Abstract BACKGROUND For brain metastases (BM), resection remains a mainstay for the upfront management of large, symptomatic lesions, while laser interstitial thermal therapy (LITT) has become a key treatment for radiographically progressive BM following stereotactic radiosurgery (SRS). Compared to LITT, resection-associated morbidity may delay systemic therapies. We evaluated functional outcomes for resection versus LITT to primary motor cortex (PMC)-associated metastases. METHODS Patients receiving resection or LITT for BM radiographically associated with the PMC from 2015-2023 were retrospectively reviewed. Demographic and survival data were collected, with patient Karnofsky Performance Status (KPS) or modified Rankin Scale (mRS) scores assessed out to 1-year by independent raters. RESULTS Forty-one patients underwent resection and 30 underwent LITT to a PMC-associated lesion. Median age was 67 (range 38 – 80) vs 65 (44 – 80) for resection vs LITT; median pre-operative KPS (70 vs 80, P = 0.1) or mRS (2 vs 2, P = 0.66) did not differ between groups. Lung was the most common primary (56.1% resections vs 56.7% LITTs). Resected lesions were of larger median diameter than LITT, 2.8 vs 1.9 cm, P = 0.0001. For resections, length of stay was longer, median 2 vs 1 day, P = 0.0002, and ICU use more frequent (75.6% versus 20.0%, P < 0.0001). At 1-month post-op, 66.7% of resection patients and 51.7% of LITT patients had stable or improved symptoms from pre-op, P = 0.21, with parity at 3-months (65.7% vs 62.9%) and therafter. Further, there was no significant decrement in KPS or mRS score out to a year for either intervention. CONCLUSIONS While there is a short-term increased risk of post-operative neurologic worsening due to LITT-associated edema, our data shows that, relative to resection, this is a transient and clinically limited phenomenon. With careful patient selection, LITT to lesions involving the PMC is feasible.

Background: Opioids are often prescribed for patients who eventually undergo lumbar decompression. Given the potential for opioid-related morbidity and mortality, postoperative weaning is often a goal of surgery. The purpose of this study was to examine the relationship between preoperative opioid use and postoperative complete opioid weaning among lumbar decompression patients. Methods: We surveyed the IBM Marketscan Databases for patients who underwent lumbar decompression during 2008-2017, had >30 days of opioid use in the year preceding surgery, and consumed a daily average of >0 morphine milligram equivalents in the 3 months preceding surgery. We used multivariable logistic regression and marginal standardization to examine the association between preoperative opioid use duration, average daily dose, and their interactions with complete opioid weaning in the 10-12 months after surgery. Results: Of the 11,114 patients who met inclusion criteria, most (54.7%, n = 6083) had a preoperative average daily dose of 1-20 morphine milligram equivalents. Postoperatively, 6144 patients (55.3%) remained on opioids. For patients with >180 days of preoperative use, the adjusted probability of weaning increased as the preoperative dose decreased. Obesity increased the likelihood of weaning, whereas older age, several comorbidities, female sex, and Medicaid decreased the odds of weaning. Conclusions: Patients who used opioids for longer preoperatively were less likely to completely wean following surgery. Among patients with >180 days of preoperative use, those with lower preoperative doses were more likely to wean. Weaning was also associated with several clinical and demographic factors. These findings may help shape expectations regarding opioid use following lumbar decompression.

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) has clinical utility in treating radiographically progressive brain metastases (BM) following stereotactic radiosurgery (SRS), while resection has been reserved for large, symptomatic lesions in the upfront setting. Resection-associated morbidity in eloquently-located metastases may hinder definitive management. METHODS Patients receiving resection or LITT for BM radiographically associated with the primary motor cortex (PMC) from 2015-2023 were retrospectively reviewed. Clinicodemographic and survival data were collected, with patient Karnofsky Performance Status (KPS) or modified Rankin Scale (mRS) scores assessed out to 1-year by independent raters. RESULTS Forty-one patients underwent resection and 30 underwent LITT to a PMC-associated lesion. Median age was 67 (range 38 – 80) vs 65 (44 – 80) for resection vs LITT; median pre-operative KPS (70 vs 80, P = 0.1) or mRS (2 vs 2, P = 0.66) did not differ between groups. Lung was the most common primary site (56.1% resections vs 56.7% LITTs). Resected lesions were of larger median diameter than LITT, 2.8 vs 1.9 cm, P = 0.0001. For resections, length of stay was longer, median 2 vs 1 day, P = 0.0002, and ICU use more frequent (75.6% versus 20.0%, P < 0.0001). At 1-month post-op, 66.7% of resection patients and 51.7% of LITT patients had stable or improved symptoms from pre-op, P = 0.21, with parity at 3-months (65.7% vs 62.9%). Further, there was no significant decrement in KPS or mRS score out to a year for either intervention. CONCLUSION While LITT-induced edema may slightly increase the risk of post-operative neurologic deficits, this is a transient and clinically insignificant phenomenon. Reduced operative footprint in the context of LITT may allow for faster definitive management of BM. For carefully selected lesions, LITT adjacent to eloquent cortex is feasible.

Abstract BACKGROUND Tumor-related epilepsy is a common sequela of both primary and metastatic brain tumors, as well as radiation necrosis (RN). Laser interstitial thermal therapy (LITT) is an effective option for lesional cytoreduction but induces transient peritumoral edema that typically resolves within 3 months of the procedure. Accordingly, we quantified the risk of seizure development early post-LITT in patients with tumors or RN of diverse histologies. METHODS Patients treated with LITT for brain tumors or radiation necrosis at a high-volume center from 2015 – 2021 with at least 3 months of clinical follow-up were evaluated for seizure risk and time to discontinuation of anti-epileptic drugs (AEDs) for at least 4 weeks, with censoring at death or last follow-up. RESULTS One-hundred and seventeen patients met inclusion criteria, and 22 (19%) experienced a post-LITT seizure within 3 months of surgery. Those with pre-LITT seizures (P = 0.03), prior whole-brain radiation (WBRT) (P = 0.0099), or lower pre-operative KPS (P = 0.04) were more likely to have a post-LITT seizure. Frontal lobe tumors appeared to be more frequently associated with seizures (68% vs 45%, P = 0.06). Prior WBRT, odds ratio (OR) 4.27 (95% CI 1.01 – 18.55), P = 0.047 and pre-LITT seizure, OR 5.39 (95% CI 1.87 – 16.31), P = 0.002 remained predictive on multivariate analyses. Successful AED weaning occurred at a median of 1.68 months (no seizure within 3-months group) versus undefined for patients experiencing seizures (P = 0.015). Post-LITT seizures within 3 months were associated with worsened post-LITT overall survival, 5.95 vs 17.2 months, P < 0.0001. DISCUSSION Prior seizure history or previous WBRT pose a risk of breakthrough seizures following laser ablation. Neurosurgeons should consider extended AED treatment or referral for management of tumor-related epilepsy in patients with these neurologic risk factors.

Abstract Purpose: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. Experimental Design: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel–based phantoms of control and GNS-infused central “tumors.” In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. Results: Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. Conclusions: Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

Abstract Laser interstitial thermal therapy (LITT) is a minimally-invasive technique for the treatment of intracranial tumors that uses a stereotactically-guided laser for ablation. Magnetic resonance thermal imaging is used to monitor ablation progress by measuring the cumulative heat energy exposure in both the tumor and the surrounding tissue to calculate thermal damage thresholds.Previous applications of GNS in laser ablation of tumors have studied extracranial tumors only and utilized externally administered near infrared radiation that cannot penetrate the cranial compartment. Herein, we present a novel platform for employing GNS in intracranial tumors. We developed GNS that exhibit maximum photothermal effects at the 1064 nm laser wavelength used in the FDA-approved clinical Neuroblate® LITT system. Monte Carlo simulations demonstrate that our GNS can accelerate and focus thermal energy distributions. Using ex vivo tumor phantom models, GNS-infused phantoms demonstrate more rapid heating, expanded ablation zones, and improved margin conformation, with surrounding areas exposed to lower temperatures than controls. In in vivo intracranial tumor models, we show that GNS selectively accumulate and are retained in CT2A glioma and B16F0 melanoma tumors at 24 and 72 hours post-injection. Using our in vivo heterotopic CT2A model, we demonstrate that systemically-delivered GNS dramatically augment laser ablation, with higher temperatures achieved in the tumor and more efficient temperature ramping. These results support the ability of GNS to optimize LITT for the treatment of intracranial tumors by improving the efficiency and safety of this platform.

Abstract Laser interstitial thermal therapy (LITT) is a minimally-invasive technique for the treatment of intracranial tumors that uses a stereotactically-guided laser and real-time magnetic resonance imaging (MRI) to monitor ablation progress. Previous applications of gold nanostars (GNS) in laser ablation of tumors have studied extracranial tumors only and utilized externally administered near infrared radiation that cannot penetrate the cranial compartment. Herein, we present a novel platform for employing GNS in intracranial tumors. We developed non-toxic GNS that exhibit maximum photothermal effects at the 1064 nm laser wavelength used in the FDA-approved clinical Neuroblate® LITT system. Monte Carlo simulations demonstrate that our GNS can accelerate and focus thermal energy distributions. Using ex vivo tumor phantom models, we found that GNS-infused phantoms demonstrate more rapid heating and improved spatial conformation of thermal energy, with neighboring material exposed to lower temperatures than controls. In our intracranial CT-2A glioma model, we quantified accumulation of radiolabeled GNS in tumor tissue via PET/CT. As further validation of tumor-selective GNS accumulation, we used two-photon luminescence to show that GNS selectively accumulate and are retained in intracranial tumors at 24 and 72 hours post-injection. We then utilized our in vivo heterotopic CT-2A model to assess the capacity of systemically-delivered GNS to augment laser ablation; we were able to achieve higher ablation temperatures and more efficient temperature ramping with LITT+GNS. Finally, we explored the potential of LITT+GNS to synergize with immunotherapy to further enhance the post-ablation immune response and found that combination therapy resulted in improved tumor control and immunologic memory that was protective against tumor rechallenge. These results support the ability of GNS to optimize LITT for the treatment of intracranial tumors by improving efficiency and safety, and illustrate the potential of this platform to synergize with immunotherapy.

[This corrects the article DOI: 10.1016/j.adro.2022.101054.].

Background The nervous and immune systems interact in a reciprocal manner, both under physiologic and pathologic conditions. Literature spanning various CNS pathologies including brain tumors, stroke, traumatic brain injury and de-myelinating diseases describes a number of associated systemic immunologic changes, particularly in the T-cell compartment. These immunologic changes include severe T-cell lymphopenia, lymphoid organ contraction, and T-cell sequestration within the bone marrow. Methods We performed an in-depth systematic review of the literature and discussed pathologies that involve brain insults and systemic immune derangements. Conclusions In this review, we propose that the same immunologic changes hereafter termed ‘systemic immune derangements’, are present across CNS pathologies and may represent a novel, systemic mechanism of immune privilege for the CNS. We further demonstrate that systemic immune derangements are transient when associated with isolated insults such as stroke and TBI but persist in the setting of chronic CNS insults such as brain tumors. Systemic immune derangements have vast implications for informed treatment modalities and outcomes of various neurologic pathologies.

Immunotherapies, such as immune checkpoint inhibition (ICI), have had limited success in treating intracranial malignancies. These failures are due partly to the restrictive blood-brain-barrier (BBB), the profound tumor-dependent induction of local and systemic immunosuppression, and immune evasion exhibited by these tumors. Therefore, novel approaches must be explored that aim to overcome these stringent barriers.LITT is an emerging treatment for brain tumors that utilizes thermal ablation to kill tumor cells. LITT provides an additional therapeutic benefit by synergizing with ICI and systemic chemotherapies to strengthen the anti-tumor immune response. This synergistic relationship involves transient disruption of the BBB and local augmentation of immune function, culminating in increased CNS drug penetrance and improved anti-tumor immunity.In this review, we will provide an overview of the challenges facing immunotherapy for brain tumors, and discuss how LITT may synergize with the endogenous anti-tumor response to improve the efficacy of ICI.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Purpose: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk.Methods and Materials: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected.Results: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS.Conclusions: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.(c) 2022 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive treatment modality for intracranial tumor and radiation necrosis (RN). A transient increase in edema following LITT typically resolves within three months post-procedure. We sought to characterize the short-term seizure outcomes during this period for patients undergoing LITT for tumor or RN. A retrospective analysis of 86 consecutive patients treated with LITT from 2015-2019 at a single institution was conducted. Data on baseline demographics, treatment details, and clinical course were collected. Thirty-one (36%) had a seizure within one year following LITT, 19 (22%) of which occurred within the first 90 days post-LITT (71% of all seizures). Forty-three (50%) patients had documented pre-LITT seizures, with 27 (63% of all seizures) of those occurring within 90 days pre-LITT. Between patients with and without post-LITT seizures within the first 90 days, there were no significant differences in gender, age, pre-LITT KPS, pre-LITT volume, pre-LITT resection, pre-LITT stereotactic radiotherapy, pre-LITT chemo- or immuno-therapy, use of AEDs or steroids before or after LITT, location, or pathology at the time of treatment. Patients with seizures in the first 90 days post-treatment were significantly more likely to have received pre-LITT whole brain radiotherapy (WBRT) (32% vs. 9%, p=0.02). Of the 18 patients with pre-LITT seizures within 90 days, 9 (50%) were entirely seizure free in the 90-day post-LITT period. In summary, seizure is a known complication of LITT for intracranial lesions, with the majority occurring in the first 90 days post-procedure. WBRT was significantly associated with 90-day post-LITT seizure, which may represent a diminished neurologic reserve in these patients. These findings may help guide clinicians in determining patients appropriate for LITT and those who may require closer monitoring and longer AED tapers in the short-term period following ablation.

Laser interstitial thermal therapy (LITT) is a growing minimally-invasive approach for treatment of intracranial tumors. Stereotactic placement of the laser catheter within the target lesion carries a theoretical risk of tract seeding, which could lead to disease progression. A retrospective analysis of patients treated with LITT for biopsy-confirmed tumor from 2016-2020 was conducted to characterize the risk of post-LITT tract seeding. Forty-two patients met inclusion criteria, of whom 23 (54.7%) had primary brain tumors and 19 (45.3%) metastases. Thirty-three (78.6%) lesions were recurrent disease at the time of LITT. On follow-up MRI, 3 patients (7.1%) were identified to have had tumor seeding along the LITT tract resulting in progressing disease. There were no significant differences in tumor histology, pre-operative maximum lesion diameter, number of LITT trajectories, rounds of lasing, or post-LITT radiotherapy or surgery between patients with and without tract seeding. All patients with tract seeding were treated for periventricular lesions (<1cm). Patients with tract seeding were also more likely to have received LITT ablations administered from the superficial to deepest elements of the lesion (p=0.05). The median time to progression post-LITT for patients with tract seeding was significantly shorter than those without (1.1 vs 5.9 months, p=0.02). Additional analyses revealed trends towards longer median tract length (4.0 vs. 2.2 cm, p=0.23) and shorter overall survival (5.4 vs. 14.2 months, p=0.17) in the tract seeding cohort. In summary, tract seeding is an infrequent complication associated with both LITT and traditional biopsy. In LITT, tract seeding progression occurs significantly faster than at the treated site, which may be associated with a worse overall prognosis. Prophylactic stereotactic radiosurgery to the LITT tract could be of benefit, however this may pose further risk to patients given the low overall frequency. More frequent monitoring may be necessary lesions in periventricular or difficult to ablate regions, or with longer LITT tracts.

Abstract Introduction Laser interstitial thermal therapy (LITT) is a minimally-invasive treatment option for radiographically-progressive (RP) brain metastases. This study compares the functional outcomes of LITT vs resection (RS) for lesions in or near the primary motor cortex (PMC). Methods Retrospective review was performed of patients treated for PMC lesions by LITT or RS. Functional outcomes were graded relative to pre-treatment symptoms and categorized as improved, stable, or worsened at 30, 90, and 180 days post-LITT/RS. Results 36 patients were identified with median follow-up of 194 days (IQR 72–503), age 64 years (57–72), and estimated baseline KPS 80 (80–90). 35 (98%) had pre-treatment weakness or motor seizure; 15 (42%) received LITT and 21 (58%) RS; all RS were performed with intra-operative motor mapping while LITT were not. All LITT patients were treated for RP lesions (radiation necrosis (RN) or disease progression) vs. 24% of RS patients (p<0.01). LITT patients trended towards smaller lesions (1.9 cm vs 2.7 cm, p=0.03) and were more likely to show RN (67% vs 5%, p<0.01) and be discharged home (87% vs 52%, p=0.04), with shorter ICU (0 vs 1 day, p<0.01) and hospital stays (1 vs. 2 days, p<0.01). At 30 days, 89% of surviving patients who received RS had stable or improved symptoms, compared to 46% of the LITT cohort (p=0.02). At 90 days, the difference was 88% to 50% (p=0.07), and at 180 days 100% to 80% (p=0.2941). Conclusion In the short term (30 days), patients with PMC lesions have better functional outcomes when treated with RS compared to LITT, while those who survive to the 180-day timepoint experience similar outcomes. These differences are likely due to transient, expected post-LITT edema that subsides with time. Taken together, prognosis and patient priorities are important considerations in the decision between LITT and RS.

Abstract INTRODUCTION Laser interstitial thermal therapy (LITT) is a minimally-invasive treatment option for radiographically-progressive (RP) brain metastases. This study compares the functional outcomes of LITT vs resection (RS) for lesions in or near the primary motor cortex (PMC). METHODS Retrospective review was performed of patients treated for PMC lesions by LITT or RS. Functional outcomes were graded relative to pre-treatment symptoms and categorized as improved, stable, or worsened at 30, 90, and 180 days post-LITT/RS. RESULTS 36 patients were identified with median follow-up of 194 days (IQR 72-503), age 64 years (57-72), and estimated baseline KPS 80 (80-90). 35 (98%) had pre-treatment weakness or motor seizure; 15 (42%) received LITT and 21 (58%) RS; all RS were performed with intra-operative motor mapping while LITT were not. All LITT patients were treated for RP lesions (radiation necrosis (RN) or disease progression) vs. 24% of RS patients (p< 0.01). LITT patients trended towards smaller lesions (1.9 cm vs 2.7 cm, p=0.03) and were more likely to show RN (67% vs 5%, p< 0.01) and be discharged home (87% vs 52%, p=0.04), with shorter ICU (0 vs 1 day, p< 0.01) and hospital stays (1 vs. 2 days, p< 0.01). At 30 days, 89% of surviving patients who received RS had stable or improved symptoms, compared to 46% of the LITT cohort (p=0.02). At 90 days, the difference was 88% to 50% (p=0.07), and at 180 days 100% to 80% (p=0.2941). CONCLUSIONS In the short term (30 days), patients with PMC lesions have better functional outcomes when treated with RS compared to LITT, while those who survive to the 180-day timepoint experience similar outcomes. These differences are likely due to transient, expected post-LITT edema that subsides with time. Taken together, prognosis and patient priorities are important considerations in the decision between LITT and RS.

Background. The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges. Methods. The IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis. Results. We identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%). Conclusions. LC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs.

Study Design. Retrospective analysis of inpatient and outpatient medical insurance claims data from a database containing >100 million individuals. Objective. The aim of this study was to quantify the health care resource utilization (HCRU) of nonsurgical treatments in the first 2 years after a chronic, refractory low back pain (CRLBP) diagnosis. Summary of Background Data. Patients with persistent low back pain (LBP) despite conventional medical management and who are not candidates for spine surgery are considered to have CRLBP and incur substantial healthcare costs over time. Few data exist on the HCRU of this specific population. Methods. The IBM MarketScan Research databases from 2009 to 2016 were retrospectively analyzed to identify US adults with a diagnosis of nonspecific LBP and without cancer, spine surgery, failed back surgery syndrome, or recent pregnancy. We required >30 days of utilization of pain medications or nonpharmacologic therapies within both the 3 to 12- and 12 to 24-month periods post-diagnosis. Annual total health care costs, costs subdivided by insurance type, and use of nonsurgical therapies were determined for 2 years after diagnosis of LBP. Results. A total of 55,945 patients with CRLBP were identified. Median total cost was $6590 (Q1 $2710, Q3 $13,922) in the first year, almost doubling the baseline cost; costs were highest for patients with Medicare Supplemental insurance, reaching $10,156 (Q1 $5481, Q3 $18,570). A total of 33,664 (60.2%) patients engaged physical therapy, 28,016 (50.1%) engaged chiropractors, and 14,488 (25.9%) had steroid injections. In total, 36,729 (65.7%) patients used prescription pain medications, most commonly opioids (N = 31,628, 56.5%) and muscle relaxants (N = 21,267, 38.0%). Conclusion. This study is one of the first to investigate the HCRU of a large, longitudinal US cohort of patients with CRLBP. These patients experience substantial health care costs. Contrary to LBP management guidelines, most patients used opioids, and several nonpharmacologic therapies were used by only a few patients.

Abstract INTRODUCTION Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges. METHODS The IBM MarketScan® Research databases were queried for adult patients diagnosed with LC between 2001 and 2015, secondary to four primary solid tumors (breast, lung, gastrointestinal, and melanoma). The primary outcome was overall healthcare resource utilization (HCRU) for each primary cancer subgroup, quantified as the total cost at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis. The secondary outcome was interventional treatments for LC. RESULTS We identified 4,961 cases of LC (46% breast cancer, 35% lung cancer, 14% GI cancer, and 5% melanoma). The median baseline Elixhauser comorbidity index was lower for patients with LC secondary to breast cancer (19) relative to those with primary lung, GI, or melanoma (22). The overall median follow-up length was 66 days. The breast and lung cancer groups had the longest and shortest post-LC diagnosis follow-up at 84 and 51 days, respectively. Cost data demonstrated high baseline total costs for the year preceding LC diagnosis (median $117,219). Cumulative median service and medication costs at 365 days post-LC diagnosis were the highest for the GI subgroup ($167,768) and lowest for the lung cancer subgroup ($145,244). In the first 30 days post-diagnosis, 66.9% sought treatments of any kind: 40% radiotherapy, 28% therapeutic lumbar puncture (TLP), and 14% Ommaya insertion. Of the 747 (15%) patients surviving and continuously enrolled to 365 days post-diagnosis, 78.8% had at least one encounter for treatments: 58% radiotherapy, 30% TLP, and 15% Ommaya insertion. CONCLUSION In this large nationwide study of LC associated with four major primary cancers, breast cancer patients had the fewest comorbidities at baseline and the longest follow-up, while those with GI cancer had the highest cost both at baseline and one year after LC diagnosis.

INTRODUCTION: The economic burden of low back pain (LBP) in the US is estimated between $84.1 and $624.8 billion. Some patients with LBP that persists despite conventional medical management are ineligible for spine surgery and are considered to have non-surgical refractory back pain (NSRBP). We investigated the healthcare resource utilization (HCRU) of patients with NSRBP. METHODS: The IBM MarketScan® Research databases were queried for adult patients with a diagnosis of LBP, excluding instability (eg, spondylolisthesis) and non-mechanical etiologies, and negative history of failed back surgery syndrome or spine surgery within the study period (2009-2016). For a patient to qualify as refractory, we required utilization for >30 d of pain medications (prescribed within 2 wk of diagnosis) or non-pharmacologic therapies within the 3 to 24 mo following initial diagnosis. Annual total costs, including inpatient and outpatient service costs and outpatient medication costs, were calculated for 2 yr. RESULTS: Among 50 801 patients, median total cost was $3,755 (IQR $1,299, $9,108) at 1 yr pre-diagnosis, reached $6,622 (IQR $2,723, $13,978) at 1 yr, and decreased to $5,977 (IQR $2,311, $13,307) at 2 yr. Costs were highest for patients with Medicare Supplemental (N = 7,053): median total cost was $10,198 (IQR $5,517, $18,584) at 1 yr, decreasing in the second year to $9,407 (IQR $4,737, $18,330). Outpatient services accounted for the majority of all costs. The proportion of patients with ≥4 outpatient visits for LBP was 56.6% within the first 6 mo, 50.0% in the 1st year, and 68.5% in the 2nd year. CONCLUSION: For patients with NSRBP, the median annual total cost at 1 yr almost doubled the 1-yr prediagnosis cost and decreased for the 2nd year; most costs were due to outpatient services. Patients with Medicare Supplemental incurred the highest total costs. Most patients saw outpatient providers multiple times in the first 6 mo and throughout the 2 yr.