Vitamin D Levels in Patients with Colorectal Cancer Before and After Treatment Initiation.

PURPOSE: We aimed to described 25-hydroxyvitamin D [25(OH)D] levels in newly diagnosed colorectal cancer (CRC) patients and to re-evaluate levels after chemotherapy. METHODS: Permanent residents of the San Francisco Bay Area with a new CRC diagnosis of any stage were recruited prior to any non-surgical therapy. Serum 25(OH)D levels were measured at time of diagnosis and 6-month follow-up. Supplement use was not restricted. The primary endpoint was the frequency of vitamin D deficiency in patients with newly diagnosed CRC of all stages. The Kruskal-Wallis and Spearman correlation tests were used to evaluate associations of patient characteristics with 25(OH)D levels. RESULTS: Median 25(OH)D level at baseline was 27.0 ng/mL (range 7.2, 59.0); 65% of patients had insufficient levels (25(OH)D < 30 ng/mL) (n = 94). Race, disease stage, multivitamin use, vitamin D supplementation, and county of residence were associated with baseline 25(OH)D levels (P < 0.05). The median change in 25(OH)D from baseline to 6 months was - 0.7 ng/mL [- 19.4, 51.7] for patients treated with chemotherapy (n = 58) and 1.6 ng/mL [- 6.4, 33.2] for patients who did not receive chemotherapy (n = 19) (P = 0.26). For patients who received vitamin D supplementation during chemotherapy, the median 25(OH)D change was 8.3 ng/mL [- 7.6, 51.7] versus - 1.6 [- 19.4, 24.3] for chemotherapy patients who did not take vitamin D supplements (P = 0.02). CONCLUSION: Among patients with a new diagnosis of CRC, most patients were found to have 25(OH)D levels consistent with either deficiency or insufficiency. In the subset of patients who received chemotherapy and took a vitamin D supplement, serum 25(OH)D levels increased, suggesting that vitamin D repletion is a feasible intervention during chemotherapy.

Cortical Brain-Computer Interface for Closed-Loop Deep Brain Stimulation.

Essential tremor is the most common neurological movement disorder. This progressive disease causes uncontrollable rhythmic motions-most often affecting the patient'sdominant upper extremity-thatoccur during volitional movement and make it difficult for the patient to perform everyday tasks. Medication may also become ineffective as the disorder progresses. For many patients, deep brain stimulation (DBS) of the thalamus is an effective means of treating this condition when medication fails. In current use, however, clinicians set the patient's stimulator to apply stimulation at all times-whether it is needed or not. This practice leads to excess power use, and more rapid depletion of batteries that require surgical replacement. In this paper, for the first time, neural sensing of movement (using chronically implanted cortical electrodes) is used to enable or disable stimulation for tremor. Therapeutic stimulation is delivered onlywhen the patient is actively using their effected limb, thereby reducing the total stimulation applied, and potentially extending the lifetime of surgically implanted batteries. This paper, which involves both implanted and external subsystems, paves the way for fully-implanted closed-loop DBS in the future.

Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: Is radiation necessary in the modern era of chemotherapy?

BACKGROUND: No consensus exists regarding the optimal neoadjuvant treatment paradigm for patients with borderline resectable pancreatic cancer (BRPC), including the respective roles of chemotherapy and radiation. METHODS: We performed a retrospective analysis, including detailed pathologic and radiologic review, of pancreatic cancer patients undergoing FOLFIRINOX, with or without radiation therapy (RT), prior to surgical resection at a high-volume academic center over a 4-year period. RESULTS: Of 26 patients meeting inclusion criteria, 22 (84.6%) received FOLFIRINOX alone without RT (median number of treatment cycles = 9). The majority of patients met formal radiographic criteria for BRPC, with the superior mesenteric vein representing the most common vessel involved. R0 resection rate was 90.9%, with 12 patients (54.5%) requiring vascular reconstruction. Treatment response was classified as moderate or marked in 16 patients (72.7%) according to the College of American Pathologists grading system. Estimated median disease-free and overall survival rates are 22.6 months and not reached (NR), respectively. CONCLUSIONS: This is one of the largest series to describe the use of neoadjuvant FOLFIRINOX, without radiation therapy, in patients with BRPC undergoing surgical resection. Given the high R0 resection rates and favorable clinical outcomes with chemotherapy alone, this strategy should be further assessed in prospective study design. J. Surg. Oncol. 2016;114:587-596. © 2016 Wiley Periodicals, Inc.

MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer.

While progress in the treatment of advanced pancreatic cancer has accelerated in recent years, this malignancy continues to have an exceedingly poor prognosis, with no standard of care options beyond front-line chemotherapy. Currently, there are a number of new therapeutic agents in varying stages of clinical development, including molecularly targeted agents, immunotherapies, and modified versions of cytotoxics. MM-398, a novel nanoliposomal formulation of irinotecan, was designed to maximize tumor exposure while minimizing systemic toxicity due to its favorable pharmacokinetic profile. Overall, across multiple clinical trials in multiple disease indications, MM-398 has been shown to have a favorable safety and tolerability profile compared with standard irinotecan. Recent results of the Phase III NAPOLI-1 trial in patients with metastatic pancreatic cancer refractory to gemcitabine-based chemotherapy have shown a significant improvement in overall survival of MM-398 when combined with 5-fluorouracil/leucovorin, compared with 5-fluorouracil/leucovorin alone. This review focuses on the development and pharmacokinetic properties of MM-398, followed by evaluation of its safety and efficacy with a primary emphasis on clinical trials in advanced pancreatic cancer.