Fox Chase

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses potential symptoms of tenosynovial giant cell tumor (TGCT).

TGCT can occur within or outside any joint. Therefore, the symptoms of TGCT are based on where the disease occurs, says Abraham.

The synovium of the affected joint will become thick and friable, causing it to break apart, says Abraham. Moreover, as the synovium breaks down, significant bleeding into the affected area can lead to swelling, irritation, and pain.

Joint swelling can result in loss of range of motion and stiffness, explains Abraham. While these symptoms are typically intermittent, they can come on suddenly and without incidental damage to the joint.

Additionally, chronic symptoms such as the disease eroding into the bone are often experienced by patients with TGCT and can cause long-term pain , concludes Abraham.

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John A. Abraham, MD, FACS, discusses potential symptoms of tenosynovial giant cell tumor.

Dr. Abraham on Potential Symptoms of TGCT

The COVID-19 pandemic has caused many institutions to transition to telemedicine to provide care for patients with cancer, a practice that may continue long after the pandemic is over, according to Hossein Borghaei, DO, MS.

Looking to the future with clinical trials, some required visits for patients are simply protocol. If a patient is not exhibiting any worrying symptoms and is comfortable with a video appointment with their doctor, they should be able to meet virtually, said Borghaei. Doing so would save many patients a long drive to the clinic.

“[After this pandemic], we might have less face-to-face time with a patient in an office setting. If a patient is doing well, we can monitor laboratories remotely, and speak with them to ensure they are symptom free,” said Borghaei. “In doing that, we might be able to reduce some of those face-to-face visits and rely on telemedicine instead. I feel this [shift] would be absolutely appropriate and good.”

This pandemic has also inspired medical institutions to develop policies that will better prepare their staff for the next time an unprecedented disaster strikes.

“As with any other disaster that has happened, we are going to learn from this and become [stronger because of it],” said Borghaei. “Through this uncertainty and fear, and by navigating through these problems, we are going to become a better healthcare system. Moving forward, we will be able to take care of any kind of emergency that happens.”

, Borghaei, chief of Thoracic Medical Oncology, professor in the Department of Hematology/Oncology, co-director of the Immune Monitoring Facility, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology at Fox Chase Cancer Center, discussed the impact of COVID-19 on clinical practice and projected how the virus will change practice for the better in the long term.

: What efforts are you making to address any disruptions in care caused by COVID-19?

: Our institution has been very proactive with this. Like many other institutions, we have been discussing the role of telemedicine in the care of our patients [for some time], but that became an emergency with this pandemic. We have, as an institution, decided to conduct many visits in a virtual setting using telemedicine. My preference is to use video conferencing to be able to see my patients and have that level of interaction. Phone calls are sometimes appropriate, and they are good in the absence of anything else.

[Telemedicine can be used for] patients who are on long-term follow-up, like those who have had surgery or adjuvant chemotherapy and they're doing well. If it is possible, the patient can get a CT scan locally so that they don’t need to go to any crowded areas, we can review the CT, and then have a telemedicine discussion reviewing the results of the scan. However, some patients still need to be seen [in person] so that we can manage any potential issues that they might have. New patients who have not been treated and require a more extensive discussion about options are still seen face-to-face with appropriate precautionary measures in place.

Our routines have been disrupted and have changed very rapidly. We still are evaluating which patients should come in and which patients are eligible for telemedicine discussions. The overall goal is to reduce the crowdedness of a waiting area and reduce the amount of interactions as much as possible. The interesting question is, "What is going to happen once the pandemic is under control and we're not dealing with this? Are we going to go back to our more face-to-face discussions or are we going to proceed with telemedicine?"

To a great extent, we are going to have to get feedback from our patients. Are they comfortable with telemedicine? Are they more comfortable with coming in person? Many patients like to review their CT images in person. How is all of that going to change? We need feedback from our patients to tell us what was good, what was not good, and we'll decide what to do from there.

Were you using telemedicine prior to the pandemic?

