Exceptional Cases of Spinal Cord Stimulation for the Treatment of Refractory Cancer-Related Pain

STRUCTURED ABSTRACT

Objectives:

Cancer pain has traditionally been managed with opioids, adjuvant medications, and interventions including injections, neural blockade, and intrathecal pump (ITP). Spinal cord stimulation (SCS), while increasingly utilized for conditions such as failed back surgery syndrome and complex regional pain syndrome, is not currently recommended for cancer pain. However, patients with cancer-related pain have demonstrated benefit with SCS. We sought to better characterize these patients and the benefit of SCS in exceptional cases of refractory pain secondary to progression of disease or evolving treatment-related complications.

Materials and Methods:

This was a single-center, retrospective case series at a tertiary cancer center. Adults ≥18 years old with active cancer and evolving pain secondary to disease progression or treatment, whose symptoms were refractory to systemic opioids, and who underwent SCS trial followed by percutaneous implantation between 2016 and 2021, were included. Descriptive statistics included mean, standard deviation, median, and interquartile range.

Results:

Eight patients met inclusion criteria. The average age at SCS trial was 60.0 (SD, ±11.6 years), and 50% were male. Compared to baseline, the median (interquartile range, IQR) change in pain score by numeric rating scale (NRS) after trial was −3 (2). At an average of 14 days post-implant, the median (IQR) change in NRS and daily oral morphine equivalents (MEQ) were –2 (3.5) and −126mg (1095mg), respectively. At a median of 63 days post-implant, the corresponding values were −3 (0.75) and −96mg (711mg). There was no significant change in adjuvant therapies after SCS implantation at follow-up. Six patients were discharged within two days after implantation. Two patients were readmitted for pain control within the follow-up period.

Conclusions:

In patients with cancer-related pain, SCS may significantly relieve pain, reduce systemic daily opioid consumption, and potentially decrease hospital length of stay and readmission for pain control. It may be appropriate to first consider SCS trial prior to ITP in select cases of cancer-related pain.

INTRODUCTION

Cancer pain, or pain that is directly caused by primary or metastatic tumor-related infiltration, compression, or inflammation, is one of the most debilitating and feared chronic pain syndromes. Most moderate-to-severe cancer pain is effectively managed with opioids as first-line therapy, followed by adjuvant medications including acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, analgesic antidepressants, alpha-2 adrenergic agonists, local anesthetics, anticonvulsants, and N-methyl-D-aspartate (NMDA) receptor antagonists. In 10–15% of cancer patients, these conventional pharmacotherapies may be insufficient [1], requiring the use of interventional therapies such as local anesthetic and/or steroid injections, sympathetic blockade from neurolytic injection and radiofrequency ablation, or neuraxial anesthesia (epidural/intrathecal catheters) [2]. Spinal cord stimulation (SCS) is considered in rare cases.

Targeting the dorsal column, SCS has evolved from its early days of twisted platinum wires providing all-or-nothing stimulation to modern-day, multimodal devices. Non-compatibility with magnetic resonance imaging (MRI) previously presented a longstanding challenge to utilizing SCS in patients with cancer pain, given the frequency with which they obtain MRI studies to monitor disease progression [3]. With modern SCS devices being MRI-conditional, SCS has become a feasible, non-pharmacologic modality to deliver substantial symptom benefit with minimal side-effects.

Indications for SCS include the treatment of intractable radicular pain secondary to failed back surgery syndrome (FBSS), complex regional pain syndrome, and other etiologies of neuropathic, sympathetically mediated, and ischemic pain [4]. A 2015 Cochrane Database review concluded that there is insufficient evidence for the role of SCS in treating refractory cancer pain [5]. However, Hagedorn et al. performed an updated literature review comprising 67 cases across multiple studies and concluded that SCS and dorsal root ganglion stimulation can be effective for nociceptive, viscerosomatic, and neuropathic cancer pain [1]. The included studies utilized solely “traditional” SCS, which delivers pulse frequencies in the 2–1200 hertz (Hz) range but most typically 40–60 Hz (low frequency). The authors also reviewed the application of SCS to 43 cases of cancer-related pain, or pain secondary to cancer treatment such as chemotherapy, radiation, or surgery. Their analysis suggested that both traditional and non-traditional SCS modes are beneficial for this indication as well.

Implantable intrathecal delivery systems (intrathecal pump, ITP) have a track record of durable efficacy in treating refractory cancer pain [6]. However, their management logistics, including pump accessibility for refills, need to be considered prior to placement. Furthermore, these devices are associated with complications such as catheter tip granulomas and opioid-related side-effects [7]. As such, the modern-day, MRI-conditional, and multimodal SCS may be a reasonable neuraxial alternative for cancer pain. Additional indications in the cancer population surround post-surgical and post-radiation sequalae leading to neuritis and neuropathy.

In certain “exceptional” cases of cancer pain that is refractory to attempted or definitive ITP therapy, is at risk for substantial opioid-related side-effects from high intrathecal opioid doses, is multifocal, and/or is rapidly progressing in the setting of worsening disease or treatment-related complications, a trial of SCS may be a reasonable next step. We present clinical outcomes after SCS for cancer pain at our institution, among patients with such exceptional circumstances.

MATERIALS AND METHODS

Patient Selection

This was a single-center, retrospective case series at a tertiary cancer center. Adults ≥18 years old with active cancer and evolving pain secondary to disease progression or treatment, whose symptoms were refractory to systemic opioids and prior interventions, and who underwent SCS trial followed by definitive implantation between 2016 and 2021, were included. This study was approved by the institutional review board (IRB #17–537) and supported by the NIH Core Grant P30 CA008748.

Spinal Cord Stimulator Placement

Anatomic SCS lead placement was determined based on clinical exam assessing for dermatomal distribution of pain and associated symptoms. Imaging data were used for secondary verification and device implantation planning. All patients underwent SCS trial prior to definitive implantation, and a positive response by pain symptoms confirmed appropriate placement.

The patient was positioned prone on the operating table under monitored anesthesia care (MAC). The appropriate interspace was identified by anterior-posterior fluoroscopic view. The skin and subcutaneous tissues were anesthetized with 0.25% bupivacaine. A 14-gauge Touhy needle was advanced percutaneously into the epidural space by loss of resistance to air and confirmed by fluoroscopy. Posterior passage of the guidewire and lead was confirmed in the lateral view. An 8-lead spinal cord stimulator lead was advanced to the desired location. Once in the appropriate location, the anesthetic was reduced, utilizing patient feedback for device testing and programming. Upon complication of testing, the leads were tunneled and connected to the implantable pulse generator. Incisions were irrigated copiously and closed appropriately.

Data Collection

All data were collected from retrospective review of patients’ electronic medical records in Allscripts (Allscripts Healthcare Solutions, Inc., Chicago, IL). The patients’ pre-SCS (i.e., “baseline”) status by clinical presentation, pain level, and pain management was obtained within one month prior to SCS trial. The same evaluation was then repeated 1) post-trial lead placement but prior to lead removal (i.e., “post-trial”), 2) within 30 days of implant placement (i.e., “short-term post-implant), and 3) around 60 days after implant placement (i.e., “longer-term post implant”). Procedure notes for the SCS trial and implant were reviewed. Industry representatives’ reports were referenced for programmed stimulation modes and frequency settings at the time of implantation.

The primary outcomes included pain scores (0–10 numeric rating scale, NRS: 0 corresponds to no pain and 10 corresponds to the worst pain imaginable) and total daily oral morphine equivalents (MEQ) to systemic opioids consumed. Systemic opioids were defined as those administered by the following routes: oral (PO), intravenous (IV), transdermal, or sublingual. Intrathecal or epidural opioids were not included as systemic opioids, but rather categorized as adjuvant pain medications. The secondary outcomes assessed were hospital length of stay after SCS implantation and readmission rate for pain control during the post-procedure follow-up period.

Statistical Analysis

All data were recorded and securely stored in Microsoft Excel (Microsoft Corporation, Redmond, WA), and portions of the data were exported for descriptive analysis in RStudio, an open-source data analysis software package (RStudio, Boston, MA). Descriptive statistics including mean, standard deviation, median, and interquartile range were calculated.

RESULTS

Demographic Data

A total of 8 cases were included in the final analysis. The mean age at SCS trial was 60.0 (SD ±11.6 years), with 50% being male (Table 1). Seven patients had cancer pain secondary to metastatic spread while one had pain originating from the primary site. Four patients (1–4) had chronic pain directly related to their cancer (cancer pain), while the other four (5–8) had chronic pain following cancer-related surgery, chemotherapy, and/or radiation (cancer-related pain). Anatomic level of implantation spanned T5-T10. Four patients received single, rather than bilateral SCS lead placement due to concern for post-surgical or radiation-induced scarring in the epidural space. Six patients (Cases 1–6) had their devices programmed to paresthesia mode (60–100 Hz), while the other two (Cases 7–8) were programmed to >200Hz, paresthesia-free settings.

Table 1:

Patient demographics and clinical summary.

Patient ID	Age at SCS* trial (yrs)	Sex (M/F)	Type of cancer	Location of pain	Type of pain	Level of SCS implant	Mode of SCS implant	Clinical summary
1	45.8	M	Non-small cell lung cancer	anterior chest wall	viscero-somatic	T5 (midline)	60–100 Hz*	45M, NSCLC* with metastases to the pleura and LNs* and encasement of left mainstem bronchus s/p* chemoradiation.
2	69.4	F	Papillary thyroid cancer	flank, sacrum, unilateral lower extremity	somatic-neuropathic (entrapment neuropathy)	T7 (right)	60–100 Hz	69F, papillary thyroid cancer with sacral metastasis s/p radiotherapy and sacral cement augmentation.
3	42	M	Multifocal peripheral schwannoma	low back, upper abdomen	neuropathic (compressive neuropathy)	T7 (midline)	60–100 Hz	42M, schwannomatosis with metastatic lesions involving the pleura and liver.
4	59.3	M	Renal cell carcinoma	lower back, hip	somatic-neuropathic (radiculopathy)	T9, T10	60–100 Hz	59M, renal cell carcinoma with metastases to bone, liver, lung, LNs, and right psoas s/p kyphoplasty, chemoradiation, and separation surgery [8].
5	63.9	F	Rectal cancer	unilateral lower extremity	Neuropathic (radiculopathy, neuritis)	T10 (midline)	60–100 Hz	63F, rectal cancer s/p chemoradiation c/b* recurrent sacral sarcoma, worsening radiation neuritis with neural foraminal stenosis.
6	77.1	F	Chordoma	unilateral lower extremity, peripheral neuropathy	somatic-neuropathic (neuritis)	T8, T10	60–100 Hz	77F, chordoma s/p XRT* and lumbar decompression/ fusion, c/b refractory postoperative neuritis.
7	58.8	F	Liposarcoma	unilateral thigh and upper extremity	neuropathic (neuritis, neuralgia)	T8 (mid), T8 (top)	>200 Hz	58F, liposarcoma s/p two right-sided peritoneal resections and radiation, c/b right thigh neuritis and neuralgia.
8	63.7	M	Renal cell carcinoma	unilateral thigh and knee	somatic-neuropathic (radiculopathy, neuritis)	T8, T9	>200 Hz	63M, renal cell carcinoma with metastases to brain and bone s/p palliative cement augmentation of right acetabulum c/b right pelvic abscess requiring drainage and chronic right groin and thigh pain.

^*SCS - spinal cord stimulator; Hz – Hertz; NSCLC - non-small cell lung cancer; LN - lymph node; s/p – status post; c/b - complicated by; XRT - external radiation therapy

Primary Outcomes

The median (interquartile range, IQR) baseline NRS pain score and MEQ were 6.5 (1.25) and 231mg (2249mg), respectively (Table 2). Most patients received a SCS trial within 15 days of initial consultation, except for patients 3 and 5 (received at 86 and 50 days, respectively). At an average follow-up of 4 days after trial placement, the median (IQR) change in pain score compared to baseline was −3 (2). Patients subsequently underwent SCS implantation within 30 days of their trial (except for patient 5, at 38 days). At an average follow-up of 14 days post-implant (short-term), the median change in pain score and MEQ compared to baseline was −2 (3.5) and −126mg (1095mg) respectively. At a median follow-up of 63 days post-implant (longer-term), the corresponding values were −3 (0.75) and −96mg (711mg), respectively.

Table 2:

Primary outcomes after SCS trial and implant.

Patient ID	Baseline NRS* pain score	Baseline MEQ*	Post-trial NRS pain score	Post-implant NRS pain score	Post-implant MEQ	Long-term post-implant NRS pain score	Long-term post-implant MEQ
1	7	4248	3	5	2460	3	10860
2	6	192	3	5	30	3	0
3	7	270	N/A, “75% relief of his chest pain”	0	180	-	-
4	3	2280	4	2	1320	5	960
5	8	120	4	6	45	N/A, “pain in her leg is well controlled”	45
6	6	20	3	N/A, “doing well”	5	3	5
7	5	126	3	2	63	3	30
8	7	2654	6	0	312	4	152

^*NRS - numeric rating scale (0–10, least to worst); MEQ -morphine equivalents (PO daily)

Secondary Outcomes

Qualitatively, there was no substantial change in the type of adjuvant therapies patients were prescribed before and after SCS implantation at both short-term and longer-term follow-up. Except for patients 4 and 8, all patients were discharged by postoperative day two (Table 3). Only two patients (1 and 3) were readmitted for pain control after SCS implantation.

Table 3:

Secondary outcomes after SCS implant.

Patient ID	Baseline adjuvant therapies	Post-implant adjuvant therapies	Long-term post-implant adjuvant therapies	Hospital stay post-SCS* implant (days)	Number of readmissions for pain control post-SCS implant and pre-long-term follow-up
1	Morphine ITP* 30mg/day with Bupivacaine 21mg/day and Clonidine 60mcg/day, Acetaminophen 650mg PO* q6h* prn*	Morphine ITP 30mg/day with Bupivacaine 21mg/day and Clonidine 60mcg/day, Lidocaine patch 1/day	Morphine ITP 30mg/day with Bupivacaine 21mg/day and Clonidine 60mcg/day, Acetaminophen 1000mg IV q8h, Dexamethasone 4mg PO q24h	2	1
2	Pregabalin 150mg PO bid*, Dexamethasone 2mg PO bid	Pregabalin 150mg PO daily	Pregabalin 150mg PO daily	1	0
3	None	None	None	0	1
4	Gabapentin 1200mg PO q8h	Gabapentin 1200mg PO q8h	Gabapentin 1200mg PO q8h	12	0
5	Duloxetine 30mg PO daily	Duloxetine 30mg PO daily, Cyclobenzaprine 10mg PO qhs	Duloxetine 30mg PO daily, Cyclobenzaprine 10mg PO qhs*	0	0
6	Nortriptyline 25mg PO daily, Gabapentin 600mg PO tid*	Nortriptyline 25mg PO daily, Gabapentin 600mg PO tid	Nortriptyline 25mg PO daily, Gabapentin 600mg PO tid	1	0
7	Pregabalin 75mg PO tid, Acetaminophen 650mg PO q6h prn	Pregabalin 75mg PO bid, Acetaminophen 650mg PO q6h prn	Pregabalin 75mg bid	0	0
8	Morphine ITP 14.6mg/day with Bupivacaine 11.7mg/day and Clonidine 220mcg/day, Acetaminophen 1000mg IV q8h	Morphine ITP 17.7mg/day with Bupivacaine 14.1mg/day and Clonidine 265.25mcg/day	Morphine ITP 17.7mg/day with Bupivacaine 14.1mg/day and Clonidine 265.25mcg/day	8	0

^*SCS - spinal cord stimulator; ITP - intrathecal pump; PO - oral; q_h - every _ hours; prn - as needed; bid - twice a day; tid - three times a day; qhs - nightly

Patient Case Summaries

Patient 1: 45-year-old man with Stage IV non-small cell lung cancer and metastases to the pleura, lung, and lymph nodes, who developed worsening pleuritic and viscerosomatic chest pain from progression of disease. Side effects from PO and IV opioids eventually warranted ITP placement. Pain relief was short-lived, and he required repeated escalation of his intrathecal opioids, Bupivacaine, and Clonidine. He underwent SCS trial six weeks later. After six days, he reported feeling “very happy” with his pain relief, particularly on the high-frequency mode. He continued to endorse pain relief with the combination of SCS, ITP, and high-dose IV morphine patient-controlled analgesia (PCA) for palliative care. Six weeks after implantation he was readmitted from hospice for difficulty with urination and anxiety, passing away several days later. This was an exceptional case for SCS given the rapidly increasing nature of the patient’s analgesic requirements in the setting of progressive end-stage disease, that did not completely respond to ITP.

Patient 2: 69-year-old female with a history of follicular thyroid cancer, who developed combined somatic and neuropathic pain secondary to entrapment from a metastasis to her sacrum, abutting the S1 and S2 nerve roots. While being admitted for ITP placement, she decided to undergo a SCS trial first after discussing both options. Three weeks after the SCS implantation, she was able to stop opioids completely and resume exercising. Four months later, she reported significant pain relief, had gained 10lbs with increased appetite, and was looking forward to tolerating longer car rides for travel. Her case was exceptional for multiple reasons: her pain intensity was exacerbated by radiotherapy prior to SCS, she failed systemic opioids due medication side-effect, and she received substantial benefit from SCS, specifically functional improvement and MEQ reduction.

Patient 3: 42-year-old male with a history of schwannomatosis (pleural- and liver-predominant multifocal peripheral schwannoma) with associated right upper quadrant and abdominal pain secondary to compressive neuropathy. Initially responsive to an intercostal nerve block and epidural steroid injection, he subsequently developed breakthrough pain from progression of disease. ITP was contraindicated given the patient’s low body habitus. Two days after an SCS trial, he reported 75% pain relief, which was sustained for several months allowing him to decrease his opioid consumption. However, over a year after SCS implantation, he returned to clinic expressing minimal benefit after having discontinued SCS due to intolerable paresthesia eight months prior. This case was novel in that SCS was used for pain secondary to peripheral nerve sheath tumors, though the patient did not tolerate the associated paresthesia.

Patient 4: 59-year-old male with a history of renal cell carcinoma, who developed a L4 metastasis causing pathologic fracture with spinal canal compression. He underwent separation surgery followed by radiation therapy and multiple lines of chemotherapy. At initial evaluation, he was bed-bound with left buttock and leg radicular/somatic pain. ITP placement was unsuccessful due to anatomic limitations. Four days after a SCS trial, the patient experienced pain relief, and was able to complete two laps around the inpatient ward. One week after implantation, he felt “very happy” about his hip and lower back pain coverage, which was sustained for several months with the use of the paresthesia-free SCS mode. This case was exceptional by demonstrating successful utilization of SCS in patients with complex spine anatomy that limited the successful placement of ITP.

Patient 5: 63-year-old female with rectal cancer, successfully treated with chemotherapy and multiple rounds of radiation, presented with long-term radiation-related neuritic right leg and radicular sacral pain. After opting for a SCS trial first, she reported >50% improvement in pain symptoms, greater activity, and improved mobility three days later. Two-and-a-half weeks after the implant, she was benefitting from the 500 Hz/500ms setting and rarely requiring Oxycodone for breakthrough. At six-week follow-up her radicular pain continued to be well-controlled with the SCS. This case was exceptional because SCS was effective as first-line therapy for new pain from progressive treatment-related scarring.

Patient 6: 77-year-old female with a lumbar chordoma treated with separation surgery followed by stereotactic body radiosurgery developed worsening right leg pain and peripheral neuropathy over several months, concerning for radiation-induced neuritis. Due to her significant opioid tolerance, she opted for a SCS trial instead of ITP. At one-week post-trial, she had decreased her opioid intake by 75%. Two-and-a-half weeks after the SCS implant, she reported decreased opioid ingestion and improved ambulation and ability to perform daily activities with limited pain. She was an exceptional case given the worsening nature of her neuropathy secondary to radiation neuritis.

Patient 7: 58-year-old female with liposarcoma of her right abdomen developed severe postoperative pain after extensive tumor resection. Her pain was described as burning in her right anterior thigh and buttock, suggestive of neuralgia from injury to the lumbar plexus. After failing multiple neuropathic medications, NSAIDs and L2-L3 sympathetic blocks, she experienced partial relief from L2-L3 peripheral nerve stimulation (PNS). SCS was therefore indicated over ITP given the favorable response with PNS. Three days after trial lead placement, she noted >50% pain relief and increased ambulation. At two-week follow-up after SCS implant, she noted >60% pain relief, 80% improved function, and increased ambulatory tolerance. Six weeks after implant, she continued to endorse sustained pain relief. She was an exceptional case given the persistent, refractory, and complex nature of her treatment-related neuropathic pain.

Patient 8: 63-year-old male with metastatic renal cell carcinoma to the right hip. After undergoing a right hemipelvectomy followed by radiation, he had a palliative cementoplasty of the right acetabulum, complicated by multiple infections requiring drainage and antibiotics, as well as neuritic right inguinal and radicular thigh pain. The pain persisted despite multiple nerve blocks, cryoablative therapy, and ITP. At baseline, he had already been followed by the pain service for over a month given multiple prior admissions for acute-on-chronic pain crises. Five days after SCS trial, he reported “excellent” pain relief and was looking forward to the implant. A little over a week after the implant, he was able to work with physical therapy and was discharged to a subacute rehabilitation facility. Two months after the implant, he was discharged home from the facility and has been able to sleep at least six hours at night without benzodiazepines. He was an exceptional case by virtue of the complexity of his pain syndrome and the extent of benefit received from SCS despite ITP therapy, ability to avoid readmission for pain control, and subsequent decrease in systemic opioid requirements.

DISCUSSION

In this retrospective case series, we sought to highlight eight patients at our institution who had direct or treatment-related cancer pain that was refractory to conventional first- and second line therapies and received substantial clinical benefit from SCS. They were all considered exceptional based on etiology and/or presentation of their pain syndrome.

As highlighted in Table 1, the cohort was composed of various oncologic presentations and variable pain generators. Our descriptive analysis suggests that these patients obtained pain relief as noted by a 2- to 3-point decrease in NRS. On the boundaries of pain relief distribution, patient 1 had a four-point reduction in NRS at longer-term follow-up, while patient 4 reported a two-point increase in pain but still had a >40% reduction in MEQ (Table 2). By MEQ, all patients except for patient 1 demonstrated a steady decrease at each evaluation period. Excluding Patient 1 from this cohort due to severe progression of disease and palliative care status, our cohort had a median MEQ reduction of −144mg (958mg), or 75.6% (24.1%) from baseline, at longer-term follow-up.

By comparison, Sindt et al reviewed 173 patients with cancer pain (93% with stage IV disease) who underwent ITP placement, demonstrating a mean MEQ decrease of 94% compared to pre-implantation [9]. It must be noted that, although ITP placement decreases MEQ, patients still receive neuraxial opioid analgesia and are at risk of opioid-related side-effects including sedation, pruritis, and constipation. In contrast, although MEQ reduction from SCS was more modest in our cohort, the competitive advantage of SCS stems from the lack of opioid-related side-effects.

The increased use of adjuvant agents in patients 1 and 5 – compared to a decrease in patients 2, 7, and 8 – are challenging to interpret in context with SCS, except to highlight that adjuvant medications do not appear to account for the changes in NRS and MEQ (Table 3). This may further suggest that SCS shows efficacy in cancer-related pain.

Each patient highlighted a unique benefit of SCS for cancer-related pain, encouraging the notion to consider a SCS trial as the next step in appropriate circumstances. Patients 1, 4, and 8 had either failed ITP placement or had inadequate pain coverage despite ITP therapy escalation, making them ideal candidates for a SCS trial. Patient 2 was a good candidate given her pain was predominantly neuropathic in nature, with rapidly progressive disease (making optimal ITP dosing as an alternative an ever-moving target), and already demonstrating signs of systemic opioid related side-effects. Patient 3 was unique in that the pain source stemmed from multiple peripheral nerve sheath tumors which responded favorably to SCS. Patient 5 had neuropathic-predominant pain similar to patient 2. Additionally, both patients had opioid tolerance, requiring increased intrathecal doses of local anesthetic, leading to concern for medication side-effects. Finally, patient 7 warranted a SCS trial prior to ITP given neuropathic-predominant post-surgical pain, with documented sensitivity to the sedating effects of prior opioid analgesics.

Determinants of the Appropriateness of SCS for Cancer-Related Pain

Patient selection is nuanced for cancer-related pain. A SCS trial may be considered for patients with longstanding cancer treatment-related pain that is predominantly neuropathic in nature. Furthermore, understanding patients’ overall disease status has a profound impact on decision-making. Even in patients with progressive disease, SCS trial leads can be placed percutaneously with minimal morbidity.

Determinants of success for cancer pain can be extrapolated from the work of Stearns et al. on the cost-benefit analysis of intrathecal drug delivery systems for cancer pain [10]. Their 14-year review of 1403 prospectively collected registry participants demonstrated benefits across various postoperative measures including hospital-based and quality-of-life metrics and patient-reported outcomes. This study can serve as a model to compose a study to better define success after SCS implantation. Measures to suggest improved benefit with SCS include shorter recovery time and less in-patient device manipulation, expediting patient benefit [11].

Although technology initially increases the cost burden of device-based interventions, early work by Stearns determined savings of $15,142 (p=0.0097) at two months and $63,498 (p=0.3) at 12 months after starting ITP [10], compared to conventional medical management [12]. Despite its high upfront costs, SCS has also been shown to be cost-effective for chronic neuropathic pain compared to reoperation and medical management [13,14]. In our cohort, patients 1, 2, 4, and 8 were admitted for pain control at time of initial evaluation. While their hospital length of stay after SCS implantation varied between 1–12 days, only one out of four was readmitted for pain control. Of note, patient 8, who had faced multiple admissions for pain control six months prior to SCS implantation, did not require readmission after his SCS implant.

Selecting the appropriate stimulation mode is paramount to the success of SCS in oncologic pain. Most patients in our cohort were programmed to conventional paresthesia mode immediately after implantation, although patients 1, 4, and 5 were reprogrammed to paresthesia-free mode (>200Hz) on follow-up evaluation with reported benefit (Table 1). This may suggest that similar to patients with non-cancer pain, certain patients with cancer pain may respond more favorably to high-frequency modes compared to conventional modes [15,16]. Given the newer waveforms available across SCS devices, they may allow for better pain control in active cancer patients.

Pearls and Tips for SCS in Cancer Pain

Multiple pearls can be identified to aid in the decision-making of SCS placement in refractory cancer and cancer-related pain. Patient selection begins with review of preoperative imaging and risk stratification to determine if the patient is an appropriate candidate for surgical management of their pain. In the event that surgical management is not appropriate or feasible, discussion regarding ITP and/or SCS may be appropriate.

In situations where the patient has mainly non-neuropathic pain and benefits from systemic opioids but requires very high doses with concern for side-effects, ITP may be a reasonable next step. However, if the patient’s pain is either refractory to systemic or neuraxial opioids from prior ITP, their low body habitus prohibits the safe subcutaneous storage of the relatively large pump unit in the abdomen, there are treatment-related changes in the spine that preclude safe access to the intrathecal space, the pain is neuropathic-predominant, and/or the pain is rapidly evolving and multifocal, SCS may be reasonably considered as the next step. In instances that fall between these two categories, we propose that a trial of SCS may still be a reasonable option, given that this technique is completely opioid sparing and is associated with minimal morbidity.

Additionally, SCS can provide functional improvement and palliation. When comparing the efficacy of low-frequency SCS to modes at frequencies above 10,000 Hz (HF10) for chronic back and leg pain, Kapural et al. quantified overall functional status using the Global Assessment of Functioning (GAF), and function in the setting of low back pain using the Oswestry Disability Index (ODI) [15,17,18]. We believe that it is important to follow the patients’ functional status after SCS for cancer pain using a metric such as the ODI, as this information may highlight a further benefit to the technique. Regarding patients for whom SCS would be palliative, functional improvement may not necessarily be a realistic goal. Additionally, we consider whether these patients in particular may benefit from bypassing trial SCS leads and going directly to implant to maximize the quantity and durability of potential pain relief.

Technical challenges exist in maintaining durable benefit of SCS in oncologic pain. Providers and patients alike must take time to understand the programming features to allow for continued titration of settings for maximum benefit. Newer paresthesia-free settings may result in improved pain control. These results have been seen in other chronic pain populations. Most devices afford higher frequency settings along with paresthesia settings, allowing for personalization in each patient. This will need to be further studied in the oncologic population.

The most common complication associated with SCS (particularly with percutaneous placement of cylindrical leads) is lead migration, compromising the durable benefit potential [19]. While oncologic disease may not be present in the thoracic spine, an MRI of the thoracic spine is valuable to identify anatomic limitations to SCS placement. Furthermore, if the spine has been exposed to radiation, the epidural space may not provide smooth tactile feedback while feeding the SCS lead. In our experience, the epidural space may have a “crunchy” feeling, but the lead can still be placed in its optimal location. Of note, it may not be feasible to place a second lead for optimal pain coverage and as insurance against lead migration if radiation- or surgery-related scarring complicates the anatomy.

Limitations and Future Direction

Given its retrospective nature, our study lacks standardized follow-up periods, making generalizability challenging. Also, given the case series categorization, focusing on robust outcomes after SCS placement, our findings may over-represent the efficacy of SCS in the general population of patients suffering from cancer-related pain. A small study cohort also limited our ability to perform comparative analysis across subgroups of cancer types and/or stages. Finally, the fact that most of our cases are dated and did not incorporate paresthesia-free settings as part of the initial SCS programming means that our findings provide limited insight into the efficacy of paresthesia-free SCS in this patient population.

Future studies should consider the following next steps: 1) establishing the efficacy of SCS for cancer-related pain prospectively and across a larger cohort; 2) differentiating its efficacy for pain that originates directly from active cancer, compared to cancer treatment-related complications, 3) differentiating SCS efficacy for refractory cancer pain in patients at terminal stages of disease with limited life expectancy; 4) more closely examining the impact of SCS on functional outcomes in addition to pain relief and systemic opioid requirements; 5) examining the cost-effectiveness of SCS for cancer pain.

CONCLUSION

In carefully selected patients with refractory cancer-related pain, SCS can lead to significant pain relief, a decrease in systemic daily opioid requirements, and improved function. SCS may potentially help reduce hospital length of stay for inpatients with poorly controlled cancer pain and decrease the likelihood for pain control associated readmissions. In some patients, it may be reasonable to consider a SCS trial prior to ITP for cancer-related pain.