Sessions began with presentations
and discussions around
Multimodality Perspectives on Clinical
Trial Development and included a discussion
in health equity in clinical trials
by Dr. Lola Fashoyin-Aje. She explored
modernizing clinical trial eligibility criteria
to allow for more diverse enrollment
with the goal of achieving better
understanding of drug effects and efficacy
across heterogeneous populations.
She also discussed the importance of
decentralizing trials to make trials available
to a diverse population as well as
the importance for leveraging technology
to allow for more efficient trials with
improved access for patients. These
might include utilizing remote assessments
and electronic consenting for
example.
Dr. Biren Saraiya gave a very
provocative talk entitled Enhancing
Patient-centered Care in Systemic
Therapy and Clinical Trials. He began
by reminding the audience of the importance
of recognizing that each provider
brings to each patient encounter a different
personal experience, cultural background,
knowledgebase and personal
bias, and that patients and caregivers
similarly bring these characteristics to
each encounter as well. Understanding
and recognizing these is a first step towards
shared decision making. He suggested
physician might consider asking
patients, “What have you learned from
Google about you condition?” He explained
that patients need time to process
information that they are given
and to deal with the emotions that are
attached, and this one of the many reasons
that integration of early palliative
care into the care of cancer patients can
be greatly beneficial. He also noted the
importance of providers recognizing
their own emotions and approach, particularly
in how they communicate the
inherent uncertainty which exists in oncology
practice.
An excellent panel discussion
around neoadjuvant trials in locally advanced
RCC prompted much discussion
about this novel approach. The goal of
such therapy would be to downstage tumors,
hopefully leading to smaller surgeries
to achieve full resection, and the
eradication of micro-metastatic disease,
while providing a window into the biology
of individual patients’ cancer and the
mechanism of action of drugs used in
this setting. Discussion around the optimal
endpoints for neoadjuvant trials
suggested that these would need to be
individualized based on the mechanism
of action of the drugs studied in a particular
trial. The question of placebo in the
neoadjuvant trials was also addressed,
although given the wide variety of active
agents in kidney cancer it was felt that
placebo-controlled trials in the neoadjuvant
setting would largely be unnecessary.
Finally, a discussion around the
important of considering combination
therapy in the neoadjuvant setting was
had.
Dr. Ivan Pedrosa gave a compelling
lecture entitled “Phenotypic
Characterization of Renal Masses – The
Virtual Biopsy,” in which he delineated
the characterization of kidney tumors
using MRI. He explained the limitations
of attempting tissue diagnosis of every
renal mass and introduced the Clear
Cell Likelihood Score, a Likert scale for
interpretation of multiparametric MRI
that allows for a non-invasive detection
of clear cell RCC and helps predict likelihood
of metastases.
The surgical management of
non-clear cell RCC was explored in a presentation
by Dr. Ronald Boris of Indiana
University. The focus of this talk was on
the importance of understanding histological
subtypes of RCC and their differences
in metastatic potential and surgical
outcomes. Dr. Boris explained that
the nature of the peritumoral pseudocapsule
differs significantly and predictably
based on histologic subtypes of
disease and can be used to personalize
surgical approach and planning.
Dr. Hassanpour discussed the
use of artificial intelligence (AI) deep
learning in histologic classification of
kidney cancer. He and his colleagues
have built a AI model to help pathologists
accurate classify tissue specimens.
Such as system can potentially aid in
automatically pre-screening slides to reduce
false-negative cases, highlight regions
of importance on digitized slides,
and provide second opinions.
The role of NF2 in tumorigenesis
in RCC was explored by Dr. Kun-
Liang Guan. NF2 is a tumor suppressor
acting upstream of the Hippo pathway
which when mutated increases risk of
developing cancerous and benign tumors,
and Dr. Guan explained that the
novel compound VT103 is in clinical
trials in NF2 mutated cancers
Dr. McGregor gave an excellent
overview of systemic therapy for nonclear
cell RCC and discussed current and
future approaches. He discussed PARP
inhibitor trials in FH/SDH-deficient
RCC, as well, as chemotherapy and immunotherapy
combinations for nonclear
cell RCCs.
The conference’s keynote lecturer
was delivered by Noble Laureate
Dr. Jim Allison from MD Anderson
Cancer Center, one of the world’s most
respected and well-known scientists
and a father of immunotherapy. Allison
reviewed the history of immune checkpoint
blockage and noting that his early
work in this area was not specific to cancer,
but instead sought to better understand
the function and control of T-cells.
Of course, this work led to the approval
of immune checkpoint inhibitors that
have revolutionized system therapy
for most solid tumors over the several
years. He reviewed work being done
around learning why some cancers respond
so well to immunotherapy, while
others do not and search for biomarkers
that might aid in therapy selection.
Following Allison’s keynote lecture,
Dr. Hakimi discussed immunological
consequences of obesity in clear cell
RCC.
* Dr. Divya Bezwada delivered a
talk entitled, “Assessing Human
Kidney Cancer Metabolism with
Intraoperative Isotope Tracing.”
A session focused on mentoring
including a presentation by Dr. Brian
Rini on the Academy of Kidney Cancer
Investigators, a formalized organization
providing research direction and career
guidance to early-career investigators.
This was followed by presentations by
three mentees regarding ongoing research
projects. Dr. Rini’s presentation
as followed by a mentorship roundtable
consisting of medical oncologists, urologists,
and translational researchers.
The panelists gave brief descriptions of
their own career journeys and answered
a multitude of questions regarding the
importance of mentorship, institutional
diversity, and other topics. The roundtable
was followed by a panel on networking
hot topics presented by Drs. Nizar
Tannir, Jeff Yorio, W. Kimryn Rathmell,
and Brian Shuch. The panel addressed
topics such as community oncology and
community-based research, grantsmanship,
networking, and other topics. An
excellent poster walk was hosted by Drs.
Eric Kauffman, Ritesh Kotecha, Nizar
Tannir, and Stephen Culp.
DAY TWO
Day two of the conference,
brought lectures on adjuvant therapies
and advocacy, an award lecture, and
abstracts. Dr. Toni Choueiri spoke on
the Future of Adjuvant Therapy in RCC.
He reviewed data on adjuvant sunitinib,
which while approved in this setting in
the US, has had largely disappointing
outcomes especially with regards to
overall survival. He then described results
of the KEYNOTE-564 study which
randomizes patients at high-risk of
recurrence to pembrolizumab vs placebo
after complete resection of RCC
(including 5.8 precent of patient with
completely resected metastatic disease).
The study achieved a disease-free
survival (DFS) of 68.1% in placebo arm
vs 77.3% in the pembrolizumab arm at
24 months, and while overall survival
is still not mature, it trended towards
favoring the pembrolizumab arm. He
also reviewed data using circulating
tumor DNA to predict who might have
residual disease and benefit most from
an adjuvant therapy approach. This
has been challenging as RCC does not
shed ctDNA at high rates. Choueiri described
cfMeDIP-sequencing that may
help improve this approach. He finally
mentioned the lack of data on adjuvant
strategies of non-clear cell histologies
and the need to explore whether strategies
giving longer or short durations of
adjuvant immunotherapy are appropriate.
Dr. Choueiri talk was followed by
a panel exploring adjuvant approaches
in RCC via an interactive case-based
discussion.
The next session of IKCS 2021
focused on advocacy, funding, and the
patient experience, starting with a talk
by Gretchen E. Vaughan, President and
CEO of the Kidney Cancer Association.
She reviewed programmatic initiatives
including the organization’s progress,
projects, and goals. Theresa Miller
spoke on Congressionally Directed
Medical Research Programs (a program
of the Department of Defense)
and specifically the Kidney Cancer
Research Program (KCRP). The KCRP
received $50 million in funding in 2021
and funding has increased each year
since 2017. She also described the
funding opportunities that include concept
awards, idea development awards
(for early career investigators and established
investigators), translational
research partnership awards, clinical
trial awards, clinical research nurse
development award, early career develop
awards for the Academy of Kidney
Cancer Investigators, and postdoctoral
and clinical fellowship awards. A legislative
advocacy roundtable followed
that included Bruce Hill and Ryan
Natzke, both patient advocates, who
encouraged physicians and researchers
to meet with their elected representatives
and their legislative/congressional
staffers.
The Andrew C. Novick Award
Lecture was given by Dr. Brian Lane
on the topic of the management of T1
renal masses. He reviewed the history
and data behind robotic partial nephrectomies
that have become the goal
standard for most T1 renal masses. He
reviewed concepts around loss of renal
function following partial nephrectomy,
noting that loss of renal function is rare
following surgery with those who has
underlying chronic kidney disease are at
greater risk. He also shared data that
showed renal functional outcomes after
partial nephrectomy are better than
open nephrectomy even with partial nephrectomy
is associated with prolonged
ischemia. He also discussed the concept
of surgical chronic kidney disease, as a
distinct entity from other forms of kidney
disease and its impact on overall
survival. He noted that open nephrectomies
may not be as bad as once thought
and described a randomized trial. He
also introduced MUSIC, the Michigan
Urological Surgery Improvement
Collaborative, an umbrella that include
many quality improvement projects.
He finally noted that with greater and
appropriate use of high-quality imaging,
renal mass biopsy, and surveillance
we can better identify patients who can
safely avoid intervention. He concluded
his presentation by sharing his own personal
story of being a patient with two
simultaneous types of cancer including
kidney cancer.
The award lecture was followed
by presentations of the conference’s top
abstracts. Dr. Pedro Barata of Tulane
University spoke on his abstract “Gene
Expression Profiling (GEP) of non-clear
cell renal cell carcinoma (nccRCC) identifies
a unique spectrum of transcriptional
signature with potential clinical
relevance.” Dr. Barata explained that
657 patient samples were sequenced
including papillary (9.6%), chromophobe
(4.6%), medullary (1.2%), collecting
duct (0.9%), and mixed (6.2%)
nccRCC subtypes. While most ccRCC
samples were classified as ‘Angiogenic’
or ‘Angio/stromal’ (50%), these molecular
subgroups comprised <10% of
nccRCC samples, which were predominately
classified as ‘Proliferative’ (49%).
Defective MMR/MSI-H and TMB-High
(≥ 10 mutations/Mb) rates were highest
(33.3%) in collecting duct carcinoma
and rarely observed (< 3.5%) in all other
histological subgroups. These observations
provide a new understanding for
personalized treatment of nccRCC, warranting
further evaluation in prospective
trials.
Dr. Sari Khaleel presented
“Outcomes of cytoreductive nephrectomy
followed by active surveillance in
metastatic renal cell carcinoma.” He
presented data on 97 systemic-therapy-
naïve mRCC patients who underwent
cytoreductive nephrectomy followed
by active surveillance between
1989 – 2020. Median follow-up was
31.8 months with an intervention-free
survival of 11.6 months. Overall survival
was 52.3 months in these patients. Of
note, IMDC risk categories did not correlate
with outcomes on multivariate
analysis.
Dr. Charlotte Spencer spoke on
her abstract entitled, “Machine learning
predicts BAP1/PBRM1 in clear cell renal
cell carcinoma: TRACERx Renal,” which
described a proof of principle study
which showed that mutational status
of two ccRCC driver genes, PBRM1 and
BAP1 can be accurately predicted with a
high degree of accuracy from digital histological
images alone.
Dr. Nizar Tannir from MD
Anderson spoke on “Frist-line nivolumab
plus ipilimumab (NIVO+IPI) versus
sunitinib (SUN) in patients with
long-term survival of ≥5 years in the
CheckMate 214 trial.” Of 550 patients
randomized to the immunotherapy
arm, long-term survival of greater than
5 years was reported in 236 (43%) patients
compared to 171 of 546 (31%) patients
in the sunitinib arm. Baseline demographic
and clinical characteristics
generally did not distinguish which patients
would achieve long-term survival,
except for lower target lesion burden,
IMDC poor risk disease, and bone metastases
at baseline.
Dr. Akash Kaushik presented
“Glutamine metabolism in clear cell
Renal Cell Carcinoma,” in which he described
metabolic reprogramming in
ccRCC, and suggested that mechanisms
beyond glutaminase-dependent metabolism
may fuel the TCA cycle in ccRCC,
such as nitrogen-dependent glutamine
and aspartate, suggesting that inhibiting
glutaminase and aspartate simultaneously
may be a useful therapeutic
approach.
The final session of the conference
focused on the role of perioperative
therapy in RCC, with Dr. Christopher
Wright speaking on the use of artificial
intelligence for RCC diagnosis with
CT scans. Dr. Wright introduced the
concept of “segmentation” or having
a computer cluster parts of an image
together that belong to the same object
class. Such segmentation could be
used to increase diagnostic certainty,
predict best treatment approaches and
outcomes, and better estimate post-operative
renal function. He asked in artificial
intelligence could be used to independently
generate an unambiguous
nephrometry score. Through crowd
sourcing, hundreds of teams were able
to generate programs that were able to
complete these tasks in ways that were
comparable to humans and were able to
predict clinical outcomes. Dr. Wright
concluded by suggesting broader future
uses of this type of technology.
Dr. Hannan explored of stereotactic
radiation (SBRT) for RCC inferior
vena cava (IVC) thrombosis. He discussed
a phase II trial of neoadjuvant
SBRT for RCC IVC thrombus to evaluated
whether this technique may reduce
the risk of RCC recurrence. Results of
the safety lead-in were encouraging,
with 2 of 3 patients with metastatic disease
at diagnosis having a response (1
complete response and 1 partial abscopal
response). The study continues to
enroll.
Dr. Mohamad Allaf spoke of
surgical consideration with perioperative
therapy. He reviewed small previous
studies of neoadjuvant axitinib
and pazopanib which suggested some
role to help downstage patients prior to
surgery but will increase risk of surgical
complications. He reviewed pre-clinical
data and data in other cancer types for
neoadjuvant immunotherapy. Finally,
he reviewed results of a small study
(n=17) of non-metastatic, high-risk RCC
patients who 3 cycles of nivolumab prior
to partial or radical nephrectomy.
Although some patients achieved tumor
shrinkage all except one had statistically
stable disease after treatment. He also
described EA8143:PROSPER RCC trial,
a large randomized study of perioperative
nivolumab which has completed
enrollment, but whose results are
forthcoming.
The 2021 Kidney Cancer
Association IKCS Meeting not only provided
researchers and providers a terrific
venue for networking and collaboration
but also disseminated a great deal
of knowledge as progress in the fight
again kidney cancer marches on.
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