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Malignant intraosseous peripheral nerve sheath tumor is a very rare malignancy most commonly seen in patients with neurofibromatosis type 1. This tumor almost exclusively occurs in the maxillofacial region, with manifestation of this tumor in other regions of the skeleton infrequently reported. We describe a 23-year-old female with previously undiagnosed neurofibromatosis type 1 presenting with lower extremity weakness, paresthesias, and bowel/bladder symptoms. The patient had an aneurysmal lytic bone lesion centered in the upper sacrum with invasion of the L5 vertebral body. On MRI, the lesion was homogeneously isointense to muscle on T1, heterogeneously hyperintense to muscle on T2, and demonstrated homogeneously avid contrast enhancement. Multiple additional small lesions with similar imaging characteristics were identified in the paraspinal soft tissues. Low grade malignant peripheral nerve sheath tumor of the sacrum was diagnosed on biopsy. The patient was treated with sacral resection and radiation therapy for local disease control. Keywords: Malignant, Peripheral, Nerve, Sheath, Tumor, Neurofibromatosis

BackgroundAdoptive cellular therapy (ACT) is a promising treatment for synovial sarcoma (SS) with reported response rates of over 50%. However, more work is needed to obtain deeper and more durable responses. SS has a ‘cold’ tumor immune microenvironment with low levels of major histocompatibility complex (MHC) expression and few T-cell infiltrates, which could represent a barrier toward successful treatment with ACT. We previously demonstrated that both MHC expression and T-cell infiltration can be increased using systemic interferon gamma (IFN-γ), which could improve the efficacy of ACT for SS.Case presentationWe launched a phase I trial incorporating four weekly doses of IFN-γ in an ACT regimen of high-dose cyclophosphamide (HD Cy), NY-ESO-1-specific T cells, and postinfusion low-dose interleukin (IL)-2. Two patients were treated. While one patient had significant tumor regression and resultant clinical benefit, the other patient suffered a fatal histiocytic myocarditis. Therefore, this cohort was terminated for safety concerns.ConclusionWe describe a new and serious toxicity of immunotherapy from IFN-γ combined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γ should not be used concurrently with HD Cy or with low dose IL-2, IFN-γ may still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γ during the immediate period before/after cell infusion.Trial registration numbersNCT04177021,NCT01957709, andNCT03063632.

Introduction: Surgical navigation systems are increasingly used to aid resection and reconstruction of osseous malignancies. In the process of implementing image-based surgical navigation systems, there are numerous opportunities for error that may impact surgical outcome. This study aimed to examine modifiable sources of error in an idealized scenario, when using a bidirectional infrared surgical navigation system. Materials and Methods: Accuracy and precision were assessed using a computerized-numerical-controlled (CNC) machined grid with known distances between indentations while varying: 1) the distance from the grid to the navigation camera (range 150 to 247cm), 2) the distance from the grid to the patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum number of bidirectional infrared markers were actively functioning. For each scenario, distances between grid points were measured at 10-mm increments between 10 and 120mm, with twelve measurements made at each distance. The accuracy outcome was the root mean square (RMS) error between the navigation system distance and the actual grid distance. To assess precision, four indentations were recorded six times for each scenario while also varying the angle of the navigation system pointer. The outcome for precision testing was the standard deviation of the distance between each measured point to the mean three-dimensional coordinate of the six points for each cluster. Results: Univariate and multiple linear regression revealed that as the distance from the navigation camera to the grid increased, the RMS error increased (p Conclusion: In our model laboratory test environment, the infrared bidirectional navigation system was more accurate and precise when the distance from the navigation camera to the physical (working) space was minimized and all bidirectional markers were active. These findings may require alterations in operating room setup and software changes to improve the performance of this system.

Background:Many treatment options exist for unicameral bone cysts (UBC), without clear evidence of superiority. Meta-analyses have been limited by small numbers of patients in specific anatomic and treatment subgroups. The purpose of this study was to report the outcomes of injecting bone marrow aspirate and demineralized bone matrix (BMA/DBM) for the treatment of proximal humerus UBC.Methods:Fifty-one patients with proximal humerus lesions treated by BMA/DBM injection were retrospectively reviewed from a single academic medical center.Results:The mean number of injections performed per patient was 2.14 (range 1-5). Eleven patients underwent only one injection (22%), an additional 19 patients completed treatment after two injections (37%), four patients healed after three injections (8%), and one patient healed after four injections (2%). The cumulative success rate of serial BMA/DBM injections was 22% (11/51), 58% (30/51), 67% (34/51), and 69% (35/51). Eleven patients (22%) ultimately underwent open curettage and bone grafting, and five patients (10%) were treated with injection of calcium phosphate bone substitute.Conclusion:A BMA/DBM injection strategy avoided an open procedure in 78% of patients with a proximal humerus UBC. The majority of patients underwent at least 2 injection treatments.Level of Evidence:Level IV retrospective cohort study.

BACKGROUND The purpose of this study was to test the validity of a consumer-oriented activity monitor in adolescents and young adults undergoing limb salvage for primary bone malignancies. METHODS A cross-sectional population of participants with an average age of 16 (range 12 to 22) years produced 472 days of activity monitoring during 25 evaluations periods alongside patient-reported outcome measures. RESULTS Average daily steps ranged from 557 to 12,756 (mean=4711) and was moderately associated with the short-form (SF) 36 physical component subscale (r=0.46, P=0.04) as well as the SF6D health state utility measure (r=0.48, P=0.04), but not the SF36 mental component subscale (P=0.66) or Toronto extremity salvage score (P=0.07). Time from surgery was strongly correlated with average daily steps (r=0.7, P

Background:The most common modes of failure for megaprostheses are aseptic loosening followed by periprosthetic infection and stem fracture. Surgical technique for bone and implant exposure is controversial and may influence the success of revision and the need for additional future revisions. The purpose of this study was to evaluate the effectiveness of cortical fenestration for megaprosthesis revision, particularly for stem fracture.Methods:From 1985-2014, 196 adult and pediatric patients underwent limb salvage with a distal femoral or proximal tibial megaprosthesis (109 cemented, 87 pressfit). A retrospective chart review was performed to assess the rate of revision based on cemented or pressfit fixation and the use of a cortical window to extract the failed stem.Results:27% (29 of 109) of cemented and 18% (16 of 87) of pressfit implants were revised for stem failure. The reasons for revision in the cemented group were loosening (62%), infection (24%), and stem fracture (13%). In the pressfit group, the reasons were loosening (43%), infection (31%), stem fracture (6%), limb-length discrepancy (6%), malrotation (6%), and local recurrence (6%). A cortical window was used in 10 of 45 initial revisions (7 cemented, 3 pressfit) including all of the stem fractures, and in 2 of 15 subsequent re-revisions.Conclusion:Cortical fenestration is an effective, bone-preserving method of implant extraction, particularly for broken or cemented stems. It is associated with low rates of loosening and no increase in periprosthetic fractures.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

