Publications by authors named "Jennifer G Le-Rademacher"

46 Publications

Hiccups in patients with cancer: a multi-site, single-institution study of etiology, severity, complications, interventions, and outcomes.

BMC Cancer 2022 Jun 15;22(1):659. Epub 2022 Jun 15.

Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: To our knowledge, previous studies have not investigated hiccups in patients with cancer with detailed patient-level data with the goal of capturing a broad spectrum of hiccup symptomatology.

Methods: This multi-site, single institution study examined consecutive medical records to better understand hiccups in patients with cancer.

Results: A total of 320 patients are the focus of this report. The median age of patients when hiccups were first reported in the medical record was 63 years (range: 21, 97 years) with 284 (89%) men and 36 (11%) women. The most common diagnose was gastrointestinal cancer. Hiccups most frequently occurred daily, as seen in 194 patients (62%), and the most common duration was less than 1 week, as seen in 146 patients (47%). However, nine patients had had daily hiccups for greater than 6 weeks, and 5 had symptoms for years. Cited etiology was non-chemotherapy medications in 36 (11%) and cancer chemotherapy in 19 (6%). Complications occurred in approximately a third and included insomnia in 51 patients (16%); hospitalization or emergency department visit in 34 (11%); and musculoskeletal pain in 23 (7%). Baclofen was the single most prescribed agent for hiccup palliation, but 100 patients received more than one medication. Medical procedures, which included acupuncture, paracentesis, or phrenic nerve block, were performed in 5 patients. In 234 patients (73%), the medical record documented hiccup cessation.

Conclusions: Hiccups appear to be highly problematic in a small subset of patients with cancer with no well-defined palliative approaches.
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http://dx.doi.org/10.1186/s12885-022-09760-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202213PMC
June 2022

Olanzapine for cisplatin-induced hiccups: observations from a 338-patient study.

Ann Palliat Med 2022 Jul 24;11(7):2314-2318. Epub 2022 Apr 24.

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Background: Several case reports suggest that olanzapine palliates hiccups. To our knowledge, however, no larger scale studies have confirmed that olanzapine prevents or palliatives hiccups. Hence, the current study sought to substantiate the conclusions from these earlier case reports.

Methods: This multi-site single institution study focused on cisplatin-treated cancer patients because this chemotherapy agent is associated with hiccups and because olanzapine is often used as an antiemetic with this agent. Relevant data were extracted from medical records. Hiccup incidence shortly after chemotherapy was compared between olanzapine exposed and non-exposed patients. Other relevant variables were also assessed descriptively in an exploratory manner.

Results: A total of 338 patients were studied. One hundred forty-one had received olanzapine and 197 had not. Twenty-one (6%) developed hiccups. Eleven (8%) of these patients with hiccups had received olanzapine, and 10 (5%) had not [odds ratio (OR): 1.58; 95% confidence interval (CI): 0.65-3.83; P=0.31]. Of note, hiccups were more often observed in men 17 of 188 (9%) than in women 4 of 150 (3%) (OR: 3.64; 95% CI: 1.20-11.02; P=0.01).

Conclusions: Despite previous case reports and despite the relatively low incidence of hiccups in this study, it does not appear olanzapine prevents or palliates hiccups. The study of other promising agents is warranted. Furthermore, this study invites caution in relying on single case reports in making clinical decisions.
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http://dx.doi.org/10.21037/apm-22-159DOI Listing
July 2022

"It's Like You Stuck a Pin in It:" African American/Black Patients Describe Cutaneous Toxicity From Epidermal Growth Factor Receptor Inhibitors.

Am J Hosp Palliat Care 2022 Apr 20:10499091221092698. Epub 2022 Apr 20.

Department of Oncology, 4352Mayo Clinic, Rochester, MN, USA.

: Epidermal growth factor receptor (EGFR) inhibitors cause cutaneous toxicity in over 90% of patients. Conceivably, healthcare providers could overlook such toxicity in African American/Black patients because of a darker complexion. This qualitative study sought to learn about such cutaneous signs and symptoms and, if present, to report them in patients' own words. : Any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor was eligible. The current report focuses on patients' responses to the following question, "What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?" All interview data were audio-recorded, transcribed, and then independently coded and analyzed by two investigators. : Fifteen patients are the focus of this report, and all described cutaneous toxicity. Patients appeared troubled by the cosmetic aspect of these drug-induced skin changes, including their acneiform appearance, describing "little pimples with little, little pus in it." Notable were comments on hyperpigmentation, "I'm a black person but…. became darker." Furthermore, patients experienced physical symptoms: "it itches;" "it's like you stuck a pin in it;" "stinging;" and "burning;". : Although cutaneous toxicity from EGFR inhibitors might be more difficult to visualize among darkly complected patients, the graphic descriptions offered in this qualitative study underscore the need for clinicians to heighten their awareness of such toxicity in African American/Black patients.
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http://dx.doi.org/10.1177/10499091221092698DOI Listing
April 2022

A Cautionary Tale: Grouping Patients on Late Events.

Mayo Clin Proc 2022 03 5;97(3):449-453. Epub 2022 Feb 5.

Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2021.11.003DOI Listing
March 2022

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients.

Medicine (Baltimore) 2021 Nov;100(47):e28033

Department of Oncology, Mayo Clinic, Rochester, MN.

Abstract: Ketogenic diets appear promising for obesity, diabetes, cancer, and other illnesses. Because older patients are more likely to contend with such illnesses and because of a paucity of dietary outcomes among these patients, we examined ketogenic diets in older patients.This multisite study focused on patients (≥65 years of age) on a ketogenic diet. Medical records were identified with the keywords "keto," "ketogenic," and "Atkins." Records were reviewed in detail with extraction of direct quotations to substantiate observations.We report on 200 consecutive patients with a median age of 70 years. Reasons for diet included weight loss, diabetes, and cancer; the majority remained on the diet for >1 month. In 134 (67%: 95% confidence interval: 60, 73%), the ketogenic diet appeared beneficial: 93 of 117 (79%) who sought weight loss lost weight ("She has lost 15 pounds and plans to lose another 8"); 36 of 67 (54%) who sought glucose control appeared to achieve the latter ("He has gone on a ketogenic diet and has been able to bring his sugars down significantly"); and 5 of 8 (63%) who sought improved cancer outcomes appeared to derive them ("He attributes part of the control of his cancer and increased QOL to adopting the keto for cancer diet"). Adverse events occurred in 30 patients (15%): dyslipidemia (n = 14), constipation (n = 9), sub-therapeutic international normalized ratio (n = 3), pancreatitis (n = 2), diarrhea (n = 1), and fatigue (n = 1).Trials that test ketogenic diets for a variety of illnesses should enroll older adults.
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http://dx.doi.org/10.1097/MD.0000000000028033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615410PMC
November 2021

Does the cancer geriatric assessment (GA) introduce bias into clinical trials? Observations from 988 prospectively recruited patients.

J Geriatr Oncol 2022 05 15;13(4):526-529. Epub 2021 Dec 15.

Division of Clinical Trials and Biostatistics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jgo.2021.12.003DOI Listing
May 2022

Dexamethasone and hiccups: a 2000-patient, telephone-based study.

BMJ Support Palliat Care 2021 Dec 13. Epub 2021 Dec 13.

Department of Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA

Objectives: Dexamethasone causes hiccups in an undefined percentage of patients, and these hiccups are often ignored ('My doctors just shook their heads like I was joking …'). This study sought to learn the percentage of dexamethasone-treated patients who develop hiccups and to explore patients' responses to the availability of educational materials on hiccups.

Methods: English-speaking, adult outpatients treated with oral, intravenous or epidural dexamethasone 2 weeks prior were contacted by phone and asked about hiccups. Educational materials were offered, and patients were queried on their opinion of the availability of such materials.

Results: One hundred and twenty-seven patients or 11% (95% CI 9% to 13%) reported hiccups. This percentage was derived from 1186 reachable patients from 2000 total patients. Fifty-four (43%) of those with hiccups desired to learn about educational materials. Of these, 49 completed a single-item, 5-point scale item: 21 (43%) viewed the availability of educational materials 'extremely helpful,' providing a 5 rating; 8 (16%) provided a 4; 4 (8%) provided a 3; and 1 (4%) provided a 2.

Conclusions: Dexamethasone-induced hiccups occur in a small percentage of patients. The fact that most patients responded favourably to learning about the availability of educational materials suggests some have unmet needs.
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http://dx.doi.org/10.1136/bmjspcare-2021-003474DOI Listing
December 2021

Observations with alpelisib in older patients (≥ 65 year of age) with breast cancer in a non-clinical trial setting.