I wasn't using telemedicine before; this is a brave new world for all of us. My experience with this is not that extensive; it takes a bit of getting used to. I must admit that I don't feel 100% comfortable with it yet; however, I'm looking for some feedback from the patients to see how they feel about it. We all understand we have to do this for now because there is no other safer way. However, like with any new technology, we are all going to learn the best practices. Who is the best patient population for the telemedicine type of an approach? What scenarios and what conditions [are appropriate for telemedicine]? It’s just very new.

We have colleagues around the country who have been doing [telemedicine] longer than many of us. Having our colleagues provide [us with] some guidance [or feedback] as to what they found to be working for their patient population in terms of best practices would be helpful. I’m sure we’ll see some of this is in the next few weeks. Already, we are getting guidelines from professional [medical] organizations trying to help us cope with all the new challenges we are facing.

How are you working to avoid treatment delays in your patients? What kind of treatment modifications are you making in light of COVID-19?

We are definitely seeing some modifications. The overarching issue is: If a patient needs treatment, we are going to treat the patient; [we don’t want to] delay treatment. That being said, modifications may occur on a case-by-case basis. For instance, we might do a little more neoadjuvant therapy as opposed to concurrent chemoradiation, especially if a patient is not comfortable or unable to come [to the cancer center] on a daily basis for radiation. Those are the kinds of issues that we've discussed with our colleagues around the country and internally at our own institution. We’re working on determining how to streamline the care of these patients.

We are doing everything we can to not delay treatment for a patient who absolutely needs it. If it is absolutely necessary to have surgery, we discuss it with our surgical colleagues. We have to be selective and careful who we take to the operating room. If someone needs adjuvant chemotherapy, can we delay that a little bit longer? Some data suggest that you can delay adjuvant chemotherapy to some extent. However, if someone absolutely needs this therapy, then it becomes a risk—benefit discussion. The overarching issue is that we’re going to have to manage both conditions and a patient who needs treatment will get the appropriate treatment with the caveat that, on a case-by-case basis, there might be minor adjustments in the treatment and what we do immediately versus what we're going to do next.

There is a lot of discussion regarding immunotherapy because there is a possibility of immunotherapy exacerbating the inflammatory response. To me, the data are not all that clear. There has been discussion about extending the period in between administering immunotherapy. From a perspective of reducing the number of visits, that makes a lot of sense. Biologically, these drugs have really long half-lives. I'm not sure that missing 1 or 2 doses is going to be all that harmful to the patient or do anything significantly in terms of potential concurrent infection with COVID-19. These are areas where more data are going to become available based on the experience of our European and Asian colleagues. We are all trying to learn from each other regarding what the best approach is.

Do you anticipate any long-term implications of the pandemic?

The biggest long-term impact might be that we reduce the number of office visits. It's the same kind of issue we're facing with clinical trials. Many of our clinical trials require repeated visits and sometimes they are absolutely essential. Other times, we are [meeting patients in person] to ensure nothing is wrong without a lot of evidence that is necessarily needed. A long-term implication of this pandemic might be that we will have less face-to-face time with our patients in an office setting. [We may be able to convert some of these appointments to virtual meetings].

Additionally, we are all going to have this sense that we have to be better prepared for the next virus or the next situation that arises. This provides us with an opportunity to think about what we're doing right and what we're not doing right and plan for other potential issues that might come up as a nation, as an institution, and individually as a physician.

Could you highlight some of the preventive, diagnostic, and therapeutic research efforts being made with regard to the virus?

The attempts to make a [COVID-19] vaccine and the new testing [method] that shows results within a few minutes are [both] important [efforts]. In terms of treatment, the one that I've been interested in exploring the idea of using antibodies from patients who survived and managed to get over the infection to see whether that has a potential therapeutic benefit. Under that category, caveats always exist. A couple of recent papers have shown that certain types of antibodies directed against a specific component of the virus might be detrimental or not quite as helpful as others. The power of the immune system becomes important here; learning how the immune system interacts with the virus in a general patient population, and a population of patients with cancer, [can inform] important treatment strategies for the future until we have an appropriate vaccine.

What is most needed to quell the COVID-19 pandemic?