BACKGROUND: The quantitative accuracy of MRI in predicting the intraosseous extent of primary sarcoma of bone has not been definitively confirmed, although MRI is widely accepted as an accurate tool to plan limb salvage resections. Because inaccuracies in MRI determination of tumor extent could affect the ability of a tumor surgeon to achieve negative margins and avoid local recurrence, we thought it important to assess the accuracy of MR-determined tumor extent to the actual extent observed pathologically from resected specimens in pediatric patients treated for primary sarcomas of bone. QUESTIONS/PURPOSES: (1) Does the quantitative pathologic bony margin correlate with that measured on preoperative MRI? (2) Are T1- or T2-weighted MRIs most accurate in determining a margin? (3) Is there a difference in predicting tumor extent between MRI obtained before or after neoadjuvant chemotherapy and which is most accurate? METHODS: We retrospectively studied a population of 211 potentially eligible patients who were treated with limb salvage surgery between August 1999 and July 2015 by a single surgeon at a single institution for primary sarcoma of bone. Of 131 patients (62%) with disease involving the femur or tibia, 107 (51%) were classified with Ewing’s sarcoma or osteosarcoma. Records were available for review in our online database for 79 eligible patients (37%). Twenty-six patients (12%) were excluded because of insufficient or unavailable clinical or pathology data and 17 patients (8%) were excluded as a result of inadequate or incomplete MR imaging, leaving 55 eligible participants (26%) in the final cohort. The length of the resected specimen was superimposed on preresection MRI sequences to compare the margin measured by MRI with the margin measured by histopathology. Arithmetic mean differences and Pearson r correlations were used to assess quantitative accuracy (size of the margin). RESULTS: All MR imaging types were positively associated with final histopathologic margin. T1-weighted MRI after neoadjuvant chemotherapy and final histopathologic margin had the strongest positive correlation of all MR imaging and time point comparisons (r = 0.846, p < 0.001). Mean differences existed between the normal marrow margin on T1-weighted MRI before neoadjuvant chemotherapy (t = 8.363; mean, 18.883 mm; 95% confidence interval [CI], 14.327-23.441; p < 0.001), T2-weighted MRI before neoadjuvant chemotherapy (t = 8.194; mean, 17.204 mm; 95% CI, 12.970-21.439; p < 0.001), T1-weighted after neoadjuvant chemotherapy (t = 10.808; mean, 22.178 mm; 95% CI, 18.042-26.313; p < 0.001), T2-weighted after neoadjuvant chemotherapy (t = 10.702; mean, 20.778 mm; 95% CI, 16.865-24.691; p < 0.001), and the final histopathologic margin. T1-weighted MRI after neoadjuvant chemotherapy compared with the final histopathologic margin had the smallest mean difference in MRI-measured versus histopathologic margin size (mean, 5.9 mm; SD = 4.5 mm). CONCLUSIONS: T1 MRI after neoadjuvant chemotherapy exhibited the strongest positive correlation and smallest mean difference compared with histopathologic margin. When planning surgical resections based on MRI obtained after neoadjuvant chemotherapy, for safety, one should account for a potential difference between the apparent margin of a tumor on an MRI and the actual pathologic margin of that tumor of up to 1 cm. LEVEL OF EVIDENCE: Level III, diagnostic study.

Background: Despite a proposed lower incidence of aseptic loosening, uncemented distal femoral implants present challenges with the intra-operative assessment of the adequacy of stem fixation within the femoral canal. Our biomechanical study was intended to assess the adequacy of oncologic implant press-fit stem fixation within the reamed canal of the distal femur for the Stryker GMRS oncologic distal femoral implant. We hoped to answer the following: #1 Does the initial stem placement in the femoral canal using a standardized force (50 N) (i.e., “Scratch Fit”) predict the (adequacy)stability of the final stem placement (and implant fixation) within the femoral canal? #2 Is there a difference in the uncemented stem fixation and stability within the femur for different stem (Stryker GMRS) diameters (13, 14, and 15 mm) for the Stryker GMRS uncemented press-fit stems/(Stryker Global Orthopaedics) Methods: Femoral cadaveric specimens were thawed and cut at the distal end of the femur, at 13 cm from the distal joint line, to e represent a distal femoral tumor resection. Stryker GMRS uncemented stems were placed, after femoral reaming, into the distal femoral canal with firm, hand pressure applied via a customized, spring-based insertion tool positioned over the standard Stryker insertion tool and calibrated to apply a standard stem insertion force of 50 N (11.2 lbs). Initial stem placement, utilizing this method, resulted in a stem that was only partially implanted into the femur with a recorded distance (defined as “Scratch Fit”) between the stem collar and the cut surface of the femoral shaft. After completing final stem impaction into the femur, stem torsional testing was performed on a multi-axis biomechanical test frame with a 3-D Vicon motion-capture system with axial torsion applied to the stems with the proximal femur fixed to a potted base. Kinematics of both the implant and the distal femur were captured using the Vicon system which tracked reflective infrared targets at a 60 Hz sampling rate. The peak torsional moment at failure was compared to “Scratch Fit” metrics for each implant diameter to address the proposed research questions. Results: Scratch fit distances ranged from 7–46 mm with a mean of 29.1±12.7 mm. Peak torques ranged from 11.5 to 57.5 Nm with a mean of 33.6±17.0 Nm. Figure shows peak (max.) torque plotted against scratch fit for all stems/specimens with good correlation (r 2 =0.6404). When separated by stem diameters, figure shows strong correlations between peak torque and scratch fit. Conclusions: while there may be multiple metrics that affect uncemented stem implant placement and stability (i.e., femoral canal size, femoral reaming, and implant type/size (diameter), there appears to be some correlation between initial stem placement (i.e., “Scratch Fit”) after femoral reaming to implant torsional (rotational) stability; this correlation is stronger when controlled for stem diameter. This suggests that a greater initial “Scratch Fit” distance may provide improved press-fit stem fixation and may provide a better operative standard for making decisions regarding the fixation or stability of these implants.

Background: Allograft reconstruction of oncologic resections involving the tibia can have unpredictable results. Prior studies have reported a high rate of complications and a long recovery period involving prolonged bracing, repeated procedures and extended periods of antibiotics. Methods: The case details of 30 tibial allografts (12 adults, 18 children; 20 intercalary, 7 hemicortical, 3 other) were reviewed retrospectively. Based on factors including function, pain, healing and infection, clinical outcomes were stratified into three categories: excellent, moderate, and poor. Results: The overall survival rate of the allografts was 66% at a mean follow-up of 42 mos (adults) and 63 mos (children). Healing for metaphyseal junctions was successful in 73% at a mean of 44 weeks and for diaphyseal junctions, 64% at 41 weeks. Intercalary allografts in adults (4 of 20) all became infected and none had excellent results. All hemicortical allografts were performed in adults and 6 of 7 had excellent results. Distal intercalary allografts in children (6 of 20) had either excellent or moderate results with no infections, but had 3 nonunions and 2 fractures. Proximal intercalary allografts in children (8 of 20) had 2 excellent results, but had 6 infections requiring a cement spacer. Five of the six spacers were ultimately revised to another allograft or an arthroplasty. Conclusion: For tibial allograft reconstruction, surgeons and patients should prepare for a prolonged treatment course that may include multiple complications and surgeries. Excellent or moderate results can be achieved eventually in most, but amputation may be necessary in 15-20% of cases.

Background: Synovial chondromatosis (SCh) can undergo malignant transformation. Pathologic diagnosis of secondary synovial chondrosarcoma (SChS) is challenging and misdiagnosis may result in over- or undertreatment. Method: A systematic review revealed 48 cases of SChS published in 27 reports since 1957. Data was collected to identify findings indicative of SChS and outcomes of treatment. Results: At median follow-up of 18 months, patients were reported as alive (10%), alive without disease (22%), alive with disease (15%), dead of disease (19%), dead of pulmonary embolism (4%), and unknown (29%). Initial diagnosis of SChS (grade: low/unknown 48%, intermediate/high 52%) was after biopsy in 58%, local resection in 29%, and amputation in 13%. Seventy-four percent of patients underwent 1.8 (mean) resections. Patients treated prior to 1992 were managed with amputation in 79% of cases compared to 48% after 1992. Symptoms were present for 72 mos prior to diagnosis of SChS. Synovial chondrosarcoma demonstrated symptom progression over several months (82%), rapid recurrence after complete resection (30%), and medullary canal invasion (43%). The SChS tumor dimensions were seldom quantified. Conclusion: Malignant degeneration of synovial chondromatosis is rare but can necessitate morbid surgery or result in death. Pathognomonic signs for SChS including intramedullary infiltration are present in the minority of cases. Progression of symptoms, quick local recurrence, and muscle infiltration are more suggestive of SChS. Periarticular cortical erosion, extra-capsular extension, and metaplastic chondroid features are non-specific. Although poorly documented for SChS, tumor size is a strong indicator of malignancy. Biopsy and partial resection are prone to diagnostic error. Surgical decisions are frequently based on size and clinical appearance and may be in conflict with pathologic diagnosis.

Pelvic Ewing sarcoma (ES) has poorer outcomes than extremity-based lesions and the method of local control is controversial.A retrospective review was performed of 40 primary pelvic or sacral ES treated by a single surgeon. All received modern chemotherapy and those that received radiation were treated with modern dosages.Fifty-five percent were disease-free at latest follow-up (median, 83.1 mos). Sixty-one percent had ≥ 99% necrosis, which was associated with 65% disease-free survival. Larger size (P = 0.016) and the absence of metastatic disease (P = 0.005) was predictive of survival. Eighty-three percent of relapsed patients were DOD. Half of patients who received surgery alone or RT alone have NED while 57% of those who received S/RT have NED. Complication rates were 69% (S/RT), 75% (surgery alone), 10% (RT alone). Functional outcomes were similar.Primary pelvic ES is localized at presentation in 50% and the absence of metastases is the strongest predictor for survival. Chemotherapy is key, but excellent histologic response is neither a guarantee nor a necessity for survival. More than one-third die despite an excellent histologic response and at least one-third with lung metastases survive. With chemotherapy, radiation, and surgery, reasonable control of disease can be achieved.Case-control or retrospective cohort study.

The effect of simulated early weight bearing on both micromotion and pullout strength of uncemented distal femoral stems was evaluated in this study. The effect of stem endosteal contact and bone quality on implant pullout strength was also analyzed. A randomized matched-pair study was performed using 8 bilateral pairs of fresh human cadaveric femoral specimens. Each specimen pair was dual-energy x-ray absorptiometry scanned, uniformly implanted, fluoroscopically imaged, and randomly assigned to the cycled or uncycled group. The cycled group received 5000 cycles of axial compressive loading (to 700 N) and the contralateral side was not cycled. Micromotion was monitored during cycling and compared with a failure threshold (150 µm), and all implants underwent direct axial distraction (pullout) testing. During cycling, minimal micromotion was observed with an asymptotic decrease in differential motion between the first and last 50 cycles. Both cycled and uncycled groups demonstrated no statistical difference in average pullout force (4888±2124 N vs 4367±1154 N; P =.43). The percentage of cortical contact for each implant was determined from panoramic fluoroscopy images using digital image analysis software. Contact area for the distal third of the stem showed the highest correlation with pullout force and with predicting pullout force. Bone quality did not correlate with pullout force ( r 2 =0.367) or stem contact area ( r 2 =0.394). In sum, press-fit uncemented femoral stems did not loosen or demonstrate decreased pullout strength with early weight bearing simulated by cyclical axial compressive loading. [ Orthopedics. 2015; 38(5):e417–e422.]

71 Background: Soft tissue sarcomas (STS) are heterogeneous tumors which are morbid and lethal. G100 is under investigation in multiple clinical trials and contains a potent TLR4 agonist (oil-in-water emulsion of glucopyranosyl lipid A) that has been tested as vaccine adjuvant. We hypothesized IT G100 would induce robust local and potentially systemic anti-tumor immune response, leading to improved outcomes. Methods: 15 metastatic STS patients with superficial lesions were treated with weekly IT G100 for 8-12 wks; 12 patients received radiation (RT) for 2 wks to start, while 3 received IT G100 for 6 wks prior to RT. Biopsies and PBMC were collected pre and post treatment, and flow cytometry was performed on biopsies. TIL and PBMC were analyzed with TCR deep sequencing. PBMC were analyzed by single cell multiplex cytokine profiling. Results: No grade ≥ 3 toxicity was observed, and local tumor control was achieved in all evaluable tumors (14/14). Treated tumors tracked post-trial (mean 156 days) had persistent local control with 1 CR (7%), 1 PR (7%), and 11 SD (79%). In 3 patients with long term follow up, treated lesions remained controlled vs index lesions (-53% vs +31% at mean 235 days, p = 0.002). In all tumors after G100 alone, T cell infiltration increased. In P14, CD3 live cells in tumor rose from < 1% to 62%. PBMC clonality increased in 8/14 tested including P06, who had 4× increase in clonality and CR in the injected lesion; PBMC and TIL TCR overlap increased from 13.4% to 21.5%. P13 had a 2.3× rise in TIL clonality; the top clone (a CD4 T cell) expanded from 0.1% to 38% and expressed more TNFα than the rest (p < 0.0001). Single cell cytokine analysis of PBMC showed 7/13 (54%) increased in polyfunctionality (producing > 2 cytokines) in CD4 T cells; no consistent increase was seen in CD8 T cells. TNFα levels in pre-treatment monocytes correlated with PFS (R2= 0.5, p = 0.02). Conclusions: IT G100 is a viable agent for local control of metastatic STS lesions. With or without RT, G100 appears to cause CD4 T cell mediated local and systemic response. Combination of G100 with other immunomodulators could induce clinically significant systemic responses, as seen in follicular NHL treated with G100. Clinical trial information: NCT02180698.

Introduction: Soft tissue sarcomas (STS) are heterogeneous mesenchymal tumors which are both morbid and lethal. G100 is a stable oil-in-water emulsion of glucopyranosyl lipid adjuvant, a highly potent toll-like receptor 4 (TLR4) agonist, which has been utilized for intratumoral (IT) injections and as vaccine adjuvants without significant toxicity. We hypothesized that IT G100 would induce a robust local and potentially systemic anti-tumor immune response in the STS microenvironment, leading to improved outcomes. Methods: 15 metastatic STS patients who had a superficial injectable lesion were treated with weekly IT G100 for 8-12 weeks; 12 patients received concurrent radiation for 2 weeks at the start, while 3 got IT G100 alone for 6 weeks prior to radiation. Biopsies and blood were collected pre and post treatment, and flow cytometry was performed on fresh tumor samples. T-cell receptor (TCR) deep sequencing of tumor-infiltrating lymphocytes (TIL) and peripheral blood mononuclear cells (PBMC) was performed on 7 patients. RECIST v1.1 and the Common Terminology Criteria for Adverse Events were used to monitor clinical outcomes. Results: Patients had a median of 3 (0~5) prior lines of therapy and mean tumor size of 5.6cm (1~20cm). No grade 3 or higher treatment-related toxicity was observed, and local tumor control was achieved in 93% (14/15). 6 (40%) had stable disease after treatment, and 1 (P06) had complete regression of injected tumor. This tumor had a high percentage of infiltrating pre-treatment immune cells (12% CD45+ on flow cytometry versus 2.7% for all other tumors). TCR sequencing showed that the increase in clonality of PBMC after treatment was greater in P06 (389%) compared to 6 other patients (mean 34%). There was also higher overlap in TCR sequence between TIL versus PBMC after treatment (13% versus 22%), suggesting systemic expansion of tumor-specific T-cells. In 7 patients evaluable for tumor-associated macrophages (tumors with >1000 CD45+CD11b+ cells), 71% had a shift from an M2 to M1 phenotype. In all patients who received G100 alone, there was an increase in T-cell infiltration into tumor after treatment. In one patient (P14), the proportion of CD3+ live cells in tumor went from Conclusion: IT G100 provides a potentially viable agent for local control of metastatic STS. With or without radiation, G100 appears to shift the tumor microenvironment into a more inflammatory state with significant infiltration of T cells. The increase in clonality in PBMC and TIL, as well as increased overlap of tumor-associated versus peripheral TCR sequences, suggest induction of a tumor-specific response. Combination of G100 with other immunomodulators may further enhance the adaptive anti-tumor response. Citation Format: Yongwoo D. Seo, Edward Y. Kim, Ernest U. Conrad, Ryan B. O'Malley, Sara Cooper, Bailey Donahue, Lee D. Cranmer, Hailing Lu, Frank Hsu, Elizabeth T. Loggers, Taylor Hain, Darin J. Davidson, Lynn Bonham, Venu G. Pillarisetty, Gabrielle M. Kane, Stanley R. Riddell, Robin L. Jones, Seth M. Pollack. Intratumoral injection of the toll-like receptor 4 agonist G100 induces a T-cell response in the soft tissue sarcoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2947. doi:10.1158/1538-7445.AM2017-2947

11017Background: Tumor associated macrophages (TAM) are critical for immune evasion in many tumors. We hypothesized that combining G100, a TLR4 agonist that stimulates innate immunity and increases...