Publications by authors named "Charles L Loprinzi"

263 Publications

Does the placebo effect on hot flashes depend on the placebo dose?

Support Care Cancer 2021 May 11. Epub 2021 May 11.

Biomedical Statistics and Informatics - Cancer Statistics, Mayo Clinic, MN, Rochester, USA.

Purpose: To investigate the presence of a placebo dose-response effect in four randomized, double-blind, placebo-controlled, multi-dose hot flash clinical trials conducted at Mayo Clinic.

Methods: Hot flash score, frequency, and hot flash-related distress for each placebo dose level were summarized at each time point by mean and standard deviation and changes from baseline were plotted to visualize a possible placebo dose-effect response. Furthermore, a meta-analysis was conducted for each endpoint in the highest and lowest dosage arms across the four trials.

Results: Longitudinal plots of mean hot flash scores, frequencies, and hot flash-related distress scores in patients taking placebo in each study showed a decline in hot flash scores over time without any clinically meaningful differences between the lowest and highest dosage arms in each study. The meta-analysis for each endpoint in the highest and lowest dosage arms across the four trials revealed no clinically important differences either.

Conclusion: While the current study cannot rule out the existence of a placebo dose-response effect in multi-dose placebo-controlled trials in patients with hot flashes or other conditions, it suggests, along with the available data in the placebo literature, that, at least in well-conducted multi-dose clinical trials in which the placebo was used as control, such an effect, if it exists at all, should be very small. Therefore, pooling data from different placebo subgroups is unlikely to compromise the validity of comparisons between the combined placebo arms and each treatment arm.
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http://dx.doi.org/10.1007/s00520-021-06244-3DOI Listing
May 2021

Natural history of nasal vestibulitis associated with paclitaxel, docetaxel, and other chemotherapy agents: a Minnesota Cancer Clinical Trials Network (MNCCTN) study.

Support Care Cancer 2021 Apr 13. Epub 2021 Apr 13.

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

Purpose: To describe the natural history of nasal vestibulitis in patients receiving taxane chemotherapy, including incidence, severity, and associated symptoms.

Methods: Eligible patients with minimal or no baseline nasal symptoms were enrolled in this natural history study at initiation of a new chemotherapy regimen. Patients completed nasal symptom logs each time they received a chemotherapy dose. This manuscript reports upon the patients who received paclitaxel, docetaxel, or non-taxane non-bevacizumab chemotherapy. The proportions of patients within each cohort reporting any treatment-emergent nasal symptoms were estimated, with corresponding exact 95% confidence intervals. A cumulative incidence function was estimated within the chemotherapy cohorts to calculate the cumulative incidence rate of treatment-emergent nasal vestibulitis, treating death and disease progression as competing risks.

Results: Of the 81 evaluable patients, nasal symptoms were reported by 76.5% (58.8%, 89.3%) receiving paclitaxel, 54.2% (32.8%, 74.5%) receiving docetaxel, and 47.8% (26.8%, 69.4%) receiving non-taxane and non-bevacizumab chemotherapy. Of the three pairwise chemotherapy group comparisons, both the tests comparing the cumulative incidence function between the paclitaxel and non-taxane non-bevacizumab chemotherapy cohorts and between the paclitaxel and docetaxel cohorts achieved statistical significance at the 5% level with a higher incidence of treatment-emergent nasal vestibulitis in the paclitaxel cohort in both comparisons (P = 0.026 and P = 0.035, respectively). These significant differences were retained in the cumulative incidence function regression analysis controlling for age, smoking history, allergies, and asthma. Most patients in the paclitaxel cohort reported nasal symptoms as moderate or severe (56%).

Conclusion: Patients receiving paclitaxel chemotherapy experience a high incidence of nasal symptoms.
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http://dx.doi.org/10.1007/s00520-021-06190-0DOI Listing
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

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

Patient-reported sexual function of breast cancer survivors with genitourinary syndrome of menopause after fractional CO2 laser therapy.

Menopause 2021 Feb 1. Epub 2021 Feb 1.

The Ohio State University Medical Center, Columbus, OH Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH Mayo Clinic, Jacksonville, FL Mayo Clinic, Rochester, MN.

Objective: The objective of this pilot study was to evaluate the change in sexual function following treatment with fractional CO2 laser therapy in breast cancer (BC) survivors with genitourinary syndrome of menopause (GSM).

