Effectiveness of Balance Exercise and Brisk Walking on Alleviating Nonmotor and Motor Symptoms in People With Mild-to-Moderate Parkinson Disease: A Randomized Clinical Trial With 6-Month Follow-up.

OBJECTIVE: To investigate the effects of balance exercise and brisk walking on nonmotor and motor symptoms, balance and gait functions, walking capacity, and balance confidence in Parkinson disease (PD) at posttraining and 6-month follow-up. DESIGN: Two-arm, assessor-blinded randomized controlled trial SETTING: University research laboratory and the community PARTICIPANTS: Ninety-nine eligible individuals with mild-to-moderate PD INTERVENTIONS: Participants were randomized to balance and brisk walking group (B&B, n=49) or active control group (n=50). B&B received ten 90-minute sessions of balance exercises and brisk walking supervised by physical therapists for 6 months (week 1-6: weekly, week 7-26: monthly), whereas control practiced whole-body flexibility and upper limb strength exercise at same dosage (180 min/wk). Both groups performed unsupervised home exercises 2-3 times/wk during intervention and continued at follow-up. MAIN OUTCOME MEASURES: Primary outcomes were Movement Disorder Society Unified Parkinson Disease Rating Scale nonmotor (MDS-UPDRS-I) and motor (MDS-UPRDS-III) scores. Secondary outcomes were mini-Balance Evaluation Systems Test (mini-BEST) score, comfortable gait speed (CGS), 6-minute walk test (6MWT), dual-task timed-Up-and-Go (DTUG) time, and Activities-Specific Balance Confidence Scale score. RESULTS: Eighty-three individuals completed the 6-month intervention with no severe adverse effects. The mean between-group (95% CI) difference for the MDS-UPDRS nonmotor score was 1.50 (0.19-2.81) at 6 months and 1.09 (-0.66 to 2.85) at 12 months. The mean between-group (95% CI) difference for the MDS-UPDRS motor score was 3.75 (0.69-6.80) at 6 months and 4.57 (1.05-8.01) at 12 months. At 6 and 12 months, there were significant between-group improvements of the B&B group in mini-BEST score, CGS, 6MWT, and DTUG time. CONCLUSIONS: This combined balance and brisk walking exercise program alleviates nonmotor and motor symptoms and improves walking capacity, balance, and gait functions posttraining, with positive carryover effects for all except nonmotor outcomes, at 6-month follow-up in mild-to-moderate PD.

Exploration of Germline Correlates and Risk of Immune-Related Adverse Events in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of many tumor types, and durable responses can be observed in select populations. However, patients may exhibit significant immune-related adverse events (irAEs) that may lead to morbidity. There is limited information on whether the presence of specific germline mutations may highlight those at elevated risk of irAEs. We evaluated 117 patients with metastatic solid tumors or hematologic malignancies who underwent genomic analysis through the ongoing Personalized OncoGenomics (POG) program at BC Cancer and received an ICI during their treatment history. Charts were reviewed for irAEs. Whole genome sequencing of a fresh biopsy and matched normal specimens (blood) was performed at the time of POG enrollment. Notably, we found that MHC class I alleles in the HLA-B27 family, which have been previously associated with autoimmune conditions, were associated with grade 3 hepatitis and pneumonitis (q = 0.007) in patients treated with combination PD-1/PD-L1 and CTLA-4 inhibitors, and PD-1 inhibitors in combination with IDO-1 inhibitors. These data highlight that some patients may have a genetic predisposition to developing irAEs.

Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial.

PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.