Somatic mutations are accumulated in normal human tissues with aging and exposure to carcinogens. If we can accurately count any passenger mutations in any single DNA molecule, since their quantity is much larger than driver mutations, we can sensitively detect mutation accumulation in polyclonal normal tissues. Duplex sequencing, which tags both DNA strands in one DNA molecule, enables accurate count of such mutations, but requires a very large number of sequencing reads for each single sample of human-genome size. Here, we reduced the genome size to 1/90 using the Bam HI restriction enzyme and established a cost-effective pipeline. The enzymatically cleaved and optimal sequencing (EcoSeq) method was able to count somatic mutations in a single DNA molecule with a sensitivity of as low as 3 × 10 ⁻⁸ per base pair (bp), as assessed by measuring artificially prepared mutations. Taking advantages of EcoSeq, we analyzed normal peripheral blood cells of pediatric sarcoma patients who received chemotherapy ( n = 10) and those who did not ( n = 10). The former had a mutation frequency of 31.2 ± 13.4 × 10 ⁻⁸ per base pair while the latter had 9.0 ± 4.5 × 10 ⁻⁸ per base pair ( P < 0.001). The increase in mutation frequency was confirmed by analysis of the same patients before and after chemotherapy, and increased mutation frequencies persisted 46 to 64 mo after chemotherapy, indicating that the mutation accumulation constitutes a risk of secondary leukemia. EcoSeq has the potential to reveal accumulation of somatic mutations and exposure to environmental factors in any DNA samples and will contribute to cancer risk estimation.

Journal of Palliative Medicine

Objectives: This study aimed to assess the effects of high-resolution natural sound with inaudible high-frequency components (HNIH) on healing, symptoms, sleep satisfaction, and autonomic nerve function among terminally ill cancer patients. Methods: We conducted a single-arm, open-label study of 4-hour HNIH for 20 terminally ill cancer patients. We evaluated the healing state, symptoms (Japanese version of the Edmonton Symptom Assessment System-Revised, ESAS-r-J), global impression, and heart rate variability at 30 minutes (T2) and 4 hours (T3) after starting HNIH and sleep satisfaction the next morning (T4). Results: A total of 18 participants were evaluated (mean age: 69.4 years; 33.3% female). Post-intervention, there was a nonsignificant increase in Healing Scale scores at T2 (mean difference: 5.3, 95% confidence interval [CI]: −1.2 to 11.8, p = 0.106), but a significant increase at T3 (mean difference: 6.6, 95% CI: 1.0 to 12.3, p = 0.024). Specific ESAS-r-J scores demonstrated significant improvements in anxiety (mean difference at T2: −1.2, 95% CI: −1.99 to −0.34, p = 0.008; T3: −1.2, 95% CI: −1.99 to −0.34, p = 0.008), tiredness (mean difference at T2: −0.6, 95% CI: −1.18 to −0.04, p = 0.037), and shortness of breath (mean difference at T2: −1.0, 95% CI: −1.72 to −0.28, p = 0.010). Moreover, 66.7% of participants reported improved general conditions at T2 and T3, whereas 50% reported enhanced sleep satisfaction at T4. Heart rate variability analysis revealed a decreased low-frequency/high-frequency ratio in 55.6% of participants at T2 and 44.4% at T3. Conclusions: The present single-arm study showed that HNIH potentially enhanced healing, alleviated symptoms such as anxiety, tiredness, and shortness of breath, and improved sleep satisfaction in terminally ill cancer patients.

Objective: To evaluate real-world data on the use of tapentadol (TAP) in cancer patients.Design: Single-center retrospective study.Setting: Curative/palliative.Patients, participants: Patients who started TAP between October 2014 and December 2018 at our institution.Main outcome measure(s): The primary outcome was the reason for TAP initiation. Secondary outcomes included prescription duration, TAP cessation rate, reason for cessation, and adverse events (AEs). Since the palliative care team (PCT) tended to prescribe to cancer patients with intractable pain more often than patients in usual care, and also tended to prescribe opioids based on their characteristics, we decided to compare patients with and without PCT intervention.Results: There were 175 patients who first received TAP during the study period, of whom 81 patients (46.3 percent) were male. The median age was 60 years. TAP was prescribed for opioid-naive patients in 45 (26 percent) cases and opioid switch in 130 (74 percent) cases. When comparing the PCT group (n = 121) and the non-PCT group (n = 54) using univariate analysis, the PCT group had a higher opioid switch rate (81.8 percent vs 57.4 percent, p < .001), higher proportion of patients with neuropathic pain (NP) (65.3 percent vs 16.7 percent, p < .001), and a higher proportion of patients with a history of nausea (41.3 percent vs 18.5 percent, p < .01). The cessation rate due to AEs was 8 percent overall.Conclusions: Palliative care physicians prescribed TAP for patients with NP or a history of nausea. Opioid-naive patients were preferred by oncologists. TAP has good tolerability in both groups, with a low dropout rate due to AEs.

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes and platinum-based agents, impairing quality of life. Duloxetine is the only drug with proven efficacy, but is often limited by tolerability. AT-04 is a portable alternating magnetic field device that activates descending pain modulatory systems and has shown safety in other pain settings. This investigator-initiated trial evaluated the efficacy and safety of AT-04 for persistent CIPN. Methods: We conducted a randomized, double-blind, sham-controlled, multicenter phase II study. Patients with CIPN lasting ≥12 weeks after chemotherapy and pain NRS ≥ 4 were enrolled. Participants used AT-04 or sham devices twice daily for 12 weeks. The primary endpoint was the change in pain NRS on day 85. Secondary endpoints included tingling NRS, numbness NRS, CIPN20 subscales, and safety. Results: Twenty-eight patients were randomized (14 per arm). No significant difference was observed in pain NRS on day 85 {AT-04: −1.74 ± 0.6 vs. sham device: −1.45 ± 0.6; one-sided p = 0.36, effect size (ES) = 0.48}. CIPN20 motor scores improved with AT-04 on days 29 (−9.82 ± 13.8 vs. 0.74 ± 8.7, respectively; p = 0.035, ES = 0.92) and 57 (−11.81 ± 10.6 vs. −0.54 ± 6.7, respectively; p < 0.01, ES = 1.26). Among patients whose last chemotherapy had ended >1 year earlier (n = 16), motor scores improved from days 29 (−12.43 ± 10.3 vs. 2.38 ± 8.9, respectively; p < 0.01, ES = 1.55) to 85 (−11.76 ± 10.1 vs. −0.07 ± 11.5, respectively; p = 0.049, ES = 1.08), while sensory/autonomic scales showed trends. No treatment-related adverse events occurred in the AT-04 group. Conclusions: AT-04 did not significantly reduce pain NRS but improved motor function in CIPN patients, especially in those >1 year after chemotherapy. AT-04 may be a promising non-pharmacological option; larger confirmatory trials are required.