Lindsay Fischer is an editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

Neoadjuvant chemoradiation followed by pancreaticoduodenectomy (NACRT) is more cost-effective than upfront pancreaticoduodenectomy and adjuvant chemotherapy (USR) in patients with resectable pancreatic cancer, according to a cost-effectiveness analysis published in the 

. Based on these findings, NACRT should be considered in all patients with resectable pancreatic cancer unless there is an absolute contraindication, study authors wrote.

Based on a case modeled after a male aged 65 years, NACRT yielded 1.61 quality-of-life years (QALY) at $45,483.52 USD/QALY. In comparison, USR had 1.47 QALYs at $38,642.56 USD/QALY. NACRT followed by resection was $6840.96 USD more expensive and resulted in 0.14 more QALYs. This produced an incremental cost-effectiveness ratio (ICER) of 48,130.70 for neoadjuvant therapy, which was below the predefined willingness-to-pay threshold and was the primary end point of the analysis.

Most one-way sensitivity analyses supported these findings. However, in the situation where 21% of patients or less were able to proceed to surgery following NACRT, USR became the most cost-effective choice. Similarly, if 85.4% or less of patents had resectable disease after NACRT, then USR was more cost-effective.

Two-way sensitivity analyses also supported the findings; however, USR became more cost-effective if many patients were unable to receive surgery after NACRT andother variables favored USR, orif patients had low NACRT resection rates and other variable favored USR. Another circumstance in which USR was more cost-effective was if the perioperative morality following USR was low and other variables favored USR.

The probabilistic sensitivity analysis supported NACRT in 94.3% of cases; and the cost-effectiveness acceptability curve showed that NACRT would be the preferred option unless the willingness to pay threshold dropped below $62,000 USD.

A secondary version of the probabilistic analysis varied costs and brand point probabilities. This version favored in NACRT in 78.4% of 100,000 simulations.

“Our study uses a cost-effectiveness analysis to compare the use of NACRT and USR in resectable [prostate cancer] and found that NACRT followed by resection is the more cost-effective approach,” wrote Simran Arjani, MD, of the Rutgers New Jersey Medical School, and co-investigators, in the study.

 “The use of NACRT would allow physicians to better identify patients with chemoresponsive disease but would delay surgery. Given the evidence in this and similar studies, the use of NACRT in [resectable prostate cancer] should still be a discussion.”

Moreover, they noted that the increase in effectiveness was equivalent to 1.7 quality-of-life adjusted months with the added cost of $1000 to $10,000, both of which may be inconsequential to some patients and extremely important to others.

Both NACRT and USR are highlighted as possible treatments for resectable pancreatic ductal adenocarcinoma in the National Comprehensive Cancer Network guidelines.

 This model divided a theoretical cohort of patients into half that received neoadjuvant FOLFIRINOX-based chemoradiation followed surgical resection and another half that received by adjuvant FOLFIRINOX-based chemotherapy.

This is not the first decision model or cost-effectiveness analysis to compare NACRT and USR. A decision model designed by VanHouten et al in 2012, compared USR against a gemcitabine-based NCART in patients with potentially resectable disease.

 Although the study assessed a slightly different patient population and some different treatment end points, this analysis found a slight benefit for neoadjuvant therapy, and authors simultaneously noted that the ideal treatment remained controversial. Moreover, their model showed that treatment decisions should be sensitive to the probability of tumor resectability and chemoradiation mortality, but not to the rates of other treatment complications.

Additionally, a 2019 cost-effectiveness model ground that neoadjuvant FOLFIRINOX represented the optimal strategy compared with upfront surgery and adjuvant gemcitabine plus capecitabine/gemcitabine monotherapy.

 This model found the neoadjuvant treatment to be linked to a 0.30 QALY gain at a cost of $46,200 USD/QALY. Similarly, a 2019 Markov cohort decision analysis model found a slight benefit to neoadjuvant strategy over upfront pancreaticoduodenectomy. In the 2019 model, this benefit translated to a 4.6-month survival gain in most models.

