News & Events | DCTD Newsletter

Last Updated: 12/11/2024

STAFF HIGHLIGHT: Hari Sankaran, MD, MSc

In this edition of the DCTD newsletter, Hari Sankaran, MD, MSc, Medical Officer, Biometric Research Program (BRP), describes his journey in the field of pediatric oncology and shares his experience working with the Cancer Therapy Evaluation Program (CTEP) as a statistical reviewer in BRP.

Why did you choose a career in pediatric hematology-oncology and global health and how did you get there?

Coming from a family of physicians, I was subtly nudged towards medicine from an early age and volunteered in medical camps abroad during my high school years. These experiences working in resource-constrained settings led me to pursue medical school in India and cemented my interest in global health. Pediatric residency was an organic decision influenced by observing my mother, who has led a fulfilling, happy career as a general pediatrician in an underserved community. During residency, the biological complexity of pediatric cancers and deep interpersonal relationships with patients led me to pursue pediatric oncology. As I had an interest in global health, my program director, Dr. Poplack, encouraged me to pursue a master’s in epidemiology during fellowship under an R25 training grant from NIH. The statistical skillsets I developed during my master’s program have proven to be invaluable and contributed to my interest in pursuing a career at NCI.

What do you enjoy about the pediatric oncology field?

I enjoy forming connections with the families. I have shared emotional experiences with the parents and their children and formed deep personal bonds with them. For patients that are in remission, I often get updates about how they are doing and for those that passed, I occasionally learn how the families are coping.

What memorable moment(s) have you had with patients?

Every patient and their parents are memorable in some way. One story that I often recount is of a young, joyful patient with refractory acute myelogenous leukemia and her mother who spent months in the hospital due to multiple complications. Unfortunately, the young girl passed from her disease, and a few years later, I was surprised to see the mother as a nurse on the oncology floor. She told me she had gone back to nursing school and was finishing her oncology nursing certification.

These stories make my career meaningful. In fact, I have seen many parents of pediatric patients with cancer return to the hospital as volunteers or to serve as volunteers in the children’s camps, such as Camp Fantastic, which NIH runs annually. My participation in these camps has provided some of my most cherished experiences as a clinician, as we see our patients outside of the hospital setting.

What made you pursue pediatric oncology in India after your fellowship?

Practicing what I had learned at Texas Children’s Hospital in a global health setting helped me to fulfill my vocational aspirations to serve in an underserved part of the world. Though underserved areas exist everywhere, even in the US, my move to India was based on familiarity with the culture and previous experience with the pediatric oncology community there. Working in community and private hospital settings gave me a comprehensive understanding of the barriers that exist in healthcare ranging from patient factors (e.g., poverty) to regulatory (e.g., drug availability, bioequivalence of generics). I also gained a healthy respect for pediatric oncologists working in those settings as they are often brilliant and have insightful research questions, but are overloaded with patient care, which limits their time to study research questions.

What brought you to NCI from India?

After working in India from 2016-2019, I wanted to answer several research questions that naturally arose from clinical practice. As an oncologist, I strongly felt that medical doctors needed the skillsets to critically appraise our ever-expanding toolkit of molecular assays and imaging to provide better care to patients. Though my master’s degree gave me the ability to do some basic statistical analyses, some of my questions were related to understanding high-dimensional data derived from targeted assays, with which I was unfamiliar.

Coincidentally, in 2019 I had attended a research protocol development workshop in which I randomly met Dr. Lisa McShane from NCI. She graciously accepted me as a fellow in BRP, and here I am almost 5 years later as a medical officer. I have expanded my knowledge of statistical considerations, especially around incorporating biomarkers in clinical trials. Being a clinician in a branch full of statisticians has helped me to better appreciate how much thoughtfulness and effort statisticians go through when evaluating protocols or biomarkers for clinical trials. I also understand how to explain statistical issues as digestible comments when I communicate with investigators in the NCTN. Working with my pediatric oncology colleagues (and mentors) in CTEP’s Clinical Investigations Branch (Drs. Malcolm Smith and Nita Seibel), has also given me a broader understanding of CTEP’s role in evaluating phase 1-3 clinical trials.

What is your role in BRP?

