Sodium thiosulfate (Pedmark) has been approved to prevent hearing loss in pediatric patients who are 1 year or older and who require cisplatin-based regimen for localized, nonmetastatic solid tumors.

The efficacy of the product was examined in pediatric patients who were undergoing treatment with cisplatin-based chemotherapy for their cancer who were included in the following 2 multicenter, open-label, randomized controlled trials: SIOPEL 6 (NCT00652132) and COG ACCL0431 (NCT00716976).

The first new drug application (NDA) submission for the agent received a priority review designation from the FDA in August 2020.

 However, a few days later, the FDA issued a 

 (CRL) to Fennec Pharmaceuticals, the drug developer, after a pre-approval inspection of the manufacturing facility for sodium thiosulfate revealed deficiencies that resulted in a Form 483, which detailed conditions or practices that needed to be addressed before the agent could receive approval.

After receipt of the final minutes from a Type A meeting with the FDA, the NDA for Pedmark was resubmitted to the regulatory in June 2021.

 The application was accepted by the FDA later that month for filing.

 However, in November 2021, a second CRL was issued to the company after manufacturing deficiencies were still identified.

 In April 2022, the FDA accepted the NDA resubmission for filing, and the target action date was set for September 23, 2022.

The multicenter, randomized, controlled, open-label, phase 3 SIOPEL 6 trial enrolled 114 patients who were between the ages of 1 month and 18 years who were receiving 6 cycles of perioperative cisplatin-based chemotherapy for standard-risk hepatoblastoma.

Study participants were randomly assigned 1:1 to receive cisplatin-based chemotherapy with (n = 61) or without (n = 53) sodium thiosulfate, which was dosed based on body weight and administered intravenously over the course of 15 minutes beginning 6 hours after completion of each cisplatin infusion. For those weighing less than 5 kg, 5 kg to 10 kg, or more than 10 kg, sodium thiosulfate was administered at 10 g/m2, 15 g/m2, and 20 g/m2, respectively.

Stratification factors included country and age (older or younger than 15 months). The primary outcome of the trial was the percentage of patients with Brock grade 1 or higher hearing loss, which was evaluated using pure tone audiometry following study treatment or at an age of at least 3.5 years—whichever was later.

Among the patients who underwent randomization, the median age was 1.1 years (range, 1.2 months to 8.2 years), and 55% were male. Moreover, 60% of patients were White, 11% were Asian, and 1.8% were Black or African American.

Data showed that the incidence of hearing loss was lower in those who received sodium thiosulfate and cisplatin vs cisplatin alone, at 39% and 68%, respectively (unadjusted relative risk 0.58; 95% CI, 0.40-0.83).

The multicenter, randomized, controlled, open-label phase 3 COG ACCL0431 trial included 125 patients between the ages of 1 year and 18 years who were receiving a chemotherapy regimen that included a cumulative cisplatin dose of 200 mg/m2 or higher, with individual cisplatin doses to be infused over 6 hours or less.

Here, study participants were randomly assigned in a 1:1 fashion to receive cisplatin-based chemotherapy with (n = 61) or without (n = 64) sodium thiosulfate. Cisplatin was given in accordance with each trial site's disease-specific treatment protocols. Participants were given sodium thiosulfate starting 6 hours following each infusion of cisplatin was completed, at a dose that was bioequivalent to the recommended dose. The infusion with the product needed to be completed at least 10 hours following the next cisplatin infusion if the treatment protocol called for several daily doses of cisplatin.

Patients were stratified based on whether they received prior cranial radiation (yes vs no). In those without prior cranial radiation, randomization was further stratified by age (<5 years vs ≥5 years) and duration of cisplatin infusion (<2 hours vs ≥2 hours).

The primary outcome for the trial was hearing loss in accordance with American Speech-Language-Hearing Association criteria, which was evaluated at baseline and 4 weeks after the final course of cisplatin.

Efficacy was examined in a subset of 77 patients who had localized, nonmetastatic solid tumors, who comprised the intention-to-treat population. The median age in these patients was 8 years (range, 1-18) and 61% were male. Sixty-two percent of patients were White, 14% were Black or African American, and 2.6% were Asian. The median Karnofsky or Lansky performance status was 90 (range, 50-100).

Twenty-seven percent of patients had an underlying diagnosis of medulloblastoma, 26% had osteosarcoma, 23% had germ cell tumor, 10% had neuroblastoma, 8% had hepatoblastoma, 2.6% had atypical teratoid/rhabdoid tumor, 1.3% had choroid plexus carcinoma, and 1.3% had anaplastic astrocytoma. Seven percent of patients previously received radiation.

Findings indicated that the incidence of hearing loss was lower in the sodium thiosulfate/cisplatin arm vs the cisplatin-alone arm, at 44% and 58%, respectively (unadjusted relative risk, 0.75;95% CI, 0.48-1.18).

Regarding safety, the most common toxicities reported in the 2 trials included vomiting, nausea, decreased hemoglobin, hypernatremia, and hypokalemia.

FDA Approves sodium thiosulfate to reduce the risk of ototoxicity associated with cisplatin in pediatric patients with localized, nonmetastatic solid tumors. News release. FDA. September 20, 2022. Accessed September 20, 2022. https://bit.ly/3BXm47E

Fennec Pharmaceuticals announces FDA filing acceptance and priority review of new drug application for Pedmark. News release. Fennec Pharmaceuticals. April 13, 2020. Accessed September 20, 2022. 

Fennec Pharmaceuticals receives complete response letter from the FDA for its new drug application for Pedmark to prevent ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic, solid tumors. News release. Fennec Pharmaceuticals. August 11, 2020. Accessed September 20, 2022. 

Fennec Pharmaceuticals resubmits new drug application to US Food and Drug Administration for Pedmark. News release. Fennec Pharmaceuticals, Inc. May 28, 2021. Accessed September 20, 2022. 

Fennec Pharmaceuticals announces FDA acceptance of new drug application resubmission for Pedmark. News release. Fennec Pharmaceuticals, Inc. June 22, 2021. Accessed September 20, 2022. 

Fennec Pharmaceuticals receives complete response letter from the FDA for its new drug application for Pedmark to prevent ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic, solid tumors. News release. Fennec Pharmaceuticals. November 30, 2021. Accessed September 20, 2022. 

Fennec Pharmaceuticals announces FDA acceptance for filing of new drug application resubmission for Pedmark. News release. Fennec Pharmaceuticals. April 27, 2022. Accessed September 20, 2022. 

Pedmark. Prescribing information. Fennec Pharmaceuticals, Inc; 2022. Accessed September 20, 2022. https://bit.ly/3R1zd3Z

Articles

The FDA has approved sodium thiosulfate to protect the hearing of pediatric patients who are at least 1 year old and are receiving cisplatin-based treatments. 

Sodium Thiosulfate Gets Green Light for Chemotherapy-Induced Hearing Loss in Pediatric Patients

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

Cancer Support Community Financial Navigation

Gordon D. 50% of Americans now carry medical debt; a new chronic condition for millions. Forbes. October 13, 2021. Accessed September 26, 2022. 

Abrams HR, Durbin S, Huang CX, et al. Financial toxicity in cancer care: origins, impact, and solutions. 

. 2021;11(11):2043-2054. doi:10.1093/tbm/ibab091

Yabroff KR, Han X, Song W, et al. Association of medical financial hardship and mortality among cancer survivors in the United States. 

. 2022;114(6):863-870. doi:10.1093/jnci/djac044

Fact sheet: the Inflation Reduction Act supports workers and families. News release. The White House. August 19, 2022. Accessed September 26, 2022. 

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. 

Rise of Oral Cancer Drugs Signal Deeper Financial Toxicity Issues for Patients 

Intensity-modulated radiation therapy (IMRT) rather than conventional radiotherapy (CRT), may become the standard of care for women with cervical or endometrial cancer undergoing postoperative pelvic radiation therapy, according to a study published in 

 Reported findings showed that, at a 3-year follow-up, rates of chronic diarrhea and urinary toxicity were reduced in those who underwent IMRT, with no differences in disease outcomes, compared with those who underwent CRT.

Specifically, among 279 patients who were enrolled to receive either CRT (n = 149) or IMRT (n = 130), there were no differences in overall survival (OS; 

 = .81). At 3-years, the OS rates were 92.4% (95% CI, 87.7-97.2) with IMRT and 97.0% (95% CI, 94.1-99.9) with CRT. The DFS rates between the 2 arms were 85.5% vs 80.8%, respectively, and the rate of locoregional failure was 3.5% vs 2.2%, respectively.

Moreover, 1 year post-radiation therapy, the rate of high-level diarrhea frequency was 3 times greater in the CRT arm (15.1%) than with IMRT (5.8%; 

 = .042). More patients in the CRT group reported taking antidiarrheal medication at least twice a day (8.6% vs 1.2%; 

= .036). There were no significant differences in regard to incontinence or abdominal pain at 1 or 3 years.

Further, after 3 years of follow-up, women in the CRT arm experienced declines in urinary function (mean change in EPIC urinary score, –6.0; SD, 14.3) whereas women in the IMRT arm continued to experience improved function (mean change, 0.5; SD, 13.0; 

“IMRT results in reduced patient-reported chronic diarrhea and urinary toxicity compared with CRT, with no difference in disease outcomes at 3 years,” wrote Anamaria R. Yeung, MD, clinical associate professor and residency program director of Radiation Oncology at the University of Florida college of medicine, and coinvestigators. “The updated results of this trial fully support its continuous use in this setting and suggest that IMRT should now be considered the standard of care.”

Postoperative radiotherapy is used to reduce locoregional recurrence in patients with cervical and endometrial cancer. Although the therapy is effective in reducing the risk of recurrence, it is also associated with significant increases in morbidity and toxicity.

Previous reports from the NRG Oncology RTOF 1203 trial

 (NCT01672892) showed that IMRT was linked to fewer gastrointestinal adverse events (GI AEs) than CRT. The trial was a phase 3, multicenter, randomized, controlled study which enrolled postoperative patients with cervical or endometrial cancer. Patients received a radiation dose of either 45 Gy or 50.4 Gy along with concurrent cisplatin (40 mg/m

) once weekly, at their physician’s discretion.

 at week 5 as determined by the Expanded Prostate Cancer Index Composite (EPIC) patient-reported outcome (PRO) instrument. Primary findings showed that after 5 weeks of radiotherapy, IMRT garnered improvements in rates of diarrhea, fecal incontinence, and interference of fecal incontinence. The difference between IMRT and CRT across these domains was 18.2% (

For this longer follow-up, patients were asked to complete the EPIC, the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), the Functional Assessment of Cancer Therapy instrument with cervix subscale, and the EuroQOL’s EQ-5D. They were asked to complete these assessments at baseline, at week 3 and week 5 of radiotherapy, 4 to 6 weeks post-radiotherapy, 1-year post-radiotherapy, and 3 years post-radiotherapy. Physicians reported toxicity using CTCAE 4.0.

Overall, 97.1% of patients completed the EPIC questionnaire at baseline. Response rates decreased to 88.9% at week 3, 86.7% at week 5, to 77.1% at 1-year post-radiotherapy and 55.1% at 3 years post-radiotherapy. At 1 and 3 years, the PROs did not reveal any significant differences in functional assessment of cancer therapy-general total scores, indicating that patient quality of life was comparable between the 2 arms.

In addition, the physician-reported outcomes showed that there were no late, grade 2 or worse urinary toxicities in either arm. Late grade severe GI toxicities were comparable between the 2 arms: 11.2% with IMRT and 11.8% in the CRT arm. No grade 5 toxicities were reported, although 1 grade 4 toxicity related to treatment reported in the CRT arm.

“It is well known that pelvic radiation therapy results in lasting GI and urinary toxicity. One way to mitigate the late toxicity of pelvic EBRT is to use IMRT. However, few prospective, randomized trials have been performed directly comparing pelvic IMRT with CRT,” Yeung concluded. “[This] study is the first large, multicenter phase 3 trial comparing pelvic IMRT and CRT using PROs to evaluate toxicity from the patients’ perspective.”

Yeung AR, Deshmukh S, Klopp AH, et al. Intensity-modulated radiation therapy reduces patient-reported chronic toxicity compared with conventional pelvic radiation therapy: updated results of a phase III trial. 

. 2022;40(27):3115-3119. doi:10.1200/JCO.21.02831

Yeung AR, Pugh SL, Klopp AH, et al. Improvement in patient-reported outcomes with intensity-modulated radiotherapy (RT) compared with standard RT: a report from the NRG oncology RTOG 1203 study. 

. 2020;38(15):1685-1692. doi:10.1200/JCO.19.02381

Intense-modulated therapy was associated with less patient-reported toxicities than conventional radiotherapy and demonstrated a comparable efficacy profile. 

Intense-Modulated Radiation Therapy Reduces Chronic Diarrhea and Urinary Toxicity in Women With Cervical or Endometrial Cancer

Florida’s First Lady, Casey DeSantis has used her role as a breast cancer survivor to advocate for new funding for the state. This started in December 2021, when the First Lady spearheaded a $100 million proposal for cancer treatment as well as research.

DeSantis is now cancer free since March 2022 after undergoing lifesaving surgery and radiation therapy.

I find that I am interested in Florida’s new program, called Florida Cancer Connect.

 It has been described as a “one stop shop”

 for patients, and DeSantis refers to it as a “centralized website.”

The goal is to streamline all the resources available to cancer patients in Florida under 1 umbrella. The website will also work as a bridge to connect patients to other patients, families, and caregivers. Florida Cancer Connect’s website is a joint effort between the Florida Department of Health and the Florida Agency for Health Care Administration. Of note, there was no new financial arrangements between the 2 entities. Instead, both departments used money already in their reserves to participate in this project.

This singular approach gives the patient and family new strategies to prevent cancer.Importantly, it will help individuals trying to work through their health insurance maze. I particularly appreciate that FLCancerConnect will have information geared towards the patients’ families, as they can often be forgotten. The site will also have insight from those who have survived cancer, granting patients links to valuable support systems online.DeSantis will also draw on her own experience with cancer to add small touches that will help support patients. She will include information that, in her experience, is often hard to find. She said in an interview“If you have to buy a wig, or if you’re looking for other things that might help with a surgery, where do I go? Where do I turn?”

All of these resources will be available via this website.

A look at the website reveals a mechanism for locating cancer resources in the state. It also has a section regarding insurance company bills. The Florida Department of Financial Services Insurance Consumer Helpline can be accessed toll free at 1-877-MY-FL-CF (1-877-693-5236) or 1-850-413-3089 if calling from another state. The website also features a health insurance consumer guide. An innovative section, called the Letters of Strength page, has specific tools for cancer survivors and their Stories of Strength that can be read and used to inspire patients and their families.

Florida is not the only state with cancer screening programs. New York State has a Cancer Services Program which at no cost offers cancer screening and diagnostic services to its’ residents. Meeting certain age, and income criteria are also mandatory. These programs offer services for breast, cervical and colorectal screening. 1-866-442-CANCER (2262) is the toll-free phone number that is available 24/7 to connect the resident to these services.

 If the screening reveals any findings that require further evaluation, there are also diagnostic services and a dedicated case manager to walk the patient through this process. Moreover, in California, the Department of Health Care Services has free breast and cervical cancer treatment for its’ residents. In addition, there are no cost breast exams, mammograms, and Pap tests as well as a prostate cancer treatment program called Impact.

I am happy to see more states turning their attention to centralizing resources for patients with cancer. I am looking forward to seeing the impact that DeSantis’ project may have on patients living in her state. As an oncology nurse and social worker, I believe that these programs are of tremendous value and I hope to see the trend continuing.

First lady Casey DeSantis announces $100 million proposal for cancer research and care in Florida. Florida Gov.com. December 8, 2021. Accessed August 22, 2022. 

Troncoso, R.Casey DeSantis comes to Jacksonville to announce statewide cancer initiative. August 3, 2022. Accessed August 22, 2022. WJCT News. 

Cancer Services Program. New York State Department of Health; New York State Cancer Services Program. Updated September 2022. Accessed September 13, 2022. 

Cancer Programs. Department of Health Care Services. Updated September, 2022. Accessed September 13, 2022. https://bit.ly/3S3TM0Z

Debi Fischer, MSW, BSN, BA, LCSW, RN, discusses the launch of the Florida Cancer Connect program and what this initiative represents for patients across the United States. 

Opinion: New Cancer Treatment Options in Florida Represent Larger Shift Toward Centralized Care

A saturated fatty acid diet, but not a high-fiber diet, may be linked to superior outcomes in patients with non–small cell lung cancer (NSCLC) receiving immunotherapy checkpoint blockade (ICB), according to Julie Malo, CCRP.

However, the mechanisms between colon epithelial integrity and immune responses are not well understood and further strategies to use the microbiome as adjuvant therapy are warranted, she added.

Malo, who is a research nurse at the University of Montreal, presented findings from a nurse-led dietary intervention at the 

European Society of Medical Oncology Congress 2022

. Immunotherapy is changing the treatment landscape across oncology, Malo said, adding that this treatment modality has had a particularly significant effect on the treatment of patients with melanoma and NSCLC.

“ICBs are now the standard therapy for a wide variety of [cancers] but are the backbone therapy for patients with NSCLC or melanoma,” she said. “We can see a significant improvement in the survival rate in patients treated with immunotherapy vs those treated with chemotherapy alone.”

For example, findings from Robert et al showed that treatment with nivolumab (Opdivo) prolonged the median survival of patients with melanoma compared with dacarbazine. At a follow-up of 18 months, the median overall survival (OS) with the immunotherapy (n = 210) was not reached compared with 10.8 months (95% CI, 9.3-12.1) with dacarbazine (n = 208). The hazard ratio was 0.42 (99.79% CI, 0.25-0.73; 

Moreover, Reck et al demonstrated that pembrolizumab improved OS for patients with lung cancer. At a follow-up of 72 months, the median OS with immunotherapy was 26.3 months (95% CI, 13.3 to 40.4) vs 13.4 months (95% CI, 9.4-18.3) with chemotherapy. The number of events associated with pembrolizumab (n = 154) was 103 (66.9%) vs 123 (81.5%) with chemotherapy (n = 151; HR, 0.62; 95% CI, 0.48-0.81).

“Despite these improvements in outcomes with ICB, resistance to these treatments is universal,” Malo explained. “Therefore, finding new strategies to increase ICB efficacy or [challenge] ICB resistance is an unmet clinical need.”

According to Malo, literature suggest that the microbiome plays a 

key role in the efficacy of immunotherapy treatments

The intestinal microbiome is the most populated of the different microbiomes in the human body, it is situated in the small intestine and the colon. Here, bacterial colonization occurs in a very gradual and specific way: the intestinal bacteria absorb oxygen and uses it to multiply and promote bacteria growth in anaerobic environment.6

Multiple factors affect the diversity of the microbiome, including where an individual was born, their current geographical location, and genetics. The microbiome increases its diversity through the first 3 to 5 years of an individual’s life, but, once established, remains relatively stable throughout adult life. Only major changes in lifestyle or diet, including the introduction of an antibiotic treatment, will upset the microbiome once it has been established. However, certain changes in the microbial composition can induce the production of toxics and create chronic inflammation. This process is called dysbiosis and it can affect the efficacy of ICB.4

Findings from Derosa et al showed that in a cohort of patients with NSCLC receiving ICB, the median OS among those who were receiving antibiotic therapy was 7.9 months, whereas, among those who were not receiving antibiotic therapy, the median OS was 24.6 months (HR, 4.4; 95% CI, 2.6-7.6;

“In light of all this information, it is important to find ways to modulate the microbiome in order to use it as an adjuvant to ICB treatment,” Malo explained.

Investigators sought to influence the gut microbiome in a noninvasive and natural way. To that end, a team of oncologists, oncology nurses, and nutritionists designed a questionnaire to ask patients about their different dietary habits, including their intake of fruits, vegetables, meat, and alcohol, as well as information about their geographical living environment. The questionnaire therefore offered a global view of their lifestyle habits.

The questionnaire was presented to patients (n = 105) with advanced NSCLC prior to their initiation of their ICB treatment. A 1-hour interview with a research nurse and a 47-question assessment captured information on the intake of 30 different nutrients. Examples of patient questions included if they ate 3 meals per day, if they fasted, if they consumed fresh or canned fruit, salad, vegetables, potatoes, chips, eggs or egg-based recipes, legumes, nuts and seeks, high-fiber breakfast cereals, whole wheat bread, other bread options, or rice.

“Our first finding was that our patients had a fairly homogeneous and relatively poor diet that was lacking variety,” Malo noted, adding that most patients reported that they do not eat bran cereal, oatmeal, or other grains, but almost all of them consume coffee.

Moreover, some foods were also associated with unexpected positive and negative responses.

“Protein drinks, white breaded fish, and other breads are associated with a negative response [whereas] other grains fruit, rice, beans, eggs and coffee are associated with a better clinical response,” Malo noted. “And unlike melanoma, where a study [conducted] by Spencer [et al] showed that a 

high fiber diet is associated with a better clinical response

 a high fiber diet did not correlate with an improved PFS [progression-free survival] for our patients with NSCLC. It is important to note here that the median fiber intake of our patient was 14 g per day compared to 20 g.”

Moreover, after focusing on foods and clinical responses, investigators observed that a fatty acid diet correlated with a favorable outcome. According to Malo, the median PFS for patients on a low saturated fatty acid diet was 9.1 months compared with a median PFS of 17.4 months for a patient with a high saturated fatty acid diet.

“With the emergence of the gut microbiome in the field of immune-oncology, providing evidence based dietary recommendation and educational tool for nurses is an important strategy to potentially increase ICB efficacy,” Malo said.

She concluded by noting that the mechanism between the bacteria of the gut and immune responses remain to be fully understood and that strategies designed to leverage the gut microbiome to enhance outcomes of adjuvant ICB therapy should be considered on a broader scale. Malo’s team is developing a new version of the food frequency questionnaire to better assess their patients intake of nutrients and the consequent effect on care.

Malo J. Impact of diet on immune checkpoint blockade; nurse-directed dietary intervention. Poster presented at: European Society for Medical Oncology Congress 2022; September 9-13, 2022; Paris, France.

Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. 

. 2021;39(21):2339-2349. doi:10.1200/JCO.21.00174

Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. 

. 2015;372(4):320-330. doi:10.1056/NEJMoa1412082

Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. 

. 2018;29(6):1437-1444. doi:10.1093/annonc/mdy103

Hanahan D. Hallmarks of cancer: new dimensions. 

. 2022;12(1):31-46. doi:10.1158/2159-8290.CD-21-1059

Clarke G, Sandhu KV, Griffin BT, Dinan TG, Cryan JF, Hyland NP. Gut reactions: breaking down xenobiotic-microbiome interactions. 

. 2019;71(2):198-224. doi:10.1124/pr.118.015768

Julie Malo, CCRP, a research nurse with the University of Montreal, discusses a nurse-directed initiative examining how the gut microbiome affects immune checkpoint blockade responses in patients with non–small cell lung cancer. 

Nurse-Led Research Links Saturate Fatty Acids to Improved Immunotherapy Responses in NSCLC

Cannabinoids are becoming more popular for patients with cancer as a pain management strategy. However, with inconsistent laws across states and federal bodies, it can be difficult for nurses and patients to comfortably discuss cannabinoids and cannabinoid use.

As the public perception and patient success stories with unconventional, alternative, and natural therapeutics shift consumer attitudes, it is important for nurses and their patients to understand the differences in the products and the adverse effects associated with each. According to a study by Butler et al in 2021, nearly half of individuals who participated in a survey who had consumed cannabidiol (CBD) did not disclose use to their health care provider.

“We see a lot of patients who have been trying to talk to us about CBD [cannabidiol], and cannabinoids and THC, [tetrahydrocannabinol]” Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, a professor of nursing at Vanderbilt University School of Nursing, said in a presentation during the Oncology Nursing Society Bridge.

Although Hande stated in her presentation that she was no expert in cannabinoids or medical cannabis, her clinical research primarily focuses on helping patients effectively manage their cancer-related pain. Therefore, she has become very interested in cannabis and has dedicated a lot of time and research to best understand the evidence-based data that exists for these products. In her presentation, “Cannabinoids for Patients With Cancer,” Hande discussed the available evidence on CBD and the possible risks, particularly in vulnerable populations.

“I think it’s just important for under us to understand a kind of broad overview about cannabinoids and THC and CBD, because this gives us a better understanding of where the laws come into play,” Hande said. She added, “It took me quite some time to try to understand all the differences and trying to make sure I give the correct information to my patients.”

A key concept for oncology nurses to understand, according to Hande, is the variations of cannabinoids.

Cannabinoids are compounds found in the cannabis plant. These compounds interact with the human endocannabinoid system. The exact relationship still required further understanding.

“Cannabis has many names for [many] strains, and hemp and marijuana are under this big umbrella of cannabis plants; they are all considered to be 1 species: the cannabis sativa plant,” she said. “This is a genus of flowering plants. And these can contain about over 100 phytocannabinoids, [and] they have a wide range of effects on the body in the brain.”

The following products are derived from cannabis: marijuana, hemp, THC, and CBD. In addition, there are man-made synthetic cannabinoids (K2/Spice); however, these agents are designed to mimic the mind-altering effects of illicit drugs. For her talk, Hande chose to focus on the products derived from the plant itself, as oncology nurses are more likely to encounter patients using plant-derived products.

If a patient reports marijuana use, this means they are using the dried flowers, leaves, stems, and seeds of the cannabis plant. Marijuana is also known as cannabis, weed, pot, or dope. Specifically, it can be defined as a plant with at least 0.3% delta-9 THC by weight. It is consumed by smoking (joints, blunts, bongs), vaping (vaporizing electronics devices), or by mixing or infusing it into foods or drinks (edibles).

“This is an important differentiating factor that I’ll be highlighting regularly through this talk,” Hande said during her presentation. “Marijuana is more than 0.3% of THC by weight.”

Marijuana is the most used federally illegal drug in the United States, with approximately 18% of Americans reported using it at least once in 2019 (~48.2 million Americans).1

Because marijuana has THC, it is associated with the following health risks: alterations in memory, learning, attention, decision-making, coordination, emotion, and reaction times.2 In terms of long-term health, marijuana has been linked to an increased risk of psychosis and schizophrenia,3 and, like other drugs, it’s use during pregnancy may increase the risk of embryo-toxicities.4 Moreover, this drug, depending on where it is sourced, may be laced with other substances. Consumers may or may not be aware of other substances in their product.

Using marijuana in combination with other agents may also result in impairment and can increase the risk of overdose.

Federally, marijuana is illegal as a recreational drug. It is classified as a schedule 1 drug, per the Drug Enforcement Agency. Although it is legal in some states for medical for nonmedical adult use, this does not mean that is safe, Hande noted. Specifically, smoking marijuana can expose users to harmful chemicals, and insufficient evidence exists to document the safest method for consuming.

Legally, hemp must contain a THC concentration of less than 0.3% by dry wright. It is the same species of plant as the cannabis plant and, along with bamboo, it is one of the fastest growing plants on Earth. There are almost no restrictions on hundreds of compounds made by the plant. Industrial hemp is cannabis sativa plant grown specifically for industrial or medicinal use.

“Many states across the country have hemp cultivation,” Hande said. “This allows cultivation of hemp from commercial or research or pilot programs. There are only a few states that do not allow cultivation of hemp.”

In 2018, the farm bill legalized the production and sale of hemp and its extracts, removing the product from the controlled substance act. Of note, per federal law, hemp cannot contain greater than 0.3% THC. If the concentration of THC surpasses this measurement, it is classified as marijuana.

As of September 2022, 47 states have enacted legislation to establish hemp production programs or cultivation research.

THC is a compound of the cannabis plant. This psychoactive agent causes, what is known as a high. It is consumed via dabbing—a specific method for inhaling THC concentrates.

Unfortunately, the concentrated forms of THC mean that there is an increased risk of additives or contaminating substances existing in the product.

CBD is another active cannabinoid found in the cannabis plant. This agent is not psychoactive and consequently does not cause a high.

CBD can be derived either directly from the cannabis plant or from a hemp product. The key difference between cannabis- and hemp-derived CBD is the concentration of THC. Hemp-derived CBD must have a THC concentration less than 0.3% to be federally legal. CBD products containing greater concentrations are federally illegal but are legal under some states.

“The main difference between cannabis and hemp-derived CBD is the amount of THC that it can contain,” Hande stressed. “Hemp-derived CBD includes less than 0.3% of the THC. [Therefore,] it’s federally legal to use hemp-derived CBD, but CBD products that contain more than 0.3% of THC are federally illegal. This is where the conflict between the state and the federal laws [can arise].”

The extraction process for CBD and THC are similar; farmers harvest the hemp and it is sent to an extractor. If the extraction is not performed with pharmaceutical grade standards, the CBD may become contaminated with THC, chemical solvents, or even pesticides. This is compounded by the fact that the US does not hold CBD supplies to a standard, and federal enforcement is lacking.

CBD can be converted into delta-8-THC, delta-9 THC, and other THC isomers through a solvent, acid, and heat. These products end up with higher concentrations of delta-8 THC than those which occur naturally in the cannabis plant. Consequently, these products may create harmful by-products that presently are not well-characterized.

Delta-8 THC products are increasing in popularity, in both marijuana- and hemp-based markets. It is appearing in markets that are operating legally under state, territorial, or tribal laws.

As of 2022, most states and territories permit full and restricted marketplaces where consumers can purchase hemp and hemp-derived CBD products.

According to Hande, there are a wide variety of delta-8 THC-containing products in the market. For example, vapes, smokable hemp sprayed with delta-8 THC extract, distillates, tinctures, gummies, chocolates, and even infused beverages can fit into this category. Moreover, the testing method for these products are still under development. This means that Delta-8 THC products may not be systematically tested for contaminants such as heavy metals, solvents, or pesticides which can cause adverse health effects.

How to Talk to Your Patient About Cannabinoid Use

Nurses hold a key role in discussing not only the risks of cannabinoid use but providing educational information for the safe consumption. Should a patient be interested in trying CBD products, counsel on the lack of evidence, contaminants, misleading labels, and legal issues of surrounding use. One approach to counter the “buyer beware” notion is to provide evidence-based patient education and to screen for any drug/drug interactions that may occur should the patient consume CBD products.

Additionally, assessing the patient’s baseline knowledge base before use will be beneficial and open communication may help establish trust and increase reported use between the patient and the health care provider. Finally, addressing the topic early on in care may remove the barrier of the stigma surrounding cannabinoid use.

Hande concluded by adding that many trials are ongoing in the cannabinoid arena and that results are expected to be published over the next several years. She noted that the oncology nurses should be up-to-date on the latest findings to provide guidance.

Marijuana and public health data and statistics. Centers for Disease Control and Prevention. June 8, 2021. Accessed September 14, 2022. bit.ly/3ROqaoi

Testai FD, Gorelick PB, Aparicio HJ, et al. Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. 

. 2022;53(4):e176-e187. doi:10.1161/STR.0000000000000396

Di Forti M, Quattrone D, Freeman TP, et al. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. 

. 2019;6(5):427-436. doi:10.1016/S2215-0366(19)30048-3

Health effects of marijuana and cannabis-derived products presented in new report. National Academies. January 12, 2017. Accessed September 14, 2022. 

Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, explains the difference between some of the popular cannabinoid products that patients with cancer may be taking.

Oncology Nurses: What Cannabinoid Is Your Patient Taking?

® spoke with Christine Miaskowski, PhD, RN

professor in the Department of Physiological Nursing and Anesthesia at UCSF School of Nursing. Miaskowski discusses results from research which showcases an increased risk of hearing loss among patients who received platinum- or taxane-based cancer treatments. She also discusses the importance of including hearing assessments as a standard of care for survivors.

Top takeaways from the discussion include:

“When we did audio metrically confirmed hearing loss [assessments], we found that between 50% to 70% of survivors had confirmed hearing loss.” 

“It’s really, very surprising because it is a group of patients with very common cancers: breast, lung, gynecologic and GI [gastrointestinal] malignancies.” 

“The good news is that the type of hearing loss these patients experience is amenable to a hearing aid. So, if we can get people tested, and they demonstrate this kind of hearing loss, we can improve their quality of life.” 

In this episode of “The Vitals,” Christine Miaskowski, PhD, RN, discusses research showcasing that adult patients receiving either a platinum-based chemotherapy, taxane alone, or a combined regimen of platinum- and taxane-based treatment may be at risk of hearing loss. 

Supportive Care

Sodium Thiosulfate Gets Green Light for Chemotherapy-Induced Hearing Loss in Pediatric Patients

Rise of Oral Cancer Drugs Signal Deeper Financial Toxicity Issues for Patients

Intense-Modulated Radiation Therapy Reduces Chronic Diarrhea and Urinary Toxicity in Women With Cervical or Endometrial Cancer

Opinion: New Cancer Treatment Options in Florida Represent Larger Shift Toward Centralized Care

Nurse-Led Research Links Saturate Fatty Acids to Improved Immunotherapy Responses in NSCLC

Oncology Nurses: What Cannabinoid Is Your Patient Taking?

Are Hearing Tests Necessary For Adult Cancer Survivors?

Better End-of-Life Options Are Needed for AYA Patients With Advanced Cancer

Satellite Clinical Trial Sites May Improve Minority Patient Accrual But Challenges Still Exist

Opinion: Understanding Spoon Theory Is Essential for Oncology Nurses