Methods: A single-arm feasibility study of BC survivors with symptoms of GSM, including dyspareunia and/or vaginal dryness, was conducted. Participants who received three treatments with fractional CO2 laser and 4-week follow-up were contacted for patient-reported outcomes and adverse events at 12 months. Sexual function was measured using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale Revised (FSDS-R). Descriptive statistics were calculated for patient demographics and disease characteristics for the set of participants who agreed to long-term follow-up and those who were lost to follow-up. FSFI and FSDS-R scores were summarized at baseline, 4 weeks and 12 months, as well as the change from baseline, and were compared using a Wilcoxon signed rank test.

Results: A total of 67 BC survivors enrolled, 59 completed treatments and 4-week follow-up; 39 participated in the 12 month follow-up. The overall FSFI score improved from baseline to 4-week follow-up (median Δ 8.8 [Q1, Q3] (QS) (2.2, 16.7)], P < 0.001). There were improvements at 4 weeks in all domains of the FSFI (P < 0.001 for each) including desire (median Δ 1.2; QS [0.6, 1.8]), arousal (median Δ 1.2; QS [0.3, 2.7]), lubrication (median Δ 1.8 (0, 3.3), orgasm (median Δ 1.2; QS [0, 3.6]), satisfaction (median Δ 1.6 (0.4, 3.2)), and pain (median Δ 1.6 (0, 3.6). The FSDS-R score also improved from baseline to 4-week follow-up (median Δ -10.0; QS [-16, -5] P < 0.001) indicating less sexually related distress. The scores of the FSFI and FSDS-R remained improved at 12 months and there were no serious adverse events reported.

Conclusions: In BC survivors with GSM, the total and individual domain scores of the FSFI and the FSDS-R improved after fractional CO2 laser therapy.

Video Summary:http://links.lww.com/MENO/A711.
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http://dx.doi.org/10.1097/GME.0000000000001738DOI Listing
February 2021

Pilot study of fractional CO laser therapy for genitourinary syndrome of menopause in gynecologic cancer survivors.

Maturitas 2021 Feb 2;144:37-44. Epub 2020 Dec 2.

The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, OH, United States.

Purpose: The objectives of this study were to evaluate the feasibility and efficacy of fractional CO laser therapy in gynecologic cancer survivors.

Methods: This was a pilot, multi-institutional randomized sham-controlled trial of women with gynecologic cancers with dyspareunia and/or vaginal dryness. Participants were randomized to fractional CO laser treatment or sham laser treatment. The primary aim was to estimate the proportion of patients who had improvement in symptoms based on the Vaginal Assessment Scale (VAS). Secondary aims included changes in sexual function assessed using the Female Sexual Functioning Index (FSFI) and urinary symptoms assessed using the the Urinary Distress Inventory (UDI-6).

Results: Eighteen women participated in the study, ten in the treatment arm and eight in the sham arm. The majority of participants had stage I (n = 11, 61.1 %) or II (n = 3, 16.7 %) endometrial cancer with adenocarcinoma histology (n = 9, 50 %). In total, 15 (83.3 %) of the participants completed all treatments and follow-up visit. There was no difference in the change in the median VAS score from baseline to follow-up. However, there was an improvement in change in the median total FSFI score with treatment compared with sham (Δ 6.5 vs -0.3, p = 0.02). The change in the median UDI-6 score was lower in the treatment arm (Δ -14.6 vs -2.1, p = 0.17), but this was not statistically significant. There were no reported serious adverse events.

Conclusions: Fractional CO laser therapy is feasible in gynecologic cancer survivors, with preliminary evidence of safety. In addition, there was preliminary evidence of improvement in sexual function compared with sham treatment. Clinicaltrial.gov Identifier: NCT03372720 (OSU-17261; NCI-2017-02051).
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http://dx.doi.org/10.1016/j.maturitas.2020.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773136PMC
February 2021

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

J Pain Symptom Manage 2020 Nov 27. 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
November 2020

Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group.

Support Care Cancer 2021 Jun 24;29(6):2821-2840. Epub 2020 Nov 24.

The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.