Breast Cancer Res Treat 2021 Jul 12;188(1):15-20. Epub 2021 Jun 12.

Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Purpose: Alpelisib is newly-available breast cancer agent that targets PIK3 mutations and confers a somewhat unusual adverse event profile. This study focused on older patients (≥ 65 years of age) treated outside a clinical trial to gain further experience on how these under-studied patients do with this new agent.

Methods: This descriptive, multi-site study relied on medical record review.

Results: Fifty-one older breast cancer patients were started on alpelisib between May 2019 and September 2020. The median age and number of comorbidities at alpelisib initiation was 71 years and 4, respectively. Thirty-five patients had stopped alpelisib (median time on drug 2.6 months (range: < 1, 9.5 months)) for the following reasons: alpelisib adverse events (n = 15), cancer progression (n = 13), and other/unknown (n = 7). Alpelisib adverse events included hyperglycemia (n = 37), diarrhea (n = 23), rash (n = 19), fatigue (n = 12), and mouth sores (n = 7); (numbers in parentheses indicate the number of patients with at least one such event). Five patients were hospitalized for hyperglycemia. At the time of report, 14 patients were deceased, and median survival had not been reached.

Conclusion: Older patients might derive further benefit from alpelisib if the adverse event profile of this agent, particularly the hyperglycemia, were able to be better managed.
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http://dx.doi.org/10.1007/s10549-021-06277-6DOI Listing
July 2021

How Did a Multi-Institutional Trial Show Feasibility of Electronic Data Capture in Older Patients With Cancer? Results From a Multi-Institutional Qualitative Study (Alliance A171902).

JCO Clin Cancer Inform 2021 04;5:442-449

Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.

Purpose: New technology might pose problems for older patients with cancer. This study sought to understand how a trial in older patients with cancer (Alliance A171603) was successful in capturing electronic patient-reported data.

Methods: Study personnel were invited via e-mail to participate in semistructured phone interviews, which were audio-recorded and qualitatively analyzed.

Results: Twenty-four study personnel from the 10 sites were interviewed; three themes emerged. The first was that successful patient-reported electronic data capture shifted work toward patients and toward study personnel at the beginning of the study. One interviewee explained, "I mean it kind of lost all advantages…by being extremely laborious." Study personnel described how they ensured electronic devices were charged, wireless internet access was up and running, and login codes were available. The second theme was related to the first and dealt with data filtering. Study personnel described high involvement in data gathering; for example, one interviewee described, "I answered on the iPad, whatever they said. They didn't even want to use it at all." A third theme dealt with advantages of electronic data entry, such as prompt data availability at study completion. Surprisingly, some remarks described how electronic devices brought people together, "Some of the patients, you know, it just gave them a chance to kinda talk about, you know, what was going on."

Conclusion: High rates of capture of patient-reported electronic data were viewed favorably but occurred in exchange for increased effort from patients and study personnel and in exchange for data that were not always patient-reported in the strictest sense.
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http://dx.doi.org/10.1200/CCI.20.00164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213258PMC
April 2021

Electronic Geriatric Assessment: Is It Feasible in a Multi-Institutional Study That Included a Notable Proportion of Older African American Patients? (Alliance A171603).

JCO Clin Cancer Inform 2021 04;5:435-441

City of Hope Comprehensive Cancer Center, Duarte, CA.

Purpose: This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting.

Methods: Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients.

Results: A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1).

Conclusion: The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.
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http://dx.doi.org/10.1200/CCI.20.00163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240783PMC
April 2021

Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms). The study population N08Cx included 692 participants from three clinical trials (North Central Cancer Treatment Group (NCCTG) N08C1, N08CA, and N08CB) who had been treated with paclitaxel, paclitaxel plus carboplatin, or oxaliplatin. The primary endpoint for the GWAS was the change from pre-chemotherapy CIPN20 sensory score to the worse score over the following 18 weeks. Study population The Mayo Clinic Breast Disease Registry (MCBDR) consisted of 381 Mayo Clinic Breast Disease Registry enrollees who had been treated with taxane or platinum-based chemotherapy. The primary endpoint for the GWAS assessed was the earliest CIPN20 sensory score available after the completion of chemotherapy. In multivariate model analyses, chemotherapy regimen ( = 3.0 × 10) and genetic ancestry ( = 0.007) were significantly associated with CIPN in the N08Cx population. Only age ( = 0.0004) was significantly associated with CIPN in the MCBDR population. The SNP most associated with CIPN was rs56360211 near ( =7.92 × 10) in N08Cx and rs113807868 near in the MCBDR ( = 1.27 × 10). Due to a lack of replication, we cannot conclude that we identified any genetic predictors of CIPN.
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http://dx.doi.org/10.3390/cancers13051084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959452PMC
March 2021

Preemptive Versus Reactive Topical Clobetasol for Regorafenib-Induced Hand-Foot Reactions: A Preplanned Analysis of the ReDOS Trial.

Oncologist 2021 07 6;26(7):610-618. Epub 2021 Mar 6.

Mayo Clinic, Scottsdale, Arizona, USA.

Background: Hand-foot skin reaction (HFSR) is the most common regorafenib-induced adverse event and is in need of effective prevention and palliation.

Materials And Methods: The Regorafenib Dose Optimization Study (ReDOS), a four-arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib.

Results: Sixty-one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p = .03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p = .35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p = .02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p = .12). Patient-reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol-induced adverse events were reported.

Conclusion: Preemptive clobetasol might lessen regorafenib-induced hand-foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort.

Implications For Practice: Regorafenib causes hand-foot skin reactions. Preemptive clobetasol, a high-potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients.
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http://dx.doi.org/10.1002/onco.13730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265366PMC
July 2021

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach.

Cancers (Basel) 2021 Feb 10;13(4). Epub 2021 Feb 10.

Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.

Health-related quality of life (HRQOL) is an important prognostic patient-reported outcome in oncology. Because prior studies suggest that HRQOL is, in part, heritable, we performed a GWAS to elucidate genetic factors associated with HRQOL in breast cancer survivors. Physical and mental HRQOL were measured via paper surveys that included the PROMIS-10 physical and mental health domain scales in 1442 breast cancer survivors participating in the Mayo Clinic Breast Disease Registry (MCBDR). In multivariable regression analyses, age and financial concerns were significantly associated with global physical health (age: = 1.6 × 10; financial concerns: = 4.8 × 10) and mental health (age: = 3.5 × 10; financial concerns: = 2.0 × 10. Chemotherapy was associated with worse global mental health ( = 0.01). In the GWAS, none of the SNPs reached the genome-wide association significance threshold of 5 × 10 for associations with either global physical or global mental health, however, a cluster of SNPs in , particularly rs112718371, appeared to be linked to worse global physical health ( = 5.21 × 10). Additionally, SNPs in and were also moderately associated with worse physical and mental health ( < 10). These biologically plausible candidate SNPs warrant further study as possible predictors of HRQOL.
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http://dx.doi.org/10.3390/cancers13040716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916362PMC
February 2021

Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis.

J Pain Symptom Manage 2021 06 27;61(6):1247-1253. Epub 2020 Nov 27.

Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Context: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN).

Objective: The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN.

Methods: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period.

Results: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life.

Conclusions: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.11.025DOI Listing
June 2021

Non-Squamous, Non-Basal Cell Cancers of the Skin: Exploring Associations Between Site of Disease and Depression.

Am J Hosp Palliat Care 2021 Aug 15;38(8):979-982. Epub 2020 Nov 15.

Division of Medical Oncology, 6915Mayo Clinic, Rochester, MN, USA.

Background: Earlier studies report a direct association between diseases of the skin-particularly those on the face-and depression. However, to our knowledge, such associations have not been examined in patients with non-squamous, non-basal call skin cancers.

Methods: The primary goal was to assess whether malignant skin disease-specifically on the face as opposed to other sites-was associated with depression. The medical records of patients with cutaneous cancer (either primary or metastatic but non-squamous, non-basal cell) were reviewed for the relevant data.

