The impact of scrambler therapy on pain and quality of life for chemotherapy-induced peripheral neuropathy: A pilot study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating disturbance among patients who received chemotherapy, with no effective treatment available. Scrambler therapy (ST) is a noninvasive treatment capable of improving multiple quality-of-life symptoms beyond pain. We aimed to evaluate the efficacy of ST for pain and nonpain symptoms related to CIPN. METHODS: Ten patients with moderate to severe CIPN symptoms for >3 months were enrolled in a single-arm trial of ST for 10 daily sessions. CIPN-related symptoms were measured throughout the treatment period and up to 6 months thereafter. RESULTS: The worst pain was reduced by 6 months (p = 0.0039). QST demonstrated the greatest improvement in pressure of 60 g (p = 0.308, Cohen's d = 0.42) and cold temperature threshold of 2.5°C (p = 0.9375, Cohen's d = 0.51) in the gastrocnemius area. Symptoms of numbness, tingling, trouble walking, and disturbed sleep had significant improvements at 6 months. 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. CONCLUSIONS: The results of this pilot trial support the use of ST by demonstrating improvement in multiple domains of quality of life for CIPN patients during an extended follow-up of 6 months. However, further large-scale studies are needed to confirm our findings.

Identification of Breast Cancer Survivors With High Symptom Burden.

BACKGROUND: While women diagnosed with breast cancer have increased survival when compared with other cancers, survivorship may include residual symptom burden from treatment and continuing endocrine therapies. OBJECTIVE: The objective of this study was to identify subgroups of breast cancer survivors experiencing similar symptom severity. METHODS: Participants were 498 women with breast cancer, not on active treatment. Symptom severity was self-reported using the MD Anderson Symptom Inventory. Target symptoms were included in a latent profile analysis. Factors related to subgroup membership and differences in quality of life (QOL) and functioning were explored using logistic regression. RESULTS: Mean age was 60.11 (SD, 11.32) years, 86.1% were white, and 79.1% were receiving endocrine therapy. Target symptoms included fatigue (reported at ≥5 by 22.8% of women), sleep disturbance (24.8%), and trouble remembering (17.2%). Two subgroups were identified: low symptom severity (77.0% of women) and high (23.0%). Older women (odds ratio [OR], 0.971; 95% confidence interval [CI], 0.952-0.989) and employed women (OR, 0.621; 95% CI, 0404-0.956) were less likely to be in the high subgroup; women with poorer performance status (OR, 1.653; 95% CI, 1.188-2.299) were more likely to be in the high subgroup. Women in the high subgroup reported lower QOL (P = .000) and greater interference with functioning (P = .000). CONCLUSIONS: Two subgroups of women with distinct symptom severity were identified. IMPLICATIONS FOR PRACTICE: Identification of women at risk for high symptoms during survivorship may allow clinicians to intensify their approach to symptom management, thereby mitigating poor outcomes and impairments in QOL.

Development and Validation of a Patient-reported Outcome Measure for Gastrointestinal Obstruction in the Setting of Advanced Malignancy.

OBJECTIVE: We sought to construct a valid and reliable patient-reported outcome measure for patients with advanced malignancy and GIO. BACKGROUND: Bowel obstruction is the most common indication for palliative surgical consultation in patients with advanced cancer; however, no validated patient-reported outcome measures exist for this population. METHODS: A total of 125 patients with GIO and 64 patients without GIO who underwent palliative surgical consultation completed the MDASI-GIO questionnaire and a single global quality-of-life question. Summary statistics were used to assess the symptom burden of GIO patients. Outcome measures were validity (construct and criterion) and reliability (internal and test-retest) for the MDASI-GIO. RESULTS: The majority of patients rated the severity of each of the 5 following GIO-specific symptoms as moderate to severe (rating of ≥5 on a 0 to 10 scale): "being unable to eat'' (72%), "being unable to have a bowel movement'' (65%), "abdominal discomfort'' (62%), "stomach feeling full'' (55%), and "abdominal cramping'' (54%). The MDASI-GIO subscale Cronbach coefficient alpha values were 0.80-0.91, and intraclass correlations were 0.72-0.84. Correlations between MDASI-GIO subscales and global quality of life were -0.39 to-0.49 ( P < 0.001 for all comparisons). GIO patients had significantly worse symptoms and higher interference than did non-GIO patients (all P < 0.05) with effect-size differences of ≥0.36, supporting known-group validity. CONCLUSIONS: The MDASI-GIO shows initial validity and reliability for assessing the severity of symptoms of patients with GIO and the interference of these symptoms in patients' daily functioning.