Cancer-related cognitive impairment (CRCI) is commonly experienced by individuals with non-central nervous system cancers throughout the disease and treatment trajectory. CRCI can have a substantial impact on the functional ability and quality of life of patients and their families. To mitigate the impact, oncology providers must know how to identify, assess, and educate patients and caregivers. The objective of this review is to provide oncology clinicians with an overview of CRCI in the context of adults with non-central nervous system cancers, with a particular focus on current approaches in its identification, assessment, and management.
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http://dx.doi.org/10.1007/s00520-020-05860-9DOI Listing
June 2021

Oncologists' Reluctance to Use the Terms and : A Bibliometric Analysis of Articles From Two High-Impact Oncology Journals.

JNCI Cancer Spectr 2020 Dec 14;4(6):pkaa065. Epub 2020 Aug 14.

University of Florida, Gainesville, FL, USA.

The words and are important terms in oncology, reflecting a balance of aspirations and realism for physicians and patients. Yet, some have suggested that oncologists are reluctant to use these terms. We tested this hypothesis by performing a bibliometric analysis of the frequency of use of these words in and the (). The text of all articles in 3 categories-primary research, editorials, and narrative essays-appearing in from 2000 to 2018 and in from 2015 to 2019 was analyzed. These analyses compared, across these categories, the proportion of articles containing the words and , as well as the proportion of total sentences containing these words. There were statistically significant differences in frequency of the use of the terms and as a function of the type of article published in the and (2-sided values ranging from .005 to <.001). Results were similar for both journals, with minor exceptions. Both and were used in a greater number of articles and sentences in the narrative and editorial categories than in primary research. Moreover, was used more often in narrative essays than in editorials. The relative reluctance to use these terms in more scientifically oriented original reports, despite concomitant improvements in oncologic outcomes, may reflect a bias worthy of future exploration.
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http://dx.doi.org/10.1093/jncics/pkaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666825PMC
December 2020

Reply to O. Huillard et al.

J Clin Oncol 2020 11 18;38(32):3819. Epub 2020 Sep 18.

Eric J. Roeland, MD, Massachusetts General Hospital Cancer Center, Boston, MA; and Charles L. Loprinzi, MD, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1200/JCO.20.02171DOI Listing
November 2020

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

JAMA Oncol 2020 Nov;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

Management of Aromatase Inhibitor-Induced Musculoskeletal Symptoms.

JCO Oncol Pract 2020 11 11;16(11):733-739. Epub 2020 Aug 11.

Department of Oncology, Mayo Clinic, Rochester, MD.

Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) were first recognized as a distinct entity in 2001, 5 years after the approval of the first aromatase inhibitor, anastrozole. Musculoskeletal symptoms can severely affect patients' quality of life and also lead to premature discontinuation of aromatase inhibitor therapy. Several interventions for managing AIMSS have been investigated in the last decade, with some demonstrating promise. This article provides an evidence-based summary to guide practicing oncologists in regard to the epidemiology, prevention, and treatment of AIMSS.
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http://dx.doi.org/10.1200/OP.20.00113DOI Listing
November 2020

Oral cinacalcet responsiveness in non-parathyroid hormone mediated hypercalcemia of malignancy.

Med Hypotheses 2020 Oct 30;143:110149. Epub 2020 Jul 30.

Department of Hematology & Oncology, Marshfield Clinic Health System, Weston Center, Weston, WI, USA.

Hypercalcemia of malignancy develops in approximately 20-30% of patients with advanced cancer and is an ominous sign. This condition is subdivided into three categories: i) humoral hypercalcemia of malignancy (80% of cases), mediated by systemic parathyroid hormone-related protein; ii) osteolytic metastases (20% of cases), mediated by inflammatory cytokines locally released by tumor cells and/or peri-tumor macrophages; and iii) ectopic production of 1,25-dihydroxyvitamin D (<1% of cases), leading to intestinal hyperabsorption of calcium and increased osteoclastic bone resorption. Humoral hypercalcemia of malignancy is seen in a variety of solid tumors, while osteolytic metastases are most common in breast cancer and multiple myeloma. Hypercalcemia of malignancy mediated by 1,25-dihydroxyvitamin D is primarily seen in lymphomas, having only rarely been reported in solid tumors. Pharmacologic management of humoral hypercalcemia of malignancy and osteolytic metastases mainly involves inhibition of bone resorption with intravenous bisphosphonates, subcutaneous denosumab, and subcutaneous calcitonin. Glucocorticoid therapy is the mainstay for management of increased 1,25-dihydroxyvitamin D. Unfortunately, management of hypercalcemia of malignancy often requires inpatient admission in the acute setting, and loss of effectiveness of antiresorptive therapy is common. We propose oral cinacalcet may be an efficacious therapy for hypercalcemia of malignancy related to elevated 1,25-dihydroxyvitamin D, and we present supporting data from two cases involving solid tumors. Furthermore, we hypothesize that this effect is primarily mediated by cinacalcet's interaction with the calcium-sensing receptor in the intestine with lesser effects at bone and kidney. Lastly, the role of 1,25-dihydroxyvitamin D in hypercalcemia malignancy may be underappreciated in solid tumors.
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http://dx.doi.org/10.1016/j.mehy.2020.110149DOI Listing
October 2020