Results: One hundred and sixty-five patients were studied. Only 23 patients (14%) had metastases to the face, and 115 (70%) had a readily viewable skin cancer. Twenty-one patients (13%) developed depression after a diagnosis of cutaneous cancer (of note, the rate of missing data for depression was 37%). Only one patient with facial cutaneous cancer manifested depression, yielding an odds ratio for not developing depression (95% confidence interval (CI)) of 4.4 (0.5,35); p = 0.13. Depression appeared to occur more often in women (62% versus 43%), patients with a history of depression (52% versus 6%), and younger patients (median age with and without depression 55 years and 67 years, respectively).

Conclusion: In contrast to other cutaneous diseases, no association was found between cutaneous cancer to the face and depression. Nonetheless, high rates of missing data underscore the need to focus on depression in patients with cutaneous cancers in the future.
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http://dx.doi.org/10.1177/1049909120969605DOI Listing
August 2021

Adverse Event Burden Score-A Versatile Summary Measure for Cancer Clinical Trials.

Cancers (Basel) 2020 Nov 4;12(11). Epub 2020 Nov 4.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.

This article introduces the adverse event (AE) burden score. The AE burden by treatment cycle is a weighted sum of all grades and AEs that the patient experienced in a cycle. The overall AE burden score is the total AE burden the patient experienced across all treatment cycles. AE data from two completed Alliance multi-center randomized double-blind placebo-controlled trials, with different AE profiles (NCCTG 97-24-51: 176 patients, and A091105: 83 patients), were utilized for illustration. Results of the AE burden score analyses corroborated the trials' primary results. In 97-24-51, the overall AE burden for patients on the treatment arm was 2.2 points higher than those on the placebo arm, with a higher AE burden for patients who went off treatment early due to AE. Similarly, in A091105, the overall AE burden was 1.6 points higher on the treatment arm. On the placebo arms, the AE burden in 97-24-51 remained constant over time; and increased in later cycles in A091105, likely attributable to the increase in disease morbidity. The AE burden score enables statistical comparisons analogous to other quantitative endpoints in clinical trials, and can readily accommodate different trial settings, diseases, and treatments, with diverse AE profiles.
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http://dx.doi.org/10.3390/cancers12113251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694214PMC
November 2020

Editorial: What about weight? Advocating for simplicity in cancer cachexia trials.

Curr Opin Support Palliat Care 2020 12;14(4):302-303

Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1097/SPC.0000000000000527DOI Listing
December 2020

Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

CA Cancer J Clin 2021 01 1;71(1):78-92. Epub 2020 Oct 1.

Department of Supportive Care Medicine, City of Hope National Medical Center, Duarte, California.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.
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http://dx.doi.org/10.3322/caac.21638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854940PMC
January 2021

Toxicity and survival outcomes in older adults receiving concurrent or sequential chemoradiation for stage III non-small cell lung cancer in Alliance trials (Alliance A151812).

J Geriatr Oncol 2021 05 16;12(4):563-571. Epub 2020 Sep 16.

Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, United States of America; Mayo Clinic, Rochester, MN, United States of America.

Introduction: Optimal treatment for older adults with stage III non-small cell lung cancer (NSCLC) remains unclear. Here we hypothesized that sequential chemoradiation therapy (sCRT) is better tolerated than concurrent (cCRT) but confers acceptable efficacy. We evaluated these strategies in older adults utilizing Alliance for Clinical Trials in Oncology data.

Materials And Methods: Pooled analyses from 6 first-line stage III NSCLC CRT trials (Cancer and Leukemia Group B 8433, 8831, 9130, 30106, 30407, 39801) were used to compare toxicity and survival outcomes with cCRT versus sCRT in patients age ≥ 65 years. Grade 3-5 adverse events (AEs), progression-free and overall survival (PFS; OS) are reported with adjustment for covariates.

Results: Four hundred older adults, of whom 106 (26.5%) had received sCRT and 294 (73.5%) had received cCRT, comprised the cohorts. Virtually all had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (99%). More grade 3-5 AEs were observed at any time-point with cCRT than sCRT (94.2% versus 86.8%; 95% confidence interval for difference in proportions, 1.3%, 15.5%) and this finding remained after adjusting for length of study treatment (P = 0.018). Comparable PFS and OS were observed with sCRT versus cCRT (median: 8.0 versus 9.2 months; median: 11.9 versus 13.4 months, respectively) even after adjustment for age, sex, ECOG PS, body mass index, pretreatment weight loss, stage, and cisplatin-based therapy (P = 0.604 and P = 0.906, respectively).

