OncologyLive® is the flagship publication of OncLive®. Each issue delivers expert insights and clinical oncology news and updates, which impact the day-to-day clinical practice of oncology professionals who work tirelessly to help improve patient outcomes.

As cancer care continues to shift away from a fee-for-service model to a value-based care model, clinicians and institutions will need to be adaptable and innovative to build effective community oncology practices of the future.

“We are part of a large, complicated environment with hospitals, payers, and plan benefit managers, and that creates market pressure and an ongoing market dynamic that we have to compete with,” Glenn Balasky, executive director of Rocky Mountain Cancer Centers in Englewood, Colorado, said in an interview with 

. “Value-based care is here to stay. We have community oncology practices that have to leverage that in order to continue to garner attention from the payers and employers alike.”

Balasky participated in a panel discussion at the 2022 Community Oncology Conference in March titled, “Building/Designing the Community Oncology Practice of the Future.”

The 6-year Oncology Care Model (OCM), initiated by the Centers for Medicare & Medicaid Services, was designed to evaluate payment strategies to promote high-quality and high-value cancer care.

 The OCM focuses on providing beneficiaries with enhanced services, such as 24-hour, 7 days-per-week clinician access and a documented care plan, use of electronic health records (EHR), and increased data utilization to improve care (

 Approximately 25% of fee-for-service chemotherapy-related cancer care—spanning more than 125 practices and 7000 practitioners—has been handled by the OCM. The model debuted July 1, 2016, and is scheduled to expire on June 30, 2022.

Balasky said that the OCM is the most comprehensive value-based care model put into practice to date and that it is unfortunate it is being paused without a next step in place. Clinical practice with the OCM has allowed clinicians to gain more experience in providing electronic screening, measurements, and assessments, Balasky noted.

He hopes that practices will continue to be committed to applying these innovations to draw patients, even as the model expires.

Balasky said that one of the biggest recent shifts in providing value-based cancer care has been in the realm of patient communication. The wide adoption of telemedicine brought on by the COVID-19 pandemic has changed the way clinicians communicate with patients in ways that extend beyond in-person vs virtual visits. Balasky noted the positive innovations that coincide with telemedicine are here to stay, which include new methods of outreach and follow-up as well as expanded offerings.

“We are growing in our ways to connect with patients better,” Balasky said. “We are trying to move away from [just talking on] the phone. It is taking a while, but we’re trying to move into more asynchronous communication, such as texting our patients appointment reminders or allowing them to check in to an appointment online. The service side needs to [continue to] progress. The care side will always progress because we’re naturally driven to provide better care.”

Increased telehealth use has received a positive response from patients, particularly among adolescents and young adults with cancer. A retrospective study by Swartz et al found that among 331 patients who were diagnosed with cancer between the ages of 15 and 39 years, 71.4% participated in telehealth and most of them were somewhat or very satisfied with their telehealth experiences (54.8%). Topics that patients preferred to address via telehealth included nutrition (34.8%), stress management (33.9%), and mental health or counseling services (32%).

Strategies to increase or continue telehealth services are being considered across the oncology landscape. For example, the National Cancer Institute is conducting a 5-part webinar series running monthly from February 2022 to June 2022 seeking to identify research gaps and opportunities for increased telemedicine use in cancer care.

 Additionally, in March 2022, Congress voted to extend COVID-19 telehealth policies for Medicare patients for an additional 5 months after the public health emergency expires.

Restructuring to address physician burnout 

Balasky also highlighted that labor and wage pressures, largely brought on by the COVID19 pandemic, present a significant challenge for providing value-based care and that issues with staffing shortages resulting from burnout must be addressed.

At the 2021 American Society of Clinical Oncology Annual Meeting, So et al presented the results of a pilot study at a tertiary cancer center in the United Kingdom to address burnout among junior oncologists. The program invited doctors to participate in 30-minute weekly well-being sessions organized by a clinical psychologist. The sessions included breathing and relaxation exercises, clinical debriefing, and suggested strategies to increase mindfulness in the workplace.

All 10 oncologists who participated in the program were either satisfied or very satisfied with the group facilitation and found the sessions helpful. Interventions that incorporate physician feedback to combat burnout are something that community oncology practices should consider, Balasky contended.

“We are going into a period where we may have no choice but to raise our wages...to keep our staff and fulfill our mission,” Balasky said, noting that the added cost may delay other areas of innovation. “[Not] only do we have to pay them more, but we also have to help engage them more. The pandemic has been hard for everybody in the country and in the world, and [as a result], we have lost some of our connectivity.”