In the Arjani et al model, the survival and quality of life following NACRT or USR was assessed using TreeAge Pro software. The decision tree assessed the costs and survival outcomes associated with these treatments in the published literature. The time horizon was limited to 1 year.

In this study, the willingness-to-pay threshold was determined to be $100,000 USD/QALY gained, and anything above that priced would mean that the benefit outweighs the cost. A negative ICER meant that the option provides a benefit at a lower cost than its comparator. Because of the study was designed with a 1-year time horizon, discounts were not a factor. Moreover, to account for probability in branch points, sensitive analyses, not one-way and two-way, were conducted, to simulated 100,000 different random samplings.

Study authors that the model has some limitations. Data from published literature was used to population the decision tree, and, wherever, possible high levels of evidence, namely, meta-analyses, were used, according to the authors. Recent studies with greater power and more prevalent treatment regimens were prioritized. However, there were situations when the highest levels of evidence were unavailable and multiple studies were consulted to provide this data. The sensitivity analyses sought to address this issue. Moreover, the model was unable to account for the impact of a patient’s inability to complete a chemotherapy regimen, and the analysis did not comment on racial/ethnic distributions, prohibiting conclusions regarding the impact of these factors on the models.

“The results of our study and those in the published literature emphasize the role of resection rates after NACRT, which is a surrogate for both chemoresponsiveness of the disease and treatment toxicity,” study authors concluded. “The future of treatment decision making lies in being able to identify chemoresponsive disease. Work in genomics, proteomics, and metabolomics to identify resistance or susceptibility to chemotherapy drugs has the potential to maximize treatment benefits and minimize treatment-related toxicity.”

Arjani S, Prasath V, Suri N, Li S, Ahlawat S, Chokshi RJ. 

Neoadjuvant treatment versus upfront surgery in resectable pancreatic cancer: a cost-effectiveness analysis.

. Published online December 22, 2022. doi:10.1200/OP.22.00536

National Comprehensive Cancer Network. Pancreatic adenocarcinoma. Version 2.2022). https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed January 24, 2023

VanHouten JP, White RR, Jackson GP. 

A decision model of therapy for potentially resectable pancreatic cancer.

. 2012;174(2):222-230. doi:10.1016/j.jss.2011.08.022

Neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced pancreatic cancer: results of a decision analysis. 

. 2019;24(7):945-954. doi:10.1634/theoncologist.2018-0114

Rieser CJ, Narayanan S, Bahary N, et al. 

Optimal management of patients with operable pancreatic head cancer: a Markov decision analysis

. 2021;124(5):801-809. doi:10.1002/jso.26589

Articles

Neoadjuvant chemoradiation followed by pancreaticoduodenectomy resulted in 0.14 more quality-of-life years than upfront surgery followed by adjuvant chemotherapy in patients with resectable pancreatic cancer. 

Neoadjuvant Treatment Crosses Cost-Effective Threshold Vs Upfront Surgery in Pancreatic Cancer

Videos

Closing their discussion, the panel shares advice for new nurse practitioners caring for patients who have endometrial cancer.

Advice for New Nurse Practitioners Working With Patients With Endometrial Cancer

Heather Jackson, PhD, FNP-BC, NEA-BC, FAANP

Complementary therapies, such as acupuncture, may help patients alleviate cancer-related pain.

 Notably, auricular acupuncture has been noted to help certain patients not only manage pain, but reduce their opioid use, according to Heather Jackson, PhD, FNP-BC, NEA-BC, FAANP.

“When we think about treating pain, if you’re going to treat the whole person you have to think about all the different aspects of the [individual],” Jackson explained, noting that complementary therapies are not panacea, but can be useful in addressing certain symptoms and treating the person in a holistic fashion.

“I said [to my patient], this could be 1 piece of the pie and then we can look at alternative medicines while we’re doing the acupuncture.”

®, Jackson, the administrative director of advanced practice for the Vanderbilt Ingram Cancer Center, discussed forms of therapy with acupuncture as well as her experience using acupuncture for a thyroid cancer survivor and how it helped him achieve his goal of coming off pain management treatment with an opioid.

Please discuss this patient’s diagnosis and the treatment that was chosen.

I had a wonderful case study that came to my clinic: a 49-year-old male who had a history of thyroid cancer, and did not have current active disease. He had completed his treatment, had surgery, and was still having a lot of facial pain [in the] left cheek, neck, and temporomandibular joint. He’d been taking oxycodone 15 mg 4 times [daily] and he came to me and said, ‘I’m a father, I’m a husband, and it’s really sedating for me, I can’t sit down at meals, I can’t enjoy social activities, anything I do is uncomfortable.’ He didn't have his full energy level.

We said: What can we do to try to get him off of the oxycodone, but still functioning and interacting with his family? I said, ‘how about acupuncture?’ and he was really interested in it. I looked at his medicine regimen and said ‘it’s not the cure-all, but it could be a piece of the pie.’

What did the conversation look like when you mentioned acupuncture and what questions did the patient have?

It’s very common where patients will say, ‘I don’t understand why we are doing this now?’

I go over the evidence with them and then I build their confidence by saying, ‘I’ve done research in this and it's safe enough that I’ve done stickers on babies all the way to needles in adult’s ears. I’ve had success in getting patients off of opioids and even reducing anxiety and depression.’

He and I looked through Google and some PubMed articles. I said feel free to look through them, read up on it, [and] bring whatever you want back… and that’s what he did. He was a very motivated patient, and he came back to me [in] clinic and said, ‘I did look through this and there is some justification to what you’re talking about. Let’s try it, what do I have to lose?’

What did acupuncture treatment look like for this patient?

The acupuncture that we do in our clinic is a modified acupuncture technique; it’s not full body, it’s limited to the ear. They call it auricular acupuncture, and [the] protocol that I use is called the battlefield protocol. Battlefield protocol was developed by the Air Force for pilots who couldn’t be on opioids long term; they couldn’t be on sedating medicines.

The battlefield pain protocol is for pain treatment. They have studs that you can put in the ear and leave in—they’ll stay in the ear for up to 5 to 7 days.

I also have the NADA protocol which was developed for patients who were in detox programs, trying to do a methadone clinic, or [use] buprenorphine treat opioid use disorder. [Investigators] have seen that it helps with physiological symptoms as well as the psychological impact of being a dependent or having a use disorder.

I talked to him about both options, the pain was the issue here, so I went to the battlefield protocol and said ‘we don't have to be so aggressive that I put studs, the needles in your ears that you walk around with, I could put some milder needles in your ear on the point, [and] you can rest for 20 to 30 minutes.

I usually turn the lights down in the exam room and I have a sound maker to try to help them relax; I step out of the room, let them relax with the needles in their ear, and then I come back and take the needles out. I offer acupressure stickers that are like a little band aid that I can put on a couple of little spots that way they can go home, they can be pressing on the area [to] give a little bit more stimulation.

I’ll tell the patient, you can come back anytime you want. There are no adverse risks except maybe a little bruising and bleeding which is quickly resolved, the needles are so small—they’re smaller than a needle you would even thread with. I will let them sort of direct [if they] want to come back in 2 weeks, in 4 weeks, [etc]. I recommend a few sessions that way [they] can build on top of each other. It doesn’t work for everyone, but if it does work you will notice different things, every patient is different.

Some patients will say ‘well, Heather I didn’t get 100% pain relief, which would be a pretty unattainable goal, but I did notice that I didn't have to take my medicine 3 times a day; I took it 2 times a day’ or ‘usually I can't sleep more than 6 hours [but] I slept 8 hours’ or ‘I could only walk in a mall for an hour and a half but I noticed after your treatments I’m able to walk for 2 hours.’

Those are the things I tell the patient you need to be looking for, I don’t expect a cure-all, but oftentimes they do complete their treatment and they’ll say ‘preprocedure I was an 8 out of 10 and now I’m a 6 or now I'm a 2 [for pain].’ That’s the conversation we usually have and what I tell the patient to be monitoring.

