Receiving a cancer diagnosis is likely to cause some level of fear or anxiety in children and adolescents old enough to understand the situation.

“One of the things that can cause fear is just being in a new place with a lot of new people and faces,” explained Amy R. Newman, PhD, RN, CPNP-PC, assistant professor at Marquette University College of Nursing in Milwaukee, Wisconsin. “A lot of children’s hospitals have come a long way in making the physical environment more child friendly, but it can still be overwhelming.”

Pediatric patients with cancer are dealing with all these new things in addition to the vulnerability that comes with not feeling well.

Fear and anxiety can present differently depending on the age of the child, Newman noted. Nurses also must consider the patient’s developmental stage and whether there is developmental delay or other sensory processing disorders.

Younger school-age children may cry or refuse to comply with different things asked of them, and they may be clingier to their parents, Newman said. Older children may refuse to engage or interact with members of the health care team.

Anxiety may also present as difficulty thinking or concentrating, irritability, increased heart rate or fast breathing, increased need for reassurance, headaches, loss of appetite, or upset stomach, constipation, or diarrhea.

Fear and anxiety may increase as pediatric patients are presented with more new information, people, and environments, Newman explained, noting that having too much information given at once may also increase fear and anxiety. In addition, loud, agitated, or anxious health care staff could increase those feelings in a patient.

Oncology nurses can play an important role in anticipating these stressors and reducing fear and anxiety for their patients.

Newman said that one of the most important things a nurse can do is maintain a calm and friendly demeanor, regardless of how the patient is acting.

“Maintain a calm presence and don’t allow yourself to get rattled when things are not going as smoothly as you would like,” Newman advised. “I encourage nurses to really engage their patients. Ask them questions about what grade they are in or what they like to do.”

Aurélie Weinstein, PhD, MA, APC, a development psychologist and child and family therapist at Atlanta Center for Wellness and an assistant professor in the Department of Psychological Science at Kennesaw State University in Georgia, echoed this advice, adding that nurses can also directly ask patients what their fears and concerns are.

“When we deny our emotions, they often become bigger,” Weinstein said. “The more we feel like someone understands, the more that fear starts to decrease.”

Weinstein and colleagues conducted a study exploring which psychological interventions nurses felt were most effective for addressing fear during medical treatment. They found 3 strategies to be effective

: educating children by explaining the procedure; providing emotional support to children by listening, answering their worries, or holding their hands; and distracting children through passive and active forms.

For young children, Newman said that nurses can help explain certain procedures involving medical equipment like a stethoscope or blood pressure cuff by showing it to patients and inviting them to touch it or try it out.

“These little gestures can help prepare them as best you can,” Newman said.

Distraction can also be an effective approach. One study looked at the use of patient-selected distractors on pain, fear, and distress during port access or venipuncture. Patients could select from several items such as bubbles, virtual-reality glasses, or handheld video games. Patients who participated in the distraction had significantly less fear and distress as reported by the nurse and a trend toward less fear as rated by the patient.

In addition, Verna L. Hendricks-Ferguson, PhD, RN, FPCN, FAAN, the Irene Riddle Endowed Chair at Trudy Busch Valentine School of Nursing at Saint Louis University in Missouri, and colleagues have used art as an outlet for pediatric patients to express fear and anxiety or as a method of distraction. In one case study, she employed an art-making project that converted a patient’s meaningful family picture into a paint-by-number canvas to provide a fun activity for the child to focus on.

“It is important to provide patients with tools to express themselves, especially patients that are school-aged or older,” Hendricks-Ferguson said. “For younger children, play therapy or music therapy may be helpful tools.”

Newman also stressed the importance of engaging the child or adolescent directly.

“Oftentimes we get caught up talking to the parents, and the children are still in the room, hearing things,” Newman said. “We should be intentional about talking to the child and explaining what is happening and what is going to happen. This allows them to be prepared and not surprised.”

Coping with fear and anxiety might be particularly difficult when pediatric patients are faced with end-of-life discussions.

Nurses play an important role in these discussions, Hendricks-Ferguson said, but may have different comfort levels with addressing these sensitive topics.

Hendricks-Ferguson and colleagues conducted a qualitative-descriptive study exploring the palliative care/end-of-life communication perspectives of a small group of novice pediatric oncology nurses. The study established several themes from its group discussions, including that the nurses felt they lacked effective communication skills and experience to openly discuss some end-of-life issues, how initiating these conversations was difficult, and the importance of being mentored in these situations.

“The more experienced nurse oftentimes feels more comfortable exploring where a child is at in these situations, whereas a nurse that has less than 1 year of experience is more likely to rely on mentors,” Hendricks-Ferguson said.

She noted that studies are lacking on effective tools for decreasing fear and anxiety in pediatric patients with cancer facing end of life. One recent randomized clinical trial study examined the effect of a legacy making intervention—an action aimed at being remembered—on quality of life among children with advanced cancer. The intervention directed children to create digital storyboards about themselves and upload photos, video, and music. Although the results were not statistically significant, children who participated in the legacy-making intervention experienced small effects in child procedural anxiety and perceived physical appearance compared with a wait-list control group.

