Dana-Farber faculty to present more than 50 research studies at American Association for Cancer Research Annual Meeting 2023

Dana-Farber Cancer Institute researchers will present more than 50 research studies at the American Association for Cancer Research (AACR) Annual Meeting 2023. The meeting is the focal point of the cancer research community, where leading scientists, clinicians, health care professionals, survivors, patients, and advocates share the latest advances in cancer science and medicine.

The AACR Annual Meeting highlights the work of the best minds in cancer research from institutions all over the world, and this year’s meeting will be held in Orlando, Florida from April 14-19.

Select presentations by Dana-Farber experts this year include:

Author: Harshabad Singh, MBBS, MD

Publishing Title: Long-term results and ctDNA correlatives for CAPOX BETR: A multi-center phase II trial of capecitabine, oxaliplatin, bevacizumab and trastuzumab for previously untreated HER2 positive metastatic gastroesophageal adenocarcinoma

Presentation Number: CT155

Poster Board Number: 17

Session Day/Time: Monday, April 17, 1:30-5:00 pm.

Addition of the drug bevacizumab to chemotherapy and a HER2-targeted agent, herceptin, showed striking activity in a clinical trial involving patients with HER2-positive metastatic gastroesophageal adenocarcinoma – comparable to the effect of current standard therapy, which includes an immunotherapy agent targeting the PD-1 protein on T cells. In the trial, 37 patients with previously untreated cancers received standard chemotherapy (capecitabine and oxaliplatin) and trastuzumab (a HER2-targeting agent), followed by bevacizumab, an anti-angiogenic drug that blocks blood vessel growth to tumors. Eighty-one percent of the participants responded to the treatment. At a median follow-up of 23.2 months, all the patients were alive, and the progression-free survival (PFS) was 14 months. That compares with a response rate of 74% for the current standard therapy, which consists of chemotherapy, trastuzumab, and the immunotherapy drug pembrolizumab. The six-month PFS for standard therapy is 70.3%, compared to 77% for the regimen including bevacizumab. The findings may lay the groundwork for a clinical trial of bevacizumab in combination with standard therapy, investigators say.

Author: James Lindsay, PhD

Publishing Title: ImmunoPROFILE: A prospective implementation of clinically validated, quantitative immune cell profiling test identifies tumor-infiltrating CD8⁺ and PD-1⁺ cell densities as prognostic biomarkers across a 2,023 patient pan-cancer cohort treated with different therapies

Presentation Number: 5706

Session Day/Time and Location: Tuesday, April 18, 2:30-4:30 pm. 

Using a new test that unites cell-imaging technology with machine learning, researchers have found that patients whose tumors contain high concentrations of specific immune cells are likely to survive longer than patients with tumors carrying lower densities of these cells. The test, called ImmunoPROFILE, uses fluorescent staining to mark different types of immune cells within a tumor, then analyzes a digital image of the tumor with machine learning technology to calculate the density of those cell types. Researchers used the test to analyze 2,023 tumor specimens collected over three years from 27 tumor types. They found that high densities of CD8⁺ T cells (which attack diseased and cancerous cells), PD-1⁺ T cells (so-called exhausted T cells), and FOXP3⁺ T cells (which regulate the T cell response) were associated with longer overall survival across tumor types regardless of therapy. The findings suggest that tests that quantify multiple immune cell populations may have greater predictive power than those that count just one, and that clinical use of multiplexed imaging assays provides previously unrealized prognostic information across multiple tumor types.

Author: Harry Klein, PhD

Publishing Title: MatchMiner: An open-source AI precision medicine trial matching platform

Presentation Number: 1067

Poster Board Number: 11

Session Day/Time: Sunday, April 16, 1:30-5:00 pm.  Section 43

A software platform that matches patients with appropriate clinical trials of targeted therapies has helped hundreds of patients at Dana-Farber enroll in such trials since the platform's launch in 2017. Called MatchMiner, it uses data on the genetic features of a patient's cancer, as well as clinical data, to identify trials at Dana-Farber for which the patient might be eligible. For clinical investigators hoping to enroll patients on a trial, MatchMiner can help recruit patients that meet the trial's eligibility requirements. At the AACR Annual Meeting 2023, the platform developers will present new information on 256 clinical trial consents facilitated by MatchMiner. Developers found, for example, that trial consents have been made for 20 cancer types and that 87% of patients who consented to join a clinical trial identified by MatchMiner actually participated in the trial. Because some patients are not ready to enroll in a targeted therapy trial because their cancer is responding to standard treatment or are in remission, the platform's developers and Dana-Farber's Kenneth Kehl, MD, MPH, are evaluating the use of artificial intelligence to identify patients at the time they are likely to need a new treatment option.

Author: Elena Ivanova, PhD

Publishing Title: Individualizing treatment using patient derived organoids, BH3 profiling and microfluidics: A proof of concept in a patient with low-grade serous ovarian carcinoma

Presentation Number: 162

Poster Number 14; Section 6

Session Day/Time: Sunday, April 16, 2023, 1:30 pm - 5:00 pm

 To date, there are no model or cellular-based systems that are able to predict if an anti-cancer therapy will have efficacy for an individual patient before it is prescribed. Researchers at Dana-Farber are investigating an N-of-1 treatment paradigm in which a patient’s cancer is developed into patient-derived organoids (PDOs), which are 3D cultures of tumor cells from an individual patient. These organoids can then be used to evaluate therapy regimens. This study describes a proof-of-concept of this approach in a patient with a diagnosis of low-grade serous ovarian cancer (LGSC).  First, the researchers obtained tumor samples from the patient at the time of surgery, and within 14 days, a PDO model was made from the patient’s tumor tissue. The patient’s personal organoids were then used to test 13 standard and non-standard of care anti-cancer therapies. Tests included BH3 profiling, which determines if the medicine is inducing cell death in the organoid, and a cell viability test that uses 3D microfluidics to determine which cells are alive and which are dead. The tests are performed in sequence, with BH3 profiling done 24 hours after treatment, and then cell viability 6 days later. The organoids showed sensitivity using both tests to two drugs, navitoclax and venetoclax, reducing cell viability by about 90% and showing high scores indicating induction of cell death. They did not show sensitivity to two drugs the patient had already tried with little response.

Author: Nadine Jackson McCleary, MD, MPH; Ellana Haakenstad, MPH

Publishing Title: Persistent patient barriers to genomic testing in ambulatory oncology

Presentation Number: 5524

Poster Board Number: 9; Section 39 

Session Day/Time: Tuesday, April 18, 2023, 1:30 pm - 5:00 pm

Tumor genomic testing and cancer clinical trial enrollment provide key access to precision cancer therapeutics and supportive care options. Certain populations of people, such as Black, Indigenous, People of Color, and people with low income, have been historically underrepresented in genomic studies and clinical trials. These populations also tend to be the most negatively impacted by a cancer diagnosis. To understand the barriers to accessing these cancer care options, researchers at Dana-Farber interviewed 16 patients diagnosed with cancer who were being seen at an ambulatory care center. The patients identified as Black, Hispanic/Latinx, another race, over 70 years old, having a primary language other than English, or living in a low-income zip code (<$50,000/year). The researchers asked about barriers to genomic testing of tumors because eligibility for precision medicine and clinical trial enrollment often require tumor genomic testing. Based on the interviews, the researchers identified three barriers to tumor genomic testing:  education, including uncertainty about the benefits or the procedure; mistrust of research, specifically concerns about data privacy; and logistics, such as cost, time away from work, and travel. The researchers identified the same barriers for participation in clinical trials. They also found that many patients were uncertain if they’d received tumor genomic testing or if it was recommended, citing the use of confusing medical terms and information overload. Those who did participate in a clinical trial appreciated the additional support and clinical monitoring. When genomic testing and a cancer clinical trial were presented as the best course of care, patients were emphatically interested, though they still had concerns about side effects. The research suggests that these barriers might be lowered with personalized education, coaching, and referral to supportive resources.

In addition, Pasi A. Jänne, MD, PhD, will be participating in a session addressing how the previously undruggable KRAS was finally defeated and the future of this critical area of cancer research. He will discuss progress in the treatment of KRAS Mutant Cancer. The session is on Saturday, April 15 at 4:15 pm in W Hall A2-3.