Utility of a Patient-Reported Symptom and Functioning Assessment Tool for Geriatric Oncology Care in China.

OBJECTIVES: Symptom and functional assessment is challenging in geriatric oncology care. This multicenter cross-sectional study examined the use of a multiple-symptom assessment tool, the MD Anderson Symptom Inventory (MDASI), on Chinese patients with cancer aged 65 years and older. METHODS: Patient-rated symptoms and functioning were assessed using MDASI and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire. RESULTS: The most severe symptoms were fatigue and poor appetite. The older group (75-84 years old, n = 224) reported a more severe difficulty remembering (effect size [ES] 0.32; P < .001), shortness of breath (ES 0.20; P = .020), and interference with general activity (ES 0.14; P = .027), with significantly worse physical functioning (ES -0.33; P < .001) and cognitive functioning on the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (ES 0.20; P < .001) than the younger group (65-74 years old, n = 555). For MDASI measures of the core symptoms and total interference with daily activity, Cronbach α coefficients were 0.90 and 0.93, respectively, for the younger group; and 0.93 and 0.94 for the older group, respectively. Moderate to severe (score ≥4) interference with general activity and walking on MDASI accurately indicated poor performance status (area under the curve 0.8089 and 0.7969, respectively) and lack of independence status of Activities of Daily Living (area under the curve 0.7993 and 0.8304, respectively). CONCLUSIONS: MDASI is psychometrically reliable, valid, and clinically sensitive for the measuring symptom burden and functional status of Chinese patients with cancer aged 65 years and older. MDASI could be adopted to measure multiple symptoms and physical functioning outcomes in geriatric oncology practice as well as for research on treatment benefits.

Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer.

PURPOSE: On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance. PATIENTS AND METHODS: We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days. RESULTS: A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (n = 6); therefore, DL1 was reexplored (n = 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics. CONCLUSIONS: The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit.

Patient-Reported Symptom and Functioning Status during the First 12 Months after Chimeric Antigen Receptor T Cell Therapy for Hematologic Malignancies.

Chimeric antigen receptor (CAR) T cell therapy is being increasingly used to treat patients with advanced hematologic malignancies; however, the symptoms related to standard of care CAR T cell therapy during the first year after treatment have not been assessed using patient-reported outcome (PRO) measurements. This study aimed to quantify patients' perspectives of symptom burden and functional status using PROs during the first year after CAR T cell therapy for hematologic malignancies, especially in patients who experienced grade 2-4 toxicities. Sixty patients were enrolled in this observational cross-sectional study at any time during their first 12 months post-treatment. All 60 had received CAR T cell therapy as standard of care at MD Anderson Cancer Center in 2019. PROs were measured using the MD Anderson Symptom Inventory (MDASI), the PROs Measurement Information System 29 (PROMIS-29), the global health tool EQ5D-5L, and the single-item health-related quality of life scale (HRQoL). Twenty-two additional symptoms related to CAR T cell therapy, as identified by an expert panel, were also evaluated. CAR T cell therapy-related toxicities were rated according to the ASTCT consensus grading criteria. The majority of patients (52 of 60; 87%) received axicabtagene ciloleucel (Yescarta). One-third of the patients developed grade 2-4 cytokine release syndrome or neurotoxicity. The first 90 days after infusion represented the most symptomatic period, in which >10% of patients rated 18 symptoms as severe (ie, MDASI symptom score of 7 to 10 on scale of 0 to 10), strongly indicating the need for effective symptom management. Physical functioning, measured by interference on the "general activity" item on the MDASI and this domain on the PROMIS-29, were significantly worse in patients who underwent therapy during the first 30 days compared with those who underwent therapy over 90 days (all P < .05 with the Hochberg step-up procedure), whereas the EQ5D-5L and single-item HRQoL did not detect such differences. Compared with patients who had mild cytokine release syndrome or neurotoxicity (grade 0-1), patients who developed grade 2-4 toxicities persistently reported multiple severe symptoms after 30 days following therapy (all P < .05). Furthermore, although using a different recall period, patient-reported scores on several PROMIS-29 domains were significantly correlated with the scores of corresponding MDASI symptom items. This real-world quantitative PRO symptoms study provides evidence of unique profiles of the physical, psychological, and cognitive symptom burden in patients undergoing CAR T cell therapy that varies within the first year after infusion and demonstrates differences among PRO measurement scales. These results support the need for validation of fit-for-purpose PRO measurements for routinely monitoring symptom and toxicity burdens in CAR T cell therapy care settings.

Minocycline for symptom reduction in patients with multiple myeloma during maintenance therapy: a phase II placebo-controlled randomized trial.

BACKGROUND: Patients with multiple myeloma (MM) experience substantial cancer/treatment-related symptom burden during maintenance therapy. This is a phase II randomized, double-blinded, placebo-controlled clinical trial to examine the effect of minocycline for symptom reduction by its potential anti-inflammatory effect. METHODS: Eligible MM patients for maintenance therapy were randomized to receive minocycline (100 mg twice daily) or placebo. The MD Anderson Symptom Inventory for MM (MDASI-MM) was used to assess multiple symptoms weekly during the trial. Clinician-rated toxicities and blood samples were prospectively collected. The effect size, area under the curve (AUC), and t tests were used to determine the symptom burden between treatment groups and identify the 5 most-severe MDASI-MM symptoms. The longitudinal analysis compared the changes in symptom severity and associated inflammatory markers between groups over time. RESULTS: Sixty-nine evaluable MM patients (33 from the intervention group and 36 from the placebo group) were included. No grade 3+ adverse events related to study medication were noted. The AUCs for the 5 worst MDASI-MM symptoms (fatigue, pain, disturbed sleep numbness/tingling, and drowsiness) were not significantly different between two arms. Regardless of group assignment, pain reduction was positively associated with decreased serum levels of soluble tumor necrosis factor-α receptors 1 and 2 during therapy (all P < 0.05). CONCLUSIONS: This pPhase II randomized study observed no statistically significant positive signal impact from minocycline on symptom reduction or inflammatory markers during maintenance therapy for MM, although using minocycline was feasible and had a low toxicity profile.

Assessment of physical function by subjective and objective methods in patients undergoing open gynecologic surgery.

OBJECTIVE: To evaluate the utility of patient-reported outcomes (PROs) to measure physical functioning in perioperative care for patients with gynecological (GYN) tumors. METHODS: 180 patients with GYN tumors undergoing open surgery participated in this longitudinal study. The physical functioning was measured by a subjective PRO tool, the Interference subscales of the MD Anderson Symptom Inventory (MDASI-I); as well as by an objective tool, the Timed Up & Go test (TUGT), perioperatively. Longer time (>20 s) needed to complete the TUGT was defined as "Prolonged". Patients completed EuroQoL-5D as well. The association between the scores of MDASI-I items and TUGT was assessed via the Spearman correlation coefficient. The known-group validity was assessed using the t-test and Cohen's D effect size. RESULTS: Compliance rates at preoperative, discharge and postoperative time points of MDASI-I were 98%, 95%, 96%; while TUGT completion rates were 92%, 75%, and 80%, respectively. Patients who had refused TUGT at discharge reported a significantly worse "MDASI-general activity" score compared to patients who completed TUGT (mean score of 7.00 vs. 5.38, P = 0.020). Patient-reported "Walking" on MDASI-I significantly differentiated patients with prolonged vs. those with frail/normal TUGT at discharge (mean score of 4.89 vs. 2.79, Cohen's d effect size = 0.82, P < 0.001). MDASI-I demonstrated excellent known-group validity per performance status and for the EuroQoL-5D subscales. CONCLUSION: Patient-reported physical functioning impairment after GYN surgery correspond with observed worse scores of the objective functioning measure test (TUGT). MDASI-I assessment represents a feasible and valid tool to evaluate functional status and warrants further implementation in the perioperative setting.

A Phase II Randomized Controlled Trial of Renshen Yangrong Tang Herbal Extract Granules for Fatigue Reduction in Cancer Survivors.

CONTEXT: Based on the traditional Chinese medicine theory, Renshen Yangrong Tang (RSYRT), which is a mixture of 12 herbs, was commonly used as a pharmacological option in China for fatigue management by correcting Qi deficiency. OBJECTIVES: This randomized controlled Phase II trial investigated the efficacy of RSYRT for reducing cancer-related fatigue. METHODS: Cancer survivors with moderate or severe fatigue (rated ≥4 on a 0-10 scale) for more than two months were randomized to take herbal extract granules of RSYRT or a low dose of a single herb (huangqi) twice a day for six weeks. Patient-reported fatigue was measured using the MD Anderson Symptom Inventory. Efficacy of RSYRT was evaluated using mixed model to test the differences over time among groups. We also conducted responder analyses and examined time to effect of symptom reduction. RESULTS: None of the 83 evaluable patients (control group 42; intervention group 41) had discomfort or Grade 3 or 4 toxicity. We observed a significantly greater MD Anderson Symptom Inventory-fatigue score reduction in the intervention group than that in the control group (time-by-group interaction: estimate = -0.61 [0.10]; P < 0.0001). More patients in the intervention group had a two-point reduction on fatigue than that of the control group (90.2% vs. 52.4%). By Week 4, between-group differences of fatigue reduction on mean severity reached large effect size (intervention group vs. control group: -2.66 vs. -1.36; Cohen's d = 1.0; P < 0.0001). CONCLUSION: Compared with control therapy, RSYRT therapy elicits a statistical and clinical improvement of fatigue severity and functioning. The effectiveness of RSYRT in managing cancer-related fatigue warrants further study in the real world.

Symptomatic and asymptomatic infections of rotavirus, norovirus, and adenovirus among hospitalized children in Xi'an, China.

Rotavirus (RV), norovirus (NoV), and adenovirus (AdV) have been reported as the common viral pathogens of acute gastroenteritis in children. To determine the prevalence of RV, NoV, and AdV infections among hospitalized children with and without symptoms of acute gastroenteritis, fecal specimens, and data on clinical symptoms were collected from 201 children with diarrhea and 53 children without diarrhea admitted to the Xi'an Children's Hospital in Xi'an, China between March 2009 and May 2010. RV, NoV, and AdV were identified in 68.7% (138/201), 20.4% (41/201), and 5.0% (10/201), respectively, of children with diarrhea. These three viruses were also detected in 13.2% (7/53), 35.9% (19/53), and 9.4% (6/53), respectively, of children without diarrhea. Diarrheal children infected with RV alone showed the average severity score of 6.5, statistically significant higher than the average score of 5.3 in children with unidentifiable viruses. GII.3 and GII.4 were the only two NoV genotypes identified, and the GII.4 sequences were genetically close to GII.4 2006b cluster. These findings highlight the importance of NoV as a causative agent of pediatric diarrhea after RV based on the clinical and epidemiological characteristics of NoV infection, and particularly convey information of asymptomatic infections of enteric viruses in young children.