Comparison of the Degree of Expanded Spinal Canal Area between the Hinge-Side Area and the Open-Side Area in Cervical Open-Door Laminoplasty.

Background: There have been reports on the significant canal cross-sectional area (CSA) expansion difference between pre- and post-operation, but no comparison of CSA expansion between the hinge-side area (Area H) and the open-side area (Area O) has been reported. This study aimed to measure the spinal CSA expansion between Area H and Area O retrospectively after open-door laminoplasty using new titanium spacers and evaluated this common decompression procedure's effectiveness. Materials and Methods: This study included 27 patients diagnosed with cervical spondylotic radiculopathy or myelopathy, ossification of the posterior longitudinal ligament, and developmental canal stenosis from February 2021 to October 2022. The CSA difference between pre- and post-cervical laminoplasty (C4-C6 levels) was measured with cervical transverse computed tomography scan images. The CSA difference in Area H and Area O between pre- and post-laminoplasty was similarly calculated. Results: The spinal canal areas of each segment after open-door laminoplasty were significantly enlarged (P < 0.05). Area O was also significantly enlarged compared to that of Area H (P < 0.05). Conclusion: Area O was more enlarged than Area H, and both sides were statistically enlarged after open-door laminoplasty.

Risk Factors of Subsidence after Anterior Cervical Discectomy and Fusion with Double Cylindrical Cages for Cervical Degenerative Diseases: Minimum Two-year Follow-up Results.

Cylindrical cages were known to cause subsidence after anterior cervical discectomy and fusion (ACDF); hence, they were gradually replaced by box-shaped cages. However, this phenomenon has been inconclusive due to limited information and short-term results. Therefore, this study aimed to clarify risk factors for subsidence after ACDF using titanium double cylindrical cages with mid-term follow-up periods. This retrospective study included 49 patients (76 segments) diagnosed with cervical radiculopathy or myelopathy caused by disc herniation, spondylosis, and ossification of the posterior longitudinal ligament. These patients underwent ACDF using these cages from January 2016 to March 2020 in a single institution. Patient demographics and neurological outcomes were also examined. Subsidence was defined as a ≥3-mm segmental disc height decrease at the final follow-up lateral X-ray compared to that on the next day postoperatively. Subsidence occurred in 26 of 76 segments (34.7%) within the follow-up periods of approximately three years. Multivariate analysis using a logistic regression model demonstrated that multilevel surgery was significantly associated with subsidence. The majority of patients achieved good clinical outcomes based on the Odom criteria. This study demonstrated that multilevel surgery was the only risk factor of subsidence post-ACDF with double cylindrical cages. Despite the relatively high subsidence rates, the clinical outcome was almost good at least during the mid-term period.

Intraoperative Cone-Beam Computed Tomography Assessment of Spinal Pedicle Screws Placement Precision Is in Full Agreement with Postoperative Computed Tomography Assessment.

OBJECTIVE: To assess agreement between pedicle screw placement evaluated on postoperative computed tomography (CT) and on intraoperative cone-beam CT (CBCT) and compare procedure characteristics when using first-generation and second-generation robotic C-arm systems in the hybrid operating room. METHODS: All patients who received pedicle screws for spinal fusion at our institution between June 2009 and September 2019 and underwent intraoperative CBCT and postoperative CT were included. The CBCT and CT images were reviewed by 2 surgeons to assess the screw placement using the Gertzbein-Robbins and the Heary classifications. Intermethod agreement of screw placement classifications as well as interrater agreement were assessed using Brennan-Prediger and Gwet agreement coefficients. Procedure characteristics using first-generation and second-generation generation robotic C-arm systems were compared. RESULTS: Fifty-seven patients were treated with 315 pedicle screws at thoracic, lumbar, and sacral levels. No screw had to be repositioned. On CBCT, accurate placement was found for 309 screws (98.1%) using the Gertzbein-Robbins classification and 289 (91.7%) using the Heary classification and on CT, these were 307 (97.4%) and 293 (93.0%), respectively. Intermethod between CBCT and CT and interrater agreements between the 2 raters were almost perfect (>0.90) for all assessment. There were no significant differences in mean radiation dose (P = 0.83) and fluoroscopy time (P = 0.82), but length of surgery using the second-generation system was estimated at 107.7 minutes (95% confidence interval, 31.9-183.5 minutes; P = 0.006) shorter. CONCLUSIONS: Intraoperative CBCT provides accurate assessment of pedicle screw placement and enables intraoperative repositioning of misplaced screws.

Safety and Validity of Anterior Cervical Disc Replacement for Single-level Cervical Disc Disease: Initial Two-year Follow-up of the Prospective Observational Post-marketing Surveillance Study for Japanese Patients.

Anterior cervical disc replacement (ACDR) using cervical artificial disc (CAD) has the advantage of maintaining the range of motion (ROM) at the surgical level, subsequently reducing the postoperative risk of adjacent disc disease. Following the approval for the clinical use in Japan, a post-marketing surveillance (PMS) study was conducted for two different types of CAD, namely, Mobi-C (metal-on-plastic design) and Prestige LP (metal-on-metal design). The objective of this prospective observational multicenter study was to analyze the first 2-year surgical results of the PMS study of 1-level ACDR in Japan. A total of 54 patients were registered (Mobi-C, n = 24, MC group; Prestige LP, n = 30, PLP group). Preoperative neurological assessment revealed radiculopathy in 31 patients (57.4%) and myelopathy in 15 patients (27.8%). Preoperative radiological assessment classified the disease category as disc herniation in 15 patients (27.8%), osteophyte in 6 patients (11.1%), and both in 33 patients (61.1%). The postoperative follow-up rates at 6 weeks, 6 months, 1 year, and 2 years after ACDR were 92.6%, 87.0%, 83.3%, and 79.6%, respectively. In both groups, patients' neurological condition improved significantly after surgery. Radiographic assessment revealed loss of mobility at the surgical level in 9.5% of patients in the MC group and in 9.1% of patients in the PLP group. No secondary surgeries at the initial surgical level and no serious adverse events were observed in either group. The present results suggest that 1-level ACDR is safe, although medium- to long-term follow-up is mandatory to further verify the validity of ACDR for Japanese patients.

Subclavian Artery Flow Dynamics Evaluated by Analytical Intraoperative Indocyanine Green Videoangiography During Surgical Treatment of Thoracic Outlet Syndrome: A Case Series.

BACKGROUND: Indocyanine green (ICG) videoangiography is rarely used during the surgical treatment of thoracic outlet syndrome (TOS). OBJECTIVE: To evaluate subclavian artery (SA) flow dynamics using the analytical ICG videoangiography during TOS surgeries. METHODS: We examined patients with neurogenic TOS who received surgical treatment and whose SA blood flow at the interscalene space was evaluated using ICG videoangiography equipped with an analytical function (FLOW800). Anterior scalenectomy with or without middle scalenectomy and first rib resection were conducted for decompression of the brachial plexus. ICG videoangiography was performed before and after decompression of the brachial plexus. After acquisition of grayscale and color-coded maps, a region of interest was placed in the SA to obtain time-intensity diagrams. Maximum intensity (MI), rise time (RT), and blood flow index (BFi) were calculated from the diagram, in arbitrary intensity (AI) units. We compared values before and after decompression. Comparisons of the three parameters before and after decompression were assessed statistically using the paired t-tests and Wilcoxon signed-rank test. RESULTS: We evaluated nine procedures in consecutively presenting patients. The observed mean values of MI, RT, and BFi before decompression were 174.1 ± 61.5 AI, 5.2 ± 1.1 s, and 35.2 ± 13.5 AI/s, respectively, and the observed mean values of MI, RT, and BFi after decompression were 299.3 ± 167.4 AI, 6.6 ± 0.8 s, and 44.6 ± 28.3 AI/s, respectively. These parameters showed higher values after decompression than before decompression, and the increase in MI and RT was statistically significant (P < .05). CONCLUSION: ICG videoangiography allows semiquantitative evaluation of hemodynamic changes during TOS surgery. A marked decrease in the velocity of SA flow was observed after decompression.

Multimodal treatment including lumbar facet joint denervation for severe low back pain in patients with neuromuscular disorders.