Discussion: These data show that sCRT was associated with less toxicity than cCRT with no associated statistically significant decrease in efficacy outcomes and that sCRT merits further study in this population.
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http://dx.doi.org/10.1016/j.jgo.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960567PMC
May 2021

The Importance of a Cause-Based Protocol to Approach Cancer-Related Nausea and Vomiting-Reply.

JAMA Oncol 2020 11;6(11):1812-1813

University of Alabama Birmingham Comprehensive Cancer Center.

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http://dx.doi.org/10.1001/jamaoncol.2020.3706DOI Listing
November 2020

Guidelines for Statistical Reporting in Medical Journals.

J Thorac Oncol 2020 11 25;15(11):1722-1726. Epub 2020 Aug 25.

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Statistical methods are essential in medical research. They are used for data analysis and drawing appropriate conclusions. Clarity and accuracy of statistical reporting in medical journals can enhance readers' understanding of the research conducted and the results obtained. In this manuscript, we provide guidelines for statistical reporting in medical journals for authors to consider, with a focus on the Journal of Thoracic Oncology.
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http://dx.doi.org/10.1016/j.jtho.2020.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642026PMC
November 2020

Understanding Verbosity: Funding Source and the Length of Consent Forms for Cancer Clinical Trials.

J Cancer Educ 2021 12;36(6):1248-1252

Section of Cancer Center Biostatistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Consent forms are an important educational tool that helps cancer patients decide on whether or not to enroll on a clinical trial, but wordiness potentially detracts from their educational value. This single-institution study examined word counts of consent forms for all phase I, II, and III solid tumor clinical trials between 2004 and 2010. Consent forms were categorized by trial funding source: (1) pharmaceutical company; (2) National Clinical Trials Network (NCTN); (3) R01- or other non-government grants; and (4) mixed (funding from multiple sources). Three hundred fifteen consent forms were studied; these included 106 (34%) pharmaceutical company; 145 (46%) NCTN; 44 (14%) R01 type; and 20 (6%) mixed. The overall median word count was 5129 words per consent form (interquartile range (IQR) range, 4226 to 6695). The median word counts per consent form (IQR) were 5648 (4814, 6803), 5243 (4139, 6932), 4365 (3806, 5124), and 4319 (3862, 5944), respectively, based on the above funding sources, showing that pharmaceutical company trial consent forms had the highest median word count. Of note, phase of trial was associated with consent form length (phase III were wordier), and consent forms manifested a consistent increase in wordiness over time. These observations underscore a timely need to find ways to limit the verbosity of consent forms, particularly in those from pharmaceutical company trials.
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http://dx.doi.org/10.1007/s13187-020-01757-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648720PMC
December 2021

Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial.

JAMA Oncol 2020 06;6(6):895-899

Mayo Clinic, Rochester, Minnesota.

Importance: Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer.

Objective: To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.

Design, Setting, And Participants: This study is a double-line, placebo-controlled, randomized clinical trial conducted from July 2017 through April 2019, with analysis conducted in 2019. Eligible participants were outpatients with advanced cancer who had persistent nausea/vomiting without having had chemotherapy or radiotherapy in the prior 14 days. Chronic nausea was present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale).

Interventions: Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days.

Main Outcomes And Measures: Patient-reported outcomes were used for study end points. Data were collected at baseline and daily for 7 more days. The primary study end point (the change in nausea numeric rating scores from baseline to the last treatment day) and the study hypothesis were both identified prior to data collection.

Results: A total of 30 patients (15 per arm) were enrolled; these included 16 women and 14 men who had a mean (range) age of 63 (39-79) years. Baseline median nausea scores, in all patients, were 9 out of 10 (range, 8-10). After 1 day and 1 week, the median nausea scores in the placebo arm were 9 out of 10 (range, 8-10) on both days, compared with the olanzapine arm scores of 2 out of 10 (range, 2-3) after day 1 and 1 out of 10 (range, 0-3) after 1 week. After 1 week of treatment, the reduction in nausea scores in the olanzapine arm was 8 points (95% CI, 7-8) higher than that of the placebo arm. The primary 2-sided end point P value was <.001. Correspondingly, patients in the olanzapine arm reported less emesis, less use of other antiemetic drugs, better appetite, less sedation, less fatigue, and better well-being. One patient, on the placebo, stopped treatment early owing to lack of perceived benefit. No patients receiving olanzapine reported excess sedation or any other adverse event.