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update.

J Clin Oncol 2020 10 14;38(28):3325-3348. Epub 2020 Jul 14.

Columbia University Medical Center, New York, NY.

Purpose: To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors.

Methods: An Expert Panel conducted targeted systematic literature reviews to identify new studies.

Results: The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update.

Recommendations: The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.
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http://dx.doi.org/10.1200/JCO.20.01399DOI Listing
October 2020

Cisplatin-associated neuropathy characteristics compared with those associated with other neurotoxic chemotherapy agents (Alliance A151724).

Support Care Cancer 2021 Feb 4;29(2):833-840. Epub 2020 Jun 4.

Mayo Clinic, Rochester, MN, USA.

Purpose: The current project was developed to obtain natural history information regarding cisplatin-induced peripheral neuropathy in males with testicular/germ cell cancers and to compare such neuropathy data with similarly obtained data in patients receiving other chemotherapy drugs in similarly conducted clinical trials.

Methods: Patients without baseline neuropathy symptoms, who were initiating cisplatin-based chemotherapy, completed the EORTC CIPN 20 patient-reported instrument to evaluate chemotherapy-induced peripheral neuropathy (CIPN). Results were compared with EORTC CIPN 20 data obtained from independent study sets regarding patients receiving (1) paclitaxel, (2) combined paclitaxel and carboplatin, (3) oxaliplatin, or (4) a combination of doxorubicin and cyclophosphamide (AC). The last study set of patients on AC was selected to evaluate the use of EORTC CIPN 20 data in patients receiving chemotherapy not known to cause CIPN.

Results: Cisplatin-induced neuropathy was more similar to neuropathy in patients receiving oxaliplatin than in those receiving paclitaxel. The cisplatin and oxaliplatin groups exhibited the coasting phenomenon and more prominent upper extremity symptoms than lower extremity symptoms during chemotherapy administration weeks. In contrast, paclitaxel-treated patients did not, on average, exhibit the coasting phenomenon; additionally, lower extremity symptoms were more prominent during the weeks when paclitaxel was administered. Cisplatin-induced neuropathy was less severe than was seen in patients in the other two groups, potentially because the cisplatin-receiving patients were younger. Patients receiving AC did not report substantial EORTC CIPN 20 changes.

Conclusion: Understanding neuropathy similarities and differences with various chemotherapy agents may help elucidate CIPN processes and facilitate means to prevent and/or treat established CIPN.

Trial Registration: NCT02677727.
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http://dx.doi.org/10.1007/s00520-020-05543-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714711PMC
February 2021

Olanzapine is an effective antiemetic agent.

Ann Palliat Med 2020 05;9(3):628-630

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

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http://dx.doi.org/10.21037/apm.2020.04.32DOI Listing
May 2020

Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice.

J Clin Invest 2020 09;130(9):4601-4606

Division of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.

Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells in oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventive strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that pharmacological targeting of OCT2 could be exploited to afford neuroprotection in cancer patients requiring treatment with oxaliplatin.
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http://dx.doi.org/10.1172/JCI136796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456253PMC
September 2020

Management of Cancer Cachexia: ASCO Guideline.

J Clin Oncol 2020 07 20;38(21):2438-2453. Epub 2020 May 20.

Mayo Clinic, Rochester, MN.

Purpose: To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer.

Methods: A systematic review of the literature collected evidence regarding nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations.

Results: The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions on efficacy. Limitations of the evidence include high drop-out rates, consistent with advanced cancer, as well as variability across studies in outcomes of interest and methods for outcome assessment.

Recommendations: Dietary counseling may be offered with the goals of providing patients and caregivers with advice for the management of cachexia. Enteral feeding tubes and parenteral nutrition should not be used routinely. In the absence of more robust evidence, no specific pharmacological intervention can be recommended as the standard of care; therefore, clinicians may choose not to prescribe medications specifically for the treatment of cancer cachexia. Nonetheless, when it is decided to trial a drug to improve appetite and/or improve weight gain, currently available pharmacologic interventions that may be used include progesterone analogs and short-term (weeks) corticosteroids.
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http://dx.doi.org/10.1200/JCO.20.00611DOI Listing
July 2020

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

A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthralgias: Alliance study A221102.

Support Care Cancer 2021 Jan 6;29(1):387-396. Epub 2020 May 6.

Mayo Clinic, Rochester, MN, USA.

Purpose: To evaluate the efficacy of testosterone supplementation for improving aromatase inhibitor musculoskeletal symptoms (AIMSS).

Methods: Postmenopausal women experiencing moderate-to-severe arthralgias while taking adjuvant aromatase inhibitors for breast cancer were enrolled in this trial. Initially, patients were randomly allocated to receive either a subcutaneous testosterone pellet versus a placebo pellet. Due to slow accrual, the protocol was modified such that additional participants were randomized to receive either a topical testosterone gel or a placebo gel. Changes in patient-reported joint pain were compared between patients receiving testosterone and those receiving placebo using a two-sample t test. Changes in hot flashes and other vasomotor symptoms were also analyzed. Further analyses were conducted to evaluate whether 27 single nucleotide polymorphisms (SNPs) in 14 genes previously associated with AIMSS were associated with testosterone supplementation benefit.

Results: While 64% of patients reported an improvement in joint pain at 3 months, there were no significant differences in average pain or joint stiffness at 3 or 6 months between testosterone and placebo arms. Patients receiving testosterone did report improvements in strength, lack of energy, urinary frequency, and stress incontinence (p < 0.05). The subset of patients receiving subcutaneous testosterone also experienced improvements in hot flashes and mood swings. An inherited variant (rs7984870 CC genotype) in TNFSF11 was more likely to be associated with improvements in hot flashes in patients receiving testosterone.

Conclusion: The doses of testosterone supplementation used in this study did not significantly improve AIMSS.

Trial Registration: ClinicalTrials.gov Identifier: NCT01573442.
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http://dx.doi.org/10.1007/s00520-020-05473-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644633PMC
January 2021

Oxybutynin vs Placebo for Hot Flashes in Women With or Without Breast Cancer: A Randomized, Double-Blind Clinical Trial (ACCRU SC-1603).

JNCI Cancer Spectr 2020 Feb 21;4(1):pkz088. Epub 2019 Oct 21.

Medical Oncology, Mayo Clinic, Rochester, MN.

Background: Hot flashes (HFs) negatively affect quality of life among perimenopausal and postmenopausal women. This study investigated the efficacy of oxybutynin vs placebo in decreasing HFs.

Methods: In this randomized, multicenter, double-blind study, women with and without breast cancer with 28 or more HFs per week, lasting longer than 30 days, who were not candidates for estrogen-based therapy, were assigned to oral oxybutynin (2.5 mg twice a day or 5 mg twice a day) or placebo for 6 weeks. The primary endpoint was the intrapatient change from baseline in weekly HF score between each oxybutynin dose and placebo using a repeated-measures mixed model. Secondary endpoints included changes in weekly HF frequency, HF-related daily interference scale questionnaires, and self-reported symptoms.

Results: We enrolled 150 women. Baseline characteristics were well balanced. Mean (SD) age was 57 (8.2) years. Two-thirds (65%) were taking tamoxifen or an aromatase inhibitor. Patients on both oxybutynin doses reported greater reductions in the weekly HF score (5 mg twice a day: -16.9 [SD 15.6], 2.5 mg twice a day: -10.6 [SD 7.7]), placebo -5.7 (SD 10.2);  < .005 for both oxybutynin doses vs placebo), HF frequency (5 mg twice a day: -7.5 [SD 6.6], 2.5 mg twice a day: -4.8 [SD 3.2], placebo: -2.6 [SD 4.3];  < .003 for both oxybutynin doses vs placebo), and improvement in most HF-related daily interference scale measures and in overall quality of life. Patients on both oxybutynin arms reported more side effects than patients on placebo, particularly dry mouth, difficulty urinating, and abdominal pain. Most side effects were grade 1 or 2. There were no differences in study discontinuation because of adverse effects.

Conclusion: Oxybutynin is an effective and relatively well-tolerated treatment option for women with HFs.
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http://dx.doi.org/10.1093/jncics/pkz088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050158PMC
February 2020

The Physical Consequences of Chemotherapy-Induced Peripheral Neuropathy.

Curr Oncol Rep 2020 04 22;22(5):50. Epub 2020 Apr 22.

Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA.

Purpose Of Review: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of numerous chemotherapy drugs. CIPN negatively impacts function and quality of life during and after treatment. We will provide a review of the data describing the physical consequences of CIPN and discuss the possible long term impact on emotional well-being and quality of life.

Recent Findings: CIPN negatively affects physical function and many aspects of quality of life. Exercise interventions are likely to reduce the risk of falls associated with CIPN. There remains a need for evidence-based interventions focused on improving symptoms, function, and quality of life in persons with CIPN.
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http://dx.doi.org/10.1007/s11912-020-00903-0DOI Listing
April 2020

A randomized phase II trial evaluating two non-pharmacologic interventions in cancer survivors for the treatment of sleep-wake disturbances: NCCTG N07C4 (Alliance).

Support Care Cancer 2020 Dec 19;28(12):6085-6094. Epub 2020 Apr 19.

Mayo Clinic Cancer Center, Rochester, MN, USA.

Purpose: Sleep disturbance is a prevalent problem for cancer survivors and effective behavioral treatments are not widely used for this population. This study evaluated home-based sleep interventions based on cognitive behavioral therapy for insomnia (CBT-I).

Methods: This phase II randomized controlled trial evaluated two manualized interventions over 7 weeks. The intervention group received sleep hygiene information, stimulus control, sleep restriction, and a bedtime imagery audio recording. The control group was similar, but without sleep restriction and used audio recordings of bedtime short stories instead of imagery. Eligibility included adult cancer survivors who had trouble falling asleep or falling back to sleep on 3 of 7 days. Patients with diagnoses of sleep or mental health disorders were excluded. The primary endpoint was change in time to fall asleep or falling back to sleep after awakening, from baseline to week 7. Two-sample T tests evaluated differences between arms for this endpoint.

Results: Ninety-three of 168 planned participants were enrolled from 20 institutions. The study closed early for poor accrual. Baseline time to sleep was 45 min and 52 min for the intervention and control group, respectively. At 7 weeks, both groups improved, the intervention group to 26 min and control group to 30 min, a non-significant difference between groups (p = 0.85). Secondary outcomes improved in both groups with no significant differences between arms.

Conclusions: Improvement in sleep outcomes in both arms was consistent with other CBT-I interventions delivered through alternative approaches to provider-delivered therapy. More research on optimal scalable delivery of CBT-I is needed.

Clinical Relevance: This study supports the effectiveness of CBT-I based behavioral interventions for sleep but also the need for better delivery methods to improve uptake and effect size.

Trial Registration: ClinicalTrials.gov identifier: NCT00993928.
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http://dx.doi.org/10.1007/s00520-020-05461-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572569PMC
December 2020

Real-world experiences with acupuncture among breast cancer survivors: a cross-sectional survey study.

Support Care Cancer 2020 Dec 6;28(12):5833-5838. Epub 2020 Apr 6.

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

Purpose: The purpose of this study was to evaluate acupuncture use among breast cancer survivors, including perceived symptom improvements and referral patterns.

Methods: Breast cancer survivors who had used acupuncture for cancer- or treatment-related symptoms were identified using an ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR). Additionally, Mayo Clinic electronic health records (MCEHR) were queried to identify eligible participants. All received a mailed consent form and survey including acupuncture-related questions about acupuncture referrals, delivery, and costs. Respondents were also asked to recall symptom severity before and after acupuncture treatment and time to benefit on Likert scales.

Results: Acupuncture use was reported among 415 participants (12.3%) of the MCBDR. Among MCBDR and MCEHR eligible participants, 241 women returned surveys. A total of 193 (82.1%) participants reported a symptomatic benefit from acupuncture, and 57 (24.1% of participants) reported a "substantial benefit" or "totally resolved my symptoms" (corresponding to 4 and 5 on the 5-point Likert scale). The mean symptom severity decreased by at least 1 point of the 5-point scale for each symptom; the percentage of patients who reported an improvement in symptoms ranged from 56% (lymphedema) to 79% (headache). The majority of patients reported time to benefit as "immediate" (34%) or "after a few treatments" (40.4%). Over half of the participants self-referred for treatment; 24.1% were referred by their oncologist. Acupuncture delivery was more frequent in private offices (61.0%) than in hospital or medical settings (42.3%). Twelve participants (5.1%) reported negative side effects, such as discomfort.

Conclusions: Acupuncture is commonly utilized by patients for a variety of breast cancer-related symptoms. However, patients frequently self-refer for acupuncture treatments, and most acupuncture care is completed at private offices, rather than medical clinic or hospital settings.
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http://dx.doi.org/10.1007/s00520-020-05442-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541443PMC
December 2020

Patient factors associated with discrepancies between patient-reported and clinician-documented peripheral neuropathy in women with breast cancer receiving paclitaxel: A pilot study.

Breast 2020 Jun 3;51:21-28. Epub 2020 Mar 3.

Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, 428 Church St, 48109, Ann Arbor, MI, USA.

Purpose: Discrepancies between clinicians' assessment of chemotherapy-induced peripheral neuropathy (CIPN) and patient-reported outcomes (PRO) have been described, though the underlying reasons are unknown. Our objective was to identify potential patient-specific factors associated with under-describing of CIPN to clinicians in women with non-metastatic breast cancer treated with paclitaxel.

Methods: Patients enrolled in an observational study (n = 60) completed weekly CIPN PRO using the EORTC CIPN20. Clinician-documented CIPN using the NCI CTCAE were abstracted from the electronic medical record and paired with CIPN20 data at weeks 7 and 10. Patients were classified as under-describers if their CIPN20 was above the 80th percentile of the CIPN20 distribution for that CTCAE grade from an independent clinical trial (N08CA). Demographics, Assessment of Survivor Concerns (ASC), Trust in Oncologist Scale (TiOS), and health literacy assessment were collected post-treatment via survey. Repeated measures cumulative logistic regression models were used to identify factors associated with under-describing CIPN.

Results: Forty-two women completed the survey (response rate 70%). Three and 9 patients were categorized as under-describers at weeks 7 and 10, respectively. Women who were not working (OR = 9.00, 95%CI 1.06-76.15), had lower income (OR = 7.04, 95%CI 1.5-32.99), and displayed higher trust in their oncologist's competence (OR = 1.29, 95%CI 1.03-1.62 for a 0.1-unit increase in score) were more likely to under-describe CIPN symptoms.

Conclusions: This preliminary study identified non-working status, low income and trust in oncologist's competence as potential factors influencing under-description of CIPN to the clinical team. Further work is needed to clarify these relationships and test additional factors.
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http://dx.doi.org/10.1016/j.breast.2020.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198332PMC
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

Contralateral Axillary Metastases in Breast Cancer: Stage IV Disease or a Locoregional Event?

Am Surg 2019 Dec;85(12):1391-1396

From the *Departments of Surgery, †Medical Oncology, ‡Radiation Oncology, Mayo Clinic, Rochester, Minnesota; and.

Contralateral axillary metastasis (CAM) in breast cancer is presently treated as a stage IV disease. We hypothesized that this disease pattern is a manifestation of direct aberrant lymphatic drainage and would behave more similar to advanced locoregional disease. This is a single-site, retrospective review of patients with biopsy-proven CAM from 2008-2017. Descriptive analysis was performed. Twenty-three patients met the inclusion criteria. The median disease-free interval from primary tumor treatment to diagnosis of CAM was 68 months (range, 36-155 months). This population had aggressive disease (74% local recurrences and 61% clinical evidence of cutaneous or underlying muscular invasion) and extensive locoregional therapy (70% radiated, 57% mastectomy, and 65% axillary lymph node dissection) before their presentation with CAM. Fifteen (65.2%) patients recurred after treatment of CAM; the median recurrence-free interval was 11 months (range, 5-23 months), and 12 (52.2%) patients developed distant metastases. The median distant metastasis-free survival was 14 months (range, 11-23 months), and the median overall survival was 31 months (range, 22-67.5 months). Development of CAM is associated with aggressive disease and extensive prior locoregional surgery and/or radiation. The short recurrence-free interval and high progression to additional stage IV disease suggest these patients behave similar to traditional stage IV patients with resected oligometastatic disease.
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December 2019

Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines.

Support Care Cancer 2020 May 14;28(5):2449-2456. Epub 2019 Dec 14.

Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA.

Purpose: To update the 2013 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines on oral cryotherapy for the management of oral mucositis (OM) caused by cancer therapies.

Methods: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The evidence for each intervention for specific cancer treatment modalities was assigned a level of evidence (LoE). The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the LoE, the guidelines were set as: recommendation, suggestion, or no guideline possible.

Results: A total of 114 papers were identified: 44 from PubMed and 70 from Web of Science. After abstract triage and merging with the 2013 database, 36 papers were reviewed. The LoE for prevention of OM with oral cryotherapy in patients undergoing autologous hematopoietic stem cell transplant using high-dose melphalan conditioning protocols was upgraded, and the guideline changed to recommendation. Additionally, the recommendation for prevention of OM with oral cryotherapy in patients receiving bolus 5-fluorouracil for the treatment of solid tumors was confirmed. No guidelines were possible for other clinical settings.

Conclusions: The evidence supports recommendations for the use of oral cryotherapy for the prevention of OM for either (i) patients undergoing autologous hematopoietic stem cell transplant with high-dose melphalan conditioning protocols or (ii) patients receiving bolus 5-fluorouracil chemotherapy.
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http://dx.doi.org/10.1007/s00520-019-05217-xDOI Listing
May 2020

Fractional CO2 laser therapy for genitourinary syndrome of menopause for breast cancer survivors.

Support Care Cancer 2020 Aug 6;28(8):3669-3677. Epub 2019 Dec 6.

The Ohio State University Medical Center, Columbus, OH, USA.

Purpose: Fractional CO2 laser therapy is an emerging treatment for genitourinary syndrome of menopause (GSM). The objective of this study was to determine the feasibility and preliminary efficacy of fractional CO2 laser therapy in breast cancer survivors.

Methods: This was a single arm feasibility study of breast cancer survivors with dyspareunia and/or vaginal dryness. Participants received three treatments of fractional CO2 laser therapy at 30-day intervals and returned for a 1-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in 80% of patients. We collected data on the Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Urinary Distress Index (UDI), and SAE.

Results: A total of 64 patients participated in the study. The majority of women had Estrogen receptor/Progesterone receptor (ER/PR) positive/Her2neu negative (n = 37; 63%), stage I (n = 32, 54%) or II (n = 19, 32%) breast cancer. Most were receiving endocrine therapy (n = 54, 92%), most commonly aromatase inhibitors (AI; n = 40, 68%). Fifty-nine (88.1%) of those enrolled completed all treatments according to protocol with no reported SAE. No patient withdrew due to SAE. The scores of the VAS (mean Δ - 0.99; 95% CI [- 1.19, - 0.79], p < 0.001)), FSFI (mean Δ 9.67; 95% CI [7.27, 12.1], p < 0.001), and UDI (mean Δ - 8.85; 95% CI [- 12.75, - 4.75], p < 0.001)) improved from baseline to follow-up.

Conclusion: Fractional CO2 laser treatment for breast cancer survivors is feasible and appears to reduce GSM symptoms across treatment and follow-up.
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http://dx.doi.org/10.1007/s00520-019-05211-3DOI Listing
August 2020

Direct Oral Factor Xa Inhibitors for the Treatment of Acute Cancer-Associated Venous Thromboembolism: A Systematic Review and Network Meta-analysis.

Mayo Clin Proc 2019 12 2;94(12):2444-2454. Epub 2019 Nov 2.

Division of Hematology and Medical Oncology, Mayo Clinic, Rochester, MN.

Objective: To explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE).

Patients And Methods: MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding.

Results: We identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with dalteparin (OR, 0.10; 95% CI, 0.01-0.82) but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding, whereas estimates in urothelial cancer were imprecise.

Conclusion: Direct oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.
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http://dx.doi.org/10.1016/j.mayocp.2019.05.035DOI Listing
December 2019