Intrathecal cervical analgesia for cancer pain: a 12-year follow-up study in a comprehensive cancer center.

BACKGROUND: Intrathecal analgesia plays a key role for patients suffering refractory cancer pain. Nevertheless, intrathecal drug delivery systems (IDDS), requiring a cervical catheter tip implantation, have been poorly described in medical literature. AIMS: A monocentric retrospective follow-up study was designed to evaluate results of cervical IDDS for cancer pain. PATIENTS AND METHODS: From January 2010 to December 2022, all intrathecal-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed in the cervical vertebral canal. Post-implant assessment of pain was determined using a numeric rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly. Pain scores were compared using the Wilcoxon's signed rank test. RESULTS: Ninety-eight patients were included in this study; all received intrathecal treatments. Implanted patients suffered from severe pain (mean presurgical maximum numerical rating score 8.02±0.24 despite a mean 562.56±127.72 mg of oral morphine equivalent daily dose). Mean survival time after intrathecal treatment start was 208.48±67 days. Intrathecal drug delivery systems provided pain relief compared with initial pain score with a significant statistical difference after 1 week, 1 month, 2 and 3 months (p<0.01). A 50% reduction in initial pain level was achieved in 93% of cases during the first week of intrathecal implant. CONCLUSIONS: Results suggest that long-term intrathecal treatment using a multidrug regimen for cancer-related pain through cervical intrathecal catheters was suitable and safe in our study population. We demonstrated a clinically and statistically significant pain reduction in patients using mainly a percutaneous lumbar approach.

Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience.

Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication.

Rationale and Recent Advances in Targeted Drug Delivery for Cancer Pain: Is It Time to Change the Paradigm?

BACKGROUND: Cancer pain prevalence remains high with more than 60% of patients with advanced cancer experiencing cancer-related pain. The undertreatment of pain due to concerns of opioid dependence or diversion, as well as the potential effect of opioids on tumor neogenesis, add to the suffering among cancer populations. OBJECTIVES: The aim of this narrative review was to assess evidence on the effectiveness, safety, cost-effectiveness, and advances of Intrathecal (IT) Drug Delivery Systems (IDDS) for the management of cancer pain. STUDY DESIGN: The present review was performed by searching for articles indexed in PubMed, MEDLINE, SciELO, Google Scholar, and Scopus. METHODS: Studies were included if they investigated patients with chronic cancer-related pain treated with IDDS and assessed experienced pain. We performed a narrative synthesis. RESULTS: IDDS have demonstrated efficacy in relieving cancer pain even in the challenging treatment of head and neck cancer pain. IDDS is also associated with a large reduction in serum opioid concentrations limiting adverse effects. When combined with other analgesics commonly used in the spinal space, but not systemically, pain relief may be dramatically improved. Advances in IT drug diffusion, including mixtures created with pharmaceutical compounding, improve the safety and accuracy of this therapy. IDDS is cost-effective and safe yet remains underutilized in this patient population. LIMITATIONS: Despite numerous clinical studies, only a small number of randomized trials have been conducted to evaluate the effectiveness of IDDS for cancer pain. CONCLUSIONS: This article presents an overview of the current state of evidence on the effectiveness, safety, cost-effectiveness, and advances of IDDS for the management of cancer pain. Despite current evidence, IDDS remains underutilized for people with cancer pain. Potential areas to facilitate its use are discussed. A shift in the paradigm of cancer pain treatment should be considered given the undertreatment rate, lack of benefits, and considerable risks associated with oral opioid medication in many patients who suffer from chronic cancer pain.

Pancreatic Cancer Related Pain: Review of Pathophysiology and Intrathecal Drug Delivery Systems for Pain Management.

BACKGROUND: Pancreatic cancer (PC) is one of the most lethal cancers and is the eleventh most common cancer worldwide. This disease is characterized by an often-fatal evolution and a high burden of symptoms, particularly pain. Several studies have demonstrated that pancreatic cancer patients have a high prevalence of pain, with up to 82% of patients reporting pain, often requiring systemic strong opioids as mainstay treatment. This comprehensive review of pancreatic cancer related pain (PCRP), focuses on current mechanisms that lead to pain including regional invasion processes, as well as the local secretion of factors that sensitize nociceptive nerves. OBJECTIVE: Our objective was to conduct a review of PCRP and provide updates on intrathecal drug delivery in PC therapeutic recommendations. STUDY DESIGN: We used a narrative review design. We present a novel perspective in the field of pain research by converging data from intrathecal drug delivery trials with previous elements of molecular pain research in PCRP. METHODS: The literature review relating to PCRP pathophysiology and intrathecal drug delivery systems (IDDS) was done with searches of English, French, and Spanish abstracts, using PubMed, Dynamed, EMBASE, SciELO, Uptodate, Google Scholar, and manual searches of the bibliographies of known primary and review articles from IDDS inception until August 2020. Different search strings based on MESH terms were used including: pain, chronic pain, cancer pain, prevalence, pathophysiology, pancreatic cancer, analgesia, invasive pain procedures, celiac plexus neurolysis, pancreatic neuropathy, intrathecal drug delivery, or a combination of these terms. A narrative review based on these sources was prepared. RESULTS: This paper reviews aspects related to pancreatic adenocarcinoma and PCRP prevalence and focuses on recent developments in pathophysiology with IDDS as a pain management strategy. We summarize the best available evidence regarding intrathecal therapy (IT) for PCRP management; 18 studies of IDDS including at least 236 PC patients are analyzed. LIMITATIONS: Some limitations include: IDDS studies heterogeneity regarding disease stage, patient population, and technical aspects, such as catheter placement and treatment regimen, do not allow integration of studies. CONCLUSION: This review analyzes both past and current literature with a critical analysis of findings and respective recommendations. Most studies of IDDS in PCRP evaluate outcomes on pain using one-dimensional pain scales, such as VAS. Other relevant results, such as performance status or quality of life, are not frequently reported. Burden of disease variables, such as cancer stage, location, and comorbidities, like depression and systemic analgesia co-prescription, are usually not presented in these studies. In the same way, most studies do not precisely inform IDDS titration and IT medication. These factors make integration of IDDS in PC studies difficult. Future studies regarding impact of IDDS on pain control on quality of life, in this particular population, may help clinicians in deciding the optimal time and approach for IDDS. The studies should report data on particular disease, comorbidities, and treatment regimens.

Risk of New Fractures in Vertebroplasty for Multiple Myeloma. A Retrospective Study.

OBJECTIVE: Vertebroplasty is a percutaneous minimally invasive procedure indicated for vertebral collapse pain treatment. Among the known complications of the procedure is the augmented risk of new vertebral fractures. There are no specific studies in this patient population describing the risk of new vertebral fractures after vertebroplasty. This study analyzed risk factors associated with new vertebral fractures after vertebroplasty in patients with multiple myeloma. METHODS: Observational retrospective study in patients with multiple myeloma. The data collection took place from January 1, 2010, to December 30, 2017, at the National Cancer Institute. Clinical data and procedural variables such as cement volume, cement leaks, fracture level, number of treated vertebrae, pedicular disease, and cement distribution pattern, with two years follow-up, were analyzed with the Wilcoxon test, and a logistic regression model was used to identify risk factors related to new vertebral fractures. A confidence interval of 95% was used for analysis. RESULTS: At one-year follow-up, 30% of fractures were reported after vertebroplasty, most of them at low thoracic and lumbar level (50% adjacent level). Vertebroplasty was most commonly performed at the thoracolumbar and lumbar area. We demonstrated a 70.7% median numerical rating scale reduction at one-year follow-up; a significant decrease in opioid consumption occurred only during the first month. CONCLUSIONS: Pedicle involvement, disc leakage, cement volume, thoracolumbar and lumbar level, and number of treated vertebrae by intervention are important risk factors when performing vertebroplasty. Prospective randomized studies are needed to evaluate these factors in this specific population.

Multimodal intrathecal therapy for phantom limb pain: a report of 2 cases / Terapia intratecal multimodal para tratamiento de dolor de miembro fantasma: Reporte de dos casos

Abstract Introduction: Phantom limb pain (PLP) is a chronic debilitating condition, frequently observed in amputees. At present, there is no standard treatment, and its optimal management requires a multidisciplinary approach in which minimally invasive treatment should be considered in more complex cases. Objective: To report successful treatment of 2 cases of PLP treated with ziconotide as part of multimodal intrathecal management. Materials and methods: Descriptive, retrospective case report developed in a multimodal pain treatment unit. Results: A total of 2 cases of patients with diagnosis of PLP refractory to medical therapy, treated with intrathecal multimodal therapy, are presented. Their favorable course, with 50% pain reduction, is described. Conclusion: Implantation of infusion systems for administration of intrathecal analgesia with ziconotide at the cervical and supraspinal level proved to be effective in the described cases; this technique should be evaluated in specific trials for the treatment of PLP refractory to other therapies.

Resumen Introducción: El dolor de miembro fantasma es una condición crónica debilitante, frecuentemente observada en pacientes amputados. En la actualidad carece de un estándar de tratamiento. Su óptimo manejo requiere un abordaje multidisciplinario en el que el tratamiento mínimamente invasivo debe ser considerado en los casos más complejos. Objetivo: Reportar el éxito obtenido en dos casos de dolor de miembro fantasma tratados mediante ziconotida, como parte del manejo multimodal intratecal. Materiales y métodos: Se trata de un reporte de casos, descriptivo y retrospectivo, desarrollado en una unidad de tratamiento integral del dolor. Resultados: Se presentan dos casos de pacientes con diagnóstico de dolor de miembro fantasma refractario a tratamiento médico, tratados con terapia multimodal intratecal; se describe su evolución favorable después del inicio de la terapia, con una reducción de dolor del 50%. Conclusiones: La implantación de sistemas de infusión para administración de analgesia intratecal con ziconotida a nivel cervical y supraespinal demostró ser eficaz en los casos descritos; esta técnica debe ser evaluada en ensayos específicos para el tratamiento del dolor de miembro fantasma en miembros superiores, refractario a otras terapias.

Optimizing Initial Intrathecal Drug Ratio for Refractory Cancer-Related Pain for Early Pain Relief. A Retrospective Monocentric Study.

OBJECTIVE: Intrathecal (IT) drug delivery has shown its efficiency in treating refractory cancer pain, but switching opioids from the systemic to the intrathecal route is a challenging phase. Moreover, associations are widely used and recommended. Few data deal with the initial dosage of each drug. Analyzing conversion factors and initial dosages used in intrathecal therapy seems essential to decreasing the length of titration and to delivering quick pain relief to patients. METHODS: We retrospectively analyzed data from consecutive adult patients implanted with an intrathecal device for cancer pain and treated at the Institut de Cancérologie de l'Ouest, in Angers, France, for four years. The main goal was to identify factors associated with early pain relief after intrathecal drug delivery system (IDDS) implantation. RESULTS: Of the 220 IDDS-treated patients, 70 (32%) experienced early pain relief (EaPR) and 150 (68%) delayed pain relief (DePR). Performance Status stage and initial IT ropivacaine:IT morphine ratio were the variables independently associated with EaPR. The best IT ropivacaine:IT morphine ratio to predict EaPR was 5:1, with a 73% (95% confidence interval [CI] = 64.8% to 79.6%) sensitivity and a 67.1% (95% CI = 54.9% to 77.9%) specificity. EaPR subjects experienced better pain relief (-84% vs -60% from baseline pain score, P < 0.0001), shorter length of hospitalization (7 vs 10 days, P < 0.0001), and longer survival (155 vs 82 days, P = 0.004). CONCLUSIONS: Local anesthetic:morphine ratio should be considered when starting IDDS treatment. EaPR during the IT analgesia titration phase was associated with better pain relief and outcomes in patients with refractory cancer-related pain.

Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-up Study Over an 11-Year Period in a Comprehensive Cancer Center.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France. Patients were followed from March 2006 to April 2017. Patients were selected for IDDS based on multidisciplinary meeting discussion. All IDDS-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed according to painful metameric level. Postimplant assessment of pain was determined using a numerical rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly until death. Pain scores were compared using the Wilcoxon signed rank test. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between groups by log rank tests. RESULTS: Ninety-three patients received IDDS, and total therapy duration accounts for 10,300 IDDS days. Implanted patients suffered from severe pain before implantation (median presurgical NRS, 8 [interquartile range, 7-9]) despite a median 360 mg (260-600) oral morphine equivalent daily dose. Median OS in the whole cohort after intrathecal treatment start was 82 days (95% confidence interval, 59-95). Median OS after surgery for implantable pump was 91 days (83-111) and for external pump 27 days (20-49; P < .0001). IDDS was associated with pain relief with a significant statistical difference between preimplantation NRS pain score and 1 week (median, -6 [-7 to -4]; P < .001), 1 month (median, -5 [-6 to -3]; P < .001), and 3 months (median, -6 [-7 to -4]; P < .001). Severe pain (NRS score, ≥7) decreased from 89.2% before surgery to 4.5% after 1 week, 6.7% after 1 month, and 10.3% after 3 months of IDDS implant (P < .01). Global complications rate was low, consistent with published literature. CONCLUSIONS: Despite our study's limitations, results suggest that long-term IDDS for refractory malignant pain due to pancreatic cancer was both efficacious and safe in pancreatic cancer pain. We have demonstrated, in the largest series of IDDS for pancreatic cancer pain reported yet, a clinically and statistically significant pain reduction in patients receiving IDDS.