations announced was that of Cable and Media giant Comcast Corporation and health plan Independence Blue Cross. This fireside chat will explore what the joint venture is all about, the backstory of how this unlikely partnership came to be, and what it might mean for our industry.
sponsored by Independence Blue Cross
Moderator:Tom Olenzak, Managing Director Strategic Innovation Portfolio, Independence Blue Cross @IBX Speakers: Marc Siry, VP, Strategic Development, Comcast Michael Vennera, SVP, Chief Information Officer, Independence Blue Cross
3:00 PM–3:15 PM
Paris Foyer
Networking Break + Showcase
3:15 PM–4:00 PM
Montpellier – 3rd Floor
Breakout: Charting the Way Forward in Gene and Cell Therapy
There is a boom underway in cell and gene therapies that are being wielded to tackle cancer and other diseases at the cellular level. FDA has approved a few drugs in the space. These innovations raise important questions about patient access, patient safety, and personalized medicine. Hear from interesting startups and experts about the future of gene therapy.
Moderator:Alaric DeArment, Senior Reporter, MedCity News Speakers: Amy DuRoss, CEO, Vineti Andre Goy, M.D., Chairman and Director of John Theurer Cancer Center , Hackensack University Medical Center
3:15 PM–4:00 PM
Paris Ballroom
Breakout: What’s A Good Model for Value-Based Care in Oncology?
How do you implement a value-based care model in oncology? Medicare has created a bundled payment model in oncology and there are lessons to be learned from that and other programs. Listen to two presentations from experts in the field.
Breakout: What Patients Want and Need On Their Journey
Cancer patients are living with an existential threat every day. A panel of patients and experts in oncology care management will discuss what’s needed to make the journey for oncology patients a bit more bearable.
sponsored by CEO Council for Growth
Moderator:Amanda Woodworth, M.D., Director of Breast Health, Drexel University College of Medicine Speakers: Kezia Fitzgerald, Chief Innovation Officer & Co-Founder, CareAline® Products, LLC Sara Hayes, Senior Director of Community Development, Health Union @SaraHayes_HU Katrece Nolen, Cancer Survivor and Founder, Find Cancer Help @KatreceNolen John Simpkins, Administrative DirectorService Line Director of the Cancer Center, Children’s Hospital of Philadelphia
5:00 PM–5:45 PM
Paris Ballroom
Early Diagnosis Through Predictive Biomarkers, NonInvasive Testing
Diagnosing cancer early is often the difference between survival and death. Hear from experts regarding the new and emerging technologies that form the next generation of cancer diagnostics.
Opening Remarks: Arundhati Parmar, VP and Editor-in-Chief, MedCity News
8:40 AM–9:25 AM
Paris Ballroom
The Davids vs. the Cancer Goliath Part 2
Startups from diagnostics, biopharma, medtech, digital health and emerging tech will have 8 minutes to articulate their visions on how they aim to tame the beast.
Liquid Biopsy and Gene Testing vs. Reimbursement Hurdles
Genetic testing, whether broad-scale or single gene-testing, is being ordered by an increasing number of oncologists, but in many cases, patients are left to pay for these expensive tests themselves. How can this dynamic be shifted? What can be learned from the success stories?
Moderator:Shoshannah Roth, Assistant Director of Health Technology Assessment and Information Services , ECRI Institute @Ecri_Institute Speakers: Rob Dumanois, Manager – reimbursement strategy, Thermo Fisher Scientific Eugean Jiwanmall, Senior Research Analyst for Medical Policy & Technology Evaluation , Independence Blue Cross @IBX Michael Nall, President and Chief Executive Officer, Biocept
10:15 AM–10:25 AM
Paris Foyer
Networking Break + Showcase
10:25 AM–11:10 AM
Paris Ballroom
Promising Drugs, Pricing and Access
The drug pricing debate rages on. What are the solutions to continuing to foster research and innovation, while ensuring access and affordability for patients? Can biosimilars and generics be able to expand market access in the U.S.?
Moderator:Bunny Ellerin, Director, Healthcare and Pharmaceutical Management Program, Columbia Business School Speakers: Patrick Davish, AVP, Global & US Pricing/Market Access, Merck Robert Dubois M.D., Chief Science Officer and Executive Vice President, National Pharmaceutical Council Gary Kurzman, M.D., Senior Vice President and Managing Director, Healthcare, Safeguard Scientifics Steven Lucio, Associate Vice President, Pharmacy Services, Vizient
11:10 AM–11:20 AM
Networking Break + Showcase
11:20 AM–12:05 PM
Paris Ballroom
Breaking Down Silos in Research
“Silo” is healthcare’s four-letter word. How are researchers, life science companies and others sharing information that can benefit patients more quickly? Hear from experts at institutions that are striving to tear down the walls that prevent data from flowing.