Conclusions And Relevance: Olanzapine, at 5 mg/d, appeared to be effective in controlling nausea and emesis and in improving other symptoms and quality-of-life parameters in the study population.

Trial Registration: ClinicalTrials.gov Identifier: NCT03137121.
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http://dx.doi.org/10.1001/jamaoncol.2020.1052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206532PMC
June 2020

Neurological safety of oxaliplatin in patients with uncommon variants in Charcot-Marie-tooth disease genes.

J Neurol Sci 2020 Apr 14;411:116687. Epub 2020 Jan 14.

Department of Health Sciences Research (Biomedical Statistics and Informatics), Mayo Clinic, Rochester, MN, USA; Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.

Oxaliplatin therapy can be complicated by chemotherapy-induced peripheral neuropathy (CIPN). Other neurotoxic chemotherapies have been linked to single nucleotide variants (SNV) in Charcot-Marie-Tooth disease (CMT) genes. Whether oxaliplatin carries increased risks of CIPN due to SNV in CMT-associated genes is unknown. 353 patients receiving oxaliplatin in NCCTG N08CB were serially evaluated for CIPN using a validated patient-reported outcome (PRO) instrument, the CIPN20 questionnaire (sensory scale). 49 canonical CMT-associated genes were analyzed for rare and common SNV by nextgen sequencing. The 157 patients with the highest and lowest susceptibility to CIPN (cases and controls) harbored 270 non-synonymous SNV in CMT-associated genes (coding regions). 143 of these were rare, occurring only once ("singletons"). CIPN cases had 0.84 singletons per patient compared with 0.98 in controls. An imbalance in favor of cases was noted only in few genes including PRX, which was previously highlighted as a candidate CIPN gene in patients receiving paclitaxel. However, the imbalance was only modest (5 singleton SNV in cases and 2 in controls). Therefore, while singleton SNV were common, they did overall not portend an increased risk of CIPN. Furthermore, testing CMT-associated genes using recurrent non-synonymous SNV did not reveal any significant association with CIPN. Genetic analysis of patients from N08CB provides clinical guidance that oxaliplatin chemotherapy decisions should not be altered by the majority of SNV that may be encountered in CMT-associated genes when common genetic tests are performed, such as exome or genome sequencing. Oxaliplatin's CIPN risk appears unrelated to CMT-associated genes.
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http://dx.doi.org/10.1016/j.jns.2020.116687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096263PMC
April 2020

Impact of MYD88 mutation status on histological transformation of Waldenström Macroglobulinemia.

Am J Hematol 2020 03 31;95(3):274-281. Epub 2019 Dec 31.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88 mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88 mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88 mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88 status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P = .003). Additionally, the MYD88 status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P = .001]), with a 5-year transformation rate of 16% for MYD88 vs 2.8% with MYD88 mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P < .001). In conclusion, the MYD88 status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.
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http://dx.doi.org/10.1002/ajh.25697DOI Listing
March 2020

Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial.

J Thromb Haemost 2020 02 28;18(2):411-421. Epub 2019 Nov 28.

Medical Oncology Department, Mayo Clinic, Rochester, Minnesota.

Background: Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, limited data support its use in cancer patients.

Objectives: The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding (CRNMB).

Patients/methods: Patients with cancer-associated VTE were randomly assigned to receive either apixaban 10 mg twice daily for seven days followed by 5 mg twice daily for six months or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg once daily).

Results: Of 300 patients randomized, 287 were included in the primary analysis. Metastatic disease was present in 66% of subjects; 74% were receiving concurrent chemotherapy. Major bleeding occurred in 0% of 145 patients receiving apixaban, compared with 1.4% of 142 patients receiving dalteparin [P = .138; hazard ratio (HR) not estimable because of 0 bleeding event in apixaban group]. Recurrent VTE occurred in 0.7% of apixaban, compared to 6.3% of dalteparin patients [HR 0.099, 95% confidence interval [CI], 0.013-0.780, P = .0281). Major bleeding or CRNMB rates were 6% for both groups.

Conclusions: Oral apixaban was associated with low major bleeding and VTE recurrence rates for the treatment of VTE in cancer patients.
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http://dx.doi.org/10.1111/jth.14662DOI Listing
February 2020

Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE trial.

Eur J Haematol 2020 Feb 11;104(2):88-96. Epub 2019 Nov 11.

Vascular Medicine Division, Gonda Vascular Center, Mayo Clinic, Rochester, Minnesota.

Background: Cancer-associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA-approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double-blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883).

Methods/design: The primary study objective is to estimate differences in the combined rate of major plus clinically relevant non-major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium.

Conclusion: We anticipate these trial results to provide evidence supporting low-dose apixaban as a safe agent for secondary prevention of cancer-associated VTE for patients who have already completed 6-12 months of anticoagulation.
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http://dx.doi.org/10.1111/ejh.13338DOI Listing
February 2020

Comparative Age-Based Prospective Multi-Institutional Observations of 12,367 Patients Enrolled to the American College of Surgeons Oncology Group (ACOSOG) Z901101 Trials (Alliance).

Ann Surg Oncol 2019 Dec 11;26(13):4213-4221. Epub 2019 Oct 11.

Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.

Background: The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients.

Methods: This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts.

Results: The study enrolled 12,367 patients. The median age was 60 years, and 36% of the patients were 65 years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65 years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3-1.7; p < 0.0001]. This association was not observed in multivariate analyses. The study protocol was completed by 97% of the patients. No association was observed between age and trial completion (OR 0.8; 95% CI 0.7-1.1; p = 0.14). Only the older gastrointestinal cancer trial patients were less likely to complete their studies compared to younger patients (OR 0.50; 95% CI 0.30-0.70; p < 0.0001).

Conclusion: Despite higher rates of adverse events, the older patients typically completed the study protocol, thereby contributing relevant data on how best to render care to older cancer patients and affirming the important role of enrolling these patients to surgical trials.
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http://dx.doi.org/10.1245/s10434-019-07851-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868343PMC
December 2019

Remarks on the design and analyses of longitudinal studies for cancer patients with anorexia and weight loss.

J Cachexia Sarcopenia Muscle 2019 12 20;10(6):1175-1182. Epub 2019 Aug 20.

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Longitudinal data serve an important role in understanding the cancer anorexia weight loss syndrome and in testing interventions to palliative and treat patients who develop this syndrome. The element of time and the interrelatedness of data points define longitudinal data and add to the richness of this type of data. However, longitudinal data can also give rise to non-random, missing data that can lead to flawed conclusions. This paper discusses these issues and suggests practical considerations for design and analysis of longitudinal cancer anorexia weight loss studies.
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http://dx.doi.org/10.1002/jcsm.12480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903440PMC
December 2019

Scrambler therapy for chemotherapy neuropathy: a randomized phase II pilot trial.

Support Care Cancer 2020 Mar 17;28(3):1183-1197. Epub 2019 Jun 17.

Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent clinical problem, with limited effective therapies. Preliminary non-randomized clinical trial data support that Scrambler Therapy is helpful in this situation.

Methods: Patients were eligible if they had CIPN symptoms for at least 3 months and CIPN-related tingling or pain at least 4/10 in severity during the week prior to registration. They were randomized to receive Scrambler Therapy versus transcutaneous electrical nerve stimulation (TENS) for 2 weeks. Patient-reported outcomes (PROs) were utilized to measure efficacy and toxicity daily for 2 weeks during therapy and then weekly for 8 additional weeks.

Results: This study accrued 50 patients, 25 to each of the 2 study arms; 46 patients were evaluable. There were twice as many Scrambler-treated patients who had at least a 50% documented improvement during the 2 treatment weeks, from their baseline pain, tingling, and numbness scores, when compared with the TENS-treated patients (from 36 to 56% compared with 16-28% for each symptom). Global Impression of Change scores for "neuropathy symptoms," pain, and quality of life were similarly improved during the treatment weeks. Patients in the Scrambler group were more likely than those in the TENS group to recommend their treatment to other patients, during both the 2-week treatment period and the 8-week follow-up period (p < 0.0001). Minimal toxicity was observed.

Conclusions: The results from this pilot trial were positive, supporting the conduct of further investigations regarding the use of Scrambler Therapy for treating CIPN.
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http://dx.doi.org/10.1007/s00520-019-04881-3DOI Listing
March 2020
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