In BRP, I serve on the Core Correlative Science Committee, reviewing laboratory correlative biomarkers for phase 2 and 3 trials for adult lymphoma and pediatric cancers. I am also a member of the Experimental Therapeutics Clinical Trials Network Data Safety Monitoring Board. My research in BRP focuses on studying the genomic differences in adolescent and young adult (AYA) and non-AYA cancers by utilizing genomic data from the NCI-MATCH trial. We recently completed this project, which has led to a new proposal to examine the associations between health disparities correlates and tumor molecular alterations in NCI-MATCH.

Through my involvement with the Pediatric Oncology Branch (POB) in the NCI Center for Cancer Research and the Developmental Therapeutics Clinic (DTC), I provide mentorship and statistical analysis on several projects, such as examining natural history and treatment data from rare cohorts including NF-1, gastrointestinal stromal tumors, medullary thyroid cancer, and alveolar soft part sarcoma. I also continue to pursue global health research by studying access to CAR-T cell trials for patients outside of the US.

Do you still see patients?

I attend in the POB Immune Deficiency Cellular Therapy Program at the NIH Clinical Center for 4 weeks per year. I also see NF-1 patients treated with selumetinib in the DTC run by Dr. Alice Chen.

What do you see on the horizon regarding biomarker development in clinical trials?

The development of biomarkers that demonstrate a treatment effect, predict toxicity, or resistance is an important yet challenging field. As a reviewer, we frequently see new biomarkers based on the latest sequencing technology. Though these new sequencing platforms offer a deeper biological insight into the molecular mechanisms of the tumor cells and tumor microenvironment, translating these complex biomarkers into a clinically meaningful benefit takes time and thoughtful consideration.

What are your hobbies/passions outside of work?

I am an avid gardener and blessed to enjoy a variety of hobbies including candle-making, mentoring a temple youth group, and playing the harmonium, an Indian reed organ.

SPOTLIGHT: The NCI Experimental Therapeutics (NExT) Program’s Chemical Biology Consortium (CBC) Convenes Its Annual Scientific Symposium

The NExT Program’s CBC held its third Annual Scientific Symposium: Catch the Wave – Innovations in Cancer Therapeutics on January 31, 2024, at the Sanford Institute for Regenerative Medicine in La Jolla, CA. The Sanford Burnham Prebys CBC center co-sponsored the event, which continued the tradition set by previous CBC members at the inaugural symposium at the University of California, San Francisco in 2018 followed by Vanderbilt University in 2019, before a COVID-19-mandated hiatus.

The annual symposia assemble the CBC members in vibrant, scientific community settings to hear presentations by local scientists on the leading edge of their fields in scientific or technological development, which are relevant to the CBC’s goal of discovering anti-cancer therapeutics. These in-person gatherings foster the exchange of information, shared learning, and best practices in cancer drug discovery and development among the academic, non-profit, and industry (pharma/biotech) scientists who attend.

As a collaborative network (managed by the Frederick National Laboratory for Cancer Research) of 19 institutes from a blend of premier universities, non-profit research institutes, and focused Contract Research Organizations (CROs) with drug discovery expertise, the CBC supports the advancement of early stage, oncology drug discovery projects in the NExT Program pipeline.

Symposium Highlights

• DCTD’s director, Dr. James Doroshow, opened the symposium by presenting on the use of rare cancer models that are available through the NCI Patient Derived Model Repository (PDMR) for therapeutic development.
• Dr. Benjamin Cravatt, Scripps Research Institute, spoke about the discovery of new cancer targets and ligands identified with novel reactive compounds and cutting-edge proteomics techniques.
• Dr. Raymond Deshaies, SVP Global Research, Amgen, discussed the development of new approaches to therapeutic development based on the concept of “multispecific medicines” (molecules that interact with more than one target to achieve greater benefit with less toxicity). Dr. Deshaies also issued an impassioned plea to new investigators to help build the future of discovering medicines.
• Drs. Matt Hall, NCATS, and Jennifer Cox, Chinook Therapeutics, recounted a CBC project team’s discovery of a lactate dehydrogenase (LDH) inhibitor and their subsequent partnership with Chinook Therapeutics. This led to the development of a clinical compound for treating the rare kidney disease, primary hyperoxaluria (PH1). Although originally determined to have limited potential as an anticancer drug, the LDH inhibitor demonstrated robust efficacy and utility in PH1.

The NExT Program and CBC hope to continue these annual events at other CBC institutions, including Curia Global, Inc. in Buffalo, NY and the Cleveland Clinic Foundation in Cleveland, OH.