Moderator:Vini Jolly, Executive Director, Woodside Capital Partners Speakers: Ardy Arianpour, CEO & Co-Founder, Seqster @seqster Lauren Becnel, Ph.D., Real World Data Lead for Oncology, Pfizer Rakesh Mathew, Innovation, Research, & Development Lead, HealthShareExchange David Nace M.D., Chief Medical Officer, Innovaccer
12:10 PM–12:40 PM
Paris Ballroom
Closing Keynote: Anne Stockwell, Cancer Survivor, Founder, Well Again
Finding Your Well Again
Anne Stockwell discusses her mission to help cancer survivors heal their emotional trauma and regain their balance after treatment. A multi-skilled artist as well as a three-time cancer survivor, Anne learned through experience that the emotional impact of cancer often strikes after treatment, isolating a survivor rather than lighting the way forward. Anne realized that her well-trained imagination as an artist was key to her successful reentry after cancer. Now she helps other survivors develop their own creative tools to help them find their way forward with joy.
Many radiologists expects that Tomosynthesis will eventually replace conventional mammography due to the fact that it increases the sensitivity of breast cancer detection. This claim is supported by new peer-reviewed publications. In addition, the patient’s experience during Tomosynthesis is less painful due to a lesser pressure that is applied to the breast and while presented with higher in-plane resolution and less imaging artifacts the mean glandular dose of digital breast Tomosynthesis is comparable to that of full field digital mammography. Because it is relatively new, Tomosynthesis is not available at every hospital. As well, the procedure is recognized for reimbursement by public-health schemes.
A good summary of radiologist opinion on Tomosynthesis can be found in the following video:
Recent studies’ results with digital Tomosynthesis are promising. In addition to increase in sensitivity for detection of small cancer lesions researchers claim that this new breast imaging technique will make breast cancers easier to see in dense breast tissue. Here is a paper published on-line by the Lancet just a couple of months ago:
Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study
Background Digital breast tomosynthesis with 3D images might overcome some of the limitations of conventional 2D mammography for detection of breast cancer. We investigated the effect of integrated 2D and 3D mammography in population breast-cancer screening.
Methods Screening with Tomosynthesis OR standard Mammography (STORM) was a prospective comparative study. We recruited asymptomatic women aged 48 years or older who attended population-based breast-cancer screening through the Trento and Verona screening services (Italy) from August, 2011, to June, 2012. We did screen-reading in two sequential phases—2D only and integrated 2D and 3D mammography—yielding paired data for each screen. Standard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read. Outcomes were measured from final assessment or excision histology. Primary outcome measures were the number of detected cancers, the number of detected cancers per 1000 screens, the number and proportion of false positive recalls, and incremental cancer detection attributable to integrated 2D and 3D mammography. We compared paired binary data with McNemar’s test.
Findings 7292 women were screened (median age 58 years [IQR 54–63]). We detected 59 breast cancers (including 52 invasive cancers) in 57 women. Both 2D and integrated 2D and 3D screening detected 39 cancers. We detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only (p<0.0001). Cancer detection rates were 5·3 cancers per 1000 screens (95% CI 3.8–7.3) for 2D only, and 8.1 cancers per 1000 screens (6.2–10.4) for integrated 2D and 3D screening. The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2.7 cancers per 1000 screens (1.7–4.2). 395 screens (5.5%; 95% CI 5.0–6.0) resulted in false positive recalls: 181 at both screen reads, and 141 with 2D only versus 73 with integrated 2D and 3D screening (p<0·0001). We estimated that conditional recall (positive integrated 2D and 3D mammography as a condition to recall) could have reduced false positive recalls by 17.2% (95% CI 13.6–21.3) without missing any of the cancers detected in the study population.
Interpretation Integrated 2D and 3D mammography improves breast-cancer detection and has the potential to reduce false positive recalls. Randomised controlled trials are needed to compare integrated 2D and 3D mammography with 2D mammography for breast cancer screening.
Funding National Breast Cancer Foundation, Australia; National Health and Medical Research Council, Australia; Hologic, USA; Technologic, Italy.
Introduction
Although controversial, mammography screening is the only population-level early detection strategy that has been shown to reduce breast-cancer mortality in randomised trials.1,2 Irrespective of which side of the mammography screening debate one supports,1–3 efforts should be made to investigate methods that enhance the quality of (and hence potential benefit from) mammography screening. A limitation of standard 2D mammography is the superimposition of breast tissue or parenchymal density, which can obscure cancers or make normal structures appear suspicious. This short coming reduces the sensitivity of mammography and increases false-positive screening. Digital breast tomosynthesis with 3D images might help to overcome these limitations. Several reviews4,5 have described the development of breast tomosynthesis technology, in which several low-dose radiographs are used to reconstruct a pseudo-3D image of the breast.4–6
Initial clinical studies of 3D mammography, 6–10 though based on small or selected series, suggest that addition of 3D to 2D mammography could improve cancer detection and reduce the number of false positives. However, previous assessments of breast tomosynthesis might have been constrained by selection biases that distorted the potential effect of 3D mammography; thus, screening trials of integrated 2D and 3D mammography are needed.6
We report the results of a large prospective study (Screening with Tomosynthesis OR standard Mammography [STORM]) of 3D digital mammography. We investigated the effect of screen-reading using both standard 2D and 3D imaging with tomosynthesis compared with screening with standard 2D digital mammography only for population breast-cancer screening.
Methods
Study design and participants
STORM is a prospective population-screening study that compares mammography screen-reading in two sequential phases (figure)—2D only versus integrated 2D and 3D mammography with tomosynthesis—yielding paired results for each screening examination. Women aged 48 years or older who attended population-based screening through the Trento and Verona screening services, Italy, from August, 2011, to June, 2012, were invited to be screened with integrated 2D and 3D mammography. Participants in routine screening mammography (once every 2 years) were asymptomatic women at standard (population) risk for breast cancer. The study was granted institutional ethics approval at each centre, and participants gave written informed consent. Women who opted not to participate in the study received standard 2D mammography. Digital mammography has been used in the Trento breast-screening programme since 2005, and in the Verona programme since 2007; each service monitors outcomes and quality indicators as dictated by European standards, and both have published data for screening performance.11,12
Procedures
All participants had digital mammography using a Selenia Dimensions Unit with integrated 2D and 3D mammography done in the COMBO mode (Hologic, Bedford, MA, USA): this setting takes 2D and 3D images at the same screening examination with a single breast position and compression. Each 2D and 3D image consisted of a bilateral two-view (mediolateral oblique and craniocaudal) mammogram. Screening mammograms were interpreted sequentially by radiologists, first on the basis of standard 2D mammography alone, and then by the same radiologist (on the same day) on the basis of integrated 2D and 3D mammography (figure). Thus, integrated 2D and 3D mammography screening refers to non-independent screen reading based on joint interpretation of 2D and 3D images, and does not refer to analytical combinations. Radiologists had to record whether or not to recall the participant at each screen-reading phase before progressing to the next phase of the sequence. For each screen, data were also collected for breast density (at the 2D screen-read), and the side and quadrant for any recalled abnormality (at each screen-read). All eight radiologists were breast radiologists with a mean of 8 years (range 3–13 years) experience in mammography screening, and had received basic training in integrated 2D and 3D mammography. Several of the radiologists had also used 2D and 3D mammography for patients recalled after positive conventional mammography screening as part of previous studies of tomosynthesis.8,13
Mammograms were interpreted in two independent screen-reads done in parallel, as practiced in most population breast-screening programs in Europe. A screen was considered positive and the woman recalled for further investigations if either screen-reader recorded a positive result at either 2D or integrated 2D and 3D screening (figure). When previous screening mammograms were available, these were shown to the radiologist at the time of screen-reading, as is standard practice. For assessment of breast density, we used Breast Imaging Reporting and Data System (BI-RADS)14 classification, with participants allocated to one of two groups (1–2 [low density] or 3–4 [high density]). Disagreement between readers about breast density was resolved by assessment by a third reader.
Our primary outcomes were the number of cancers detected, the number of cancers detected per 1000 screens, the number and percentage of false positive recalls, and the incremental cancer detection rate attributable to integrated 2D and 3D mammography screening. We compared the number of cancers that were detected only at 2D mammography screen-reading and those that were detected only at 2D and 3D mammography screen-reading; we also did this analysis for false positive recalls. To explore the potential effect of integrated 2D and 3D screening on false-positive recalls, we also estimated how many false-positive recalls would have resulted from using a hypothetical conditional false-positive recall approach; – i.e. positive integrated 2D and 3D mammography as a condition of recall (screening recalled at 2D mammography only would not be recalled). Pre-planned secondary analyses were comparison of outcome measures by age group and breast density.
Outcomes were assessed by excision histology for participants who had surgery, or the complete assessment outcome (including investigative imaging with or without histology from core needle biopsy) for all recalled participants. Because our study focuses on the difference in detection by the two screening methods, some cancers might have been missed by both 2D and integrated 2D and 3D mammography; this possibility could be assessed at future follow-up to identify interval cancers. However, this outcome is not assessed in the present study and does not affect estimates of our primary outcomes – i.e. comparative true or false positive detection for 2D-only versus integrated 2D and 3D mammography.
Statistical analysis
The sample size was chosen to provide 80% power to detect a difference of 20% in cancer detection, assuming a detection probability of 80% for integrated 2D and 3D screening mammography and 60% for 2D only screening, with a two-sided significance threshold of 5%. Based on the method of Lachenbruch15 for estimating sample size for studies that use McNemar’s test for paired binary data, a minimum of 40 cancers were needed. Because most screens in the participating centres were incident (repeat) screening (75%–80%), we used an underlying breast-cancer prevalence of 0·5% to estimate that roughly 7500–8000 screens would be needed to identify 40 cancers in the study population.
We calculated the Wilson CI for the false-positive recall ratio for integrated 2D and 3D screening with conditional recall compared with 2D only screening.16 All of the other analyses were done with SAS/STAT (version 9.2), using exact methods to compute 95 CIs and p-values.
Role of the funding source
The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author (NH) had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
7292 participants with a median age of 58 years (IQR 54–63, range 48–71) were screened between Aug 12, 2011, and June 29, 2012. Roughly 5% of invited women declined integrated 2D and 3D screening and received standard 2D mammography. We present data for 7294 screens because two participants had bilateral cancer (detected with different screen-reading techniques for one participant). We detected 59 breast cancers in 57 participants (52 invasive cancers and seven ductal carcinoma in-situ). Of the invasive cancers, most were invasive ductal (n=37); others were invasive special types (n=7), invasive lobular (n=4), and mixed invasive types (n=4).
Table 1 shows the characteristics of the cancers. Mean tumour size (for the invasive cancers with known exact size) was 13.7 mm (SD 5.8) for cancers detected with both 2D alone and integrated 2D and 3D screening (n=29), and 13.5 mm (SD 6.7) for cancers detected only with integrated 2D and 3D screening (n=13).
Of the 59 cancers, 39 were detected at both 2D and integrated 2D and 3D screening (table 2). 20 cancers were detected with only integrated 2D and 3D screening compared with none detected with only 2D screening (p<0.0001; table 2). 395 screens were false positive (5.5%, 95% CI 5.0–6.0); 181 occurred at both screen-readings, and 141 occurred at 2D screening only compared with 73 at integrated 2D and 3D screening (p<0.0001; table 2). These differences were still significant in sensitivity analyses that excluded the two participants with bilateral cancer (data not shown).
5.3 cancers per 1000 screens (95% CI 3.8–7.3; table 3) were detected with 2D mammography only versus 8.1 cancers per 1000 screens (95% CI 6.2–10.4) with integrated 2D and 3D mammography (p<0.0001). The incremental cancer detection rate attributable to integrated 2D and 3D screening was 2.7 cancers per 1000 screens (95% CI 1.7–4.2), which is 33.9% (95% CI 22.1–47.4) of the cancers detected in the study population. In a sensitivity analysis that excluded the two participants with bilateral cancer the estimated incremental cancer detection rate attributable to integrated 2D and 3D screening was 2.6 cancers per 1000 screens (95% CI 1.4–3.8). The stratified results show that integrated 2D and 3D mammography was associated with an incrementally increased cancer detection rate in both age-groups and density categories (tables 3–5). A minority (16.7%) of breasts were of high density (category 3–4) reducing the power of statistical comparisons in this subgroup (table 5). The incremental cancer detection rate was much the same in low density versus high density groups (2.8 per 1000 vs 2.5 per 1000; p=0.84; table 3).