Right now, social distancing has been shown to be very effective. There are multiple examples of other countries that did this effectively. We are currently missing wider and more inclusive [COVID-19] testing. If we know who is potentially carrying the virus, we might be able to do a better job with the social distancing. Assuming everyone is positive until proven otherwise is an approach that we seem to have adopted right now. Until we get this under control, social distancing and making [COVID-19] testing more available are imperative.

I am confident that we will have a vaccine [for COVID-19]. Whether we are going to have a specific treatment for this virus, I'm not sure; that is going to take a little bit longer. My hope is that we'll be able to manage the peak [of the virus]. People are going to get exposed and we know that this virus is probably going to be with us for a long time; however, if we can manage to have less people get sick from this over a longer duration of time, we can manage patients even if they need to be in an intensive care unit (ICU). The risk right now is having 100,000 people simultaneously needing treatment in the ICU when you only have 20,000 ICU beds. While we're working on the vaccine and potential new treatments, [COVID-19] testing and practicing social distancing is the best way to proceed.

People are doing a lot [in the fight against this virus]. We hear stories about communities coming together to make masks and gowns for physicians. I saw on Twitter that in some parts of the country, people dropped off packages, food, and snacks for their physicians in hospitals or medical facilities. It's really fantastic to see this level of caring for each other.

Obviously, we are all saddened to see our colleagues getting exposed to this disease and, unfortunately, we hear in other countries that our colleagues have lost their lives as a result of this infection. That's always difficult to see, just like it is difficult to see our patients die of this. The amount of support that we have seen people give to healthcare providers all over the world has been fantastic. My hat is off to our colleagues in China, Japan, Italy, Spain, and New York, who are dealing with this pandemic head on. We should provide as much support and help as we can for all our colleagues.

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Hossein Borghaei, DO, MS, discusses the impact of COVID-19 on clinical practice and projected how the virus will change practice for the better in the long term.

Borghaei Shares Long-Term Implications of COVID-19 on Cancer Care

, a program leader for the Cancer Epigenetics Program at Fox Chase Cancer Center, was recently awarded the American Lung Association’s Lung Cancer Discovery Award, a $100,000 grant to research epigenetic factors affecting lung cancer.

Epigenetics is the study of how DNA is modified or utilized in order to control its stability, expression, and organization without making changes to the DNA sequence. Therefore, understanding epigenetics assists in understanding what causes disease, which will lead to novel preventive and treatment strategies.

“The American Lung Association is really devoted to basic science discovery that can influence our understanding of lung cancer. I am really proud that they have continued to fund us and allow us to make these important discoveries,” said Whetstine, the 

Lung cancer is the leading cause of cancer-related deaths in the United States. Lung cancer is often difficult to treat because of the heterogeneity, or diversity, of the disease, especially in regard to DNA amplification—an increase in the number of copies of a gene&mdash;which can contribute to genome instability. This lack of stability contributes to lung-cancer associated risk and drug resistance.

 to follow up on previous work investigating epigenetic factors that control copy number gains, which contribute to heterogeneity within lung tumors. They discovered eight enzymes that lead to localized copy gains of regions linked to drug-resistant lung cancer.

“In the context of EGFR [epidermal growth factor receptor], for example, the research will also try to understand the interplay of those epigenetic factors that influence EGFR amplification in lung cancer,” Whetstine said.

The main goal of the new research is to build a network of the regulatory input signals that are influencing heterogeneity through copy number mechanisms. “By understanding what those are in lung cancer, we can have better biomarkers and possibly identify therapeutic targets,” Whetstine said.

“The American Lung Association is honored to fund research projects that are changing the face of medicine. Whetstine’s research in epigenetics has the potential to help us uncover new approaches to treat aggressive, drug-resistant lung cancer and ultimately save more lives,” said Albert A. Rizzo, MD, FACP, chief medical officer at the American Lung Association.

Additionally, the research will hopefully identify novel drug targets for lung cancer and investigate the use of chemistry or tools to change and control copy number.

Whetstine also received the Lung Cancer Discovery Award in 2014 and 2017.

Johnathan R. Whetstine Awarded Lung Cancer Discovery Award

We recently traveled to Pittsburgh, Pennsylvania, for a State of the Science Summit™ on Lung Cancer. At the meeting, faculty from the University of Pittsburgh Medical Center and Fox Chase Cancer Center discussed how chemoimmunotherapy has changed the standard of care in stage IV nonsquamous non—small cell lung cancer (NSCLC), highlighted how up-front immunotherapy has become a pivotal part of treatment in squamous NSCLC, and explained how immunotherapy’s success in lung cancer has set the stage for future research.

In addition, faculty examined PD-L1 and tumor mutational burden as biomarkers of immunotherapy response in NSCLC, and provided insight into overcoming acquired resistance to targeted therapy.

 State of the Science Summit™ in your area? 

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We traveled to Pittsburgh, Pennsylvania, for a State of the Science Summit™ on Lung Cancer, which featured insights from the UPMC and Fox Chase Cancer Center faculty.

Unpacking IO Innovations in Lung Cancer in Pittsburgh

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, professor, Department of Hematology/Oncology, co-director, Immune Monitoring Facility, Lung Cancer and Mesothelioma TRDG member, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology, Fox Chase Cancer Center, discusses immunotherapy alone or in combination with chemotherapy in combination with immunotherapy in patients with advanced NSCLC.

PD-L1 expression is one of the first factors considered for patients undergoing a comprehensive genomic analysis with a sequencing panel. The next step of treatment involves assessing patients for genetic alterations, such as 

 mutations, and then directing them toward appropriate targeted therapy based on the testing results.

Genomic testing provides a genomic profile of NSCLC tumors. If a patient’s PD-L1 expression level is >50% (PD-L1—high) then the possibility of treatment with pembrolizumab (Keytruda) alone can be explored, or, potentially in the near future, with atezolizumab (Tecentriq), concludes Borghaei.

Hossein Borghaei, DO, MS, discusses immunotherapy alone or in combination with chemotherapy in combination with immunotherapy in patients with advanced NSCLC.
 

Dr. Borghaei on Immunotherapy versus Chemotherapy and Immunotherapy in NSCLC

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, professor, Department of Hematology/Oncology, co-director, Immune Monitoring Facility, Lung Cancer and Mesothelioma TRDG member, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology, Fox Chase Cancer Center, discusses immune-related adverse events (AEs) in patients with lung cancer who received immunotherapy/chemotherapy combinations.

The rates of immune-related AEs, including pneumonitis and colitis, do not appear significantly higher; however, Borghaei still recommends paying close attention to the side effect profile of each patient.

In KEYNOTE-189, patients received a chemotherapy backbone of carboplatin/pemetrexed with pembrolizumab (Keytruda). The regimen was associated with higher rates of renal disfunction. That is something physicians need to be aware of as they closely monitor their patients. If there is a change in renal function, Borghaei urges the patient be investigated to ensure they receive appropriate care.

Hossein Borghaei, DO, MS, discusses immune-related adverse events in patients with lung cancer who received immunotherapy/chemotherapy combinations.

Dr. Borghaei on Immune-Related Adverse Events in Lung Cancer

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, professor, Department of Hematology/Oncology, co-director, Immune Monitoring Facility, Lung Cancer and Mesothelioma TRDG member, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology, Fox Chase Cancer Center, discusses emerging biomarkers of response to immunotherapy in non—small cell lung cancer (NSCLC).

In addition to PD-L1 and tumor mutational burden, other T-cell activation markers have been investigated as potential predictors of response to immunotherapy, including an interferon gamma messenger RNA signature, says Borghaei. Additional research groups are looking at composite markers, such as PD-L1 and infiltrating lymphocytes. Drug-specific biomarkers could provide even more predictive value. For example, certain lymphocyte populations have been shown to be predictive of response to combination therapy. However, these data are not robust enough to draw conclusions from, says Borghaei. 

Equally important are predictors of lack of response to immunotherapy. 

 has emerged as one such marker and could help identify patients who should not receive immunotherapy. However, these data are retrospective and require prospective validation, concludes Borghaei.

Hossein Borghaei, DO, MS, discusses emerging biomarkers of response to immunotherapy in non–small cell lung cancer (NSCLC).

Dr. Borghaei on Emerging Biomarkers in NSCLC

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, professor, Department of Hematology/Oncology, co-director, Immune Monitoring Facility, Lung Cancer and Mesothelioma TRDG member, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology, Fox Chase Cancer Center, discusses the clinical utility of PD-L1 in advanced non—small cell lung cancer (NSCLC).

The combination of chemotherapy plus immunotherapy has become standard of care for patients who have PD-L1 expression <50%, irrespective of histology, according to the results of several phase III clinical trials.

For patients with PD-L1 expression ≥50%, chemotherapy plus immunotherapy can also be considered, particularly for patients who have significant disease burden. However, these patients can also consider pembrolizumab (Keytruda) monotherapy based on data from the phase III KEYNOTE-024 trial, which demonstrated a significant improvement in progression-free survival versus platinum doublet chemotherapy alone. Currently, there is no head-to-head comparison of pembrolizumab versus chemotherapy/pembrolizumab in patients with PD-L1 >50%, but those data may emerge in the future, concludes Borghaei.

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, professor, Department of Hematology/Oncology, co-director, Immune Monitoring Facility, Lung Cancer and Mesothelioma TRDG member, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology, Fox Chase Cancer Center, discusses the clinical utility of PD-L1 in advanced non–small cell lung cancer (NSCLC).

Dr. Borghaei on the Clinical Utility of PD-L1 in Advanced NSCLC

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, associate professor, Department of Hematology/Oncology, Fox Chase Cancer Center, discusses necessary research and anticipated trials evaluating immunotherapy in advanced non—small cell lung cancer (NSCLC).

Although PD-L1 has shown some utility in predicting response to immunotherapy, better biomarkers are needed, says Borghaei. Over the course of the past several years, tumor mutational burden (TMB) has emerged as a potential biomarker. However, there are no prospective data to suggest that TMB is a robust marker. Moreover, TMB has yet to be standardized, so there is a lot of variability in terms of the cutoff and methodology for using this marker, explains Borghaei.

In addition to more data surrounding TMB, phase III trials of immunotherapy alone are also anticipated, such as MYSTIC, CheckMate-227, and NEPTUNE. The CheckMate-227 trial had shown preliminary progression-free survival benefit. At the 2019 ESMO Congress, investigators reported an overall survival benefit with the frontline combination of nivolumab (Opdivo) and ipilimumab (Yervoy) versus chemotherapy alone regardless of PD-L1 expression. The field is eagerly awaiting mature data from all of these studies because they will shed more light on the use of novel immunotherapy combinations without chemotherapy and potentially TMB, concludes Borghaei.

Hossein Borghaei, DO, MS, chief, Division of Thoracic Medical Oncology, director, Lung Cancer Risk Assessment, associate professor, Department of Hematology/Oncology, Fox Chase Cancer Center, discusses necessary research and anticipated trials evaluating immunotherapy in advanced non–small cell lung cancer (NSCLC).

Dr. Borghaei on Anticipated Trials Evaluating Immunotherapy in NSCLC

The renal cell carcinoma space (RCC) has witnessed a shift in the role of surgery with the introduction of immunotherapy, combination regimens, and novel agents; however, it is still an important modality to consider, explained Robert G. Uzzo, MD, MBA, FACS.&#8239;

"Twenty years ago when the Von Hippel-Lindau gene was identified, nobody would have realized the monumental shift in patient care, which benefits not only longevity of life but quality of life," explained Uzzo. "Before that, it was interferon and/or clinical trials. Now we have so many therapies for patients with advanced kidney cancer."

Even with the addition of these systemic regimens, surgery continues to have an integral role, and a growing one for patients with metastatic disease, he added.

 &#8239;during the 2019 Kidney Cancer Research Summit, Uzzo, &#8239;professor of surgery, Temple University Health System, chair of the Department of Surgical Oncology, senior vice-president, Physician Services, Fox Chase Cancer Center, discussed the evolving yet relevant role of surgery in RCC.&#8239;

: What do you see coming down the pipeline in RCC?

: I'm a surgeon, so I spend much of my time thinking about the biology of the tumor and whether or not surgery can intervene for a therapeutic benefit. In the past, when we did not have a lot of systemic therapy, surgery usually was the answer. It may be uncommon for a surgeon to talk about a diminishing role in the management of kidney cancer; however, there is a growing role [for surgery] in patients with metastatic disease.&#8239;

A lot of new data, mostly from the CARMENA and SURTIME trials, has emerged regarding whether surgery should be upfront for patients with metastatic disease. There is recognition now that patients may be served by having upfront systemic therapy. These patients get upfront systemic therapy and then become good responders and prolonged, durable complete responses or partial responses. The question then becomes, “How do you consolidate the results of the systemic therapies with surgery?”

We are talking about the idea of lifelong therapies for people who are not cured. If we could get them to a point where they have got a significant partial response from dual therapy or from combinations, and then we could take them to the operating room and excise them, can we now give them a period of time where they are off of therapy?&#8239;

Yes, we could discuss the mechanistic aspects of new therapies that are coming down, the HIF inhibitors and other combinations and sequential therapies, but surgery is evolving. The role of surgery in patients with metastatic disease may look a lot different 3 to 5 years from now.

What factors determine whether a patient should receive neoadjuvant therapy, adjuvant therapy, or upfront surgery?

The question about adjuvant therapy and neoadjuvant therapy is something that is still not settled. There are a lot of clinical trials and level 1 evidence to suggest that we haven't hit on the right combination, certainly for adjuvant therapy.&#8239;

Right now, in the immunotherapy era, a lot of studies are asking questions, such as, “Do you need to use immunotherapy before surgery or after?” We haven't gotten to the point where we have multiple agents being used in the adjuvant setting, though there are existing trials.&#8239;

The jury is out, and it is a hard conversation to have with a person. From a surgical perspective, you bring a patient to the operating room, you remove their stage III kidney cancer—essentially rendering them surgically NED or R0. However, the risk of recurrence is high. You want to give the patient good news, but you have to temper that enthusiasm with the risk of recurrence.&#8239;

In terms of the neoadjuvant setting, most people think that based on CARMENA and SURTIME, that patients with metastatic, high-risk disease ought to have systemic therapy first. The real question surrounds the favorable-risk, young patient with lung-only metastatic disease. Most likely, there is a portion of patients who would benefit from surgery upfront followed by a potential period of time off of systemic therapy. The goal isn't just longevity but quality of life, which is impacted both by surgery and systemic therapies.&#8239;

Is there a rationale to try the combinations that are approved in the metastatic setting either before or after surgery?

Certainly, the idea is that if it works for stage IV disease, it probably works in the adjuvant setting—or it should work. The question is, “How robust of a signal can we get?” Those data take a long time to mature. I suspect that the earliest read out that we will see for immunotherapy in the adjuvant setting is going to be another 2 to 3 years.&#8239;

What other research are you a part of that you want to highlight?

One of the sessions I co-chaired at the [2019 Kidney Cancer Research Summit] was on novel delivery mechanisms. We discussed about whether there are ways to focally deliver novel systemic therapies, such as immunotherapies or nanoparticles directly injected into the tumor. Those delivery mechanisms and the engineering of them is the next frontier.&#8239;

Would you like to add anything about the Kidney Cancer Research Summit for those who could not attend this year?

The most important thing that clinicians should know about—and we do intuitively know about&mdash;the science drives the cure. This was a discussion about how the science today may look for the cure not just 10 years from now, but perhaps with a compressed time frame. We live in the year where the big data are allowing us to deliver [cures] much quicker. Clinical trials take a long time, but discovery to therapeutic benefit is compressed. That's an important point.&#8239;

Robert G. Uzzo, MD, MBA, FACS, discusses the evolving yet relevant role of surgery in renal cell carcinoma.