TIES Cancer Research Network
Y3 Face to Face Meeting
U24 CA 180921
Session 6 User Stories and Pilot Studies
October 9th, 2015
University of Pennsylvania
Philosophy behind the Pilot Projects
• Eat your own dogfood
• Educate ourselves about the steps required
• Test every center and every type of study (aggregate, data,
biospecimen)
• Identify gaps and problems and deal with them before we
have rushed users (e.g. email sent to wrong person)
• Develop materials to help guide users through the process
• In addition, we have targeted a small number of users to work
with us, but always with a TCRN partner on the other side
• Based on the number of issues we saw in the first five projects
– we may need another 5 this year to get to saturation
• Identify target date for open use for network users
TCRN Pilot Projects
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RPCI
– Small ulcerated breast cancers – should they be T4?
• Dr. Thaer Khoury and Dr. Rebecca Jacobson (UPCI)
• TIES Data and Ancillary Data (Cancer Registry)
University of Pennsylvania
– Is there an infectious agent behind Rosai Dorfman Disease?
• Dr. Mike Feldman and Dr. Liron Pantanowitz (UPCI)
• TIES Data and FFPE
– Breast Papillomas – Value of subsequent resection
• Dr. Mike Feldman
• TIES Data
University of Pittsburgh
– Barret’s esophagus with and without subsequent HG dysplasia/cancer
• Dr. Yang Liu and Dr. Michael Feldman (Penn)
• TIES Data and FFPE
Georgia Regents University
– Pigmented Villonodular Synovitis (PVNS) case series
• Dr. Roni Bollag
• TIES Data and Ancillary Data
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TCRN F2F Meeting 2015
RPCI Pilot Project
Pilot Project Summary
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Title: Does tumor size matter in tumor pathology stage 4 (pT4) ?
Background: The AJCC guidelines stage breast cancer (BC) with skin
ulceration (SU) as pT4b (locally advanced disease) regardless of the
tumor size.
Purpose: To evaluate if SU is an independent risk of survival.
Motivation for Using TCRN: insufficient number of cases at any single
institution
PIs: Dr. Thaer Khoury (RPCI) and Rebecca Jacobson (UPMC),
Cases Source and Number:
• TCRN
• RPCI: 22
• UPMC: 55 (out 99 identified by TIES)
• Non-TCRN: 33 (Vanderbilt, Ohio State, Wash U, SW Dallas,
Montefiore)
• Data: Pathology reports, therapy modality, outcomes
Pilot Project
Benefits and Challenges
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Access to a valuable unique new resource
Broader collaboration
Access to a large number of cases
Quick turnaround time
Publications
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Challenges
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Three Abstracts submitted to USCAP Conference
One manuscript in preparation
CR and pathology data format difference
Needed data management support to clean data for analysis
Navigating from individual reports to case set (system familiarity)
Lessons learned: A network with the appropriate infrastructures can
make a big difference. “I am going to do another project.”
Pilot Project Abstracts
• Inconsistency in Following the AJCC
Reporting Guidelines for T-Staging of
Breast Cancer with Skin Ulceration
• Skin Ulceration in Breast Cancer Carries
No Increased Risk of Disease Free or
Overall Survival
• Breast Cancer with Skin Ulceration:
Should All Cases Be Staged as pT4b?
Q&A
Thanks!
Questions or comments?