Overall recall—any recall resulting in true or false positive screens—was 6.2% (95% CI 5.7–6.8), and the false-positive rate for the 7235 screens of participants who did not have breast cancer was 5.5% (5.0–6.0). Table 6 shows the contribution to false-positive recalls from 2D mammography only, integrated 2D and 3D mammography only, and both, and the estimated number of false positives if positive integrated 2D and 3D mammography was a condition for recall (positive 2D only not recalled). Overall, more of the false-positive rate was driven by 2D mammography only than by integrated 2D and 3D, although almost half of the false-positive rate was a result of false positives recalled at both screen-reading phases (table 6). The findings were much the same when stratified by age and breast density (table 6). Had a conditional recall rule been applied, we estimate that the false-positive rate would have been 3.5% (95% CI 3.1–4.0%; table 6) and could have potentially prevented 68 of the 395 false positives (a reduction of 17.2%; 95% CI 13.6–21.3). The ratio between the number of false positives with integrated 2D and 3D screening with conditional recall (n=254) versus 2D only screening (n=322) was 0.79 (95% CI 0.71–0.87).
Discussion
Our study showed that integrated 2D and 3D mammography screening significantly increases detection of breast cancer compared with conventional mammography screening. There was consistent evidence of an incremental improvement in detection from integrated 2D and 3D mammography across age-group and breast density strata, although the analysis by breast density was limited by low number of women with breasts of high density.
One should note that we investigated comparative cancer detection, and not absolute screening sensitivity. By integrating 2D and 3D mammography using the study screen-reading protocol, 1% of false-positive recalls resulted from 2D and 3D screen-reading only (table 6). However, significantly more false positives resulted from 2D only mammography compared with integrated 2D and 3D mammography, both overall and in the stratified analyses. Application of a conditional recall rule would have resulted in a false-positive rate of 3.5% instead of the actual false-positive rate of 5.5%. The estimated false positive recall ratio of 0.79 for integrated 2D and 3D screening with conditional recall compared with 2D only screening suggests that integrated 2D and 3D screening could reduce false recalls by roughly a fifth. Had such a condition been adopted, none of the cancers detected in the study would have been missed because no cancers were detected by 2D mammography only, although this result might be because our design allowed an independent read for 2D only mammography whereas the integrated 2D and 3D read was an interpretation of a combination of 2D and 3D imaging. We do not recommend that such a conditional recall rule be used in breast-cancer screening until our findings are replicated in other mammography screening studies—STORM involved double-reading by experienced breast radiologists, and our results might not apply to other screening settings. Using a test set of 130 mammograms, Wallis and colleagues7 report that adding tomosynthesis to 2D mammography increased the accuracy of inexperienced readers (but not of experienced readers), therefore having experienced radiologists in STORM could have underestimated the effect of integrated 2D and 3D screen-reading.
No other population screening trials of integrated 2D and 3D mammography have reported final results (panel); however, an interim analysis of the Oslo trial17 a large population screening study has shown that integrated 2D and 3D mammography substantially increases detection of breast cancer. The Oslo study investigators screened women with both 2D and 3D mammography, but randomised reading strategies (with vs without 3D mammograms) and adjusted for the different screen-readers,17whereas we used sequential screen-reading to keep the same reader for each examination. Our estimates for comparative cancer detection and for cancer detection rates are consistent with those of the interim analysis of the Oslo study.17 The applied recall methods differed between the Oslo study (which used an arbitration meeting to decide recall) and the STORM study (we recalled based on a decision by either screen-reader), yet both studies show that 3D mammography reduces false-positive recalls when added to standard mammography.