How did you measure this patient’s pain and how did he respond to the acupuncture treatment?

We looked at medicine doses because he wanted to be off oxycodone, and he had been so motivated to get off of the oxycodone that he had quit it cold turkey and had some reactions because his body was used to that for so many years. He realized [he] needed some help coming off of it, we talked about that. I said ‘let’s do the acupuncture and then gradually come down on the medicine, but it’s going to be a timed thing. It’s not going to happen overnight, we have to be patient, [and] you can’t push yourself too hard because we also don’t want the pain to flare up.’ That was how we walked through it, and he was amenable to that.

He did feel some pain relief right after the intervention and we ended up doing a series of 3 [treatments] for the actual acupuncture and he felt the pain was getting under control. Then we were able to reduce and completely wean him off the oxycodone, he was very motivated, within 4 months. He reported 100% relief of his right-side face pain and 50% relief on the left side after he had completed his treatments, and this would be reported to me in the follow-up when he came in 4 weeks later.

A big point that he shared with me was: ‘Heather, I can eat with my family, now I can go out to eat.’ He had young kids, middle school teenage [aged and] you can imagine the quality of life that was being impacted. He was so thrilled to be able to say now I can eat with my family.

[Today] he is not in my clinic anymore because we got him off of everything and he [only] needed help getting through that period of getting off the medicine. He’s not in our clinic anymore for cancer pain, but he’s under surveillance and should we need to intervene in the future we absolutely will.

Is there any monitoring or questions that you ask patients when they’re undergoing treatment?

You [may] have concerns [if] the patient has hemophilia, [which] some patients [do on] very rare occasions, or, if you have a patient with a pain condition—sometimes stimulation with a needle are not a good idea. It depends on what type of pain a person has.

If a person has a central sensitization, where there's pain everywhere the body, sometimes an event like a needle will trigger more pain. That’s something to be cautious with. You sort of have to interview with the patient, to get a gut feeling for the patient and know if this is going to be a good fit or not. Usually, the patients that are very motivated that have tried chiropractic or massage are open to other options— that’s a good indicator that this is probably going to be a successful treatment.

Otherwise, [concerns] would be very mild bleeding that can occur. If that does occur, [use] a cotton swab or a tissue, hold it on there and take it off.

I’ve never [seen] any bruising [with my patients]. Some patients don’t like the stickers that I’ve put on for acupressure, so we don’t use them if they don’t like them, but most people like them.

Do you have any clinical pearls to wrap up what you learned from this case study?

My advice would be to always consider [acupuncture] as an adjunct [therapy]. There’s a lot of miscommunication with complementary therapies and people will assume that’s the only option and that’s not what we’re saying when we say complementary, we say complementary [as] in addition to. We can all work together, we can all collaborate like we do multidisciplinary treatments for our patients, but this could be an option to add too.

Jackson HJ, Peal K. Auricular acupuncture for the treatment of cancer-related pain. 

.2022;37(4):32-35. doi:10.1080/10463356.2022.2079353

Montgomery AD, Ottenbacher R. Battlefield acupuncture for chronic pain management in patients on long-term opioid therapy. 

. 2020;32(1):38-44. doi:10.1089/acu.2019.1382

Carter K, Olshan-Perlmutter M. NADA protocol: integrative acupuncture in addictions.

. 2014;25(4):182-287. doi:10.1097/JAN.0000000000000045

Heather Jackson, PhD, FNP-BC, NEA-BC, FAANP, provides a case-based perspective on the benefit of auricular acupuncture as a tool for managing cancer pain.

Auricular Acupuncture Offers Complimentary Approach to Manage Cancer Pain

The panel shares the most critical unmet needs for patients with endometrial cancer.

Greatest Unmet Needs for Patients with Endometrial Cancer

The FDA has approved pembrolizumab (Keytruda) for the adjuvant treatment of patients with completely resected stage IB (T2a ≥ 4 cm diameter), II, or IIIA non–small cell lung cancer (NSCLC) following platinum-based chemotherapy. The approval is based on data from the KEYNOTE-091 trial (NCT02504372).

Findings from the trial showed that treatment with pembrolizumab (n = 580) reduced the risk of disease symptom development by 27% compared with placebo (n = 581). The median disease-free survival (DFS) was 58.7 months (95% CI, 39.2-not reached [NR]) vs 34.9 months (95% CI, 28.6-NR) for pembrolizumab vs placebo, respectively (HR, 0.73; 95% CI, 0.60-0.89).

The label comes with a warning for immune-mediated pneumonitis, which was reported in 41 patients (7%) treated with pembrolizumab in KEYNOTE-091 with 26 patients discontinuing treatment. Events were fatal (0.2%), grade 4 (0.3%), and grade 3 (1%) in nature. Patients who developed symptoms were treated with high-dose corticosteroids for a median duration of 10 days (range, 1 day to 2.3 months). Dose interruptions were reported for 54% of patients receiving pembrolizumab, 63% discontinued treatment, and 71% resolved symptoms.

The label notes that other adverse events (AEs) observed in KEYNOTE-091 were consistent with previously reported data for patients with NSCLC receiving pembrolizumab. However, rates of hypothyroidism were higher at 22%.

 Additional AEs of note in the study were hyperthyroidism (11%), and pneumonitis (7%) with pembrolizumab.

KEYNOTE-091 enrolled patients with stage IB/II-IIIA NSCLC who have undergone complete resection of either lobectomy or pneumonectomy with or without adjuvant chemotherapy. Individuals were randomly assigned to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 1 year. The primary outcome was DFS with secondary end points of overall survival and lung cancer specific survival.

The median age of patients who received adjuvant treatment following resection and chemotherapy was 64 years (range, 35-84), and 49% were 65 years or older. Among the overall populations 68% were men, 77% were White, 18% were Asian, and 86% were current or former smokers.

In terms of disease stage, 11% of patients had stage IB, 57% had stage II, and 31% had stage IIIA disease. Tumor proportion score (TPS) was reported as follows: 39% had PD-L1 TPS lower than 1%; 33% had TPS 1% to 49%, and 28% had TPS at least 50%.

The median duration of exposure to pembrolizumab was 11.7 months with 68% of patients in the pembrolizumab arm exposed to the agent for at least 6 months.

 Investigators performed an exploratory subgroup analysis of patients who did receive adjuvant chemotherapy (n = 167); the HR for DFS was 1.25 (95% CI, 0.76-2.05).

KEYNOTE-091 reported during a 2022 ESMO Plenary session

 showed that among allcomers DFS met the primary end point of the study, but was not statistically significant among patients with a TPS of at least 50%.

FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. FDA. January 26, 2023. Accessed January 26, 2023. 

Keytruda. Prescribing information. Merck; 2023. Accessed January 26, 2023.

Study of pembrolizumab (MK-3475) vs placebo for participants with non-small cell lung cancer after resection with or without standard adjuvant therapy (MK-3475-091/KEYNOTE-091) (PEARLS). ClinicalTrials.gov. Updated July 17, 2020. Accessed January 26, 2023.

Pembrolizumab has been approved by the FDA as an adjuvant treatment for patients with stage IB, II, or IIIA following resection and platinum-based chemotherapy.

Adjuvant Pembrolizumab Gets FDA Approval in NSCLC

Findings from the phase 3 SUNLIGHT study showed that adding bevacizumab to trifluridine/tipiracil boosted overall survival in metastatic colorectal cancer.

Trifluridine/Tipiracil Plus Bevacizumab Improves OS in Refractory Metastatic Colorectal Cancer

Investigators identified underrepresentation and imbalances in demographic and geographic representation in clinical trials leading to FDA approvals. 

Pivotal Multiple Myeloma, Leukemia Trials May Not Represent the Populations They Serve

Patients with breast cancer who carry BRCA1, BRCA2, CHEK2, or PALB2 germline pathogenic variants may be at a greater risk for contralateral breast cancer and may benefit from enhanced surveillance and risk-reduction strategies. 

Patients With Breast Cancer and BRCA1, BRCA2, CHEK2, or PALB2 Germline Pathogenic Variants May Benefit From Enhanced Surveillance

The median overall survival with frontline liposomal irinotecan/NALIRIFOX was 11.1 months vs 9.2 months with nab-paclitaxel plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.

Frontline Liposomal Irinotecan/NALIRIFOX Confers OS Benefit in Metastatic Pancreatic Ductal Adenocarcinoma

The median overall survival with nivolumab plus chemotherapy was 12.8 months, vs 10.7 months with chemotherapy alone, in patients with treatment-naïve advanced esophageal squamous cell carcinoma.

CheckMate 648 Update Showcases Long-Term Survival Benefit With Frontline Nivolumab in ESCC 

An analysis of 141 children who had prenatal exposure to maternal cancer showed promising cognitive and behavioral functions at age 9 years. 

Children Exposed to Maternal Cancer Show Normal Cognitive and Behavioral Outcomes

Both the gastric and breast cancer HER2 scoring algorithms may be useful in determining which patients with metastatic colorectal cancer may derive benefit with tucatinib/ trastuzumab.

Retrospective MOUNTAINEER Analysis Sheds Light on Optimal HER2 Testing Practices in mCRC

Debi Fischer is a nurse at the University of Miami surgical oncology step down unit. Prior to that she worked in orthopedics and neurology for many years. In addition to her nursing experience, she has earned a master’s degree in social work. Becoming a Licensed Clinical Social Worker was a long-sought-after goal which she finally attained. She is a caregiver for her family and her dogs as well.

January is cervical cancer awareness month. This third article in a series highlights current cervical cancer treatment options.

Nurses Must Stay Up-to-Date With Treatments and Clinical Trials for Patients With Cervical Cancer

Gina Mauro currently serves as Vice President of Content at MJH Life Sciences, overseeing 

®. Gina joined the company in 2015 and has held various positions on 

Prior to joining MJH Life Sciences, she worked at Gannett as a full-time reporter with the Asbury Park Press. Email: gmauro@onclive.com

For patients with CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma, treatment with zolbetuximab/mFOLFOX6 yielded a progression-free survival (PFS) of 10.61 months whereas placebo/mFOLFOX6 resulted in a PFS of 8.67 months.

Zolbetuximab Plus mFOLFOX6 Extends Survival for Patients with CLDN18.2+ Advanced Gastric/GEJ Adenocarcinoma

Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

In an all-randomized population of patients with advanced gastric cancer, gastroesophageal junction, or esophageal adenocarcinoma, adding nivolumab to chemotherapy yielded a 21% reduction in the risk of death. 

Firstline Nivolumab/Chemotherapy Continues To Outperform Chemotherapy Alone for Advanced Gastric/GEJ/Esophageal Cancer At 3-Year Follow-Up

Patients with advanced hepatocellular carcinoma experienced similar health-related quality of life scores whether they received a combination of pembrolizumab and lenvatinib or lenvatinib and placebo.

Adding Pembrolizumab to Lenvatinib Yields Similar HRQOL Scores As Lenvatinib Alone in HCC

Kimberly A. Spickes, CNP, discusses how often patients with endometrial cancer have dose reductions or interruptions at her institution, and who is involved in the decision to dose-reduce.

Discussing Dose Reductions and Interruptions with Patients on Therapy for Endometrial Cancer

Nurse Practitioner Kimberly Halla explains the proactive measures she takes to ensure patients with endometrial cancer are prepared to experience and manage the adverse effects of treatment.

Proactive Adverse Effect Management for Patients on Therapy for Endometrial Cancer

Jamie Carroll, APRN, CNP, MSN, offers her perspective on emerging data from the 2022 San Antonio Breast Cancer Symposium. 

Carroll Highlights Data Presented at SABCS from the CARRIERS and RIGHT Choice Studies

The FDA has approved zanubrutinib for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The prescribing label comes with warnings for hemorrhage, infections, cytopenias, second primary malignancies, and cardiac arrythmias.


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