Nearly 50% of patients with high-risk neuroblastoma achieved a response following treatment with a 4-drug combination of irinotecan, temozolomide, dinutuximab (Unituxin), and granulocyte-macrophage colony-stimulating factor (GM-CSF), according to retrospective findings published in the 

In total, 48.6% (n = 71) of patients achieved an objective response, including a complete response (CR), partial response (PR), and minor response in 29%, 14%, and 5% of patients, respectively. This includes 47% of the 133 patients with metastatic soft tissue and bone disease. Additionally, investigators detected a marrow response in 73% of the 58 patients with available posttreatment bone marrow data.

“Data regarding response timing and duration will aid clinicians in balancing the risks and benefits of continuing treatment of [irinotecan/temozolomide/dinutuximab/GM-CSF] in patients with relapsed [high-risk neuroblastoma],” lead study author Benjamin J. Lerman, MD, MS, of the Children’s Hospital of Philadelphia and the University of Pennsylvania, and colleagues, wrote in the journal article. “The survival outcomes described in this study provide a new point of reference for evaluating novel therapeutics in relapsed [high-risk neuroblastoma].”

This retrospective study sought to describe response and progression-free survival (PFS) in patients with relapsed high-risk neuroblastoma who received the regimen of irinotecan, temozolomide, dinutuximab, and GM-CSF.

To be eligible, patients needed to be under 30 years old at diagnosis of high-risk neuroblastoma and received at least 1 cycle of irinotecan/temozolomide/dinutuximab/GM-CSF for progressive disease (PD) or relapsed disease. Patients also needed to have an objective response or stable disease after standard initial frontline therapy.

Patients were excluded if they had primary refractory disease and progressed through induction therapy. Those who received the combination for suboptimal response to induction treatment were also excluded.

In total, 146 patients were analyzed in this study, which included those who received at least 1 cycle of irinotecan/temozolomide/dinutuximab/GM-CSF outside the context of a clinical trial from January 1, 2015, to June 1, 2020. The study regimen consisted of intravenous (IV) irinotecan at 50 mg/m2 once daily, temozolomide at 100 mg/m2 once daily on days 1 though 5, IV dinutuximab at 17.5 mg/m2 once daily on days 2 through 5, and subcutaneous GM-CSF at 250 µg/m2 once daily on days 6 through 12 of a 21-day cycle.

Regarding patients who received the combination for multiple distinct relapse events, the study only used data related to the first relapse event treated with the combination.

Patients received a median of 4.5 cycles of study treatment (interquartile range, 2-7; range, 1-31) over a median of 87 days. Of the 23% (n = 34) patients who received concurrent treatment at some point during their time on the combination, 5 received surgery, 23 received radiation, 2 received meta-iodobenzylguanidine therapy, and 5 received another anticancer therapy.

The median age of patients at diagnosis was 51 months (interquartile range, 31-72), and 58.2% (n = 85) were male. A total of 67.8% (n = 99) of patients received the study treatment after their first relapse or progression. In addition, 63.0% (n = 92) of patients had measurable disease at relapse or progression, and 55.5% (n = 81) had received anti-GD2 therapy prior to study treatment.

In total, 50 (37%) of the 134 patients had known tumor MYCN status, and 43 of those patients (32%) had tumors with 

 amplification. Additionally, 94 patients had known tumor 

 status, and 21 of those patients (22%) had tumors with 

A total of 58.2% (n = 85) of patients discontinued study treatment because of stable disease (SD) or PD, 13.0% (n = 19) discontinued because of unacceptable acute or chronic toxicity, 23.3% (n = 34) discontinued because of a transition to another anticancer therapy, and 19.9% (n = 29) discontinued because of planned treatment completion. Patients who stopped treatment with the combination because of toxicity received a median of 3 cycles (range, 1-15) before discontinuing. At the time of data collection, 4 patients were still on the study therapy.

The primary end point was the proportion of patients with objective response after receiving the combination, which was defined as CR, PR, or minor response on a disease evaluation after initiation of study treatment; PFS; and duration of response (DOR) after objective response. Investigators sought to evaluate timing and durability of response and to identify molecular and clinical factors associated with PFS in these patients.

Patients who achieved an objective response received a median of 2 cycles (range, 1-9) from the beginning of study treatment to their first disease evaluation showing objective response. One patient required over 6 cycles to reach a first objective response; this patient received 9 cycles of treatment.

The median time between diagnosis and first relapse was 26 months (range, 17-38) in patients who achieved an objective response vs 18 months (range, 12-35) in those who did not respond (

 = .04). Additionally, White patients were most likely to respond, as 71.2% (n = 40) of White patients responded and 53.3% (n = 51) did not respond (

 = .03). Responders were also more likely to have received prior anti-GD2 therapy, at 64.8% (n = 46) vs 46.7% (n = 35; 

 = .03) in those who did not respond, and tumor 

 aberrations were less frequent in responders, at 11.3% (n = 8) vs 17.3% (n = 13; 

Furthermore, the median age of responders (54 months; range, 33.0-80.5) was older than that of non-responders (44 months; range, 30.5-64.5; 

 = .15), and more responders had stage M disease, at 97.2% (n = 69) vs 89.3% (n = 67; 

 = .13). Responders were also less likely to have measurable disease at the time of receiving study therapy, at 56.3% (n = 40) vs 69.3% (n = 52; 

Although all the above distinctions met the criteria for inclusion in the multivariate model, after multivariate adjustment, only the comparison between White and non-Black and non-White patients retained statistical significance. No covariates were independently associated with PFS.