An editorial in The Lancet18 might indeed signal the closing of a chapter of debate about the benefits and harms of screening. We hope that our work might be the beginning of a new chapter for mammography screening: our findings should encourage new assessments of screening using 2D and 3D mammography and should factor several issues related to our study. First, we compared standard 2D mammography with integrated 2D and 3D mammography the 3D mammograms were not interpreted independently of the 2D mammograms therefore 3D mammography only (without the 2D images) might not provide the same results. Our experience with breast tomosynthesis and a review6 of 3D mammography underscore the importance of 2D images in integrated 2D and 3D screen-reading. The 2D images form the basis of the radiologist’s ability to integrate the information from 3D images with that from 2D images. Second, although most screening in STORM was incident screening, the substantial increase in cancer detection rate with integrated 2D and 3D mammography results from the enhanced sensitivity of integrated 2D and 3D screening and is probably also a result of a prevalence effect (ie, the effect of a first screening round with integrated 2D and 3D mammography). We did not assess the effect of repeat (incident) screening with integrated 2D and 3D mammography on cancer detection it might provide a smaller effect on cancer detection rates than what we report. Third, STORM was not designed to measure biological differences between the cancers detected at integrated 2D and 3D screening compared with those detected at both screen-reading phases. Descriptive analyses suggest that, generally, breast cancers detected only at integrated 2D and 3D screening had similar features (eg, histology, pathological tumour size, node status) as those detected at both screen-reading phases. Thus, some of the cancers detected only at 2D and 3D screening might represent early detection (and would be expected to receive screening benefit) whereas some might represent over-detection and a harm from screening, as for conventional screening mam mography.1,19 The absence of consensus about over-diagnosis in breast-cancer screening should not detract from the importance of our study findings to applied screening research and to screening practice; however, our trial was not done to assess the extent to which integrated 2D and 3D mammography might contribute to over-diagnosis.
The average dose of glandular radiation from the many low-dose projections taken during a single acquisition of 3D mammography is roughly the same as that from 2D mammography.6,20–22 Using integrated 2D and 3D entails both a 2D and 3D acquisition in one breast compression, which roughly doubles the radiation dose to the breast. Therefore, integrated 2D and 3D mammography for population screening might only be justifiable if improved outcomes were not defined solely in terms of improved detection. For example, it would be valuable to show that the increased detection with integrated 2D and 3D screening leads to reduced interval cancer rates at follow-up. A limitation of our study might be that data for interval cancers were not available; however, because of the paired design we used, future evaluation of interval cancer rates from our study will only apply to breast cancers that were not identified using 2D only or integrated 2D and 3D screening. We know of two patients from our study who have developed interval cancers (follow-up range 8–16 months). We did not get this information from cancer registries and follow-up was very short, so these data should be interpreted very cautiously, especially because interval cancers would be expected to occur in the second year of the standard 2 year interval between screening rounds. Studies of interval cancer rates after integrated 2D and 3D mammography would need to be randomised controlled trials and have a very large sample size. Additionally, the development of reconstructed 2D images from a 3D mammogram23 provides a timely solution to concerns about radiation by providing both the 2D and 3D images from tomosynthesis, eliminating the need for two acquisitions.
We have shown that integrated 2D and 3D mammography in population breast-cancer screening increases detection of breast cancer and can reduce false-positive recalls depending on the recall strategy. Our results do not warrant an immediate change to breast-screening practice, instead, they show the urgent need for randomised controlled trials of integrated 2D and 3D versus 2D mammography, and for further translational research in breast tomosynthesis. We envisage that future screening trials investigating this issue will include measures of breast cancer detection, and will be designed to assess interval cancer rates as a surrogate endpoint for screening efficacy.
Contributors
SC had the idea for and designed the study, and collected and interpreted data. NH advised on study concepts and methods, analysed and interpreted data, searched the published work, and wrote and revised the report. DB and FC were lead radiologists, recruited participants, collected data, and commented on the draft report. MP, SB, PT, PB, PT, CF, and MV did the screen-reading, collected data, and reviewed the draft report. SM collected data and reviewed the draft report. PM planned the statistical analysis, analysed and interpreted data, and wrote and revised the report.
Conflicts of interest
SC, DB, FC, MP, SB, PT, PB, CF, MV, and SM received assistance from Hologic (Hologic USA; Technologic Italy) in the form of tomosynthesis technology and technical support for the duration of the study, and travel support to attend collaborators’ meetings. NH receives research support from a National Breast Cancer Foundation (NBCF Australia) Practitioner Fellowship, and has received travel support from Hologic to attend a collaborators’ meeting. PM receives research support through Australia’s National Health and Medical Research Council programme grant 633003 to the Screening & Test Evaluation Program.
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A very good and down-to-earth comment on this article was made by Jules H Sumkin who disclosed that he is an unpaid member of SAB Hologic Inc and have a PI research agreement between University of Pittsburgh and Hologic Inc.
