publication date: May. 29, 2020

Clinical Roundup

AI could predict risk of lung cancer recurrence

Computer scientists working with pathologists have trained an artificial intelligence tool to determine which patients with lung cancer have a higher risk of their disease coming back after treatment—part of Cancer Research UK’s landmark TRACERx study.

The AI tool was able to differentiate between immune cells and cancer cells, enabling researchers to build a detailed picture of how lung cancers evolve in response to the immune system in individual patients.

The paper was published in Nature Medicine May 27 and is showcased alongside eight other TRACERx publications on the Nature website.

Although this research is in its early stages, the approach could speed up how doctors predict which patients are more likely to see their lung cancer return, so they can be closely monitored with tailored treatment plans.

The AI tool—developed by researchers at The Institute of Cancer Research, London, in collaboration with scientists at University College London Cancer Institute and the Francis Crick Institute—was trained by pathologists to pick out immune cells from cancer cells. This allowed the tool to map out areas in tumours where the number of immune cells were high compared to the number of cancer cells, in patients with lung cancer.

Using the AI tool, the team found that while some parts of the tumor were packed with immune cells, described as hot regions, other parts of the tumour appeared to be completely devoid of them, which they described as cold regions.

When the researchers followed the progress of patients who had a higher number of cold regions, they found patients were at a higher risk of relapse.

This study is part of the TRACERx* (Tracking Cancer Evolution through therapy [Rx]) lung study—a £14 million, 9-year study funded by Cancer Research UK.

In the study, led by Yinyin Yuan, of The Institute of Cancer Research, and researchers from the UCL Cancer Institute and the Francis Crick Institute, AI pathology image-mapping technology was combined with next-generation sequencing. They used this tool to analyse samples from 100 patients with non-small cell lung cancer who took part in the TRACERx study.

The team’s work revealed that cancer cells found in immune cold regions may have evolved more recently than cancer cells found in immune hot regions that are packed with immune cells.

The researchers suggest that areas of the tumour with fewer immune cells may have developed a cloaking mechanism under evolutionary pressure from the immune system allowing them to hide from the body’s natural defences.

Their AI tool can assess how many regions with this cloaking mechanism exist within a tumor.

“Our research has revealed fresh insights into why some lung cancers are so difficult to treat, and we wouldn’t have been able to do this without the scale and scope of the TRACERx project,” Yuan said.

TRACERx is Cancer Research UK’s single biggest investment in lung cancer.


Study confirms effective, less toxic alternative to standard treatment for adults with Burkitt lymphoma

In a study, an alternative treatment regimen that is less toxic than standard dose-intensive chemotherapy was found to be highly effective for adults with Burkitt lymphoma across all age groups and independent of HIV status.

In addition to being better tolerated, the regimen, called dose-adjusted (DA) EPOCH-R, is already an option for diffuse large B-cell lymphomas and can be administered in an outpatient setting.

The findings were published May 26, 2020, in the Journal of Clinical Oncology. The study was led by researchers in the Center for Cancer Research at NCI, and sponsored by NCI’s Cancer Therapy Evaluation Program. It was conducted at 22 research centers across the country. The DA-EPOCH-R regimen was originally developed by NCI researchers led by Wyndham Wilson, at the NIH Clinical Center in Bethesda, Maryland.

“We knew Burkitt lymphoma is curable with dose-intensive chemotherapy, but that treatment can be acutely toxic for adult patients,” lead author Mark Roschewski, of NCI’s Lymphoid Malignancies Branch, said in a statement. “With this finding, we not only have a potentially curative treatment option for these patients that’s less toxic, but one that appears effective for most adults, including elderly patients and those with HIV and other comorbidities who might not be able to receive standard treatment.”

Burkitt lymphoma is a rare but aggressive B-cell lymphoma that is more common in children than adults. The dose-intensive chemotherapy that’s been developed to cure Burkitt lymphoma in pediatric patients is much better tolerated by children than adults, who can have severe side effects, especially if they are older or have other serious health conditions, such as being infected with HIV. People living with HIV/AIDS have an increased risk for Burkitt lymphoma.