“This is a pioneering area of research, and we need to do more work like this,” Hendricks-Ferguson said. 

She recently published results of a pilot study examining the effects of COMPLETE, a communication plan designed to improve end-of-life outcomes via earlier hospice enrollment and reduced pain and suffering among children with cancer at the end of life.

 COMPLETE involves a series of conversations including a pediatric oncologist and registered nurse dyad working collaboratively to guide discussions about goals of care, using conversation guides and visual aids that begin at diagnosis.

Hendricks-Ferguson noted that it is difficult to conduct studies with pediatric patients during end-of-life care because parents are often very protective of their children, even adolescents. For that reason, a lot of strategies employed in the day-to-day practice of medicine are those that nurses have heard about anecdotally or established themselves after years of experience.

Meditation Techniques to Reduce Fear, Anxiety

Guided imagery, deep-breathing exercises, and mindfulness activities are other strategies to consider.

For example, Newman has seen procedural anxiety in pediatric patients, like those diagnosed with acute lymphoblastic leukemia, who require a lot of procedures, specifically lumbar punctures.

“Even just anticipating those procedures, kids can get anxious,” Newman said, noting that she has observed nurses “use guided imagery to calm patients down and get through procedures.”

Hendricks-Ferguson has witnessed nurses effectively use deep-breathing techniques or mindfulness activities to help patients get through painful procedures. “These are 2 techniques that most nurses, even if they did not have much experience, will probably get mentored on by senior nurses,” she said.

Weinstein also mentioned witnessing
effective use of deep-breathing exercises.

“These can include things like blowing bubbles or blowing out a candle,” Weinstein said. “When our body is experiencing fear, it tenses. Deep breathing helps to relax the body. If our body is relaxed, our mind will also relax.”

Weinstein emphasized that although nurses play a vital role in easing the fear and anxiety of pediatric patients, they also function as part of a greater team. Integrating child life specialists and psychologists can be helpful, and including the child’s parents or guardians is equally important.

“Nurses are not facing this alone,”
Weinstein said. 

1. Anxiety in children and teens with cancer. St. Jude Children’s Research Hospital. Updated January 2019. Accessed September 2, 2021. 

https://together.stjude.org/en-us/care-support/psychology/anxiety.html

2. Weinstein AG, Henrich CC. Psychological interventions helping pediatric oncology patients cope with medical procedures: a nurse-centered approach.

2013;17(6):726-731. doi:10.1016/j.ejon.2013.04.003

3. Windich-Biermeier A, Sjoberg I, Dale JC, Eshelman D, Guzzetta CE. Effects of distraction on pain, fear, and distress during venous port access and venipuncture in children and adolescents with cancer. 

 2007;24(1):8-19. doi:10.1177/1043454206296018

4. Bultas MW, Saini S, Marty J, Hendricks-Ferguson VL. Art making from the HEART: a pediatric case study about coping and distraction during oncology treatments. 

 2017;19(6):565-570. doi:10.1097/NJH.0000000000000389

5. Hendricks-Ferguson VL, Sawin KJ, Montgomery K, et al. Novice nurses’ experiences with palliative and end-of-life communication. 

2015;32(4):240-252. doi:10.1177/1043454214555196

6. Akard TF, Dietrich MS, Friedman DL, et al. Randomized clinical trial of a legacy intervention for quality of life in children with advanced cancer. 

 2021;24(5):680-688. doi:10.1089/jpm.2020.0139

7. Hendricks-Ferguson V, Newman A, Brock KE, et al. COMPLETE (Communication Plan Early Through End of Life): development of a research program to diminish suffering for children at end of life. 

Articles

Anticipating these stressors and implementing specific strategies can help ease the distress and vulnerability felt by children and adolescents.  

Nurses Can Minimize Fear, Anxiety in Pediatric Patients With Cancer

The FDA approved injectable technetium Tc 99m tilmanocept (Lymphoseek), a radiopharmaceutical agent that targets lymphatic mapping and guiding for sentinel lymph node biopsies (SLNB), for use in pediatric patients with melanoma, rhabdomyosarcoma, and other solid tumors, according to Cardinal Health, the manufacturer of the product.

"This new indication opens the door for physicians, oncologists and nuclear medicine specialists to more accurately stage the spread of disease using lymphatic mapping in pediatric cancer patients," said Tiffany Olson, President of Nuclear & Precision Health Solutions at Cardinal Health, in 

. "Ultimately, this may help more families to be able to get answers to some of their most concerning questions."

A clinical trial showed that the diagnostic agent technetium Tc 99m tilmanocept is safe and effective in patients 1 month and older. Less than 1% of patients experienced injection site irritation and/or pain in the trials, and there were no serious adverse events reported.

Technetium Tc 99m tilmanocept can be used with or without scintigraphic imaging to achieve lymphatic mapping with a handheld gamma counter that locates lymph nodes that re draining to a primary tumor site in adult and pediatric patients with solid tumors or the guiding of sentinel lymph node biopsies with a handheld gamma counter in patients with clinically node-negative squamous cell carcinoma of the oral cavity, breast cancer, or melanoma.

Cardinal Health. Cardinal Health™ Nuclear & Precision Health Solutions Receives U.S. Food and Drug Administration Approval for New LYMPHOSEEK® Pediatric Indication. Published June 10, 2021. 

https://ir.cardinalhealth.com/news/press-release-details/2021/Cardinal-Health-Nuclear--Precision-Health-Solutions-Receives-U.S.-Food-and-Drug-Administration-Approval-for-New-LYMPHOSEEK-Pediatric-Indication/default.aspx

The FDA approved injectable technetium Tc 99m tilmanocept (Lymphoseek), a radiopharmaceutical agent that targets lymphatic mapping and guiding for sentinel lymph node biopsies (SLNB), for use in pediatric patients with melanoma, rhabdomyosarcoma, and other solid tumors.

FDA Approves Radiopharmaceutical Diagnostic Agent for Pediatric Patients

The integration of the anti-CD30 antibody-drug conjugate (ADC) brentuximab vedotin (Adcetris) into the frontline treatment of pediatric patients with high-risk Hodgkin lymphoma resulted in favorable clinical outcomes with promising tolerability and a reduction in radiation exposure, according to data from a phase 2 HLHR130 trial (NCT01920932) published in the 

The ADC replaced vincristine in the OEPA/COPDac regimen (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) per the GPOH-HD2002 treatment group 3; 2 cycles of AEPA and 4 cycles of CAPDac were given. Residual node radiation (RNRT) was given at the end of all chemotherapy to nodal sites that did not achieve complete response (CR) at the early response assessment (ERA) following 2 cycles of therapy.

Compared with 17% of patients in the historical control who experienced a CR at ERA, 35.1% (n = 27) of 77 patients enrolled to the study had achieved a CR following 2 cycles pf AEPA (95% CI, 24.5-46.8; 

 = .004) and were spared exposure to radiation. Of 50 patients who did receive radiation, 74% (n = 37) experienced a metabolic CR at all sites in the absence of an anatomic CR to at least 1 site; 36% (n = 13) did not achieve either anatomic or metabolic CR at all sites.

At a median follow-up of 3.4 years, the 3-year event-free survival (EFS) rate among patients, while the median overall survival (OS) was 97.4%, while the 3-year overall survival (OS) rate was 98.7%; these rates were 80.8% (

 = .311), respectively, in the historical control. No events were observed in the nonirradiated patients (n = 25/77).

“We have already reduced the use of radiation for [patients with] low-risk Hodgkin lymphoma,” Matthew Krasin, MD, co-senior author, and faculty member in the St. Jude Department of Radiation Oncology, stated in a press release.2 “In this study, we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity-modulated radiation.”

Over the past 2 decades, research efforts have focused on improving upon chemotherapy combinations, while reducing radiation for patients who are achieving inadequate responses to chemotherapy to minimize late toxicities. For the study, investigators sought to maintain favorable outcomes without intensifying chemotherapy and its related adverse effects (AEs) by substituting brentuximab vedotin for vincristine in OEPA/COPDac; based on response to the regimen, some then went on to receive RNRT.

To be eligible for enrollment, patients needed to be 18 years of age or younger with treatment-naïve Ann Arbor stage IIB, IIIB, or IV and classical CD30-positive Hodgkin lymphoma. Those who were CD30 negative or had received prior therapy for Hodgkin lymphoma were excluded.3

Patients received 2 cycles of AEPA, followed by 4 cycles of CAPDac. After the 2 cycles of AEPA, patients underwent an ERA with PET/CT, contrast-enhanced CT scan or MRI. In patients who did not achieve a CR, RNRT was delivered to the individual lymph nodes at ERA vs initial staging.

Lymph nodes that achieved a CR at ERA were not irradiated, while those who did not were targeted on radiation simulation studies following chemotherapy completion; this led to a further reduction in the targeted volume. Two to 4 weeks after chemotherapy was completed, radiation was given at 25.5 Gy in 17 fractions of 1.5 Gy.

The median age of study participants was 16 years (range, 6-19), and the majority were female (51%), White (65%) and presented with stage IVB disease (59%) and nodular sclerosing histology (77%). Patient demographics did not significantly differ between this study and the historical control in terms of age (

 = .194). More patients with stage IIB were enrolled to the historical control group vs the HLHR13 group, at 43% vs 37% (

An exploratory analysis was done to examine normal tissue exposure in patients who received residual nodal radiation with proton beam (n = 15; 31%) vs those treated with photon-based techniques. Patients who received proton beam received a significantly lower integral radiation dose vs photons (

 = .002). Moreover, the reduction in tissue exposure by proton beam was also found for the volume of tissue receiving 5 Gy (

 = .04). Investigators found difference by modality when higher radiation doses were assessed.

The most common adverse effects (AEs) were hematologic events that mostly occurred during the first 2 cycles of therapy. Two patients (2.6%) received platelet transfusions, while 13 (17%) received packed red blood cell transfusions, and 19 (25%) received filgrastim during the first cycle (n = 8), second cycle (n = 7), or both cycles (n = 3). Additionally, 8 patients (20%) were hospitalized 12 times with febrile neutropenia.

“Being able to offer [patients with] Hodgkin lymphoma a targeted therapy in the frontline setting is an exciting development,” Melissa Hudson, MD, co-senior author, and director of the St. Jude Cancer Survivorship Division, added in the release. “We are constantly learning from research and applying new findings to the next iteration of clinical trials.”

Metzger M, Link M, Billett A, et al. Excellent outcome for pediatric patients with high-risk Hodgkin Lymphoma treated with brentuximab vedotin and risk-adapted residual node radiation. 

. Published online April 7, 2021. doi:10.1200/JCO.20.03286

Excellent outcomes reported for first targeted frontline therapy for high-risk pediatric Hodgkin lymphoma. News release. St. Jude Children's Research Hospital. April 8, 2021. Accessed April 8, 2021. 

Adcetris (brentuximab vedotin), combination chemotherapy, and radiation therapy in treating younger patients with stage IIB, IIIB and IV Hodgkin Lymphoma. ClinicalTrials.gov. Updated December 7, 2020. Accessed April 8, 2021. 

https://www.clinicaltrials.gov/ct2/show/NCT01920932

This article was originally published on OncLive as, "

Incorporation of Brentuximab Vedotin Into Frontline Pediatric High-Risk Hodgkin Lymphoma Treatment Yields Favorable Outcomes

Adding the antibody-drug conjugate to the frontline treatment of patients with pediatric high-risk Hodgkin lymphoma resulted in favorable clinical outcomes. 

Adding Frontline Brentuximab Vedotin in Pediatric High-Risk Hodgkin Lymphoma Treatment Improves Outcomes

The United States Preventive Services Task Force (USPSTF) now recommends colorectal cancer (CRC) screening to begin at 45 years of age, rather than the previous recommended age of 50. These new recommendations, which were published in 

 now align with those of the American Cancer Society.

These recommendations finalize draft guidelines that were issued in October 2020, and, in doing so, will mandate insurance coverage for CRC screening (colonoscopies and stool tests) in adults starting at age 45.

Nurses should encourage all eligible patients to get screened, especially those who are at increased risk.

“We know that black adults get colorectal cancer more often and are more likely to die from colorectal cancer than people of other races and ethnicities,” said John B. Wong, MD, interim chief scientific officer at Tufts Medical Center, primary care physician, and member of the USPSTF said.

“Clinicians, nurses, physicians, and others should reach out to their black patients to help make sure they get screened… What’s really important [to take home] is that colorectal cancer screening helps people ages 45 to 75 liver longer and healthier lives.”

The guidelines come after a concerning increase in CRC incidence in people under the age of 50. While this has been a trend since the mid 1990s, researchers are still unsure why younger adults are seeing higher CRC rates, especially since CRC diagnoses have been going down in the over-50 population due to modifying risk behaviors.

“Our recommendation calls out for additional research to try to understand better what the causes are, and to see if we can find [out] because once you find and determine the cause, then maybe we can do something to prevent that from happening going forward,” Wong said.

Most young-onset CRC diagnoses and deaths occur in people between the age of 45 and 49–so there is hope that the new recommendations will catch cancers earlier and decrease the number of CRC fatalities.

However, the rate of young-onset CRC is actually growing most in individuals who are even younger. Colon cancer incidence is increasing by about 2% every year in the 20- to 29-year-old cohort, compared to 1.3% in the 40- to 49-year-old cohort. Similarly, rectal cancer is also increasing at a steeper rate in the 20- to 29-year-old group than the 40- to 49-year-old group, at 3.2% yearly and 2.3% yearly, respectively.

“We are now seeing patients even younger than 45–in their 20s and 30s–who are being diagnosed with this cancer and often at very late stages,” said Kimmie Ng, MD, MPH, guideline author, in a statement. “Clearly the USPSTF recommendation to start screening at age 45 will not be enough to catch those young people who are being diagnosed.”

The USPSTF will continue to analyze data and update recommendations, if needed.

“As part of our normal process at the USPSTF, we want our recommendations to be as up-to-date as possible. So roughly every 5 years, we re-examine the evidence, look for new research, look to see if there are any changes in the evidence that might alter the recommendations we make,” Wong said.

US Preventive Services Task Force. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. May 18, 2021.

The United States Preventative Services Task Force now recommends colorectal cancer screening to start at 45 years old. 

USPSTF Lowers CRC Screening Age, Forcing Insurance Coverage

Provider communication is extremely important, especially when dealing with a pediatric cancer diagnosis. In this episode of “The Vitals,” Bryan A. Sisk, MD, MSCI, assistant professor of pediatric hematology and oncology at the Washington University School of Medicine discusses his recent research on communication barriers between healthcare providers and children with cancer and their families.

While some of these issues can be found in the broader cancer space, others – like how much information to give a 6-year-old versus a 16-year-old – align more with the intricacies of pediatrics. Sisk talks about this, and the improvements he hopes to see in this space in years to come.

Podcasts

A Chat on Communication Barriers in Childhood Cancer

The FDA has granted a rare pediatric disease (RPD) designation to the p-STAT3 inhibitor WP1066 for the treatment of patients with ependymoma, a rare type of tumor that can develop in the brain or the spinal cord.

“The FDA’s recognition of the high prevalence and unmet needs in the treatment landscape for ependymoma, especially in pediatric patients is a significant milestone as we continue to advance and expand the WP1066 development program,” Walter Klemp, chairman and chief executive officer of Moleculin, stated in a press release. “We currently have orphan drug designation for WP1066 for the treatment of brain tumors, as well as RPD designation for 3 other pediatric indications, and believe that ependymoma represents another important rare indication.”

In January 2021, WP1066, which is an agent that appears to directly elicit tumor cell death and rouse the immune system to eliminate tumors, was granted 3 

 designations in diffuse intrinsic pontine glioma, medulloblastoma, and atypical teratoid rhabdoid tumor.

Waldemar Priebe, PhD, professor of medicinal chemistry in the Department of Experimental Therapeutics of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, made the discovery that led to the development of the agent.

Priebe examined naturally-occurring compounds in propolis, which offered the opportunity to evaluate the ability of caffeic acid benzyl ester (CABE) to inhibit p-STAT3, which is an important target for cancer therapeutics.

By looking at CABE, Priebe was able to identify novel compounds that could more strongly inhibit p-STAT3. WP1066 moved to the head of the pack after it proved to be able to successfully inhibit p-STAT3 and other important oncogenic transcription factors like c-Myc, HIF-1α and HIF-2α.

WP1066 has been shown to have antitumor efficacy spanning a wide array of tumor cell lines; the agent has also resulted in a survival benefit in several animal models. Moreover, WP1066 can enhance antitumor effects of the immune system and its response to tumor activity. Investigators postulate that the agent may have a dual-action mechanism that permits it to treat an array of resistant tumors and to be more amenable to be paired in novel combinations for unresponsive tumors.

Additionally, the addition of WP1066 to checkpoint inhibitors could lead to additive or synergistic effects that could improve outcomes in patients who are receiving the immunotherapy, according to Moleculin Biotech, the drug developer.

In ATL-T, SLVL, and human brain malignant cell lines, WP1066 was found to significantly abrogate PD-L1/2 expression in a recent study. Incubation of the drug obstructed the growth of lymphoma cells and induced cell apoptosis.

 Results from another study suggested that the agent could have efficacy when paired with a CTLA-4 inhibitor, as CTLA-4–induced immune suppression mostly occurs via the STAT3 pathway.

“We continue to be encouraged by the data WP1066 has demonstrated to date and believe it has potential to be an effective therapy for pediatric patients with ependymoma,” Klemp added in the release. Ependymoma begins in the ependymal cells within the brain and spinal cord that line the passageways where cerebrospinal fluid flows. Although this disease can present at any age, it is mostly reported in young children.

The RPD Priority Review Voucher Program was developed as a way to incentivize the development of novel treatments for pediatric patients with rare diseases. Under the FDA’s rare pediatric disease designation program, the regulatory agency can grant a priority review voucher to a sponsor who receives an approval for a product for a rare pediatric disease, which is defined as a serious or life-threatening disease that primarily impacts those up to 18 years of age.

If WP1066 is approved for this indication, the pharmaceutical company would be able to receive a voucher that could be redeemed to receive priority review for a subsequent marketing application for a different product candidate or that could be either sold or transferred.

Moleculin awarded new rare pediatric disease designation from US FDA for WP1066 for the treatment of ependymoma. News release. Moleculin Biotech, Inc. April 14, 2021. Accessed April 14, 2021. 

Moleculin announces FDA approves 3 rare pediatric disease designations for WP1066. News release. Moleculin Biotech, Inc. December 1, 2020. Accessed April 14, 2021. 

WP1066. Moleculin Biotech, Inc website. Accessed April 14, 2021. 

Technology. Moleculin Biotech, Inc website. Accessed April 14, 2021. 

Ma C, Horlad H, Pan C, et al. Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines. 

. 2017;57(1):21-25. doi:10.3960/jslrt.17006

Herrmann A, Lahtz C, Nagao T, et al. CTLA4 promotes Tyk2-STAT3–dependent B-cell oncogenicity. 

. 2017;77(18). doi:10.1158/0008-5472.CAN-16-0342

FDA Grants Rare Pediatric Disease Designation to WP1066 for Ependymoma

The FDA has granted a rare pediatric disease designation to the p-STAT3 inhibitor WP1066 for the treatment of patients with ependymoma, a rare type of tumor that can develop in the brain or the spinal cord.

Rare Pediatric Disease Designation Granted to WP1066 for Ependymoma

Adavosertib plus irinotecan showed early activity in a cohort of pediatric patients with neuroblastoma, thus meeting the protocol-defined efficacy end point of the 1/2 ADVL1312 trial (NCT02095132), which was presented virtually during the AACR Annual Meeting 2021.

Moreover, adavosertib plus irinotecan also showed the potential to benefit patients with 

-mutant tumors, with further validation required for this effect.

“In order to look for an early signal of activity and to obtain more information regarding toxicity of the recommended phase 2 dose, the ADVL1312 trial proceeded with a phase 2 expansion in 3 pediatric disease-specific cohorts,” presenting author Kristina A. Cole, MD, PhD, of Children’s Hospital of Philadelphia and Perelman School of Medicine of the University of Pennsylvania, said in the presentation of the data.

The 3 pediatric cohorts analyzed in the expansion phase of this trial included neuroblastoma (n = 20), medulloblastoma with central nervous system (CNS) embryonal tumors (n = 10), and rhabdomyosarcoma (n = 10).

Overall, 3 objective responses were recorded from 16 eligible patients in the neuroblastoma cohort, which met the protocol-defined efficacy end point. Meanwhile, there was 1 recorded objective response in the group with medulloblastoma and CNS embryonal tumors and no responses with rhabdomyosarcoma, respectively.

The investigative team also sought to determine factors correlated with clinical response, focusing on the 

 chromatin remodeler gene. Twelve of the archival ADVL1312 tumors were evaluated.

Ultrabright telomeric foci (UBTF) were present in tumors from 2 of the 3 patients who experienced an objective response. More, ATRX deficiency was present in 4 of the 9 patients with clinical response or stable disease.

Common grade 3 or higher adverse events included neutropenia (5 events in the neuroblastoma cohort; 4 events in medulloblastoma; and 3 events in rhabdomyosarcoma), lymphopenia (4 events; 2 events; and 1 event, respectively), and leukopenia (2 events vs 2 events vs 0 events).

More, the toxicity profile of ADVL1312 featured no dose-limiting toxicities at cycle 1 or later at the maximum-tolerated dose. Regardless of this finding, and although the combination was well tolerated, the investigative team notes that oral irinotecan is not palatable.

The investigative team utilized the phase 2 data from irinotecan to inform the efficacy end point for the combination therapy analyzed in the expansion portion of ADVL1312. In order to define the therapy as effective in the neuroblastoma and rhabdomyosarcoma cohorts, 3 objective responses out of 20 eligible patients were required. More, 6 response out of 19 eligible patients were required for efficacy in the medulloblastoma with CNS embryonal tumors cohort.

“Several of the limitations of this study relate to the fact that it was a phase 2 expansion,” explained Cole. “For example, patients were eligible for response regardless of if they completed a cycle of therapy or had their disease reevaluated. One-third of patients discontinued therapy with stable disease or better.”

Median age for patients in the neuroblastoma cohort was 9 years (range, 6-19), with a majority of patients being male (65%) and White (60%). In the medulloblastoma cohort, the median age was 13.5 years (range, 6-20), with a majority of patients female (60%) and White (70%). Lastly, the rhabdomyosarcoma cohort reported a median age of 11 years (range, 4-16) with 80% of patients reporting as male and 90% of patients reporting as White.

Looking ahead, because of the satisfaction with the preliminary findings in this expansion trial, Cole noted that an adavosertib pediatric development plan is being discussed.

Cole KA, et al. Pediatric phase 2 trial of the WEE1 inhibitor adavosertib (AZD1775) and irinotecan; A Children’s Oncology Group Study (ADVL1312). Presented at: AACR Annual Meeting 2021; April 10-15, 2021; Virtual. Abstract CT029.

Adavosertib/Irinotecan Shows Early Activity in Pediatric Neuroblastoma

Overall, 3 objective responses were recorded from 16 eligible patients in the neuroblastoma cohort, which met the protocol-defined efficacy end point.

Drug Combo Shows Early Activity in Pediatric Neuroblastoma Treatment

The National Comprehensive Cancer Network (NCCN) has issued guidelines for the management of children with a rare type of kidney cancer referred to as Wilms Tumor, or nephroblastoma.

The document highlights evidence-based recommendations for how to maximize benefits while minimizing toxicities in this patient population. Notably, the guidance comprises critical information for providers who treat pediatric tumors, hematologic malignancies, and other blood disorders that may be encountered relatively infrequently. The guidelines also contain diagnostic information for primary care pediatricians to ensure that the cancer is identified early and managed in a way that results in fewer toxicities for the patients.

“Keeping up with all of the current literature for the broad array of children’s oncologic and hematologic malignancies can be daunting. The NCCN Guidelines for Wilms Tumor provide compiled, annotated, and vetted recommendations for diagnosis, treatment, and follow up—in keeping with NCCN’s goals for streamlining and improving care so that patients can live better lives,” Elizabeth Mullen, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, who is also a member of the NCCN Guidelines Panel for Wilms Tumor, stated in a press release.

Wilms tumor is the most common cancer of the kidneys in children and it is known to affect those between the ages of 3 years and 4 years.3 In the majority of patients, the tumor will present in just 1 kidney, although it has been identified in both kidneys at the same time.

One factor that may increase the risk of Wilms tumor is African-American race; these children tend to be at a slightly higher risk for this cancer compared with other races. Additionally, Asian-American children may be at lower risk than children of other races. Another risk factor is having a familial history of the cancer.

Wilms tumor is also known to occur more commonly in children with aniridia or hemihypertrophy at birth; it has also been shown to occur as part of other rare syndromes like WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedemann syndrome.

“The treatment of Wilms tumor is guided by the results of a series of sequential clinical trials that started back in the 1960s,” Frank M. Balis, MD, professor of pediatrics, Louis and Amelia Canuso Family Endowed Chair for Clinical Research in Oncology, of the Children’s Hospital of Philadelphia/Abramson Cancer Center at the University of Pennsylvania, and chair of the NCCN Guidelines Panel for Wilms Tumor, added in the release. “Treatment approaches have been refined through these clinical trials, making treatment selection more and more complex and nuanced.”

Balis added that treatment decisions should be based on clinical and biological risk factors, the presence of unilateral versus bilateral disease, and patient response to treatment.

NCCN clinical practice guidelines in oncology (NCCN guidelines): Wilms tumor. National Comprehensive Cancer Network. Accessed February 17, 2021.

New NCCN guidelines analyze evidence for cancer type found almost exclusively in children. News release. National Comprehensive Cancer Network. February 17, 2021. Accessed February 17, 2021. 

Wilms’ tumor. Mayo Clinic website. Updated April 24, 2020. Accessed February 17, 2021. 

NCCN Issues First-Ever Guidance for Pediatric Solid Tumor

The National Comprehensive Cancer Network has issued guidelines for the management of children with a rare type of kidney cancer referred to as Wilms Tumor, or nephroblastoma.

NCCN Publishes Guidelines for Pediatric Solid Tumor

Parents of pediatric patients with cancer were found to be more likely to believe misinformation about the coronavirus disease 2019 (COVID-19) than parents of children without a cancer history, according to recent research published in 

This puts oncology nurses in the prime position to talk with caregivers of pediatric patients, and show them where to find reliable information on COVID-19.

The researchers surveyed 735 parents of children between the ages of 2 and 17 – 315 parents had children who were currently in cancer treatment, while 420 had children without a cancer history. In the survey, participants were asked to rate COVID-19 information based on whether they thought it was “definitely untrue,” “likely untrue,” “not sure if untrue/true,” “likely true,” and “definitely true.” The survey included 17 common and untrue COVID-19 myths from the World Health Organization’s website.

“For the correct pieces of information, there was no difference between the parents of kids with cancer and the parent control group,” said Jeanine P.D. Guidry, PhD, assistant professor at the Virginia Commonwealth University Robertson School of Media and Culture and director of the Media+Health Lab said in an interview with 

“For the pieces of misinformation, parents of pediatric cancer patients were more likely to say, ‘this is correct information,” Guidry explained.

Eating garlic can help prevent infection with the COVID-19 virus

Gargling with or swallowing bleach will help get rid of COVID-19

Drinking a sip of water every 15 minutes can prevent COVID-19

While eating garlic or drinking water every 15 minutes are not unhealthy actions, they can become harmful if a person believes that they are protected from COVID-19 and, as a result, does not follow CDC guidelines. Drinking bleach, however, is outright dangerous, Guidry said.

Guidry explained that parents of pediatric patients with cancer already are experiencing the stress of a diagnosis, and as a result may be more included to believe in quick fixes to mitigate the anxiety of COVID-19.

Study findings supported this: Those who reported that they were more stressed were also more likely to believe misinformation about COVID-19.

“For people who are already in a very stressful situation in their lives, [the COVID-19 pandemic] just adds to it,” she said. “And the desire to see things resolved and to not have this additional level of uncertainty may make people more vulnerable to believing misinformation, because it gives a sense of reassurance.”

The development of COVID-19 vaccines is another area that is abound with myths and misinformation around it.

“I think one of the areas with misinformation that we have to be really careful of is, of course, misinformation related to the vaccine. We have a way out of this pandemic,” Guidry said, explaining that the high efficacy rates seen with the FDA-approved vaccines are very exciting.

“This is a better outcome vaccine-wise than we thought we would get. But that doesn’t mean anything if the vaccinations don’t get in people’s arms.”

Guidry said that some vaccine misconceptions are easier to dispel. For example, if a person is worried that it was not studied enough or corners were cut in the quick development process, they can be given scientific literature to read. But other theories – like powerful people putting microchips in the vaccine to track us – might be a bit harder to approach.

“Misinformation really just plays into our fears,” Guidry said.

Oncology Nurses Can Promote Reliable Info

Since oncology nurses are typically on the frontlines of communication with patients and their caregivers, they are in an ideal spot to talk about COVID-19 misinformation and how it can be harmful – especially in more vulnerable populations like children with cancer.

“Being aware that this is an issue is probably the biggest thing,” Guidry said. “People may be more vulnerable; keep an eye on that. Talk to them about preventative measures, talk to them about the vaccine. Right now, we’re not vaccinating children, but we are vaccinating parents.”

On a broader level, Guidry concluded, “If there’s 1 thing I would wish for our society, it’s a greater trust in science. It’s not perfect, but it’s the best we have.”

Guidry J, Miller CA, Ksinan AJ, et al. COVID-19–Related Misinformation among Parents of Patients with Pediatric Cancer. 

. 2021;27(2):650-652. doi:10.3201/eid2702.203285.

Parents of pediatric patients with cancer were more likely to believe COVID-19 misinformation than parents of children without cancer. 

COVID-19 Misinformation: Parents of Patients May Fall for It 

Ruxolitinib (Jakafi), when administered using a pediatric dosing algorithm, was found to elicit responses in patients with chronic graft-versus-host disease (GVHD) with acceptable safety, according to preliminary findings from a retro review presented during the 2021 Transplantation & Cellular Therapy Meeting.1

The FDA approved ruxolitinib for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older in 2019 based on its ability to achieve a high rate of objective responses, as seen in Study INCB 18424-271 (NCT02953678). Despite this progress, there are limited data and understanding on how to administer ruxolitinib in patients with chronic disease and specifically how to dose the drug.2

A retrospective review of 20 patients with chronic GVHD, 4 of whom presented with overlap syndrome was conducted with the goal of providing more understanding on dosing ruxolitinib in pediatric patients with chronic GVHD. Investigators led by YunZu Michele Wang, MD, member, Division of Bone Marrow Transplantation and Immune Deficiency and instructor, Department of Pediatrics at the University of Cincinnati in Ohio, followed a weight-based dosing algorithm by which patients < 25 kg received 2.5 mg of ruxolitinib twice daily and those whose weight was ≥ 25 kg received at 5 mg dose of ruxolitinib twice daily. Patients in the study who were also being treated with tri-azole antifungal therapy had a 50% dose reduction of ruxolitinib upfront. The study protocol allowed for progressive dose increases of up to 10 mg twice daily. Response to ruxolitinib was assessed at the time of therapy initiation as well as a minimum of 30 days after treatment was initiated. Responses were evaluated per the National Institutes of Health 2014 Criteria.

The study population was compiled of patients aged 5 to 26 years. At baseline, information obtained for each patient showed that the underlying disease in the population was beta-thalassemia, DNA ligase intravenous deficiency, chronic neutrophilic leukemia, myelodysplastic syndrome, B-cell acute lymphoblastic leukemia (ALL), Epstein-Barr Virus, and hemophagocytic lymphohistiocytosis, acute myeloid leukemia, chronic disease, hemoglobin sickle cell disease, T-cell ALL, hyper-IgM syndrome, Fanconi anemia, and chronic myeloid leukemia.

Sixteen of the patients were steroid-refractory, but there were also 4 steroid-dependent patients included in the study. As prior systemic therapy, patients received a wide range of agents, some of which were rituximab (Rituxan), imatinib (Gleevec), infliximab (Remicade), and ibrutinib (Imbruvica). Most patients had also received a steroid.

Further assessment of disease characteristics in these patients showed that for the majority, chronic GVHD had affected major organs. The skin was the site of the most impact, which was observed in 11 patients. In addition, the eyes or sclerotic skin were impacted in 7 patients each, the gastrointestinal tract was affected in 6 patients, and the lungs, liver, and genitourinary system were impacted in 3 patients each. There were 2 patients whose joints were affected by their chronic GVHD and 1 whose muscles were compromised.

At the time of ruxolitinib initiation, 16 patients were also on treatment with prednisone at a median dose of 0.5 mg/kg daily (range, 0.08 mg-1.5 mg). The median time from diagnosis to ruxolitinib dosing was 181 days (range, 17-1792 days). Ruxolitinib was administered at a median dose level of 5 mg daily (range, 2.5 mg-10 mg). Notably, 6 patients in the study received the maximum daily ruxolitinib allotment of 20 mg.

Childhood/AYA Cancer