Research study Rosai Dorfman Disease
• Rosai Dorfman disease is an idiopathic reactive
condition characterized by exuberant
macrophage reaction in lymph nodes or soft
tissue
• Etiology is unknown but some studies have
implicated a virus, Herpes virus 6 in some cases
• Pathochip is a microarray technology
– All known pathogenic virus and bacteria and
fungi arrayed
– Allows FFPE to be probed for infectious
signature in lesional tissue compared to
normal controls
Rosai Dorfman Query
• Penn ~ 10 cases identified
– Tissue blocks have been cut and ready for extraction
• Pitt ~ 40 cases identified
– Case are currently being pulled together for cutting
– Collaborator at Pitt is Dr Liron Pantanowitz
– Control tissue will be reactive lymph nodes
“Breast Papilloma study”
• Find all breast needle cores with diagnosis of a
papilloma or papillomatosis
– but nothing worse (atypia, DCIS, IDC, LCIS, ILC)
at the time of the core biopsy who then went
on to a subsequent resection
– In the resection after the papilloma core
biopsy, what is the frequency of finding either
in situ or invasive carcinoma
– Compare the carcinoma rate to carcinoma in a
random core biopsy population with BIRADS4
Query
Breast
Core
Papilloma
Carcinoma
Atypia
Atypical hyperplasia
Results
• Penn – 24 patients, 73 reports
• Pitt – 410 patients, 1225 reports
• Reviewing quality of results, numbers seem low
Pitt Pilot Study
Yang Liu, PhD
University of Pittsburgh
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Recent Yang Liu Publication citing TIES
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Identifying cohort with specific progression sequence
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Progress
• Approximately 40 patients at Pitt
– Rather surprising to us, so we investigated in other
sources to see if we had sizable cohort with repeat
endoscopy and surveillance
• Number of cases identified is small at Penn (~15
including both HG dysplasia and cancer)
• Workaround using case sets developed from
other sources from Penn (useful trick)
• Potential to try this across all four centers
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Pilot Project:
Demographic
Characterization of
Tenosynovial Giant Cell
Tumor
Roni J. Bollag, MD, PhD
Suash Sharma, MD
PVNS/GCT
• Pigmented Villonodular Synovitis (PVNS)
• Tenosynovial Giant Cell Tumor (TGCT) = Giant Cell Tumor of Tendon
Sheath
• Incidence ~ 600 new cases per year in US, often young adults
• Clonal neoplastic process resulting in over-expression of CSF1 in
synovium
 Frequently due to genetic translocation: t(1;2) CSF1:COL6A3
 Propagation of neoplastic clone (autocrine)
 Reactive inflammatory process with proliferation & recruitment
of
CSF1R-expressing cells: macrophages, giant cells, osteoclasts
• Surgery is standard of care (e.g., joint replacement, amputation)
• Pharmaceutical target: blockade of CSF-1 Receptor (orphan drug
designation?)
Proposal for TCRN Submission
• Tenosynovial giant cell tumor, also known as Giant cell
tumor of the tendon sheath and pigmented villonodular
synovitis are benign tumors of connective tissue. The
subclassification is based primarily on the site of
occurrence, broadly subdivided into localized-type distal
(hands or feet) and diffuse-type proximal (knee, hip,
shoulder joint space) respectively. Surgical excision is
definitive, but at present no adjuvant therapeutic options
are available. Moreover, demographic data on incidence,
age at diagnosis, race and sexual predilection is also scant.
With novel directed therapies targeting CSF-1 receptor
blockade, more precise tumor demographic data are
desirable. With the advent of multidisciplinary pathological
archival data made possible by the TCRN network,
improved demographic characterization may be possible.
Mining TCRN
By mining aggregate diagnostic information in the TCRN database,
we hope to derive a more extensive understanding of:
• Overall incidence
• Age at diagnosis
• Sexual predilection
• Racial predilection
• Recurrence status
The demographic features are to be stratified for proximal and
distal incidences, and where possible, longitudinal follow-up data
including median lifespan and other outcome data shall be
sought. Separate characterization of the extraordinarily rare
malignant sarcomatoid variant may also derive from the aggregate
data review.
CSF1R Blockade Phase I Trials (July
2015)
Demographic Analysis of PVNS
• Citation of WHO
• Compilation of older clinicopathologic case series
(next slides)
TCRN Access!
Tenosynovial Giant Cell Tumor comprehensive
Tenosynovial Giant Cell tumor (C1318543): total
1590 reports (1437 patients)
UPENN: 370 reports (347 patients)
UPMC: 1160 reports (1035 patients)
Roswell Park: 8 reports (7 patients)
GRU: 52 reports (48 patients)
Tenosynovial Giant Cell Tumor by
age
TGCT - Demographics
PVNS Demographics
Summary
• Project approved!
• Preliminary Data compelling
• Age/gender/racial predilection … benchmark?
• Concept library evaluation
• TGCT – 1590
• PVNS – 508
• TGCT, PVNS – 508
• Aggregate data useful to power up demographic
analysis
New Pilot Projects
• How many more Pilot Projects do we need to run?
• What parts of the machinery have not yet been
exercised enough?
• How much longer until we provide broader access to
investigators?