Shikha Jain, MD, FACP, assistant professor of medicine, director of communication strategies in medicine, University of Illinois (UI) College of Medicine, associate director of oncology communication and digital innovation, UI Cancer Center, medical oncologist, Department of Hematology and Oncology, UI Health, discusses the push toward personalized treatment approaches in colorectal cancer (CRC) with liver metastases.

Emerging data from clinical trials have demonstrated the utility of neoadjuvant chemotherapy for patients with CRC and liver metastases, Jain says. Additionally, surgical and oncological advances with conversion therapy that has the goal of converting a non-operative candidate to an operative one have been made, Jain adds.

These advances allowed treatment for this patient population to become personalized to the individual’s overall liver function, performance status, and tumor biology. Moreover, this shifted the field away from a one-size-fits-all approach in which all patients with more than 1 liver lesion received systemic therapy only. Now, stratified patients may be eligible for surgery plus systemic therapy to improve their overall survival, Jain concludes.

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Shikha Jain, MD, FACP, discusses the push toward personalized treatment approaches in colorectal cancer with liver metastases.  



Dr. Jain on the Push Toward Personalized Treatment Approaches in CRC With Liver Metastases 

Shikha Jain, MD, FACP, assistant professor of medicine, director of communication strategies in medicine, University of Illinois (UI) College of Medicine, associate director of oncology communication and digital innovation, UI Cancer Center, medical oncologist, Department of Hematology and Oncology, UI Health, discusses the importance of communication in patients with colorectal cancer (CRC) and liver metastases who are receiving multidisciplinary care. 

Communication is a key aspect to optimizing multidisciplinary care in patients with CRC and liver metastases because not all patients receive the same course of treatment, Jain explains. Some patients may receive neoadjuvant chemotherapy, whereas others will proceed directly to surgery. As such, it is critical to include surgeons, radiation oncologists, pathologists, radiologists, and medical oncologists in treatment decision discussions, such as tumor boards, to ensure patients are matched to the optimal treatment for their disease, Jain explains. Moreover, it is important to include patients on these discussions, especially those with newly diagnosed disease for whom a treatment course is being determined. 

As medical oncologists tend to have the most sustained interaction with patients, it is important that these clinicians are in constant communication with the multidisciplinary team to solidify a comprehensive treatment course before initiating therapy, Jain concludes. 

Shikha Jain, MD, FACP, discusses the importance of communication in patients with colorectal cancer and liver metastases who are receiving multidisciplinary care.  



Dr. Jain on the Importance of Communication for Multidisciplinary Care in CRC 

Shikha Jain, MD, FACP, assistant professor of medicine, director of communication strategies in medicine, University of Illinois (UI) College of Medicine, associate director of oncology communication and digital innovation, UI Cancer Center, medical oncologist, Department of Hematology and Oncology, UI Health, discusses the need to enroll heterogenous patient populations to clinical trials in colorectal cancer (CRC).

Significant disparities in the patient populations being enrolled on clinical trials in CRC have been observed, Jain says. Patient education for what clinical trials entail, as well as a lack of trust in the health care system among underserved communities may account for some of this disparity.

As such, it is important to ensure clinical trials are enrolling heterogenous and diverse patient populations so that the results of the studies can be widely applicable to all patients with CRC, Jain explains. Moreover, as a rising incidence of CRC has been observed among younger African American populations, all patients irrespective of their background or history should be considered for clinical trials. It’s also critical to answer all questions a patient has before enrolling onto a clinical trial so they are armed with the information as to why a clinical trial may be the best treatment option for them, Jain concludes.

Shikha Jain, MD, FACP, discusses the need to enroll heterogenous patient populations to clinical trials in colorectal cancer.



Dr. Jain on the Need to Enroll Heterogenous Populations to Clinical Trials in CRC 

Shikha Jain, MD, FACP, assistant professor of medicine, director of communication strategies in medicine, University of Illinois (UI) College of Medicine, associate director of oncology communication and digital innovation, UI Cancer Center, medical oncologist, Department of Hematology and Oncology, UI Health, discusses advances with surgical interventions and systemic therapies in colorectal cancer (CRC) with liver metastases.

Significant changes have been made regarding the treatment of patients with CRC and liver metastases. Historically, patients with more than 1 liver lesion were not considered candidates for curative-intent treatment; however, these patients are the subject of more up-front discussion to determine whether chemotherapy or surgery should be considered, Jain says. 

Notably, data are emerging that have demonstrated utility with neoadjuvant chemotherapy or conversion therapies that can make a non-operative candidate eligible for surgery, Jain says. Moreover, personalized care that is based on patient factors, overall liver function, performance status, and tumor biology is being integrated to modify treatment approaches to individual patients. This offers additional treatment options beyond systemic therapy to patients with more than 1 liver lesion. Moreover, some of these patients are recommended for surgery plus systemic therapy, which can render them cancer free and improve overall survival, Jain concludes. 

Shikha Jain, MD, FACP, discusses advances with surgical interventions and systemic therapies in colorectal cancer with liver metastases.  



Dr. Jain on Advances With Surgery and Systemic Therapy in CRC With Liver Metastases   

In the past decade, immunotherapy has been incorporated into the standard of care for many malignancies. Agents have shown efficacy in malignant melanoma, kidney cancer, and non–small cell lung cancer, and investigators are examining the efficacy of checkpoint inhibitors in less immunogenic tumors such as colon cancer, particularly in tumors with high microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) genes.

The DNA MMR genes MLH1, MSH2, MSH6, and PMS2 are involved in correcting errors that occur in DNA replication. If these genes are deficient, the cells are unable to correct errors and they accumulate mutations that ultimately lead to malignant potential. Deficiency in these MMR genes is MSI or dMMR, and tumors with heavily mutated MMR genes are identified as MSI-H. Testing for MSI can be done by immunohistochemistry that stains for tumor expression, or polymerase chain reaction alone or within a next-generation sequencing panel.

MSI/dMMR mutations can be somatic or germline mutations and testing for them has been part of the standard of care for patients with colon cancer since around 2013.

The genes with germline mutations are present in familial colon cancer syndromes such as hereditary nonpolyposis colorectal cancer, or Lynch syndrome, which makes up approximately 2% to 4 % of all colon cancer diagnoses. Therefore, if MSI/dMMR is detected, it has implications for the patient’s treatment and prognosis as well as for the patient’s family members, who may have the same mutations.

Patients with MSI-H/dMMR colon cancer typically present with lower-stage disease and have a better prognosis. The availability of mutational status at diagnosis helps to determine if adjuvant therapy would benefit patients with stage II colon cancer. If a patient presents with stage II MSI-H colon cancer, the prognosis is better and clinicians typically do not recommend adjuvant therapy. Alternatively, patients with stage II microsatellite stable colon cancer have a less favorable prognosis and, in certain cases, clinicians recommend adjuvant treatment with a f luorouracil (5-FU)–based therapy.

Until recently, MSI-H/dMMR metastatic colon cancer was treated with standard cytotoxic 5-FU–based chemotherapy plus VEGF or EGFR inhibitors depending on the tumor mutational status. In 2017, data from the CheckMate 142 trial (NCT02060188) showed that the anti–PD-1 agent nivolumab (Opdivo) alone or nivolumab plus the anti–CTLA-4 agent ipilimumab (Yervoy) could be used as a second-line therapy in patients with metastatic colon cancer not believed to be candidates for intensive chemotherapy and who had not received prior immunotherapy agents, and whose cancer was MSI-H.

Results from the phase 2 study demonstrated an objective response rate (ORR) of 60%, a 12-month progression-free survival (PFS) rate of 77%, and an overall survival (OS) rate of 83% with the combination of nivolumab and ipilimumab.

 In addition, results from KEYNOTE-164 (NCT02460198) showed the anti–PD-1 agent pembrolizumab (Keytruda) to be an effective subsequent therapy in metastatic MSI-H/dMMR colon cancer. The ORR was 33%, and the 12-month OS rate was 76% for patients who had received more than 1 prior line of therapy.

Neither of these studies compared immunotherapy with standard of care. Immunotherapy did not show efficacy in patients with metastatic colon cancer that was MSI-low or with proficient MMR genes.

Until this year, there were minimal data to support immune checkpoint inhibitors as first-line therapy for patients with MSI-H/dMMR metastatic colon cancer. KEYNOTE-177 (NCT02563002) was a multicenter, open label, randomized control trial that evaluated pembrolizumab versus standard of care with 5-FU–based therapy plus bevacizumab (Avastin) or cetuximab (Erbitux) for metastatic MSI-H/dMMR colon cancer. The study findings showed a PFS of 55% with pembrolizumab versus 37% with chemotherapy at 12 months, and 48% versus 19%, respectively, at 24 months.

Investigators did not report OS as the study is ongoing; however, 83% of patients who received pembrolizumab continued to show response to therapy at 24 months. Patients tolerated pembrolizumab better than chemotherapy, in addition to its being more efficacious.

 On June 29, 2020, the FDA approved pembrolizumab for first-line therapy for patients with metastatic MSI-H/dMMR colon cancer.

The MSI-H/dMMR subset of patients with colon cancer is a special population that requires a nuanced approach to determine therapy. Immunotherapy with checkpoint inhibitors has a role in the treatment of these patients, specifically in those with metastatic disease. However, given that MSI-H/dMMR colon cancer has a unique tumor biology, immunotherapy may have a role in local disease as well. Studies are evaluating the efficacy of immunotherapy in both the adjuvant and neoadjuvant settings, as well as the efficacy of immunotherapy plus chemotherapy in this patient population. As investigators gather more data, it is likely that the role of immunotherapy will continue to extend into the other stages of colon cancer.

NCCN. Clinical Practice Guidelines in Oncology. Colon cancer: NCCN evidence blocks, version 4.2020. Accessed November 6, 2020. https://www.nccn.org/professionals/physician_gls/pdf/colon_blocks.pdf

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Ganesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. 

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Lonardi S, Andre T, Wong KYM, et al. Combination of nivolumab (nivo) + ipilimumab (ipi) in the treatment of patients (pts) with deficient DNA mismatch repair (dMMR)/high microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC): CheckMate 142 study. 

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Lenz HJJ, Van Cutsem E, Limon ML, et al. Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). 

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Andre T, Shiu KK, Kim TW, et al. Pembrolizumab vs chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: the phase 3 KEYNOTE-177 study. 

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FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. FDA. Updated June 30, 2020. Accessed November 6, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-first-line-treatment-msi-hdmmr-colorectal-cancer

Articles

December 14, 2020 - Immunotherapy agents have shown efficacy in malignant melanoma, kidney cancer, and non–small cell lung cancer, and investigators are examining the efficacy of checkpoint inhibitors in less immunogenic tumors such as colon cancer, particularly in tumors with high microsatellite instability and deficient mismatch repair genes.

Biomarkers Drive ICIs in Colon Cancer

Oncology practices across the United States have rapidly increased telehealth use in 2020 to mitigate the risk of coronavirus disease 2019 (COVID-19) to patients with cancer who are at particular risk of complications. The initial results from the COVID-19 and Cancer Consortium Registry cohort study (NCT04354701) showed a case-fatality rate of 13% (compared with 2.9% among the general population, according to the Johns Hopkins Coronavirus Resource Center

) among patients with a history of cancer and COVID-19, with increased age, increasing comorbidities, worse performance status, and active cancer as independent risk factors for increased mortality.

 Not only do patients with cancer face higher risks of morbidity and mortality if they contract the virus, they also face the challenges that arise with the inevitable delays in anticancer therapy during recovery f rom COVID-19.

At the University of Illinois Cancer Center (UICC), we have seen a marked increase in the use of telehealth services from March 2020 that continues as we enter month 6 of the COVID-19 pandemic. Shifting selected in-person clinic visits to telehealth has helped us both reduce patients’ exposure risks and protect health care providers and patients who require in-person care from additional exposures. As health systems across the nation begin shifting to “business as usual,” many cancer practices and their patients will continue to use telehealth as a risk-reduction tool to augment cancer care. However, careful attention is needed to address barriers to delivering high-quality medical care via telehealth.

In March 2020, the Centers for Medicare & Medicaid Services (CMS) released an interim final rule that reduced barriers to telehealth access as COVID-19 cases grew in the United States (FAST FACTS

).Whereas CMS previously covered telehealth only when a patient was receiving care in a facility in a nonurban area or in an area in a health professional shortage, telehealth could not be delivered directly to a patient’s home prior to the pandemic. CMS also dropped the requirement for telehealth recipients to have a prior relationship with a health care professional, allowing physicians to conduct new patient consultations via telehealth. The loosening of Health Insurance Portability and Accountability Act regulatory requirements on telehealth technologies for providers acting in good faith also allowed physicians and their patients to use widely available commercial audiovisual platforms such as Zoom and Skype. Finally, CMS increased compensation for telehealth visits to match the fee schedule for in-person services.

The loosening of regulatory requirements led to a boom in telehealth use across health care. Findings of a study of New York University urgent care visits showed a 135% increase in telehealth visits from March 2, 2020, to April 14, 2020.

According to results of an April 2020 McKinsey & Company consumer survey, consumer adoption of telehealth jumped from 11% in 2019 to 46% in 2020. The burst in telehealth usage also led to an increase in patients who feel comfortable using telehealth, with 76% of survey respondents reporting they were “highly” or “moderately” likely to use telehealth going forward.

Choosing Visits Appropriate for Telehealth 

Successful implementation and integration of telehealth into cancer care requires identifying which in-person services can be rendered safely and effectively with this modality. The American Society of Clinical Oncology special report on cancer care during the COVID-19 pandemic identifies eligible telemedicine visit types: COVID-19–positive infections, nonurgent high-risk patient populations, and symptom management.

 At UICC, to ensure patients scheduled for telehealth visits are appropriate, our team triages clinic schedules 1 week in advance to allow patients time to adjust their schedules and arrange transportation. Although attending physicians determine which visits may be converted to telehealth encounters, patients with more urgent questions or clinical needs are always offered the option of in-person services. Our teams have found telehealth to be an effective means of communicating with patients regarding nonurgent matters, and patients often appreciate not having to commit the time and transportation resources for issues that can be addressed with a phone call.

Challenges in Equitable Telehealth Delivery 

COVID-19 has further exposed disparities in access to care for vulnerable populations. Although opportunities exist for telehealth to address and improve upon inequities in the health care system, the rapid shift to telehealth services also has the potential to widen disparities in access to care. Accessibility to a stable phone or broadband connection can be a challenge in rural areas or for patients with limited income. Among Americans older than 65 years, who make up 18% of the American population and are most likely to need chronic disease management, just 55% to 60% own a smartphone or have home broadband access. Low-income individuals have lower rates of smartphone ownership (71%), home broadband access (59%), internet use (82%), and basic digital literacy (53%).

 Also limiting the effectiveness of telehealth is the comfort of both physician and patient with use of telehealth technologies and digital health literacy. In our experience, we have found most patients to be comfortable with telephone-only visits, with a minority comfortable consistently using audiovisual communication. Patient subgroups with known limited digital literacy and access include older adults, low socioeconomic status, limited health literacy, limited English proficiency, and racial and ethnic minorities.

Although many of the conversions from in-person visits to telehealth encounters are well intentioned and provide opportunities for more accessibility for certain populations, for 

patients with limited access to telehealth, we opt to prioritize a return to in-person visits. As we traverse this pandemic and nimbly adapt and implement effective strategies to provide exceptional patient care to all our patients, it is essential that we assess the risks and benef its of the transition to telehealth visits with the potential barriers and limitations that may unintentionally negatively affect our patients. Every effort should be made to reduce the risk of COVID-19 to our patients, but we must also take into consideration how to best deliver equitable medical care to our at-risk patient populations and whether that can be delivered effectively with telehealth.

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Bentsennyy O, Gilbert G, Harris A, Rost J. Telehealth: a quarter-trillion-dollar post-COVID-19 reality? McKinsey & Company Healthcare Systems & Services. May 29, 2020. Accessed September 30, 2020. https://www.mckinsey. com/industries/healthcare-systems-and-services/our- insights/telehealth-a-quarter-trillion-dollar-post-covid- 19-reality

ASCO special report: a guide to cancer care delivery during the COVID-19 pandemic. American Society of Clinical Oncology. May 19, 2020. Accessed September 30, 2020. https://www.asco.org/sites/new-www.asco.org/files/ content-files/2020-ASCO-Guide-Cancer-COVID19.pdf

Nouri S, Khoong EC, Lyles CR, Karliner L. Addressing equity in telemedicine for chronic disease management during the COVID-19 pandemic. NEJM Catal Innov Care Deliv. Published online May 4, 2020. https://catalyst.nejm.org/ doi/full/10.1056/cat.20.0123

Oncology practices across the United States have rapidly increased telehealth use in 2020 to mitigate the risk of coronavirus disease 2019 (COVID-19) to patients with cancer who are at particular risk of complications.

Telehealth Is Here to Stay: Opportunities and Challenges for Cancer Care

Shikha Jain, MD, hematologist/oncologist, Rush University Medical Center, discusses results of a study that explored the disparities between male and female professionals at medical conferences.

According to data pulled from the 2017 and 2018 ASCO Annual Meetings, female speakers were less likely to receive a professional introduction compared with male speakers (61% versus 81%). Many females were introduced by their first name only compared with male speakers (17% vs 3%). Specifically, male introducers were more likely to address female speakers by their first name compared with female introducers (24% vs 7%).

Not receiving a professional introduction contributes to the unconscious bias of attendees because it makes the person appear less qualified than their colleagues, Jain explains. This research is important, she says, because when more women are seen in leadership positions, it improves the role of females in healthcare.

Shikha Jain, MD, hematologist/oncologist, Rush University Medical Center, discusses the disparities between male and female professionals at medical conferences, specifically the American Society of Clinical Oncology (ASCO) Annual Meeting.

Shikha Jain, MD