BACKGROUND: Severe low back pain (LBP) is an occasional complaint in patients with neuromuscular disorders (NMDs). Accurate diagnosis and treatment are required to manage LBP; however, the precise pathophysiology differs for each patient. This study aimed to evaluate the efficacy of lumbar facet joint denervation (FJD) and adjunctive modalities in the treatment of LBP in patients with NMD-associated kyphoscoliosis. METHODS: A total of 16 patients (22 sites) with NMD (bilateral, n = 6; unilateral, n = 10) and LBP treated with lumbar FJD were evaluated. The patients were divided into two groups: those treated with FJD alone (group 1) and those treated with multimodal treatment, including FJD along with radiofrequency ablation for sacroiliac joint pain, piriform muscle block, botulinum toxin injection into the paraspinal muscles, spinal cord stimulation, or any of their combinations (group 2). All patients were followed up for 48 weeks postoperatively. The two groups were compared with respect to the duration required for improvements in LBP by more than 50% (numerical rating scale ≤ 5). RESULTS: There was no significant difference between the groups regarding the age, duration since the onset of Parkinson's syndrome, and radiographic analysis. The effective period of improved pain was greater in group 2 than in group 1 (30.7 vs. 8.4 weeks, P < 0.01). CONCLUSIONS: Multimodal treatment including FJD is safe and relatively effective in patients with NMD-associated kyphoscoliosis. Hence, it is a potential substitute for conventional spinal fixation surgery, which has a higher risk of complications.

Use of a Simulation Model to Investigate the Mechanisms of Sports-related Head Injuries.

A simulation model was developed to better understand the mechanisms of brain injuries in sports. A three-dimensional model comprising approximately 1.22 million elements was constructed from cranial computed tomography images of adult male volunteers by the voxel method. To simulate contact sports that permit actions such as tackling, a sinusoidal wave with duration of 10 ms and maximum acceleration of 2000 m/s2 was applied to the lowest point of the model to apply rotational acceleration to the head from different directions. The von Mises stress was then observed at five points in the coronal plane of the brain: cingulate gyrus (CG), corpus callosum (CC), brain stem (BS), lateral temporal lobe (LT), and medial temporal lobe (MT). LS-DYNA universal finite element analysis software with explicit time integration was used for the analysis. Concentrations of stress started to appear in the CC and BS at 10 ms post-impact, after which they also became evident in the CG and MT. The maximum changes in stress at each location occurred 10-15 ms post-impact. The von Mises stress was 9-14 kPa in the CG, 8-24 kPa in the CC, 12-24 kPa in the BS, 7-12 kPa in the LT, and 12-18 kPa in the MT. The highest stress in every part of the brain occurred after lateral impact, followed by oblique impact and sagittal impact. Such simulations may help elucidate the mechanisms of brain injuries in sports and help develop measures to prevent chronic traumatic encephalopathy.

Cervical lateral mass screw length analysis in men versus women.

Posterior fixations with lateral mass screws have become popular. The Roy-Camille and the Magerl techniques have been established and screw length was identified as a particularly important element. Sex and ethnicity are significant factors in cervical spine morphology, but few studies have been performed for screw length. We performed measurements using computed tomography (CT) images of adult patients hospitalized for surgery of the cervical spine, with targeted 3D data analysis. The final number of patients was 47 (33 men, 14 women) and 235 vertebrae. With the Roy-Camille technique, the screw length was longest at C3 (men: 13.0 mm ± 1.9 mm, women: 13.0 mm ± 1.9 mm) and smallest at C7 (men: 10.8 mm ± 1.8 mm, women: 9.4 mm ± 1.2 mm). With the Magerl technique, the screw length was smallest at C3 (men: 14.8 mm ± 1.6 mm, women: 14.3 mm ± 1.6 mm) and longest at C7 for men (16.8 mm ± 2.8 mm), and at C6 for women (15.4 mm ± 3.0 mm). To differ from spinal canal or pedicle, cervical lateral mass showed no obvious morphological differences from that of subjects of other ethnicity. The placement of a standard lateral mass screw would not cause complications in Japanese patients, even with the use of devices designed in North America or Europe. However, the anatomical background is essential because it is important to optimize the selection for each patient to avoid complications considering sex and individual differences.

MRI characteristics of syringomyelia associated with foramen magnum arachnoiditis: differentiation from Chiari malformation.

BACKGROUND: It is important to distinguish foramen magnum arachnoiditis (FMA) from Chiari malformation (CM) before surgery because the operative strategies for these diseases differ. In the current study, we compared pretreatment magnetic resonance imaging (MRI) of FMA with CM and investigated the MRI findings useful to differentiate between these diseases. METHODS: We retrospectively reviewed patients with FMA or CM aged ≥ 18 years who underwent surgeries at our institution between 2007 and 2019. The morphologies of the syrinx, neural elements, and posterior cranial fossa were preoperatively evaluated with MRI. We used the receiver operating characteristic (ROC) curve for the fourth ventricle-to-syrinx distance (FVSD). RESULTS: Ten patients with FMAs and 179 with CMs were included. FVSD in the FMA group was significantly shorter than that in the CM group (7.5 mm [IQR, 2.8-10 mm] in FMA vs. 29.9 mm [IQR, 16.3-52.9 mm] in CM, p < 0.0001). The other MRI findings that showed the height, size, and length of the syrinx; size of the foramen magnum; degree of cerebellar tonsillar descent; shape of the cerebellar tonsil; and dorsal subarachnoid space at the foramen magnum differed significantly between the two groups. The ROC curve analysis showed that patients whose FVSD was less than 11 mm could be diagnosed with FMA with a specificity of 90% and sensitivity of 96%. CONCLUSIONS: A more cranial syrinx development (FVSD < 11 mm) appears to be the characteristic MRI finding in FMA.