“ The results of the study by Stefano Ciatto and colleagues1 are consistent with recently published prospective,2,3 retrospective,4 and observational5 reports on the same topic. The study1 had limitations, including the fact that the same radiologist interpreted screens sequentially the same day without cross-balancing which examination was read first. Also, the false-negative findings for integrated 2D and 3D mammography, and therefore absolute benefit from the procedure, could not be adequately assessed because cases recalled by 2D mammography alone (141 cases) did not result in a single detection of an additional cancer while the recalls from the integrated 2D and 3D mammography alone (73 cases) resulted in the detection of 20 additional cancers. Nevertheless, the results are in strong agreement with other studies reporting of substantial performance improvements when the screening is done with integrated 2D and 3D mammography.
I disagree with the conclusion of the study with regards to the urgent need for randomised clinical trials of integrated 2D and 3D versus 2D mammography. First, to assess differences in mortality as a result of an imaging-based diagnostic method, a randomised trial will require several repeated screens by the same method in each study group, and the strong results from all studies to date will probably result in substantial crossover and self-selection biases over time. Second, because of the high survival rate (or low mortality rate) of breast cancer, the study will require long follow-up times of at least 10 years. In a rapidly changing environment in terms of improvements in screening technologies and therapeutic interventions, the avoidance of biases is likely to be very difficult, if not impossible. The use of the number of interval cancers and possible shifts in stage at detection, while appropriately accounting for confounders, would be almost as daunting a task. Third, the imaging detection of cancer is only the first step in many management decisions and interventions that can affect outcome. The appropriate control of biases related to patient management is highly unlikely. The arguments above, in addition to the existing reports to date that show substantial improvements in cancer detection, particularly with the detection of invasive cancers, with a simultaneous reduction in recall rates, support the argument that a randomised trial is neither necessary nor warranted. The current technology might be obsolete by the time results of an appropriately done and analysed randomised trial is made public.”
In order to better link the information given by “scientific” papers to the context of daily patients’ reality I suggest to spend some time reviewing few of the videos in the below links:
The following group of videos is featured on a website by Siemens. Nevertheless, the presenting radiologists are leading practitioners who affects thousands of lives every year – What the experts say about tomosynthesis. – click on ECR 2013
Breast Tomosynthesis in Practice – part of a commercial ad of the Washington Radiology Associates featured on the website of Diagnostic Imaging. As well, affects thousands of lives in the Washington area every year.
The pivotal questions yet to be answered are:
What should be done in order to translate increase in sensitivity and early detection into decrease in mortality?
What is the price of such increase in sensitivity in terms of quality of life and health-care costs and is it worth-while to pay?
An article that summarises positively the experience of introducing Tomosynthesis into routine screening practice was recently published on AJR:
Stephen L. Rose1, Andra L. Tidwell1, Louis J. Bujnoch1, Anne C. Kushwaha1, Amy S. Nordmann1 and Russell Sexton, Jr.1
Affiliation: 1 All authors: TOPS Comprehensive Breast Center, 17030 Red Oak Dr, Houston, TX 77090.
Citation: American Journal of Roentgenology. 2013;200:1401-1408
ABSTRACT :
OBJECTIVE. Digital mammography combined with tomosynthesis is gaining clinical acceptance, but data are limited that show its impact in the clinical environment. We assessed the changes in performance measures, if any, after the introduction of tomosynthesis systems into our clinical practice.
MATERIALS AND METHODS. In this observational study, we used verified practice- and outcome-related databases to compute and compare recall rates, biopsy rates, cancer detection rates, and positive predictive values for six radiologists who interpreted screening mammography studies without (n = 13,856) and with (n = 9499) the use of tomosynthesis. Two-sided analyses (significance declared at p < 0.05) accounting for reader variability, age of participants, and whether the examination in question was a baseline were performed.
RESULTS. For the group as a whole, the introduction and routine use of tomosynthesis resulted in significant observed changes in recall rates from 8.7% to 5.5% (p < 0.001), nonsignificant changes in biopsy rates from 15.2 to 13.5 per 1000 screenings (p = 0.59), and cancer detection rates from 4.0 to 5.4 per 1000 screenings (p = 0.18). The invasive cancer detection rate increased from 2.8 to 4.3 per 1000 screening examinations (p = 0.07). The positive predictive value for recalls increased from 4.7% to 10.1% (p < 0.001).
CONCLUSION. The introduction of breast tomosynthesis into our practice was associated with a significant reduction in recall rates and a simultaneous increase in breast cancer detection rates.
Here are the facts in tables and pictures from this article
Other articles related to the management of breast cancer were published on this Open Access Online Scientific Journal: