Safety and Efficacy of Intrathecal Drug Delivery Pumps for Intractable Pain in Cancer Patients

Introduction

Pain management in cancer patients is a critical issue in palliative care, as clinicians strive to improve patients’ quality of life and alleviate their suffering. Most cancer patients experience cancer-related pain, and 30%-40% of them suffer from intractable pain despite maximum pharmacological treatment. Intrathecal pain pumps (ITPs) have become an option for controlling pain in cancer patients. Given the potential benefits of ITPs, we aimed to investigate the long-term outcomes of using this pain management approach at a cancer center.

Paper Source

This study was conducted by Graham M. Winston, Jeffrey H. Zimering, Christopher W. Newman, Anne S. Reiner, Noel Manalil, Natasha Kharas, Amitabh Gulati, Neal Rakesh, Ilya Laufer, Mark H. Bilsky, and Ori Barzilai from the Department of Neurological Surgery at Memorial Sloan Kettering Cancer Center. The paper was published online in the journal Neurosurgery on May 3, 2024.

Research Methods

Study Population

The researchers retrospectively reviewed the medical records of all adult cancer patients who underwent ITP implantation at a comprehensive tertiary cancer center between 2013 and 2021.

Study Procedures

The study included the following steps:

a) Baseline Data Collection

This included age, gender, race, body mass index, preoperative numerical rating scale (NRS) pain scores, past medical history, medication use, coagulation profile, and more. Data on cancer type, pain type (neuropathic, nociceptive, or mixed), and pain location were also collected.

b) Surgical Procedure

All patients underwent ITP implantation under general anesthesia in a lateral decubitus position. A small incision was made at the lumbar level, and the dura was punctured through an intervertebral space to insert the catheter into the intrathecal space. Another incision was made on the ipsilateral abdomen to create a pocket for the pump. The catheter was connected to the pump.

c) Pain Assessment

Postoperative follow-up visits were conducted to assess changes in NRS pain scores.

d) Adverse Event Recording

Postoperative complications were recorded, including cerebrospinal fluid leakage, hematoma and edema, catheter migration/fracture, pump dislocation/failure, wound dehiscence, surgical site infection, and others like deep vein thrombosis and pulmonary embolism.

e) Survival Assessment

Patients’ overall survival was recorded.

f) Data Analysis

Statistical methods were used to analyze pain relief, complication rates and cumulative incidence, overall survival, and more.

Main Research Findings

a) Baseline Patient Characteristics

A total of 193 patients were included, with a median age of 59 years, and 54% were female. The most common cancer types were non-small cell lung cancer (10.9%), colorectal cancer (10.4%), breast cancer (9.3%), multiple myeloma (8.8%), and pancreatic cancer (8.3%). Ninety-six percent of patients had nociceptive pain, and 73% had neuropathic pain. The most common pain locations were the back/thoracic/lumbar spine (40.4%), lower extremities (38.3%), pelvis/sacrum (27.5%), and abdomen/visceral (27.5%).

b) Postoperative Pain Relief

After ITP implantation, the mean NRS pain score decreased significantly by 4.08 points (standard deviation 2.13, p<0.01), from a preoperative mean of 7.38 to 3.27 postoperatively. Among the 185 patients with both pre- and postoperative scores, 176 (95.1%) experienced pain relief, 5 (2.7%) had no change, and 4 (2.2%) had worsening pain. One hundred forty-nine patients (80.5%) had an NRS score decrease of ≥3 points, and 70 (37.8%) had a decrease of ≥5 points.

When categorizing pain as mild (NRS≤4), moderate (5-6), or severe (≥7), 98 patients improved from severe to mild, 38 improved from moderate to mild, 31 improved from severe to moderate, and only 2 worsened from mild to moderate.

c) Survival

The median overall survival after ITP implantation was 3.62 months (95% CI: 2.73-4.54 months). The 1-year, 2-year, and 3-year survival rates were 27.1% (95% CI: 21.0%-33.6%), 16.3% (95% CI: 11.3%-22.1%), and 11.3% (95% CI: 7.0%-16.7%), respectively.

d) Adverse Events

During the study period, 42 adverse events occurred in 33 patients. The 1-year cumulative incidence of any complication was 15.6% (95% CI: 10.9%-21.1%), and that of severe complications (Clavien-Dindo grade 3-5) was 5.7% (95% CI: 3.0%-9.7%).

The most common complications included pneumonia (7 cases), urinary tract infection (6 cases), surgical site infection (5 cases), deep vein thrombosis (4 cases), and wound dehiscence (4 cases).

Eleven patients required reoperation, including 3 for wound dehiscence, 2 for pump dislocation, 1 for surgical site infection, 1 for cerebrospinal fluid leakage, 1 for catheter migration, 1 for catheter fracture, 1 for pump failure, and 1 for hematoma. The 1-year cumulative incidence of reoperation was 4.2% (95% CI: 2.0%-7.7%).

e) Research Significance

This study demonstrated that ITP implantation is a safe and effective method for managing intractable cancer-related pain, with a low complication rate. It provides strong support for the use of ITPs in palliative care. Future prospective studies are needed to determine the optimal timing for ITP implantation.

Research Value and Innovation

This study is the largest longitudinal study to date on the use of ITPs for pain management in cancer patients, confirming the safety and efficacy of this approach. The main innovative aspects include:

1. The large sample size provided sufficient statistical power to evaluate the clinical efficacy and safety of this therapy.

2. The use of standard statistical methods to analyze various clinical outcome measures, including pain relief, overall survival, and complication rates, lends strong credibility to the results.

3. The study results provide a solid theoretical basis for the clinical application of ITPs in palliative care.

4. The concept of early ITP implantation is proposed, which may further optimize pain management and quality of life for cancer patients, and warrants further investigation.

5. Barriers to pain management are analyzed, providing suggestions for improving clinical practice in this area.

6. Compared to existing literature, this study covers a broader range of professional fields, including neurosurgery, oncology, pain medicine, and palliative care.

This large retrospective study provides critical evidence-based medicine for the application of ITPs in cancer patients, and it has significant implications for promoting the further adoption of this therapy in clinical practice.