The increased role of genetic testing for the optimization of cancer care is another factor that will need continued monitoring. During the panel discussion, Balasky said that his practice hired a staff member to exclusively handle payments for genetic testing to accommodate the volume of billing. Balasky noted that genetic testing workflow and operations processes, still in their infancy, must be optimized to address complications with ordering and how clinicians see the results.

The increased prevalence and evolving efficacy of EHRs may present a possible solution to the problem of effectively integrating genetic testing into a value-based health care model. In a retrospective study of an OCM multisite community-based practice, Mendenhall et al looked at the effect of provider education and the addition of discreet data fields to the genetic testing fields added to the EHR concerned to better track the incidence of genetic screenings in patients with breast cancer.

Results from the study showed that of the 631 patients deemed to have met the National Comprehensive Cancer Network testing criteria, 92.7% were referred for genetic counseling and testing. The new screening practice also resulted in a 163% increase in genetic referrals for other cancer types outside breast cancer. Investigators concluded that the workflow practice was effective, scalable, and financially viable in terms of genetic and practice growth.

Even as value-based care appears to be on its way toward permanent integration in oncology care at the community level, challenges in adopting the model remain. For example, results of a 2021 survey of 307 oncologists across the US highlighted some of the barriers to participating and succeeding within a value-based care model. Among practices that participate in commercial value-based care programs (n = 60), half the respondents found it neither easy nor difficult to perform favorably within the model, 30% said it was difficult, and 5% said it was very difficult. Similarly, most practices that participated in the OCM or the Merit-Based Incentive Payment System (n = 150) found favorable performance neither easy nor difficult (51%); 31% and 6% found it difficult or very difficult, respectively.

The primary challenges for favorable performance among 153 responders who completed the survey included navigating the payer landscape and reimbursements (27%), identifying cost-reduction opportunities (20%), and tracking costs across an episode (18%). Responders were also asked to suggest solutions to better support value-based care reimbursement; the most common answers cited seamless integration into current workflows (49%), increased interoperability across platforms (42%), and increased awareness of cost information (29%), among others.

Survey responders represented practices in the privately owned community setting (44%), the public community setting (29%), and the noncommunity setting (27%). The median time spent in direct patient care was 90% (range, 0%-100%), and the median patient volume per day was 20 (range, 3-60). Investigators concluded that further research is needed to better design and implement value-based care systems and the technology they require.

“The analogy that I have used a lot during the [COVID-19] pandemic is that we [are] in the same storm, just in different boats,” Balasky said. “How do we get our boats back together? How do we line up and continue to learn from each other? How do we continue to do that with the community at large across the country? [We need to] bring that spirit back to our offices, back to our clinics, to give that benefit to our staff, our physicians, and most importantly, our patients.”

Oncology care model overview. Centers for Medicare & Medicaid Services. February 2021. Accessed March 22, 2022. 

Swartz MC, Roth M, George G, et al. Satisfaction with and recommendations to improve telehealth visits among adolescents and young adults with cancer during the COVID-19 pandemic. 

. 2021;39(suppl 28):280. doi:10.1200/JCO.2020.39.28_suppl.280

Telehealth and cancer: studying its role in cancer control and care delivery webinar series. National Institutes of Health. Updated March 15, 2022. Accessed March 28, 2022. 

The AMA salutes Congress for passing omnibus telehealth provisions. News release. American Medical Association. March 14, 2022. Accessed March 28, 2022. 

So AC, Hunter S, Chan K, et al. A pilot study to prevent burnout in junior oncology doctors during the COVID-19 pandemic in a tertiary U.K. center. 

. 2021;39(suppl 15):11015. doi:10.1200/JCO.2021.39.15_suppl.11015

Mendenhall M, Guinigundo A, Burneka E, et al. Strategic integration of genetic testing and counseling in patients with breast cancer in an oncology care model (OCM) multisite community-based practice. 

. 2021;39(suppl 28):231. doi:10.1200/JCO.2020.39.28_suppl.231

Gajra A, Simons D, Jeune-Smith Y, Valley AW, Feinberg BA. Barriers to participation and success in value-based care (VBC) models. 

. 2021;39(suppl 28):70. doi:10.1200/JCO.2020.39.28_suppl.70

Articles

Building the Community Oncology Practice of the Future Demands a Comprehensive Approach

Although the microorganisms colonizing our bodies have long been linked to human health and various disease states, an understanding of the potential impact of the microbiota on cancer has just begun to emerge in the past 20 years. Novel strategies to modulate the microbiota are now an area of robust investigation.

Components of the microbiota are linked not only to the development of a number of malignancies but also to response to cancer treatment and the risk of therapy-related toxicity.

 Arguably, “one of the most exciting and potentially translational aspects of cancer microbiome research” is the evolving understanding of the impact of the microbiota on outcomes, including the finding that specific gut bacteria are associated with improved response to immune checkpoint inhibitors (ICIs).

As interest in the modulation of the microbiota as a potential avenue for the treatment of cancer and other diseases has grown, the FDA has created a new regulatory class to encompass these therapeutics.

 Among the “live biotherapeutic products” (LBPs) in development is fecal microbiota transplantation (FMT). Attention on FMT, already used in the treatment of recurrent 

 has now turned to its potential in cancer.

An area of intense ongoing research in the ICI field is examining ways to boost these agents’ efficacy, given that only a minority of patients responds to these groundbreaking drugs.

 Recently, the first clinical evidence emerged that transplanting the microbiota from a responder could boost the efficacy of ICIs in patients with melanoma who are refractory to these drugs.

Numerous microbiome-focused biotech companies have sprung up in recent years and are pursuing novel orally administered alternatives to FMT,

 using single-strain or multistrain bacterial consortia with strong evidence of potential to enhance patients’ response to cancer therapy.

These novel LBPs also are being explored in the prevention or management of treatment-related toxicity. The most notable example is graft-vs-host disease (GVHD), a complication associated with hematopoietic stem cell transplantation (HSCT) that causes significant morbidity and mortality in patients with hematologic malignancies.

Most of the clinical studies evaluating LBPs and other novel approaches to modulating the microbiota in patients with cancer are in the early stages, with academic investigators playing a significant role in the research (

The concept of modulating the microbiota to promote health and prevent disease started in the early 1900s and has since grown into the multibillion-dollar probiotics industry. Probiotics, defined as bacteria that “confer a health benefit to hosts when consumed in adequate amounts,” are largely marketed as dietary supplements. Free from rigorous regulatory review, the evidence supporting their proposed health claims is often inadequate.

In the oncology arena, a handful of microorganisms have been directly linked to the development of cancer. Among them are viruses, including human papillomavirus, which is responsible for almost all cases of cervical cancer worldwide,10 and hepatitis B and C viruses, which are major contributing factors to hepatocellular carcinoma.

 Meanwhile, approximately 90% of gastric cancers worldwide are attributable to the bacterium 

, which is recognized by the World Health Organization as a type I carcinogen.

Numerous other microbial species likely play a role in the development of cancer. For example, a substantial body of evidence links the bacterium 

 to the development of colorectal cancer (CRC).

Thanks to the ability to rapidly sequence microbial genomes, there is growing appreciation that carcinogenesis involves not just individual microbial species but also may encompass the composition of the microbiota as a whole. In a healthy individual, the gut is typically populated by bacteria of the 

 species, but in patients with CRC there is a global shift in the microbial species that make up the gut microbiome, with an overrepresentation of 

These associations have not yet been proven to equal causation, but identifying the mechanisms underlying the link between microbiota disruption and carcinogenesis is a significant focus of ongoing research. The prospect of detecting unique microbial signatures that are predictive of the development of certain cancers offers a tantalizing prospect for cancer diagnosis.

In addition to findings about the gut microbiota’s role in cancer development, there is a growing body of evidence demonstrating that microbiota composition and diversity can influence patients’ response to chemotherapy, radiation therapy, and immunotherapy, as well as patient outcomes after HSCT, via a variety of mechanisms.

Conversely, the composition of the microbiota also has been shown to be affected by the use of cancer therapy or associated supportive treatments. Particularly noteworthy in this respect are antibiotics, which are commonly indicated to treat infections that result from the myelosuppressive impact of cancer therapy.

Antibiotics could potentially eliminate indigenous microbiota in addition to the pathogenic microorganisms responsible for the infection, which might have unintended negative consequences on patient outcomes. Findings from a recent study that examined the impact of the microbiota and antibiotic use on chimeric antigen receptor (CAR) T-cell therapy outcomes showed that the use of certain antibiotics before CAR T-cell therapy in patients with B-cell malignancies led to worse outcomes.

However, results of another study suggest that the impact of antibiotic use on CAR T-cell therapy outcomes is nuanced. In this study, investigators found that the antibiotic vancomycin was associated with greater CAR T-cell expansion and inflammatory cytokine levels in a small cohort of patients with B-cell acute lymphoblastic leukemia.

The composition of the microbiota also has been shown to influence the risk of treatment-related toxicity. Several species of gut bacteria have been linked to a reduced incidence of immune-related toxicity. For example, Bacteroidetes are more abundant in patients colitis related to ipilimumab (Yervoy) therapy.

 Specific types of gut bacteria also have been shown to be associated with a reduced risk of developing GVHD after allogeneic HSCT.

Further disentangling the relationship between the microbiota and therapeutic outcomes in cancer could allow specific microbial signatures to serve as biomarkers to predict clinical response and risk of developing complications.

A particularly exciting avenue of ongoing research relates to potential applications of the microbiota in predicting response to ICIs. A series of studies in mice identified specific groups of bacteria that were associated with improved response to ICIs. 

, were linked to the antitumor immune response associated with ICIs targeting CTLA-4,

 and Ruminococcaceae were key to the antitumor response to PD-L1–targeted and PD-1–targeted drugs,

 respectively. That different bacterial taxa were associated with the efficacy of each agent highlights the complexity of the microbiota and the challenge in defining “beneficial” microbial signatures.

Investigators also have demonstrated that tumor-bearing mice whose guts were colonized with feces from patients whose cancer had responded to ICI therapy had better responses to ICIs compared with mice whose guts were colonized with the feces of nonresponders.

 Another study showed that colonizing the gut of germfree mice with a rationally chosen consortium of 11 human bacterial strains could enhance the efficacy of ICIs.

 These findings have potential implications for the development of novel therapeutic strategies to boost the efficacy of ICIs.

Microbiota-modulating therapies represent an area of intense ongoing research, with perhaps the best-known example being FMT. This process involves the use of donated stool from healthy individuals, which is purified, processed, and then administered to a patient via colonoscopy, enema, or oral capsules.

The results of 2 studies recently published in 

 demonstrated the clinical potential of using FMT to promote response to ICIs in patients with ICI-refractory melanoma. In both studies, FMT was derived from donors who had responded to PD-1–targeted therapy and was given, in combination with PD-1–targeted therapy, to patients with melanoma who were refractory to ICIs.

In the first study (NCT03341143), the combination was well tolerated, and clinical benefit was observed in 6 of 15 patients.

 In the second study (NCT03353402), clinical responses were observed in 3 of 10 patients, including 2 partial responses (PRs) and 1 complete response (CR).

 In both trials, FMT was associated with favorable changes in the microbiota composition, immune cell infiltrates, and the tumor microenvironment (TME).

Numerous clinical trials of FMT are ongoing, including some testing its potential to boost the efficacy of anticancer therapy, as well as others evaluating FMT for the prevention and management of treatment-related adverse events and the management of acute GVHD (aGVHD).

Although FMT could establish proof of concept for targeting the gut microbiota, it is not without its challenges. There is no standard definition of FMT, and the mechanism underlying its efficacy is poorly understood. Feces contain many species of microorganisms, in addition to other components, such as metabolites, that could have a therapeutic effect.

FMT is not a traditional drug or medicinal product, and initially it was not regulated by the FDA. In 2012, the agency created a new category for drugs containing live microorganisms that are used for therapeutic purposes, and the use of these LBPs now requires an investigational new drug application.

Despite this increased regulation, FMT has encountered safety issues. In March 2020, the FDA issued a safety alert following infections with pathogenic 

 strains detected in 6 patients who received investigational FMT products supplied by a stool bank company as treatment for 

 infection. Additionally, 2 patients with chronic medical conditions died after receiving the FMT product from the stool bank; however, the FDA said the 

infection was not detected in the stool of 1 of the patients and it was unclear whether the infection contributed to the death of the other. The FDA now mandates additional screening of donor feces for these dangerous strains.

To overcome some of these challenges, ongoing development of microbiota-modulating therapies is focused on the use of defined single strains or microbial consortia cultivated in the laboratory to produce pure live cultures free from contamination by pathogenic strains.

Among such products in development is 4D pharma’s MRx0518, which contains a single strain (

) that has been shown to elicit strong proinflammatory responses in preclinical studies.

 Several clinical trials of MRx0518 are ongoing, including a phase 1/2 study (NCT03637803) with a safety phase (part A) and cohort expansion (part B) evaluating MRx0518 in combination with pembrolizumab (Keytruda) in patients with advanced solid tumors who previously progressed on ICIs.

Among 12 patients with metastatic renal cell carcinoma and non–small cell lung cancer treated during part A of the study, the disease control rate was 42%, including PR in 3 patients and stable disease lasting at least 6 months in 2 additional patients, with a median duration of treatment of 13.2 months among the 5 responders.

A biomarker analysis revealed that patients who experienced clinical benefit from the combination demonstrated a significantly greater density of CD3+FOXP3+ regulatory T cells and CD3+Ki67+ proliferating T cells in tumors at baseline. Nonresponders had a significantly higher density of CD68+ macrophages in the TME.

Part B is enrolling 30 patients with each tumor type, and as of February 2021, 24 patients had been enrolled and a safety review of the first 10 patients revealed no dose-limiting toxicities.

 Last year, the company also announced plans for a study evaluating MRx0518 in combination with avelumab (Bavencio) for the treatment of patients with urothelial carcinoma in collaboration with Merck and Pfizer.

MaaT Pharma is developing several orally administered full-ecosystem microbial therapies known to produce anti-inflammatory short-chain fatty acids.

 One of these products, MaaT013, is poised to enter phase 3 testing in the ARES trial (NCT04769895) in patients with gastrointestinal (GI) aGVHD refractory to JAK inhibitor therapy with ruxolitinib (Jakafi) and corticosteroids, pending further discussions with the FDA.

MaaT013 therapy demonstrated safe and effective outcomes for immunocompromised patients with GI aGVHD in results from the phase 2 HERACLES trial (NCT03359980) and an early access program (EAP) in France that were reported at the 63rd American Society of Hematology Annual Meeting and Exposition in December 2021.

A total of 76 patients with steroid-refractory GI aGVHD were treated in the HERACLES study (n = 24) and the EAP (n = 52; steroid-dependent cases also allowed). In HERACLES, the GI overall response rate (GI-ORR) was 38%, including 5 CRs, 2 very good PRs (VGPRs), and 2 PRs. In the EAP, GI-ORR was 60%, including 16 CRs, 11 VGPRs, and 4 PRs. The 6-month and 12-month overall survival rates were 29% and 25%, respectively, in HERACLES, and 48% and 37%, respectively, in the EAP.

MaaT Pharma also is testing another microbial therapy, MaaT033, in the phase 1 CIMON trial (NCT04150393) in patients with hematologic malignancies undergoing intensive chemotherapy. The company recently reported that it plans to wrap up the trial early, after promising data from the first 4 cohorts, and progress into a larger phase 2/3 trial in patients with acute myeloid leukemia.

Cullin N, Azevedo Antunes C, Straussman R, Stein-Thoeringer CK, Elinav E. Microbiome and cancer. 

. 2021;39(10):1317-1341. doi:10.1016/j.ccell.2021.08.006

Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. 

. 2019;25(3):377-388. doi:10.1038/s41591-019-0377-7

Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. 

. 2020;52(9):1397-1406. doi:10.1038/s12276-020-0437-6

Rouanet A, Bolca S, Bru A, et al. Live biotherapeutic products, aroad map for safety assessment. 

. 2020;7:237. doi:10.3389/fmed.2020.00237 

Hoffmann DE, Palumbo FB, Ravel J, Rowthorn V, von Rosenvinge E. A proposed definition of microbiota transplantation for regulatory purposes. 

. 2017;8(3):208-213. doi:10.1080/19490976.2017.1293223

Marin-Acevedo JA, Kimbrough EO, Lou Y. Next generation of immune checkpoint inhibitors and beyond. 

. 2021;14(1):45. doi:10.1186/s13045-021-01056-8

Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. 

. 2021;371(6529):595-602. doi:10.1126/science.abf3363

Baruch EN, Youngster I, Ben-Betzalel G, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. 

. 2021;371(6529):602-609. doi:10.1126/science.abb5920

Zipkin M. Fecal microbiota potentiate checkpoint inhibitors, unleash microbiome startups. 

. 2021;39(5):529-532. doi:10.1038/d41587-021-00002-w

Burd EM. Human papillomavirus and cervical cancer. 

. 2003;16(1):1-17. doi:10.1128/CMR.16.1.1-17.2003

Ringelhan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. 

. 2017;372(1732):20160274. doi:10.1098/rstb.2016.0274

Knippel RJ, Drewes JL, Sears CL. The cancer microbiome: recent highlights and knowledge gaps. 

. 2021;11(10):2378-2395. doi:10.1158/2159-8290.CD-21-0324

Wu J, Li Q, Fu X. Fusobacterium nucleatum contributes to the carcinogenesis of colorectal cancer by inducing inflammation and suppressing host immunity. 

. 2019;12(6):846-851. doi:10.1016/j.tranon.2019.03.003

Jain T, Sharma P, Are AC, Vickers SM, Dudeja V. New insights into the cancer–microbiome–immune axis: decrypting a decade of discoveries. 

. 2021;12:622064. doi:10.3389/fimmu.2021.622064 

Cheng WY, Wu CY, Yu J. The role of gut microbiota in cancer treatment: friend or foe? 

. 2020;69(10):1867-1876. doi:10.1136/gutjnl-2020-321153

Smith M, Dai A, Ghilardi G, et al. The intestinal microbiota correlates with response and toxicity after CAR T cell therapy in patients with B-cell malignancies. 

. 2021;138(suppl 1):253. doi:10.1182/blood-2021-153945

Ruella M, Uribe-Herranz M, Beghi S, et al. Gut microbiota tuning promotes tumor-associated antigen cross presentation and enhances CAR T antitumor effects. 

. 2021;138(suppl 1):163. doi:10.1182/blood-2021-151093

Holler E, Butzhammer P, Schmid K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. 

. 2014;20(5):640-645. doi:10.1016/j.bbmt.2014.01.030

Kakihana K, Fujioka Y, Suda W, et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. 

. 2016;128(16):2083-2088. doi:10.1182/blood-2016-05-717652

Shono Y, Docampo MD, Peled JU, et al. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. 

. 2016;8(339):339ra71. doi:10.1126/scitranslmed.aaf2311

Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. 

. 2015;350(6264):1079-1084. doi:10.1126/science.aad1329

Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. 

. 2015;350(6264):1084-1089. doi:10.1126/science.aac4255

Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. 

. 2018;359(6371):97-103. doi:10.1126/science.aan4236

Tanoue T, Morita S, Plichta DR, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. 

. 2019;565(7741):600-605. doi:10.1038/s41586-019-0878-z

Merrick B, Allen L, Masirah M Zain N, Forbes B, Shawcross DL, Goldenberg SD. Regulation, risk and safety of faecal microbiota transplant. 

. 2020;2(3):100069. doi:10.1016/j.infpip.2020.100069

Fecal microbiota for transplantation: safety alert -risk of serious adverse events likely due to transmission of pathogenic organisms.FDA. March 12, 2020. Updated April 7, 2020. Accessed February 25, 2022. 

Update to March 12, 2020 safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse events likely due to transmission of pathogenic organisms. FDA. March 13, 2020. Accessed March 20, 2022. https://bit.ly/3N8IpTt

Lauté-Caly DL, Raftis EJ, Cowie P, et al. The flagellin of candidate live biotherapeutic Enterococcus gallinarum MRx0518 is a potent immunostimulant. 

. 2019;9(1):801. doi:10.1038/s41598-018-36926-8

4D pharma announces clinical benefit data from part A of combination trial of MRx0518 and Keytruda: 42% disease control rate exceeds predefined threshold for expansion. News release. 4D pharma. August 26, 2020. Accessed February 25, 2022. 

Parra ER, Adriani M, Lima CFP, et al. 1024P Baseline biomarkers associated with clinical benefit in patients with solid tumors refractory to immune checkpoint inhibitors (ICIs) treated with live biotherapeutic MRx0518 in combination with pembrolizumab. 

. 2021;32(suppl 5):S858-S859. doi:10.1016/j.annonc.2021.08.1408

Enrollment progressing well for both expanded part B of MRx0518 and Keytruda combination study, and pancreatic cancer study: further analysis of biomarker data in ongoing MRx0518 neoadjuvant monotherapy study. News release. 4D pharma. February 3, 2021. Accessed February 25, 2022. 

4D pharma announces clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer to evaluate MRx0518 in combination with BAVENCIO for the treatment of locally advanced or metastatic urothelial carcinoma. News release. 4D pharma. February 8, 2021. Accessed February 25, 2022. 

Pipeline. MaaT Pharma. Accessed February 25, 2022. 

MaaT Pharma microbiota as a therapy. MaaT Pharma corporate presentation. January 2022. Accessed March 21, 2022. 

Malard F, Loschi M, Cluzeau T, et al. Pooled allogenic fecal microbiotherapy MaaT013 for the treatment of steroid-refractory gastrointestinal acute graft-versus-host disease: results from the phase IIa HERACLESstudy and expanded access program. 

. 2021;138(1):262. doi:10.1182/blood-2021-147709

Taylor NP. MaaT wraps up cancer microbiome trial early to power into phase 2/3 this year. January 24, 2022. Accessed February 25, 2022. 

Pathways

Novel strategies to modulate the microbiota are now an area of robust investigation

Microbiota Modulation Offers Hope of Expanding the Benefits of Immunotherapy

Lung cancer remains the most common cause of cancer death in the United States. Individuals who identify as Black and/or Hispanic are at even greater risk of mortality. Lung cancer screening (LCS) has been recommended since 2013, but remains underutilized, especially in economic and socially marginalized communities. Incidental lung nodules, commonly found on imaging done for other purposes, such as trauma evaluations, are often diagnosed later as cancers and represent a source of morbidity and mortality. 

Many vulnerable groups and marginalized communities receive care in the emergency department setting, where follow-up of incidental nodules is fragmented and incomplete. Low rates of LCS and inappropriate follow-up of incidental pulmonary nodules (IPNs), thus, represent 2 significant drivers of cancer care inequities. Research initiatives aimed towards understanding and combating systemic inadequacies contributing to these inequities have the potential to improve outcomes in populations that are in need.

Addressing Morbidity and Mortality in Minority Populations

Data from the Commission on Cancer demonstrates a large proportion of individuals diagnosed with non–small cell lung cancer over a 4-year period identified as Black (39%) or Hispanic (33%), compared with 23% who identified as White at the Montefiore Einstein Cancer Center (Montefiore) in the Bronx, New York. These figures are in stark contrast to other New York health care settings, where 81% of patients are White. Our patient population is also more likely to be diagnosed at later stages. When compared with other New York hospitals, the proportion of patients at Montefiore who are diagnosed with stage I lung cancer is markedly lower (25% vs 31%), and the proportion of those with stage IV disease is higher (45% vs 37%) (FIGURE

Other data from Montefiore have demonstrated additional inequities in patients with primary lung cancers diagnosed between 2013 and 2016. Only 417 (55%) were found in patients with an in-network primary care provider, illustrating the need for a better support system and for a systematic approach to identify and guide these patients. Furthermore, of the 175 of these patients who were eligible for LCS, only 33 had completed appropriate screening. A large proportion of this population with lung cancers that were identified outside of screening was composed of Black (46%) and Hispanic (34%) patients with a median per capita income of approximately $20,000 (TABLE).

Addressing Inadequacies of Lung Cancer Screening

Screening is particularly challenging in individuals from racial and ethnic minority groups and in those who have been socioeconomically marginalized. For example, of more than 50,000 people enrolled in the seminal National Lung Screening Trial, only 4.5% of participants identified as Black and 1.7% as Hispanic. This is in sharp contrast to the screening population described at our institution.

More work needs to be done to study and implement LCS in these patient populations. To this end, we have formed a collaboration with the LUNGevity Foundation with the objective of, “Increasing access to lung cancer screening in the Bronx in Latino and African American communities.” Known as Project URBANA, the initiative seeks to increase uptake of, and compliance with, LCS through educational initiatives and engagement with a unique community peer navigation program—the Bronx Oncology Living Daily (BOLD) program. Drawing from the principles of Community-Based Participatory Research, Project URBANA focuses on increasing access to care among African American and Latino community members. At its core, this project is targeted outreach with educational materials developed in partnership with communities with content that is both relevant and language appropriate. This content coupled with trained peer navigators from within the community strives to address social constructs of health care often overlooked in daily practice.

Reducing the Burden of Incidental Pulmonary Nodules

Each year, more than 1.5 million individuals are diagnosed with an IPN.

 Guidelines exist for the follow-up of IPNs; however, treatment adherence is often poor.

 This is especially true in Black and Hispanic populations where approximately 50% of patients are notified of IPNs and have significantly lower rates of adhering to follow-up imaging. This population also has increased odds of delaying follow-up appointments.

With continued support from LUNGevity, we have devised a multipronged approach to develop an incidental pulmonary nodule management program for our community. Through the incorporation of software to automatically detect notation of lung nodules in radiology reports, we will shift to more active identification of people with concerning nodules who will be proactively referred to our high-risk lung nodule clinic. Individual risk for malignancy will be evaluated using artificial intelligence–based calculators derived from the electronic medical record to facilitate guideline concordant care. 

Finally, we will evaluate a blood-based cancer biomarker to further risk stratify patients and will prospectively apply it to individuals already enrolled in our nodule clinic. Our overall objective is to facilitate earlier diagnosis of lung cancer in our community and decrease risk of advanced disease and death.

Research initiatives provide us with the ability to advocate for historically marginalized people by generating hypotheses that seek to increase knowledge of inequities of care. Studies focusing on implementation of care in the setting of racial and ethnic inequities are critically needed.

Deficiencies in lung cancer care are multifactorial, and occur at the levels of screening, diagnosis and management. Through research that incorporates culturally sensitive patient navigation, use of available technologies and a multidisciplinary approach to patient care, there are significant opportunities to improve screening, cancer care, and outcomes for everyone.

Su CT, Bhargava A, Shah CD, et al. Screening patterns and mortality differences in patients with lung cancer at an urban underserved community. Clin Lung Cancer. 2018;19(5):e767-e773. doi:10.1016/j.cllc.2018.05.019  

National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395409. doi:10.1056/NEJMoa1102873 

Gould MK, Tang T, Liu IL, et al. Recent trends in the identification of incidental pulmonary nodules. Am J Respir Crit Care Med. 2015;192(10):1208-1214. doi:10.1164/rccm.201505-0990OC 

Farjah F, Monsell SE, Gould MK, et al. Association of the intensity of diagnostic evaluation with outcomes in incidentally detected lung nodules. JAMA Intern Med. 2021;181(4):480-489. doi:10.1001/ jamainternmed.2020.8250 

Schut RA, Mortani Barbosa EJ Jr. Racial/ethnic disparities in follow-up adherence for incidental pulmonary nodules: an application of a cascade-of-care framework. J Am Coll Radiol. 2020;17(11):1410-1419. doi:10.1016/j.jacr.2020.07.018

Oncology Live®

Lung cancer remains the most common cause of cancer death in the United States. 

Beyond the Clinic: Leveraging Research  to Tackle Lung Cancer Disparities

Cancer pathology has undergone radical changes in recent years. Analysis of a seemingly small number of tumor types, classed almost entirely by anatomic site, has become analysis of dozens of tumor types, classified by a combination of genomic aberrations and location. Pathologists who once performed largely visual analysis now supplement their eyes and experience with hard data from a variety of assays.

But one fact remains constant: Your pathologist still wants better tissue samples. In the lung cancer field, for example, shortcomings in specimens provided to laboratories are a significant cause of molecular testing failures, according to findings from a survey conducted by The International Association for the Study of Lung Cancer (

“It’s a cliché, but we always do want better samples. There are all these challenges to working with tissue that just don’t exist for other diagnostics like radiology, which gives you this digital image that loads right into the record, never degrades, and follows patients around forever. If a biopsy is too small, it doesn’t give you the data you need. If it’s not processed correctly, it can get lost. If it’s placed in the container carelessly, it can stick to the side, dry up, and fall apart before you can analyze it. And if any of these things happen, you either get limited pathologic info, or you go back to the patient and set up another procedure,” said Lynette M. Sholl, MD, in an interview with 

Sholl, an associate professor of pathology at Harvard Medical School and a pathologist at Brigham and Women’s Hospital, both in Boston, Massachusetts, has spent much of her 20-year career focusing on integrating molecular pathology into oncology practice. A lung cancer specialist, she has played a leading role in developing protocols for tissue handling and workflows as well as in launching and validating assays and sequencing panels.

At the same time, Sholl has been an advocate of communication between pathologists and other oncology specialists to make the most of the treatment opportunities that molecular diagnostics can provide for patients. On June 25, Sholl will cochair the 

 International Congress on Oncology & Pathology

: Toward Harmonization of Pathology and Oncology Standards, a virtual, interactive conference hosted by Physicians’ Education Resource

“People think of pathology as generating very black and white results and sometimes it does, but sometimes there’s a tremendous amount of uncertainty because the specimen wasn’t well fixed or it’s an intermediate-grade tumor or any number of other problems,” Sholl said. “There are countless variables that can create uncertainty in pathological analysis, and oncologists should have a sense of what those variables are.”

The conference also offers an opportunity to explore biomarkers important to the treatment landscape in a range of tumor types. Sholl believes that the genetic literacy so central to molecular diagnostics is lacking in the oncology community. “It is essential to understand the basics of mutations—germline vs somatic—and [the implications for] an individual patient when we report out specifics around those mutations, such as what a variant allele fraction means,” she said.

Lynette M. Sholl, MD, discusses why cancer pathologists still want better tissue samples. 

Vol. 23/No. 8 | Oncology Live®

Building the Community Oncology Practice of the Future Demands a Comprehensive Approach

Microbiota Modulation Offers Hope of Expanding the Benefits of Immunotherapy

Beyond the Clinic: Leveraging Research to Tackle Lung Cancer Disparities

Tissue Is Still the Issue: Pathology Expert Discusses Clinical Needs in the Molecular Era

Targeted Treatment Arsenal for Myelofibrosis Set to Explode

Nivolumab Plus Relatlimab Aims to Become Primary Treatment Option for Advanced Melanoma

Pragmatic Clinical Trials Can Play a Key Role in Oncology