Thoracic and lumbar spine pedicle morphology in Japanese patients.

PURPOSE: Pedicle morphology is important for intraoperative surgical anatomy and to define pedicle screw design and parameters. However, differences of pedicle size according to ethnicity and gender are not well studied. The purpose of this study is to investigate morphological characteristics of the pedicle in Japanese patients for determining adequate screw size and optimal surgical planning. METHODS: We investigated thoracic and lumbar pedicle morphology in Japanese patients using computed tomography (CT) measurements and analyzed the standard size of pedicles on upper thoracic to lumbar spine CT images in 227 Japanese patients. RESULTS: Gender had a larger impact on the shape and size of pedicles than racial differences. In the distribution of pedicle width, we calculated the ratio of values less than 4.5 mm, that in females resulted to be over 30% for the Th3-Th9 segment, and particularly high, above 60% at Th4 and Th5. CONCLUSION: Our measurement analysis showed that pedicle morphological parameters in Japanese patients showed tendency to be smaller to those found in other studies, and particularly in female patients, they were statistically significantly smaller. Adequate transpedicular instrumentation for Japanese patients will require smaller size pedicle-related devices that will match our anatomical findings to achieve safe device placement. In addition, serving ethnically non-homogenous patient population can require further to spinal morphometric for precise device selection.

Cervical Extradural Arteriovenous Fistula without Intradural Drainage Successfully Treated with Endovascular Treatment Using Both Transvenous and Transarterial Approach: Case Report and Review of Literatures.

The classification of spinal extradural arteriovenous fistulas (AVFs) was reported based on a case series treated by microsurgery in 2009 and endovascular interventions in 2011. The present report describes a patient with extradural AVFs at the cervical spine manifesting gradual progressive radiculomyelopathy of bilateral upper extremities. Magnetic resonance imaging (MRI) revealed a mass sign from C1 to C4 at the right ventral side and the spinal cord was deviated to the left and indicated as a flow void sign. Diagnostic angiography revealed an extradural AVFs located at the C1-C4 level that was supplied by bilateral radicular artery from the vertebral artery (VA) and right ascending cervical artery (ACA). The shunting points were recognized multiply at C2/3 and C3/4 levels on the right. The transvenous embolization to the enlarged extradural venous plexus around the shunting points via right hypoglossal canal and the transarterial embolization against multi-feeders of the branch of left radicular artery, right ACA achieved complete occlusion of the lesions. His symptom was gradually recovered, and angiography performed 2 weeks after embolization showed no recurrence. When the arteriovenous shunts in the upper cervical spine were high flow shunts, transvenous approach via the hypoglossal canal might be one option for the treatment of spinal extradural AVFs.

Clinical predictors of surgical outcomes of severe carpal tunnel syndrome patients: utility of palmar stimulation in a nerve conduction study.

BACKGROUND: Carpal tunnel syndrome is a common peripheral nerve compression disorder. However, there is no established opinion regarding the predictors of symptom improvement after surgery. This study aimed to identify the predictors of surgical outcomes of severe carpal tunnel syndrome patients. METHODS: In the patients who underwent a carpal tunnel syndrome surgery, we selected the patients who had a preoperative Bland's classification of grade 5 or 6, and assessed for the changes in Bland's classification grade before and after surgery. Those who showed improvement from preoperative grades 5-6 to postoperative grades 1-4 comprised the improvement group. In contrast, those who did not show improvement and had postoperative grades 5 or 6 comprised the non-improvement group. In a nerve conduction study, amplitudes of the compound muscle action potential and sensory nerve action potential of the palms were assessed between the improvement and non-improvement groups. RESULTS: Among the 60 hands of 46 patients who had a preoperative Bland's classification of grade 5 or 6, 49 hands of 37 patients comprised the improvement group, and 11 hands of 9 patients comprised the non-improvement group. The amplitudes of the compound muscle action potential and sensory nerve action potential of the palms before surgery were significantly higher in the improvement group. The degree of improvement in Bland's classification grade was correlated with the degree of clinical symptom improvement. CONCLUSIONS: Amplitudes of compound muscle action potential and sensory nerve action potential before surgery induced by palmar stimulation can predict improvements in nerve conduction study scores and clinical findings after surgical treatment.

Total Spinal Epidural "Blood Patch" Application Through a Racz Catheter in Spontaneous Intracranial Hypotension.

BACKGROUND: Epidural "blood patch" (EBP) is a standard treatment of spontaneous intracranial hypotension (SIH). In recent years, there are some reports of Racz catheter use for EBP performance at upper cervical spine levels. However, the practical use of Racz catheter for single-entry multisite EBP has never been reported until now. CASE DESCRIPTION: We treated a 60-year-old man diagnosed with SIH presenting with cerebrospinal fluid leaks from the cervical to the sacral segments. We discuss the advantages of the single-entry multisite EBP and the convenience of Racz catheter use in such cases. CONCLUSIONS: The Racz catheter can be a convenient means to deliver large-volume EBPs from a single entry point in the treatment of SIH.

Spinal Extradural Arteriovenous Fistula with Cowden Syndrome: A Case Report and Literature Review Regarding Pathogenesis and Therapeutic Strategy.

We report the case of a patient with a spinal extradural arteriovenous fistula (AVF) associated with Cowden syndrome (CS) that was successfully treated by endovascular surgery. CS is an autosomal dominant disorder associated with diverse symptoms caused by a deleterious mutation in the phosphatase and tensin homolog (PTEN) gene. A 67-year-old woman was diagnosed with CS based on her medical history of multiple cancers for which she underwent abdominal surgery, macrocephaly, Lhermitte-Duclos disease, and facial papules. Her genetic testing demonstrated a PTEN mutation. She presented with progressive paraparesis and her MRI of the thoracolumbar spine showed the spinal cord edema along with flow voids. A spinal angiogram demonstrated a spinal extradural AVF with the perimedullary drainage. The AVF was successfully treated by endovascular surgery. The PTEN mutation can accelerate angiogenesis; thus, vascular anomalies are one of the diagnostic criteria of CS. However, only two cases of vascular anomalies involving the spinal cord in patients with CS have been reported previously. As the present case, both cases had a history of abdominal or retroperitoneal cancer. The PTEN mutation accompanied with abdominal surgery might have caused this vascular anomaly as the consequences of venous congestion around the thoracolumbar spine. A spinal extradural AVF should be considered in patients with CS who present with myelopathy, especially when the patient has a history of abdominal or retroperitoneal surgery. Regarding the treatment strategy, endovascular surgery should be considered because surgical insult could prompt secondary vascular anomalies resulting from neovascularization due to the PTEN mutation.

In vitro biomechanical evaluation of a monocoque plate-spacer construct for cervical open-door laminoplasty.

PURPOSE: To evaluate biomechanical differences between two surgical procedures for cervical open-door laminoplasty using human cadaveric spines. METHODS: Twenty-four cervical vertebrae (C4-C6) from eight fresh-frozen human cervical spines were subjected to mechanical testing after being instrumented for open-door laminoplasty using a newly designed plate-spacer device with a monocoque structure (plate-spacer group; n = 12) or by conventional miniplate-alone fixation (miniplate group; n = 12). Cantilever bending testing was performed by applying a compressive load in the cranio-caudal direction to the base of the spinous process of the reconstructed laminar arch constructs until failure and strength and stiffness of the laminar arch were determined. The results are presented as mean ± standard deviation. RESULTS: The plate-spacer group was approximately twice as strong as the miniplate group (27.6 ± 16.5 N vs. 13.5 ± 7.3 N, p < 0.05). Stiffness in the plate-spacer group exhibited the same trend (19.6 ± 9.3 N/mm vs. miniplate group: 11.4 ± 6.9 N/mm, p < 0.05). CONCLUSION: The fixation with the monocoque plate-spacer construct for open-door laminoplasty provided higher structural properties when compared against the plate-alone fixation. The spacer in the plate-spacer construct appears to contribute by preventing large deformations of the laminar arch caused by bending in cranio-caudal direction. Future studies will be required to investigate stress/strain distribution in the laminar arch constructs.

Immune-related Genes to Dominate Neutrophil-lymphocyte Ratio (NLR) Associated With Survival of Cetuximab Treatment in Metastatic Colorectal Cancer.

BACKGROUND: Few clinical studies have investigated the association between neutrophil-lymphocyte ratio (NLR) and treatment with cetuximab-based chemotherapy in metastatic colorectal cancer (mCRC). The NLR may reflect immune cells modulating specific cytokine signals in the tumor microenvironment; however, which immune-related genes affect the NLR remain unclear. PATIENTS AND METHODS: In 77 patients with KRAS exon2 wild-type mCRC from prospective trials of first-line chemotherapy with cetuximab, expression levels of 354 immune-related genes were measured in tissue samples obtained from all patients by the HTG EdgeSeq Oncology Biomarker Panel. The association between the NLR and clinical outcomes was evaluated using the Spearman rank correlation coefficient. In addition, 2-sample t tests were performed to investigate which genes among the top 100 genes associated with survival had significantly different expression levels between the NLR-low and NLR-high groups among all measured genes. RESULTS: NLR data were available for 71 patients. The NLR was associated with progression-free survival and overall survival (r = -0.24; P = .040 and r = -0.29; P = .010, respectively). When stratified by the median value of the NLR, the Kaplan-Meier curve of NLR-low versus NLR-high differed significantly for both progression-free survival (median, 11.8 vs. 9.1 months; P = .036) and overall survival (median, 42.8 vs. 26.7 months; P = .029). The 2-sample t test revealed that the expression levels of the LYZ, TYMP, and CD68 genes differed significantly between the NLR-low and NLR-high groups (t test P-value < .005; false discovery rate P-value < .15). CONCLUSION: NLR is significantly associated with survival in patients with mCRC treated with first-line chemotherapy with cetuximab. Genes encoding for activities on macrophages may affect the NLR.

Concomitant Intracranial and Lumbar Chronic Subdural Hematoma Treated by Fluoroscopic Guided Lumbar Puncture: A Case Report and Literature Review.

A 40-year-old man presented with a severe headache, lower back pain, and lower abdominal pain 1 month after a head injury caused by falling. Computed tomography (CT) of the head demonstrated bilateral chronic subdural hematoma (CSDH) with a significant amount in the left frontoparietal region. At the same time, magnetic resonance imaging (MRI) of the lumbar spine also revealed CSDH from L2 to S1 level. A simple drainage for the intracranial CSDH on the left side was performed. Postoperatively, the headache was improved; however, the lower back and abdominal pain persisted. Aspiration of the liquefied spinal subdural hematoma was performed by a lumbar puncture under fluoroscopic guidance. The clinical symptoms were dramatically improved postoperatively. Concomitant intracranial and spinal CSDH is considerably rare so only 23 cases including the present case have been reported in the literature so far. The etiology and therapeutic strategy were discussed with a review of the literature. Therapeutic strategy is not established for these two concomitant lesions. Conservative follow-up was chosen for 14 cases, resulting in a favorable clinical outcome. Although surgical evacuation of lumbosacral CSDH was performed in seven cases, an alteration of cerebrospinal fluid (CSF) pressure following spinal surgery should be reminded because of the intracranial lesion. Since CSDH is well liquefied in both intracranial and spinal lesion, a less invasive approach is recommended not only for an intracranial lesion but also for spinal lesion. Fluoroscopic-guided lumbar puncture for lumbosacral CSDH following burr hole surgery for intracranial CSDH could be a recommended strategy.

CEA Response and Depth of Response (DpR) to Predict Clinical Outcomes of First-Line Cetuximab Treatment for Metastatic Colorectal Cancer.

BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment. PATIENTS AND METHODS: Associations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC from two phase II trials of first-line therapy: the JACCRO CC-05 trial of cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was performed using Spearman's rank correlation coefficient. A 75% decrease in the CEA was used as the cut-off value to define the CEA response and discriminate CEA responders on the basis of the results of a previous study. RESULTS: Ninety-two patients were eligible for analyses of both CEA and DpR. The median CEA decrease was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (rs = 0.56, P < 0.0001; rs = 0.39, P = 0.0090, respectively); moreover, the CEA decrease correlated with PFS (rs = 0.56, P < 0.0001), as well as OS (rs = 0.35, P = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months, hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with the DpR (rs = 0.44, P < 0.0001). CONCLUSIONS: Our study demonstrates that both DpR and CEA response correlate with clinical outcomes of first-line treatment with cetuximab. The CEA decrease may serve as a surrogate for DpR in patients who receive first-line cetuximab treatment (UMIN000004197, UMIN000007022).

Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

INTRODUCTION: Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. PATIENTS AND METHODS: The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. RESULTS: A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. CONCLUSION: Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy.