Smith, Thomas J

Abstract Background: Up to 68% of patients will experience CIPN. There are no FDA or ASCO recommended therapies. The pain (P), numbness (N), and tingling (T) can persist for month, years or even lifetime. Duloxetine reduces pain scores by 0.6-1.0 on the 0-10 scale but does not help N or T. Scrambler therapy (ST) is a novel form of neuromodulation that uses EKG electrodes on the dermatomes to capture the pain c-fiber receptors, and generate an action potential of “non-pain” information to replace the pain information. It appears to reset central sensitization by altering cerebral blood flow and re-establishing the balance of neuropeptides (e.g., NGF, GDNGF) in the blood (Smith et al NEJM 2023). Yet many professionals and patients are unaware of it. Methods: We reviewed all available studies. Results: Smith et al (2010, VCU) noted a 59% P reduction (5.8 to 2.4 at the end of 10 days (P<0.0001)) in 16 subjects, and 4 had 0 pain at day 10. Pachman et al (2015, Mayo) in 37 subjects showed a 53% P reduction by day 10; a 44% reduction in T; and a 37% reduction in N. In a randomized trial of 50 patients using ST versus TENS (transcutaneous electrical nerve stimulation), Loprinzi et al (2020, Mayo), in a randomized trial, showed more than twice as many ST patients reported a 50% improvement (36-56%) vs. TENS (16-28%). At 8 weeks the reductions were important: 33%P, 28%N, 41%T. In a subsequent crossover trial (Childs 2021) of the TENS patients to ST, 6 of 12 ST patients achieved a 50% reduction in P and T. Smith et al (2021 Hopkins) did a randomized sham-controlled trial with 35 patients but observed no lasting effect; in retrospect, the electrodes and electrode placement were incorrect in this trial. Abdi et al (2024, MDACC) did a Phase II trial of ST in 10 patients and found symptoms of N, T, trouble walking, and disturbed sleep had significant improvements at 6 months. Worst pain was reduced at 6 months by 3 points. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. Wang Z. et al (Hopkins, unpublished data 2025) showed a 60% reduction in pain (6.2 to 2) in twelve subjects, with one achieving complete remission. Strouse et al (2025, UCLA) will soon report similar results in over 60 patients. Wang E. et al (2023, Hopkins) reviewed 1152 patients treated with ST and found just 3 adverse events: one hematoma and two red spots under the EKG electrodes. The only other therapy that reduces all the symptoms of CIPN is spinal cord stimulation (Gupta 2024) but that is invasive, expensive, and can cause a multitude of adverse events. Conclusions: Scrambler Therapy is a safe and effective treatment for the P, N, and T of CIPN with rare and minimal side effects in a syndrome with no other effective treatment. It is hindered by reimbursement ($32/30 minutes, the same as TENS even though the technology is completely different). Scrambler Therapy should become more available in the future. Citation Format: Z. Wang, C. L. Loprinzi, S. Abdi, T. B. Strouse, T. J. Smith. Scrambler Therapy: a safe and effective way to treat chemo-induced neuropathy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-02-17.

PURPOSE Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer. PATIENTS AND METHODS Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash–Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms. RESULTS Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 ( P = .02), and 6.89 ( P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 ( P = .07), and 13.95 ( P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg ( P = .042) and 5 mg ( P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo. CONCLUSION Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual . The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only).

AbstractObjectiveThe objective was to qualitatively synthesize all reported cases of complications, adverse effects, side effects, or harms arising from the use of scrambler therapy (ST).Methods and DesignA systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Embase, Scopus, Web of Science, United States National Library of Medicine clinical trials registry, and Cochrane Central Register of Controlled Trials databases were searched from database inception to December 10, 2021. Case reports/series, abstracts, retrospective studies, and prospective studies (e.g., open-label trials, randomized controlled trials) pertaining to ST and any description of a complication, adverse effect, side effect, or harm were screened. The search protocol was developed a priori and registered via the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021291838).ResultsA total of six RCTs, 19 prospective open-label trials, and 11 case series / case reports met the inclusion criteria, comprising 1,152 total patients. Two patients experienced contact dermatitis, and one patient reported minor ecchymosis that resolved without intervention. This yielded a composite complication rate of 0.26% (3/1,152). There were zero reported serious adverse events.ConclusionsWhen used in accordance with the treatment protocols described by the United States Food and Drug Administration and device manual, ST is associated with a reported composite complication rate that is orders of magnitude lower than those of invasive neuromodulation devices. ST neuromodulation is a safe alternative for patients who cannot undergo invasive neuromodulation device implantation because of either risk or preference.

Abstract 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); P &lt; .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]; P &lt; .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.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) affects 30% to 40% of patients with cancer with long-lasting disability. Scrambler therapy (ST) appeared to benefit patients in uncontrolled trials, so we performed a randomized sham-controlled Phase II trial of ST. Methods: The primary end point was “average pain” after 28 days on the Numeric Rating Scale. Each received ten 30-minute sessions of ST on the dermatomes above the painful areas, or sham treatment on the back, typically at L3-5 where the nerve roots would enter the spinal cord. Outcomes included the Brief Pain Inventory (BPI)-CIPN and the EORTC CIPN-20 scale. Patients were evaluated before treatment (day 0), day 10, and days 28, 60, and 90. Results: Data regarding pain as a primary outcome were collected for 33 of the 35 patients. There were no significant differences between the sham and the “real” ST group at day 10, 28, 60, or 90, for average pain, the BPI, or EORTC CIPN-20. Individual responses were noted during the ST treatment on the real arm, but most dissipated by day 30. There was improvement in the sensory subscale of the CIPN-20 at 2 months in the “real” group ( P = .14). All “real” patients wanted to continue treatment if available. Discussion: We observed no difference between sham and real ST CIPN treatment. Potential reasons include at least the following: ST does not work; the sham treatment had some effect; small sample size with heterogeneous patients; misplaced electrodes on an area of nonpainful but damaged nerves; or a combination of these factors.