NCI researchers have tested several approaches to determine whether less toxic treatments could still be effective for Burkitt lymphoma in adults. In an earlier pilot study with 30 adult patients treated only at NCI, the DA-EPOCH-R chemotherapy regimen was effective. The DA-EPOCH-R regimen is tailored to an individual patient’s ability to tolerate chemotherapy.

The regimen infuses chemotherapy over 96 hours for each cycle, and “dose-adjusted” means that later cycles can use higher doses of chemotherapy if it is well tolerated. This is compared to “dose-intensive” chemotherapy, which uses very high doses in all patients from the beginning.

To confirm these findings, the researchers conducted a larger, multicenter phase II study, enrolling 113 patients identified as having low- or high-risk disease, based on characteristics such as tumor bulk and performance status. The median age was 49 years, and 62% were 40 years or older. At a median follow-up of almost 5 years, the researchers calculated that the 4-year rate of event-free survival was 84.5%, meaning that percentage of patients had not seen any sign of their cancer’s return.

Overall survival was 87%. For low-risk patients, event-free survival was 100%, and for high-risk patients it was 82%. The treatment was effective across age groups, including patients in their 70s and 80s, and regardless of HIV status. The treatment was well-tolerated with a relatively low number of patients experiencing the severe side effects commonly associated with dose-intensive chemotherapy.

These findings suggest that highly dose-intensive chemotherapy may not be necessary for cure, and that carefully defined low-risk patients may be treated with limited chemotherapy. Furthermore, patients can receive EPOCH-R in an outpatient setting, an alternative to the prolonged hospitalization required to receive highly dose-intensive chemotherapy.

Five treatment-related deaths occurred in the study.

The researchers found that patients in the study who had disease in the central nervous system, specifically in cerebrospinal fluid (CSF), had the highest risk of treatment-related death or treatment failure.


Fox Chase researchers investigate perceived barriers to discussing sexual issues in breast cancer patients

Researchers at Fox Chase Cancer Center found that breast cancer patients describe having thoughts and feelings that can prevent them from discussing cancer-related sexual issues with their healthcare providers, even if they would like to.

“Overall, there is growing interest in the importance of women’s sexual health after breast cancer because of the impact it can have on women’s quality of life,” Lauren Zimmaro, lead author on “Patients’ perceived barriers to discussing sexual health with breast cancer healthcare providers,” published in Psycho-Oncology, said in a statement.

Zimmaro is a senior postdoctoral fellow with Jennifer Barsky Reese, of the Cancer Prevention and Control Research Program at Fox Chase, who was the principal investigator and senior author on the paper.

Zimmaro said sexual issues, including those directly resulting from treatment, are common among breast cancer patients. In some cases, chemotherapy and hormonal treatments may cause vaginal dryness, discomfort during sexual activity, and loss of sexual desire, she said. In other instances following mastectomies and other breast cancer surgeries, sexual concerns may include body image issues or changes in breast sensation, which can negatively impact women’s sexual arousal.

“These changes are often very distressing, and although they seem to be quite common, we know that women are rarely bringing up these concerns with their cancer providers, so we were interested in learning more about why this might be,” Zimmaro said.

This paper is part of a program of research in Reese’s lab focusing on understanding and improving patient-provider communication about sexual health. The researchers sought to learn more about the kinds of barriers that were preventing women from feeling comfortable discussing sexual concerns with their healthcare providers.

A total of 144 women treated for breast cancer at Fox Chase who were participating in a trial of a sexual health communication training program led by Reese completed questionnaires assessing their beliefs about discussing sexual issues with providers.

The researchers found that women cited two major barriers to discussing sexual issues with their healthcare providers. One was their own thoughts or feelings, which could impede them in discussing sexual issues with their providers, and the other was the women’s beliefs about their providers’ reactions to discussions of sexual health.

“Overall, women tended to view their own discomfort in discussing sexual concerns as the bigger barrier to discussing these issues with their providers than discomfort they attributed to their breast cancer providers,” Zimmaro said.

She said these results could be helpful in showing patients that it is common to have some doubts or hesitations about their ability or comfort in discussing sexual concerns. However, it may be important for women to recognize these barriers so that they can have their sexual concerns addressed appropriately.

“Now that we have a clearer understanding of the types of barriers preventing women from raising the topic of sexual issues with their providers, we can work towards addressing them,” said Zimmaro. “In fact, the findings helped confirm the need for programs that can help women feel more comfortable discussing sexual issues with their providers like the ones being evaluated in Dr. Reese’s lab.”


Evidence from two studies demonstrates efficacy of Immunoscore

Two Immunoscore clinical studies in stage III colon cancer patients validated the clinical value of Immunoscore to refine patients stratification and predict which patients benefit most from 6 months adjuvant chemotherapy.

Immunoscore is sponsored by HalioDx SAS.

Published in JNCI Cancer Spectrum, the Immunoscore-N0147 study was conducted in collaboration with clinicians and researchers from the Mayo Clinic. The Immunoscore-IDEA France study, published in Annals of Oncology, was conducted in collaboration with PRODIGE, a digestive oncology intergroup gathering the GERCOR, the FFCD and UNICANCER organizations. Objectives of these retrospective studies in prospectively conducted trials were to examine and validate the ability of Immunoscore to identify patients at high-risk of relapse and investigate survival differences according to Immunoscore in predefined subgroups, including Tumor/Node Stage and treatment duration.

The two studies were performed on independent large phase III randomized clinical trials cohorts, and included 559 patient samples from the FOLFOX alone arm of the NCCTG N0147 trial3, and 1062 patient samples from both arms (3 versus 6 months) of the IDEA France trial4 (as part of the IDEA international collaboration5). Consistent prognostic performances were obtained, and Immunoscore predictive performance was demonstrated for FOLFOX therapy duration.


MK-6482 induced positive response in Hippel-Lindau disease–associated kidney cancer

In an international trial led by researchers at The University of Texas MD Anderson Cancer Center, treatment with MK-6482, the small molecule inhibitor of hypoxia-inducible factor (HIF)-2a was well tolerated and resulted in clinical responses for patients with von Hippel-Lindau disease–associated renal cell carcinoma.

The results of the phase II trial were shared today in an oral presentation May 28 at the 2020 American Society of Clinical Oncology virtual annual meeting by principal investigator Eric Jonasch, professor of genitourinary medical oncology at MD Anderson.

The trial met its primary endpoint and showed an objective response rate in RCC tumors per RECIST by independent review. The confirmed response rate was 27.9%. When also considering the eight patients with unconfirmed response, the objective response rate was 41.0%. Additionally, 86.9% of patients had a decrease in the size of their target lesions. The median time to response was 5.5 months.

RCC affects approximately 40% of people with VHL disease and is one of the most common causes of disease-related death in people with VHL disease.

The VHL mutation causes cells to lose their ability to respond to oxygen levels properly, and leads to a buildup of HIF proteins inside the tumor cell. This process incorrectly signals that the cells are starved of oxygen, causing the formation of blood vessels and driving tumor growth. The inactivation of the VHL tumor-suppressor protein also is observed in more than 90% of sporadic RCC tumors. MK-6482 directly targets HIF-2a, hindering cancer cell growth, spread and abnormal blood vessel development.

Treatment of VHL disease-associated renal tumors consists of active surveillance until surgery is required for tumors larger than 3 cm to prevent metastatic disease. Repeated surgical procedures can carry significant complications as many patients develop renal insufficiency. Surgery will not cure VHL disease patients with RCC; surgery only is intended to prevent death from metastatic kidney cancer.

As of data cut-off, the single-arm clinical trial had enrolled 61 patients. The study enrolled adult patients with a germline mutation diagnosis of VHL disease, no prior systemic cancer therapy, measurable non-metastatic RCC tumors and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients received MK-6482 orally once daily until disease progression, unacceptable toxicity, or investigator’s or patient’s decision to withdraw. Tumor size was evaluated at screening and every 12 weeks thereafter. No patients had progressive disease on treatment and 58 patients (95.1%) remain on treatment.

Copyright (c) 2020 The Cancer Letter Inc.