NEWS ACROSS DCTD

DCTD-supported Research at the American Society of Clinical Oncology (ASCO) and American Association for Cancer Research (AACR) Annual Meetings

DCTD staff presented research findings at the annual spring meetings of ASCO and AACR. View the lists of presentations that included DCTD staff co-authors at ASCO and AACR.

NIH Convenes Digital Pathology in Imaging Workshop

DCTD’s Cancer Diagnosis Program held a virtual Workshop on Digital Pathology Imaging (DPI) in Cancer Clinical Trials and Research on March 6-7, 2024. Nearly 400 attendees from academia, industry, government, and non-government organizations discussed the expanding role of DPI in translational cancer research, biomarker studies, clinical trials, and pharmaceutical development. Read highlights from the workshop and listen to the recordings.

The NCI Virtual Clinical Trials Office (VCTO)

A new NCI initiative aims to tackle the steep decline in participation in NCI-funded cancer clinical trials that is due in part to clinical trials staffing shortages that were exacerbated by the COVID-19 pandemic. These shortfalls have hampered clinical trials activities across the country, particularly in rural and underserved areas. Through the new NCI VCTO, a centralized team of support staff — including research nurses, clinical research associates, and clinical data specialists — will work remotely to assist NCI-Designated Comprehensive Cancer Centers and community practices with their clinical trials activities. This assistance can include screening patients for eligibility, enrolling patients into trials, educating patients about research protocols, and performing data entry. Read the VCTO NCI Media Advisory.

New Guidance for Clinical Trial Operations from the Cancer Therapy Evaluation Program (CTEP)

New guidance, based on efforts from CTEP, provides recommendations for IND-exempt trials and are aimed at limiting clinical trial data collection to only those elements essential for the trial’s primary and secondary objectives. The NCI Clinical Trials and Translational Research Advisory Committee’s ad hoc Streamlining Clinical Trials Working Group (SCTWG) developed these recommendations to streamline data collection in NCTN IND-exempt cancer treatment trials beginning with new concepts and protocols with activations dates after January 1, 2025.

The SCTWG identified these opportunities for reducing data collection:

• Adverse events
• Medical history
• Concomitant medications
• Imaging and other assessment procedures
• Patient-reported data

Read the new NCTN streamlined data standard practices for IND-exempt trials under the “Policies and Guidelines for Protocol Development.”

New Consensus Recommendations from the NCI-funded Patient-Derived Xenograft (PDX) Development and Trial Centers Research Network (PDXNet)

The PDXNet working group, an expert panel and DCTD staff recently developed consensus recommendations to harmonize PDX study design and analysis, and emphasized the need for meaningful translational endpoints in drug-response studies using PDX models.

PDX models are valuable for pre-clinical research and cancer drug development, but the lack of a standard approach to measure tumor drug responses could be problematic. These recommendations and suite of tools are now publicly available for universal use.

Consensus recommendations for PDX research centered on:

• Experimental design
• Assessment of anti-tumor activity
• Treatment duration
• Combination treatment
• Biomarker analysis

As part of the Cancer Moonshot, PDXNet was established to coordinate collaborative, large-scale development and preclinical testing of targeted therapeutic agents using patient-derived models to advance cancer precision medicine.

Congressional Staffers Visit with NCI’s Pediatric Oncologists

On May 29, 2024, staff to Sens. Jack Reed (RI), Shelley Moore Capito (WV), Chris Van Hollen (MD), and John Boozman (AR), as well as staff to Reps. Michael McCaul (TX), Ami Bera (CA), Susan Wild (PA), and Bonnie Watson Coleman (NJ), visited NCI for a tour focused on childhood cancer research.

The group met with NCI extramural program leaders (Drs. Malcolm Smith, Nita Seibel, Greg Reaman, and Emily Tonorezos), leadership of NCI’s Pediatric Oncology Branch (POB, Drs. Brigitte Widemann and John Glod), and POB investigators on two lab tours: 1) Drs. Nirali Shah, Christopher Chien, and Victoria Giordani; 2) Drs. Rosandra Kaplan, Anandani Nellan, James Cronk, and Sabina Kaczanowska.

The staff also met with NCI Director Dr. Kimryn Rathmell and participated in a tour of The Children’s Inn at NIH, which provides free lodging and services for many families with children, adolescents, and young adults participating in clinical trials at NCI and other NIH Institutes and Centers.

Nanotechnology Characterization Laboratory (NCL) Annual Report

NCL released their 2023 annual report highlighting areas of progress made in research and application trends including:

• NCL’s assay cascade (submission and application trends)
• Protocols and new technologies
• Nanotechnology formulation
• Publication of methods

NCI founded the NCL in collaboration with FDA and NIST, as a public-private partnership to advance the science needed to expedite the development of promising nanotech therapies and diagnostics. NCL, part of the Frederick National Laboratory for Cancer Research (FNLCR) and funded through DCTD’s Nanodelivery Systems and Devices Branch, has tested more than 500 unique nanomaterials submitted by more than 125 investigators worldwide.

Cancer HealthCast Podcast Features Dr. Henry Rodriguez

This edition of the Cancer HealthCast podcast features Dr. Henry Rodriguez, director of DCTD’s Office of Cancer Clinical Proteomics Research. The podcast is about how sharing molecular cancer research data can expand cancer treatment and care. NCI collaborates with GovCIO to develop the Cancer HealthCast podcast to bring a variety of cancer research topics to the public.

Stopping ASPS ASAP

CCR’s 2024 Milestones highlights clinical research conducted in the NIH Clinical Center on alveolar soft-part sarcoma (ASPS). The story includes comments by Drs. James Doroshow and Alice Chen.

Selected Staff Publications

Kunkel MW, Coussens NP, Morris J, et al. HTS384 NCI60: The next phase of the NCI60 Screen. Cancer Res. 2024 Jun 11. Online ahead of print.
PubMed

Abdel-Wahab M, Coleman CN, Eriksen JG, et al. Addressing challenges in low-income and middle-income countries through novel radiotherapy research opportunities. Lancet Oncol. 2024 Jun;25(6):e270-e280.
PubMed

Dunn A, Takebe N, Chen A, et al. The effect of liver dysfunction on the pharmacokinetic disposition of belinostat and its five metabolites in patients with advanced cancers. Cancer Chemother Pharmacol. 2024 Mar 14. Online ahead of print.
PubMed

Tandon P, Abrams ND, Avula LR, et al. Unraveling links between chronic inflammation and Long COVID: Workshop Report. J Immunol. 2024 Feb;21(4):505-512.
PubMed

MATCH Publications

Gong J, Mita AC, Wei Z, et al. Phase II study of erdafitinib in patients with tumors with FGFR amplifications: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol K1. JCO Precis Oncol. 2024 Apr:8e2300406.
PubMed

Gong J, Mita AC, Wei Z, et al. Phase II study of erdafitinib in patients with tumors with FGFR amplifications: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol K2. JCO Precis Oncol. 2024 Apr:8e2300407
PubMed

Connolly RM, Wang V, Hyman DM, et al. Trastuzumab and pertuzumab in patients with non-breast/gastroesophageal HER2-amplified tumors: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol J. Clin Cancer Res. 2024 Apr 1;30(7):1273-1280.
PubMed

 

FUNDING UPDATES

Title	Announcement Number	Closing Date	Activity Code
Specialized Programs of Research Excellence (SPOREs) in Cancer Health Disparities and Minority Health (CHD-MH) (Clinical Trial Optional)	NOT-CA-24-020	September 27, 2024	U54
Request for Information (RFI): Seeking input to identify and explore experiences utilizing the whole person perspective and evidence for its value in the care of people with cancer	NOT-CA-24-061	Response Date: by August 18, 2024

IN MEMORIAM

— Written by staff from the Biometric Research Program —

It is with great sorrow that we report the death of Dr. Richard Simon on May 9, 2024. Dr. Simon was the Associate Director of the Biometric Research Program, DCTD, until his retirement in 2017. Dr. Simon was a true giant and one of the most recognized figures in his field, making fundamental and important contributions to biostatistics and statistical genomics, as well as facilitating and mentoring the careers of numerous successful biostatisticians and computational biologists. He began his career in the NIH Clinical Center and then moved into the NCI Division of Cancer Treatment and Diagnosis, always following, and promulgating the precept that the successful biostatistician must have in-depth knowledge of the subject matter and integral involvement in applied research. He founded and developed the current NCI Biometric Research Program, one of the leading NIH biostatistics and bioinformatics groups.

Dr. Simon’s numerous and seminal methodologic biostatistics contributions include the Norton-Simon model of tumor growth, which informed curative chemotherapeutic late intensification in pediatric leukemia, Pocock-Simon adaptive stratification, Lan-Simon-Halperin futility monitoring, the Gail-Simon test for qualitative treatment by subset interaction (awarded the Snedecor prize for best publication in biometry in 1985), the optimal 2-stage design, which quickly became the most used phase 2 trial design in oncology, the accelerated titration design to reduce under treatment in phase 1 trials, and early papers on the design of therapeutic equivalence trials. He was internationally regarded as an expert in the evaluation of prognostic and predictive classifiers.

Dr. Simon was recognized as one of the foremost international experts in the design and analysis of studies using high dimensional genomic data and the use of genomics in clinical trial design. He was the lead author of the book “Design and Analysis of DNA Microarray Investigations,” with other members of the Biometric Research Program, and the author of the book “Genomic Clinical Trials and Predictive Medicine.” He established a post-doctoral training program in statistical genomics and bioinformatics, which has continued for approximately 20 years. He designed, developed, and maintained a suite of DNA microarray data analysis tools, including BRB-ArrayTools, implemented to be rigorous and yet accessible to early career computational biologists with little statistical sophistication. BRB-ArrayTools amassed over 26,000 registered users in approximately 65 countries, has been cited in over 3000 publications, is licensed from NIH by approximately 30 companies, and won the 2012 National Federal Government Award for Excellence in Technology Transfer.

Dr. Simon’s other awards and accomplishments include more than 748 published papers (with an h-score of 143: 143 publications with at least 143 citations each). His “Design and analysis of clinical trials” chapter in all 12 editions of DeVita, Hellmann and Rosenberg’s reference book “Cancer: Principles and Practice of Oncology” is a testament to the importance and centrality of his contributions to the field of oncology. His receipt of the 2013 Karl Peace Award from the American Statistical Association “for outstanding statistical contributions for the betterment of society”, and the 2017 Marvin Zelen Leadership Award from Harvard University, are testaments to the importance and centrality of his contributions to the field of biostatistics. Finally, his legacy is being ably carried forward and extended by his sons Dr. Jonathan Simon, Associate Professor in the Stanford Physics Department and Dr. Noah Simon, Associate Professor in the University of Washington Biostatistics Department. Dr. Simon will be fondly remembered by the many NCI staff who benefited from his wisdom, teachings, collaborations, and leadership.

Additional tribute from The Cancer Letter: “Richard Simon, NCI’s Visionary Biostatistician, Dies at 80”

 

— Excerpt from C. Norman Coleman, MD (1945-2024); written by Jeffrey C. Buchsbaum, Frank S. Govern, and Pataje Prasanna in Radiation Research —

Radiation oncology, medicine, and the world lost one of its most kind-hearted, gifted leaders, and mentors on March 1, 2024, with the passing of Dr. C. Norman Coleman. His life was fully dedicated to service to others and marked by numerous achievements, providing inspirational mentoring, caring, and generosity. His impact on those he touched directly and on all who benefitted from his leadership in cancer research and treatment is impossible to calculate. It is a tragic irony that a giant in the field succumbed to advanced cancer. Although much progress has been made in cancer diagnosis and treatment, Dr. Coleman's loss illustrates that our work is far from being done.

Norm was truly a remarkable person. He accomplished so much yet was so humble in his achievements. He was an amazing man who loved to sit and talk science over coffee and a treat, and made time if you needed him. He understood context in ways most did not spend the time and energy to do. He read broadly and was open to the newest thinking and approaches. He tackled some very complex projects and meetings — he knew how to stand back and watch, learn, hear, and listen. He is someone we will always miss and always wish we could just call to share news or a story or to strategize. And then there is how he would create witty and beautiful poems for people at events such as a residents graduation dinner or for retirements. And we don't even want to start to talk about his triathlons — he even qualified for the world championships this year (again). He was simply amazing. He liked to talk about the Tour de France a lot and all the climbs. Norm inspired and helped us all as we make our own climbs.

Additional tributes from the Lancet and the International Cancer Expert Corps: C Norman Coleman and C. Norman Coleman, MD, 1945-2024; Establishing a Legacy of Mentorship and Partnership