Of the total population, 21% (n = 31) had SD, and 30% (n = 44) progressed on the study treatment. Of the 79 patients who initially had SD, minor response, or PR, 72% (n = 57) achieved their best response by the first disease evaluation. Of the 22% of patients with SD or better at first post–study treatment disease evaluation who experienced an improvement in response designation in a subsequent evaluation, 5 had initial SD, 3 had initial minor response, and 14 had initial PR.

In the overall study population, the median PFS was 13.1 months (95% CI, 9.8-16.5), the 6-month PFS rate was 62% (95% CI, 55%-71%), the 1-year PFS rate was 51% (95% CI, 43%-60%), and the 2-year PFS rate was 28% (95% CI, 20%-40%).

In all patients who had an objective response, the median DOR was 15.9 months (95% CI, 14-not available [NA]), the 6-month PFS rate was 86% (95% CI, 78%-95%), the 1-year PFS rate was 68% (95% CI, 57%-81%), and the 2-year PFS rate was 44% (95% CI, 32%-61%).

Additionally, 21 patients who achieved an objective response discontinued study treatment and received no further anticancer therapy, with a median additional PFS of 10.4 months (95% CI, 7.4-NA). Of those patients, 14 had CRs and 7 had PRs. Of these patients, the 6-month PFS rate was 73% (95% CI, 54%-99%), and the 1-year PFS rate was 26% (95% CI, 10%-67%).

In total, 108 patients relapsed or progressed 0 to 30 months after initiating study treatment. Of these, 56% (n = 60) experienced relapse while actively receiving study treatment, 31% (n = 33) relapsed after transitioning from study treatment to another anticancer therapy, and 14% (n = 15) relapsed after discontinuation of study treatment without additional therapy.

Bone was the most common site of relapse (76.9%; n = 83), followed by metastatic soft tissue 54.6% (n = 59) and lymph nodes in 54.6% (n = 59), bone marrow in 30.6% (n = 33), lung in 16.7% (n = 18), and brain in 5.6% (n = 6).

“These data establish a new baseline of response and survival for comparison during future trials in patients with relapsed/progressive neuroblastoma in the chemoimmunotherapy era,” the study authors concluded.

Lerman BJ, Li Y, Carlowicz C, et al. Progression-free survival and patterns of response in patients with relapsed high-risk neuroblastoma treated with irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor. 

 Published online October 7, 2022. doi:10.1200/JCO.22.01273

Articles

Among 71 patients with neuroblastoma, 48.6% achieved an objective response and 29% achieved a complete response with a 4-drug combination. 

Chemoimmunotherapy Yields Promising Objective Responses in Patients With High-Risk Neuroblastoma 

Reirradiation, in addition to concurrent bevacizumab (Avastin), improved progression-free survival (PFS) but not overall survival (OS) outcomes in patients with recurrent glioblastoma (GBM), according to findings published in the 

 The treatment was found to be tolerable, with no delayed grader 3 or greater treatment-related central nervous system (CNS) adverse events.

Findings from the NRG Oncology/RTOG1205 prospective study showed that, among 170 patients who were randomly assigned to receive either concurrent bevacizumab and reirradiation or bevacizumab alone, the median PFS at a 12.8-month follow-up was 7.1 months. In comparison, among those receiving bevacizumab alone, the median PFS was 3.8 months (HR, 0.73; 95% CI, 0.53-1.0; 

 = .05). The median OS was 10.1 months (95% CI, 9.5-11.3) vs 9.7 months (80% CI, 9.0-11.2). The HR for OS was 0.98 (80% CI, 0.79-1.23; 

Moreover, the addition of irradiation had manageable tolerability. Between the 2 treatment arms, 8 patients receiving irradiation and 4 patients receiving bevacizumab monotherapy experienced grade 5 AEs. Of these cases, all but 2 were determined to be unrelated to treatment.

“Although the combination of re-irradiation and bevacizumab did not significantly improve OS for patients with bevacizumab-naïve recurrent GBM, NRG Oncology/RTOG1205 confirmed meaningful improvement in PFS, including the 6-month PFS rate, with concurrent re-RT and BEV compared with BEV alone, which most patients consider clinically beneficial,” Christina Tsien, MD, FRCP, professor of radiation oncology and molecular sciences at Johns Hopkins School of Medicine, and co-investigators wrote. “This is especially true when considering that treatment was safe and well-tolerated with no delayed CNS treatment–related toxicities.”

Unfortunately, there is a paucity of effective treatment options for glioblastoma, despite it being the most common primary brain tumor in adults. Radiation has been shown to significantly improve OS in newly diagnosed GBM and irradiation is now offered to certain patient with localized recurrences.

Existing studies have indicated that reirradiation improves disease control and is well tolerated in the recurrent population. By delaying disease progression, providers may be able to help their patients mitigate chronic steroid use and potentially decreased neurologic symptoms. However, recurrent GBM is a heterogenous disease, and analyses documenting the benefit are insufficient.

Bevacizumab is an anti-VEGF therapy that has been shown to improve PFS, if not OS, in this setting. It received FDA approval for this indication in 2009. Various trials have combined bevacizumab with other therapy regimens, including temozolomide, irinotecan, and nitrosoureas, without improved efficacy. Investigators noted that there were multiple reasons to combine irradiation with bevacizumab, but they specifically hypothesized that the combination would enhance the radiotherapy response, by increasing the anti-VEGF effect using radiotherapy to targeted resistant glioma stem-cell-like cells, thereby lowering the incidence of radiation necrosis and CNS toxicity.

In the NRG Oncology/RTOG1205 study , bevacizumab was administered intravenously every 2 weeks at a dose of 10 mg and irradiation was administered in 10 fractions of 35 Gy.

Eligibility criteria for this trial included a diagnosis of recurrent glioblastoma with histopathologically confirmed or unequivocal imaging evidence of tumor progression within 21 days of study registration.

Of note, 12 patients randomly assigned to the bevacizumab arm eventually received irradiation as salvage therapy. The 6-month PFS rate was also found to improve with irradiation. The rate with bevacizumab alone was 29.1% (95% CI, 19.1%-39.1%) and was 54.3% (95% CI 43.5%-65.1%) in the combination group (

A multivariable cox model showed that older age (HR, 1.51; 80% CI, 1.13-2.01; 

= .065) and lower KPS (HR, 3.97; 80% CI, 2.37-6.66; 

 < .001) were also associated with worse OS. Ultimately, 85% of patient died from recurrent GBM on trial.

“Radiation plays an important role in the initial treatment of brain tumors. The current study shows that a second course of radiation with concurrent bevacizumab is well tolerated and prolongs progression-free survival in patients with recurrent GBM,” added Ingo K. Mellinghoff, MD, neuro-oncologist, internist, chair of the department of neurology and chief of brain tumors services at Memorial Sloan Kettering, in response to findings. “Although this treatment did not prolong OS, local disease control remains an important goal in this disease with limited treatment options.” 

“Re-irradiation remains a reasonable option for patients with small volume of recurrence, methylated MGMT promoter status, and good KPS,” study authors added. “Re-irradiation should not be withheld on the basis of age as treatment remains safe and results in comparable outcomes. Future cooperative group studies should consider prospectively evaluating the neurocognitive, symptom burden and [quality of life] benefit of salvage interventions in this patient population.”

Tsien CI, Pugh SL, Dicker AP, et al. NRG Oncology/RTOG1205: a randomized phase II trial of concurrent bevacizumab and reirradiation versus bevacizumab alone as treatment for recurrent glioblastoma. 

. Published online October 19, 2022. doi:10.1200/JCO.22.00164

Concurrent treatment with reirradiation and bevacizumab prolonged progression-free survival, but not overall survival, in patients with recurrent glioblastoma.  

Reirradiation May Play a Role in Recurrent Glioblastoma, Although Optimal Treatment Remains Controversial 

Transformative solutions in nursing are ones that are sustainable, according to Linda Laskowski-Jones, MS, APRN, ACNS-BC, CEN, NEA-BC, FAAN. To come up with a transformative solution, leaders need to engage their employees and see how new strategies affect their working environment.

“Transformation oftentimes [is a] term bantered about and used freely in healthcare institutions today across the board but without understanding what it means, what it looks like, and how much time it takes—because it's not a short walk,” Laskowski-Jones said. She added, “as an oncology nurse, I think you can advocate best through helping to enable others to grow and when you do that you grow yourself and you also learn to take risks in your profession.”

®, Laskowski-Jones, who is editor-in-chief of 

 and president of the Delaware Emergency Nurses Association, and who has spent nearly 4 decades working in trauma and emergency nursing, as well as served as a manager, director and vice president in her hospital’s trauma and emergency departments, discussed how meeting problems with transformative solutions can help improve the working conditions of nurses across a unit.

Understanding the problem: Nursing Shortages

In her presentation, Laskowski-Jones highlighted that, although there are 4.3 million nurses in the US, because of new roles, more jobs, retirements, better staffing ratios, and RN’s leaving the profession, 11 million more nurses are needed to avoid shortages. Moreover, RN employment is projected to be the occupation requiring the most growth through 2026.

