Simon Thomson

The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation

OBJECTIVEAfter randomizing 100 failed back surgery syndrome patients to receive spinal cord stimulation (SCS) plus conventional medical management (CMM) or CMM alone, the results of the 6-month Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation (i.e., PROCESS) showed that SCS offered superior pain relief, health-related quality of life, and functional capacity. Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment. METHODSPatients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses. RESULTSThe 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P ≤ 0.01), and functional capacity (P = 0.0002); and 13 patients (31%) required a device-related surgical revision. At 24 months, of 46 of 52 patients randomized to SCS and 41 of 48 randomized to CMM who were available, the primary outcome was achieved by 17 (37%) randomized to SCS versus 1 (2%) to CMM (P = 0.003) and by 34 (47%) of 72 patients who received SCS as final treatment versus 1 (7%) of 15 for CMM (P = 0.02). CONCLUSIONAt 24 months of SCS treatment, selected failed back surgery syndrome patients reported sustained pain relief, clinically important improvements in functional capacity and health-related quality of life, and satisfaction with treatment.

Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial)

Background: Chronic back and leg pain conditions result in patients’ loss of function, reduced quality of life and increased costs to the society.

Spinal Cord Stimulation vs. Conventional Medical Management: A Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome (PROCESS Study).

Introduction.  Since its first application in 1967, numerous case series indicate that spinal cord stimulation (SCS) is an effective treatment for the management of failed back surgery syndrome (FBSS). However, only one randomized controlled trial has demonstrated that SCS provides more effective pain relief than re‐operation and conventional medical management. The PROCESS randomized, controlled, multicenter trial aims to assess the clinical effectiveness and cost‐effectiveness of SCS when added to conventional medical management compared to conventional medical management alone in patients with FBSS.

Demographic Characteristics of Patients with Severe Neuropathic Pain Secondary to Failed Back Surgery Syndrome

Background:  Neuropathic pain commonly affects the back and legs and is associated with severe disability and psychological illness. It is unclear how patients with predominantly neuropathic pain due to failed back surgery syndrome (FBSS) compare with patients with other chronic pain conditions.

The Appropriate Use of Neurostimulation: Avoidance and Treatment of Complications of Neurostimulation Therapies for the Treatment of Chronic Pain

The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes.

A Retrospective, Long-term, Third-Party Follow-up of Patients Considered for Spinal Cord Stimulation.

The objective of this study was to follow up patients considered for spinal cord stimulation and assess outcomes and patient selection factors associated with outcome. A retrospective study of patients considered for spinal cord stimulation was performed. This included three groups: A) those who did not have a temporary trial of stimulation, B) those who did not go on to have long‐term stimulation after a trial, and C) those who did go on to have long‐term stimulation after a trial. Patient notes were obtained, a structured telephone interview conducted, and patients returned a questionnaire. VAS scores, percentage pain reduction reported, quality of life reports, Oswestry Disability Index and Hospital Anxiety and Depression Indices were recorded. Fifty‐two percent of patients who had long‐term stimulation reported 50% or greater pain reduction. In the subset of these patients with the diagnosis of failed back surgical syndrome, 51% reported 50% or greater pain reduction. Significant improvements in VAS, Oswestry Disability Index, and depression were reported pre and post long‐term stimulation. There were significant differences in the quality‐of‐life reports between the patients who received long‐term stimulation (who showed a positive outcome) and those who did not (who showed a negative outcome); 80% of patients receiving long‐term stimulation reported an improvement in their quality of life. Follow‐up of a cohort of patients receiving long‐term stimulation demonstrated some reduction of treatment efficacy. Use of a psychological interview aided patient selection, but no other factors showed a correlation with reported pain reduction. No serious adverse effects were demonstrated. A revision rate of 23.5% occured in long‐term stimulated patients. We conclude that spinal cord stimulation is an efficacious therapy which is not associated with serious side effects. There is some reduction in therapeutic efficacy over time. Patients deteriorate without treatment.

Ventriculoperitoneal shunt 30-day failure rate: a retrospective international cohort study.

BACKGROUND With the need for transparency of surgical results, 30-day outcome measures have become increasingly important. Ventriculoperitoneal (VP) shunt failure is a substantial burden to patients and health care systems. OBJECTIVE This study introduces the 30-day VP shunt failure rate as a possible barometer of surgical outcome and demonstrates its use in a national (United Kingdom [UK]) study and makes comparison with 2 published randomized, controlled trials (RCT). METHODS A cohort study of all (except 1) pediatric neurosurgical centers in the UK and Ireland. All new and revision VP shunt operations were recorded for 2008 and 2009. Both newly placed and revised VP shunts were subject to Kaplan-Meier analysis, and 30-day failure rate was obtained. Data from 2 RCTs investigating new VP shunt technology were analyzed, and the 30-day failure rate was extracted for comparative purposes. RESULTS The overall 30-day and 1-year failure rates for new shunts were 12.9% and 28.8%, respectively. The 30-day failure rate from 2 RCTs was comparable (14% and 16%, respectively). The failure rate of the subsequent revision of those new shunts was 20.7% at 30 days and 40.4% at 1 year. According to these data, shunt survival appears to be better if performed by a consultant pediatric neurosurgeon for revision surgery only. CONCLUSION VP shunt survival in the UK is comparable to the published multicenter data investigating shunt survival. The 30-day failure rate may represent a better barometer of surgical outcome and should be used as a separate outcome measure in the design of future trials.

Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial ‘ an early report

Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored. The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels. Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment. This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored.The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels.Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment.This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.

Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade

Intravenous infusion of oncolytic reovirus in patients leads to infection of brain tumors, infiltration by cytotoxic T cells, and up-regulation of PD-L1. Viruses team up with cancer immunotherapy Immune checkpoint inhibitors have shown great promise for cancer therapy, but they do not treat all cancers, and neither breast nor brain tumors are usually treatable with these drugs. However, Bourgeois-Daigneault et al. discovered a way to address this for breast cancer, and Samson et al. discovered a way to address this for brain tumors. In both cases, the authors found that oncolytic virus treatment given early, before surgical resection, alters the antitumor immune response and potentiates the effects of subsequent treatment with immune checkpoint inhibitors. Although these studies differ in the details of their methods and the immune effects induced by the oncolytic viruses, they indicate the potential of such viruses for enhancing the potential of checkpoint therapy and expanding it to new types of cancer. Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade. Oncolytic viruses (OVs) represent a promising form of cancer immunotherapy. For brain tumors, almost all studies to date have used direct intralesional injection of OV, because of the largely untested belief that intravenous administration will not deliver virus to this site. We show, in a window-of-opportunity clinical study, that intravenous infusion of oncolytic human Orthoreovirus (referred to herein as reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor infiltration relative to patients not treated with virus. We further show that reovirus up-regulates IFN-regulated gene expression, as well as the PD-1/PD-L1 axis in tumors, via an IFN-mediated mechanism. Finally, we show that addition of PD-1 blockade to reovirus enhances systemic therapy in a preclinical glioma model. These results support the development of combined systemic immunovirotherapy strategies for the treatment of both primary and secondary tumors in the brain.

Implementation of neuro-oncology service reconfiguration in accordance with NICE guidance provides enhanced clinical care for patients with glioblastoma multiforme

Background:Brain tumours account for <2% of all primary neoplasms but are responsible for 7% of the years of life lost from cancer before age 70 years. The latest survival trends for patients with CNS malignancies have remained largely static. The objective of this study was to evaluate the change in practice as a result of implementing the Improving Outcomes Guidance from the UK National Institute for Health and Clinical Excellence (NICE).Methods:Patients were identified from the local cancer registry and hospital databases. We compared time from diagnosis to treatment, proportion of patients discussed at multidisciplinary team (MDT) meetings, treatment received, length of inpatient stay and survival. Inpatient and imaging costs were also estimated.Results:Service reconfiguration and implementation of NICE guidance resulted in significantly more patients being discussed by the MDT—increased from 66 to 87%, reduced emergency admission in favour of elective surgery, reduced median hospital stay from 8 to 4.5 days, increased use of post-operative MRI from 17 to 91% facilitating early discharge and treatment planning, and reduced cost of inpatient stay from £2096 in 2006 to £1316 in 2009. Patients treated with optimal surgery followed by radiotherapy with concomitant and adjuvant temozolomide achieved outcomes comparable to those reported in clinical trials: median overall survival 18 months (2-year survival 35%).Conclusions:Advancing the management of neuro-oncology patients by moving from an emergency-based system of patient referral and management to a more planned elective outpatient-based pattern of care improves patient experience and has the potential to deliver better outcomes and research opportunities.