Feasibility of a tailored home-based exercise intervention during neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: To evaluate the feasibility of a home-based moderate-to-vigorous intensity, phased (introduction, intermediate, maintenance), exercise prescription in breast cancer patients receiving cardiotoxic neoadjuvant chemotherapy. METHODS: Nineteen breast cancer patients were randomized to intervention or control for the duration of chemotherapy (16-24 weeks). The intervention was one aerobic exercise session at 80-90% VO2max for 25 min/week and 65%-75% VO2max for ≥ 50 min/week. Adherence to the tailored home-based program was assessed by heart rate monitors. Acceptability, tolerability, feasibility, efficacy, change in VO2max, and patient reported outcomes, safety, and clinical events were assessed. RESULTS: 25.7% of eligible women consented (acceptability). Adherence was 87.6%. Women were not able to maintain exercise intensity as chemotherapy progressed (23.7% of exercise minutes were completed at prescribed heart rate during maintenance). Efficacy of the intervention was demonstrated by maintenance of VO2max (-1.0 ± 13.2%) compared to (-27.5 ± 7.4%) the control group. Further, during and after therapy, patients in the intervention arm reported less fatigue (control-baseline: 14.4 ± 15.9; midpoint: 19.0 ± 11.4; follow-up: 29.4 ± 20.0; intervention-baseline: 29.2 ± 24.6; midpoint: 24.6 ± 14.4; follow-up: 23.6 ± 11.9), impairment in activities (control-baseline: 13.7 ± 16.0; midpoint: 32.8 ± 17.0; follow-up: 58.6 ± 27.9; intervention-baseline: 38.7 ± 31.8; midpoint: 47.1 ± 27.5; follow-up: 47.5 ± 31.0), and pain (control-baseline: 80.8 ± 17.1; midpoint: 73.9 ± 20.7; follow-up: 50.7 ± 25.7; intervention-baseline: 68.7 ± 28.4; midpoint: 61.4 ± 22.5; follow-up: 65.3 ± 22.4). There were no differences in adverse events, treatment delays, or pathological complete response. CONCLUSIONS: Neoadjuvant breast cancer patients maintained approximately one hour/week of moderate-intensity exercise over the course of their treatment. Further, this volume of exercise was sufficient to maintain fitness capacity and quality of life compared to the control group. TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT03280836, prospectively registered 9/13/2017, https://clinicaltrials.gov/ct2/show/NCT03280836 .

Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.

We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on synergy between conventional or targeted cytotoxic therapy and immunotherapy in cancer treatment.

Fatal malignant metastastic epithelioid angiomyolipoma presenting in a young woman: case report and review of the literature.

Epithelioid angiomyolipomas (EAMLs) are rare mesenchymal tumors whose malignant variant is extremely uncommon and highly aggressive. Treatment strategies include chemo radiation, transcatheter arterial embolization and surgical resection, which has remained the mainstay treatment. Targeted therapies including mammalian target of rapamycin (mTOR) inhibitors such as Temsirolimus may offer some hope for progressive malignant EAMLs that are not amenable to other treatment modalities. We report a fatal case in a young female who presented with rapidly progressive metastatic EAML that did not respond to mTOR therapy. The literature has shown reduction in tumor burden with the use of mTOR inhibitors, but unfortunately due to the rarity of malignant EAML, a meaningful approach to treatment remains challenging.