The effect of the COVID-19 pandemic on the nursing landscape paired with outside pressures as well as internal elements such as workloads, expectations, and patient factors, have left the field needing transformative solutions to address the causes of turnover along with burnout. Based on geography and specialty, the average turnover of nursing staff ranges from 8.8% to 37% and the American Nurses Association declared the nursing shortage a national crisis on September 1, 2021, to the Department of Health and Human Services.

In speaking about the nursing shortage, Laskowski-Jones noted that the “great resignation” had already begun in 2019, before the COVID-19 pandemic. “In 2019 there was this uptake of resignations across the board in all professions—not just in healthcare…. hospitals were starting to ratchet down on staffing. They were trying to cut corners and reduce resource utilization, [even though] we had organizations saying: we expect high patient experience scores.”

Laskowski-Jones noted that hospitals were being held to higher standards as the patient experience scores are publicly reported and with that came pressure. Additionally, an increase of violence in health care, and lawsuits piled on.

Of course, in 2020, the pandemic compounded these issues, and by 2021, many nurses were burnt out.

“In 2020, we had the pandemic, and everybody was engaged because nurses rise to the challenges, we always rise to the challenges, they’re all in; they’re being battered with what they’re dealing with between the personal protective equipment needs, the complex patients, potentially being pulled to a unit where they never worked before, having to learn new skills, and dealing with devastating situations in many cases,” Laskowski-Jones said.

“[However,] 2021 was a different story,” she said. “Even with vaccines, the pandemic had not ended. The biggest thing was that there was this latent demand in the community for services [because some patient’s] cancer wasn't diagnosed or their heart disease wasn't diagnosed and now they were all coming in where they had been too afraid to even use the hospital [before].” 

With a large increase in patients coming to hospitals, nurses were working in environments that were at overcapacity and nurses “did not feel that they were being supported, they were valued, and they were starting to see shortages that weren't necessarily being addressed.”

While issues were still active, travel nurses had a large positive affect in care, but this impacted the dynamic in the hospital as travel nurses receive high contract pay which may have led some nurses who had been at institutions for a long time to feel undervalued and leave.

In her presentation, Laskowski-Jones noted that creating a healthy workplace environment is a crucial solution in beginning to rebuild the nursing field. The root causes for burnout, turnover and unhappiness must be addressed, and nurses should not be expected to be able to handle everything with a lack of support; psychological safety must be developed. Key points under that umbrella include developing non-defensive listening skills, promoting a clear vision with team alignment, innovation, respectful communication, and generating a culture across the organization of effective teamwork.

Transformative is a broad term, but it essentially refers to solutions that are sustainable, according to Laskowski-Jones. She highlighted some examples of unsustainable solutions vs sustainable ones.

“Transformation means going from this vision of what you think should be to sustainably getting there.” Laskowski-Jones gave the example, “let’s say there is a directive that when the patient comes in staff have only a specified amount of time to get a certain type of work done (eg, their admission process, or their discharge process, etc.).

In this hypothetical example, Laskowski-Jones said, someone looked at data and determined that all patients should be discharged in 6 hours. All nurses are trying to get patients discharged within a 6-hour time-frame. However, if they are struggling to do it, are exhausted, and are consequently cutting corners, that would be an unsustainable goal as currently performed.

Sustainable solutions should make work easier and more effective, Laskowski-Jones noted. This means that when new strategies are implemented, leaders should be asking employees how they feel about the change, and whether it is making things better.

Laskowski-Jones’s presentation emphasized the importance of creating a healthy work culture and assessing one’s own style and reputation to encourage positive change in the environment. Emotional intelligence is key in the workplace and establishing trust to build relationships with coworkers and teams is crucial while being mindful of short- and long-term goals that are set.

When discussing issues in the workplace, Laskowski-Jones said that she encourages nurses to come-up with solutions to the problems that they pose to her.

“If you bring me a problem,” she said, “and I don’t care what it is, you need to bring me your idea of what the solution is... If we make this change that you recommend, how is that going to affect other people?”

Lastly, Laskowski-Jones emphasized that leadership must value their staff.

“You have to show empathy,” she said. “Value is not just giving somebody a little gift… or some sort of recognition day, value is being able to have a conversation where you witnessed someone having a difficult day or a challenging patient,” she said. “It’s when a manager says ‘I was impressed with how you handled that.’ Or that must have been difficult for you, do you want to talk about it? I am here to listen, I’ve been there, and I know how hard this is.” 

Laskowski-Jones L. Finding your voice: how nurses can create a healthy work culture to enhance a thriving work environment. Presented at: ONS Bridge; September 13-15, 2022; virtual.

Linda Laskowski-Jones, MS, APRN, ACNS-BC, CEN, NEA-BC, FAAN, discusses how oncology nurse leaders can help improve working environments for their staff. 

Nurse Leaders Must Foster Change to Develop a Healthy Workplace Environment

Over the past few decades, the number of advanced practice providers (APPs) in oncology has increased dramatically and the role they play expanded greatly. One reason for this is that there are more patients who need oncologists in the US than there are physicians practicing the specialty. According to the American Society of Clinical Oncology, the nation will see a shortage of more than 2200 oncologists by 2025 and an increase of 40% in demand for cancer treatment during the next 6 years.

 This growth in demand is driven not only by new patients, but by those who have completed active treatment and require follow-up care. Thanks to advanced therapies, better outcomes are being achieved and survival rates are improving. Cancer survivors—even with complex comorbidities—are living longer than ever before.

Survivorship care can readily be performed by APPs, given their wide breadth of expertise and training. A closer look at how these highly skilled professionals deliver survivorship care will provide some insight into why they areideally suited to lead these programs, meeting a critical need that will only grow in the future.

In many practices, APPs are the backbone of survivorship programs, playing a key role in their planning and execution. They are well suited to lead these programs because of their extensive education, training, and scope of practice.

They also develop strong relationships with patients and caregivers during active treatment. As trusted members of the care team, it makes sense for them to discuss the key elements of survivorship with patients, some of which—like lifestyle changes and advance care planning—can be difficult to talk about.

Many patients are under the misconception that survivorship doesn’t begin until they have finished active treatment. According to the National Cancer Institute, however, a patient is considered to be a survivor from the time of diagnosis until the end of life.

APPs can help patients understand that survivorship encompasses everything from diagnosis onward—be they undergoing treatment, in remission, or facing recurrence.

A Critical Role at All Stages of Survivorship

APPs make valuable contributions at all stages of the survivorship journey.

They manage patients during active treatment, helping them keep side effects under control so that they can adhere to treatment. They educate patients about what to look for so that side effects can be caught early and dealt with more easily. They support the psychological well-being of patients by addressing their expectations and fears. They talk with patients early on about the emotional impact of the diagnosis, teach them stress-coping skills, and refer them to mental health professionals if and when necessary.

Once active treatment ends, the focus shifts to long-term surveillance. Patients may not be cured but they may be in remission, so ongoing follow-up care is critical, from a clinical and psychological standpoint.

By this stage, a long-term care plan has been developed that spells out exactly what treatment has been given and what follow-up care is needed and when. It details intervals between office visits and the imaging, lab tests, and other surveillance that may be needed. It also includes information that helps patients and their care team recognize signs of recurrence, the emergence of a secondary cancer, and potential long-term side effects like cardiotoxicity.

The transition away from active treatment is always stressful for patients because they must adjust to many changes, including less frequent office visits, which may make them feel as if they lack support. APPs play an important role at this stage, as by now they have a good relationship with patients and their caregivers. They can thus communicate effectively about such sensitive topics as patient emotions, lifestyle changes, and advance care planning. APPs are able to recognize signs of distress during this transition and provide appropriate assistance, whether that be by getting patients into support groups, referring them to mental health professionals, or prescribing medication.

Once active treatment concludes, patients may transition to receiving most of their care from a primary care physician. A detailed survivorship plan makes the PCP intimately familiar with a patient’s condition and needs. And APPs are always available to offer advice about mutual patients.

There is always a concern that the patient may not adhere to a survivorship plan. Because they interact less frequently with the oncology care team, they may lose motivation. APPs must make sure patients understand not only the plan but the need for them to become more responsible for their own health.

This is also a time when APPs are very vigilant about checking for anxiety and depression so that they can catch the conditions before they get out of control. Primary care providers can also be brought into the discussion and intervene if need be.

A survivorship plan is key to providing high-quality, patient-centered care. It must be developed early on to ensure the best patient experience and quality of life. APPs are ideally situated to manage or lead cancer survivorship because of the close relationship they establish with patients and their caregivers. Practices also benefit from such work because it allows physicians to focus on other priorities. Integrating APPs into survivorship care is a trend that will only grow in the future owing to the tremendous benefits it offers to the practice and its patients.

Finnegan J. Another physician shortage: oncologists.Fierce Healthcare

https://www.fiercehealthcare.com/practices/another-physician-shortage-oncologists

Survivor. NCI Dictionary of Cancer Terms. National Cancer Institute. Accessed July 13, 2022. 

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/survivor

Advanced practice providers are the future of survivorship care because of the tremendous value they offer to the practice and its patients. 

Advanced Practice Providers Are Uniquely Suited for Survivorship Care

As the cancer treatment landscape continues to evolve, the role of front-line nurses in clinical trials remains essential, according to Anne Delengowski, RN, MSN, AOCN, CCCTM.

“I don’t know if nurses today can truly appreciate where we’ve come because they were never there, [but] I have had the honor and privilege of being there,” Delengowski, who has been an oncology nurse for 42 years, and is the director of Oncology Nursing Education at Thomas Jefferson University Hospital, said in an interview. “In the past, we had very few cancer drugs, we had minimal second-line therapies which are standard now, we didn’t have targeted therapy or immunotherapy, and we had poor symptom management.” 

Delengowski recently presented at the 2022 Oncology Nursing Society Bridge, highlighting notable improvements spanning the course of her career and the excitement that comes with being a part of a clinical trial from start to finish. In a post-presentation interview with 

®, Delengowski offered a personal perspective into how the field has changed during her career as a frontline nurse.

“When I first started as a cancer nurse, we didn’t have the antiemetics we have today, and it was awful. I did a study back then with a colleague from the school of nursing looking at anticipatory nausea and vomiting because the patients would come in vomiting prior to getting their drugs because they were anticipating it happening, [but] very rarely do you see that anymore. We [also] didn’t have growth factors; we didn’t have the colony stimulators to be able to prevent neutropenic fevers, so patients were hospitalized for most of the course of their disease. Today, all the stuff we talked about here came through clinical trials.”

She also highlighted how pain management strategies have significantly improved.

“I worked a lot in nightshift when I was in graduate school, and we didn’t have sustained release narcotics,” she said. “We used to have to wake people up in the middle of the night to give them pain medicine because if we didn’t their pain would be out of control in the morning. Once again, it was revolutionized that we have PCA [patient-controlled analgesia] pumps now, we have sustained release therapy. The nightmare of seeing patients in pain, you kind of weighed the fact if I didn’t wake them up, they’d be in a lot of pain in the morning and if I did wake them up, I interrupted their sleep, and it wasn’t good.”

Throughout her career, she shared that she has been inspired by the advances that clinical trials have brought about. She noted that patients are living longer, healthier lives, and that clinical trials are allowing providers to achieve “magical things.”

She noted, as an example, the breakthrough findings from Memorial Sloan Kettering Cancer Center where 100% of patients with rectal mismatch repair-deficient locally advanced rectal cancer achieved a complete response with dostarlimab-gxly (Jemperli).

Delengowski shared that, prior to working in clinical trials, she did not understand much about the process or have proper understanding or the extent of the behind-the-scenes work. For example, in her presentation, she explained how clinical trials must receive approval form a multidisciplinary disease group and a facilitation committee, along with a protocol review committee. In addition, there is a site initiation visit which provides the principal investigator and the team with training on all aspects of the trial, prior to its initiation.

Teamwork is also critical and research coordinators who understand the trial have been involved from the inception to guide nurses.

As part of her presentation, Delengowski outlined the different phases of clinical trials. Phase 1 trials are specifically designed to find a safe dose of a novel regimen for humans. This step determines how much a new treatment should be given (ie, oral or intravenous administration), and what the maximum-tolerated dose is.

Delengowski stressed, “A lot of times in phase 1 [trials] we don’t know what the symptoms or outcomes might be, so we need to be cognizant of the fact that anything that happens to that patient we need to document. We need to make sure we do it and we need to follow the protocol to dot the i, cross the t and do it all perfectly because if everyone chooses to do something different than it really doesn't make the trial valuable.”

“I remember giving my very first phase 1 [treatment] and I took a step back thinking ‘You want me to give this to a human being now? It’s the first time a human being has received this drug,’” she said. “I was humbled and wowed at the same time. It was wonderful for all involved, but a little frightening it was for us [as nurses] to administer.”

Phase 2 trials are larger and are designed to determine if the new treatment is effective against a certain cancer, as well as its safety profile. Phase 3 trials compare the new treatment (or new use of a treatment) against the current standard of care.

Across the trial continuum, supporting patients during the trial remains a significant part of the nurse’s role as patients can be overwhelmed throughout treatment. Delengowski highlighted that knowing where to get information for patients and helping to educate them is important for front-line nurses.

“It becomes very exciting when you know you’re part of [clinical trials],” she said. “Some frontline nurses may not exactly understand the value they bring, but [they’re] invaluable; We’re the frontline, we’re the last line, we’re the point where the person gets the medication or the therapy.”

However, phase 3 trials, which are usually randomized, can be difficult for nurses, because patients may not be happy to learn they were randomly assigned to receive the standard of care.

Delengowski explained “It's very hard when you talk up a study and the patient was randomized to standard of care. Often a frontline nurse will be confronted with [patients who say] ‘I signed on thinking I was going to get the new therapy and now I got standard of care drug.’ ”

“What I tell [patients] is in phase 3 studies we don’t know that standard care might be the best therapy. We don’t know and that’s what this is all about. I’ve been involved in phase 3 [trials], where the [experimental drug] was not better than standard of care; it was good, but not as good. It’s just part of the process and once you give that information to the patient, they feel a bit better about it.”

When looking back on all the various phases of clinical trials she has been a part of, Delengowski said it was an exciting feeling to think, “Wow, I was part of that, and we were there when it happened. Some of the trials didn’t come to fruition, but a lot of them did and when you look at that and know that you were part of it, it is so exciting…. As cancer nurses we see the patient go through from diagnosis to hopefully a long life, but in between there’s roadblocks. If they fail first-line therapy and other therapies and go onto a clinical trial, we walk that walk with them. I think that understanding that there is that next step [is important].”

Future steps in improving the clinical trial process include ensuring that inclusivity is a priority and that trials will be brought to the community. Historically, clinical trials have been performed in large academic centers which can be difficult to get to and exploring ways to bring them to patients and working with a community-based staff can be beneficial in making the clinical trials more comfortable for patients.

“[Clinical trials] give that glimmer of hope to someone that there may be other outcomes out there,” Delengowski said. “Even if it’s not something that’s going to be beneficial for that individual, which is not always the case, but it leads to phase 2 and phase 3 [trials] where there seemingly is some hope for a disease process that might not have had a whole lot of other options.”

Delengowski A. Clinical trials on the frontline: the changing landscape of clinical trials nursing. Presented at: ONS Bridge; September 13-15, 2022; virtual.

Cercek A, Lumish MA, Sinopoli JC, et al. Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer. 

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Anne Delengowski, RN, MSN, AOCN, CCCTM, discusses the evolving role of the oncology nurse in clinical trial research.

Clinical Trials Continue to Propel Field of Oncology with Nurses on The Frontline

I recently cared for a 32-year-old woman who was admitted to the Inpatient Oncology Unit 2 months after giving birth to her first child. She had been transferred to us for a higher level of care and was diagnosed with acute leukemia. The joy of having a baby quickly turned to insomnia, and she began having panic attacks about her disease as well as treatment-related nausea.

She also had a history of depression and suicidal behavior, which posed a significant challenge for her care team. Our attempts to manage the mental problems that were beginning to become manifest during her third week were unsuccessful. Eventually, the nursing staff started to feel that they had “failed” to “help her feel better” and no longer wanted to have her as a patient.

No patient assignment was conducive to caring for her and helping her cope. After many failed attempts, the woman requested alternative therapy for anxiety and insomnia and to cope with not being able to see her baby and was eventually prescribed medicinal cannabis.

Unfortunately, 30% of patients with cancer develop a mental disorder during the course of their illness.

 Those currently recognized in the literature include anxiety and mood disorders, which can have a negative impact on treatment, lead to suicidal ideation, and create additional difficulties for health care workers. Initially, the hospital stay can be prolonged.

But as time passes, patients may become dissatisfied and not adhere to treatment.

Diminished overall quality of life can lead to increased mortality.

Oncology nurses have also identified suicidal ideation as challenging to manage. Currently, there are no protocols they can follow in terms of who should be contacted, who should complete the documentation, and who should assess patients.

 Although nurses are trained to assess the psychosocial needs of patients, they need better resources to mitigate patient mental health problems.

Oncology nurses face a number of obstacles when addressing a patient’s mental health, including lack of training, increased workload, and lack of resources or access to resources.

 In addition, the stigma surrounding mental disorders continues to plague health care and to make patients hesitant to seek treatment.

Increased workloads significantly hinder a nurse’s ability to manage mental health disorders.

 The complexity of the care inpatients require doesn’t lend itself to prompt treatment escalation. Even when patients are coping badly, nurses may prioritize the care that is most urgently needed.

Moreover, the number of psychologists, psychiatrists, and social workers in hospitals is extremely limited. During the pandemic, many were working from home and triaged emergency cases to maximize safety.

Standardized mental health assessment tools are essential for nurses to recognize the problem early, and clear guidelines are needed to respond to a mental crisis once identified.

 Low-intensity cognitive therapy can be extremely effective, but nurses need to be taught how to deliver it.

Oncology nurses can also help reduce the stigma attached to mental health care, which not only prevents timely treatment but leads to seclusion.

 Nurses can work to increase awareness about how this stigma reduces quality of life.

Nurses are gatekeepers who can identify disorders early and triage patients. Although oncology nurses in particular are trained to show empathy and offer support, it is clear from the literature that they lack the competence to care for patients with acute mental health problems. It is equally clear that patients with such problems must be promptly identified and assessed by nurses who are trained and possess the correct guidelines.

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Although oncology nurses are trained to show empathy and offer support, they lack the resources to adequately care for patients with acute mental health problems. 

Oncology Nurses Need Better Resources to Help Patients With Mental Health Problems

The rise in popularity of oral anticancer therapy has introduced problems of access and insurance coverage that oncology nurses previously did not have to deal with, according to expert presenters at the 2022 Oncology Nurse Society Bridge. However, many resources are available to nurses, and a key first step is to ask patients how they are faring financially.

“Even though you might not have all the answers right then and there when you’re talking to the patient, don’t shy away from a discussion you can have [about] their finances,” said Mary Anderson, BSN, RN, OCN, an oral oncolytic nurse navigator at Norton Cancer Institute.

Anderson presented alongside Christina Bach, MBE, MSW, LCSW, OSW-C, FAOSW; and Nora Hansen, CPhT, in a presentation titled “Managing Oral Cancer Therapies: What Are Your Tools?” The team highlighted the scope of the problem of financial-related toxicities, best practices for financial toxicity assessment, and resources to help nurses connect their patients to the care they need. 

When assessing patients for the first time, oncology nurses are encouraged to ask the following questions:

Are you able to get to the pharmacy to pick up your medications?

Are you able to get medications delivered to your home?

Other key questions include asking the patient to describe their insurance coverage plan, to highlight any other expenses they are worried may arise during their cancer care (ie, transportation, parking, child care, loss of income), if they are concerned about job loss, if they have had difficulty getting a prescription in the past, if their out-of-pocket expenses are what they expected, and if they are worried about financial toxicity affecting their quality of life.

“I start with making sure that folks understand that I’m not trying to be intrusive or overstep my bounds in asking really personal and private questions that we just don’t [normally talk about],” Anderson said. “I always say; ‘I know this is personal. I know a lot of people don’t want to talk about it. But knowing this information, is going to help me help you. And this is all between the two of us.’”

“We are validating that this is uncomfortable,” she added. “We’re also validating that it’s hard to ask for help—and also giving them permission at any time to say, ‘You know what, I don't want to answer that question.’”

Unfortunately, medical debt represents the number 1 cause of personal bankruptcy in the United States.

 Since 2010, cancer care spending has increased by approximately $175 billion. It is expected to continue to grow and reach $246 billion by 2030.

 Moreover, the average out of pocket expenses per patient increased from $1800 to $2900 per month since 2010.

“We have a major crisis when it comes to medical debt in this country,” Bach, an oncology social worker with OncoLink added. “A lot of that has to do with the way cancer [treatment] has changed a great deal in terms of oral oncolytics.”

“What is available to patients and how they access them is quite different than it was when I started as an oncology social worker in 2000,” she added. “[In 2000,] almost [every patient] was admitted for all their treatment for multiple days, it was covered by their major medical [insurance], and there were very few oral medications available.”

Presenters noted that solutions to help patients are also unfortunately limited: assistance from co-pay foundations are limited to certain diseases, procedures, and availability. In private practice oncology settings, which are often the only geographical option available to patients, charity care is not usually offered.

In addition, the Unites States has historically not regulated drug prices or had a system for drug price negation and a diagnosis of cancer does not equate to automatic approval for disability. Paid family leave varies across states but is generally limited—meaning that job loss (and consequent health insurance loss) is a reality faced by many Americans with cancer.

“Our solutions are limited,” Bach said. “I often feel like my hands are tied. It is very frustrating and also very morally distressing.”

Because of these increasing costs, it is not uncommon for patients to delay or forego treatments because of their financial burden. However, it is documented in the literature that financial toxicity is often linked to poorer outcomes.

Financial hardships often also extend into survivorship; 54% of survivors are between the ages of 18 and 64 years, 42% of whom reported experiencing financial hardships following diagnosis. Debt is most prevalent in populations under the age of 64 years, as well as in Black communities.

Previously, the problem in the United States was that most patients were uninsured. However, in 2022, the problem has become that patients are underinsured.

The speakers noted that it can be difficult for patients and nurses alike to understand the difference between Medicare A, B, and D. They outlined the general difference between plans as part of their presentation:

Medicare Part A is hospital insurance and is often premium-free;

Medicare part B is outpatient medical, and patients must opt in and pay a monthly premium;

Medicare part D is voluntary prescription drug coverage, patient pays premium and co-insurance (deductible and up to 25%);

Medicare part C is known as the “advantage plan;” it is offered by private insurance plans that contract with Medicare, it covers the same services as Medicare A, B, and some drug coverages, and patients choose their provider and plan, such as HMO;

Patients may also have Medicare supplements, which is optional additional coverage for co-insurance and deductibles. 

Insured patients are responsible for paying a premium, a deductible, the copay, the co-insurance, but may be unaware of additional items that are not covered. These may include cancer related needs or services, such as wigs, supplements, lymphedema garments, some durable medical equipment, private duty assistance, and indirect costs, including transportation, parking, child/elder care, loss of income/wages, and caregiving. This represents a heavy financial burden for many, speakers agreed.

The recently approved Inflation Reduction Act is expected to help ease some of the financial toxicity that patients face by capping the amount that a patient is expected to pay per year and lowering premium prices.

 Moreover, the act introduced the concept of price drug negations the consequences of which could be monumental for patients, according to Bach. However, despite the act’s approval, many of the benefits are many years away.

In the meantime, nurses should know that although they play a crucial role in helping connect patients to the resources they need, they are part of a team of players who can help patients navigate the world of insurance. Other professionals who can be leveraged include private brokers, social workers, financial navigators/advocates, state health insurance assistance programs (SHIAPS) counselors, ACA navigation assistance, private brokers. Because there are so many people invested in helping connect patients to help, nurses should not feel alone or intimidated to bring up the conversation: they are not expected to solve the problem, but they can help improve the situation.

The experts also recommend that oncology nurses leverage online resources, such as, 

ONS Guidelines™ to Support Patient Adherence to Oral Anticancer Medications

Mary Anderson, BSN, RN, OCN; and Christina Bach, MBE, MSW, LCSW, OSW-C, FAOSW, discuss approaches to help patients navigate financial toxicity and insurance coverage in the age of oral anticancer drugs. 

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