Recent Publications by CFE Educators

BACKGROUND

Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC).

METHODS

We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high- and moderate-intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews.

RESULTS

Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty-three men (82%) completed the 12-week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others.

CONCLUSIONS

Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer.

OBJECTIVE

Tumors compressing the trigeminal nerve can cause facial pain, numbness, or paresthesias. Limited data exist describing how these symptoms change after resection and what factors predict symptom improvement. The objective of this study was to report trigeminal pain and sensory outcomes after tumor resection and identify factors predicting postoperative symptom improvement.

METHODS

This retrospective study included patients with tumors causing facial pain, numbness, or paresthesias who underwent resection. Trigeminal schwannomas were excluded. Logistic regression, recursive partitioning, and time-to-event analyses were used to report outcomes and identify variables associated with facial sensory outcomes.

RESULTS

Eighty-six patients met inclusion criteria, and the median follow-up was 3.1 years; 63 patients (73%) had meningiomas and 23 (27%) had vestibular schwannomas (VSs). Meningioma patients presented with pain, numbness, and paresthesias in 56%, 76%, and 25% of cases, respectively, compared with 9%, 91%, and 39%, respectively, for patients with VS. Most meningioma patients had symptoms for less than 1 year (60%), whereas the majority of VS patients had symptoms for 1-5 years (59%). The median meningioma and VS diameters were 3.0 and 3.4 cm, respectively. For patients with meningiomas, gross-total resection (GTR) was achieved in 27% of patients, near-total resection (NTR) in 29%, and subtotal resection (STR) in 44%. For patients with VS, GTR was achieved in 9%, NTR in 30%, and STR in 61%. Pain improved immediately after tumor resection in 81% of patients and in 92% of patients by 6 weeks. Paresthesias improved immediately in 80% of patients, increasing to 84% by 6 weeks. Numbness improved more slowly, with 52% of patients improving immediately, increasing to 79% by 2 years. Pain recurred in 22% of patients with meningiomas and 0% of patients with VSs. After resection, the Barrow Neurological Institute (BNI) facial pain intensity score improved in 73% of patients. The tumor diameter significantly predicted improvement in BNI score (OR 0.47/cm larger, 95% CI 0.22-0.99; p = 0.047). Complete decompression of the trigeminal nerve was associated with qualitative improvement in pain (p = 0.037) and decreased pain recurrence (OR 0.08, 95% CI 0.01-0.67; p = 0.024).

CONCLUSIONS

Most patients with facial sensory symptoms caused by meningiomas or VSs experienced improvement after resection. Surgery led to immediate and sustained improvement in pain and paresthesias, whereas numbness was slower to improve. Patients with smaller tumors and complete decompression of the trigeminal nerve were more likely to experience improvement in facial pain.

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.