Radar-Guided Localization and Resection for Metastatic Nodal and Soft Tissue Melanoma: A Single-Institution Retrospective Study.

BACKGROUND: Radar-guided localization (RGL) offers a wire-free, nonradioactive surgical guidance method consisting of a small percutaneously-placed radar reflector and handheld probe. This study investigates the feasibility, timing, and outcomes of RGL for melanoma metastasectomy. METHODS: We retrospectively identified patients at our cancer center who underwent RGL resection of metastatic melanoma between December 2020-June 2023. Data pertaining to patients' melanoma history, management, reflector placement and retrieval, and follow-up was extracted from patient charts and analyzed using descriptive statistics. RESULTS: Twenty-three RGL cases were performed in patients with stage III-IV locoregional or oligometastatic disease, 10 of whom had reflectors placed prior to neoadjuvant therapy. Procedures included soft tissue nodule removals (8), index lymph node removals (13), and therapeutic lymph node dissections (2). Reflectors were located and retrieved intraoperatively in 96% of cases from a range of 2 to 282 days after placement; the last reflector was not able to be located during surgery via probe or intraoperative ultrasound. One retrieved reflector had migrated from the index lesion, thus overall success rate of reflector and associated index lesion removal was 21 of 23 (91%). All RGL-localized and retrieved index lesions that contained viable tumor (10) had microscopically negative margins. There were no complications attributable to reflector insertion and no unexpected complications of RGL surgery. CONCLUSION: In our practice, RGL is a safe and effective surgical localization method for soft tissue and nodal melanoma metastases. The inert nature of the reflector enables implantation prior to neoadjuvant therapy with utility in index lymph node removal.

There are a variety of tools available to localize melanoma that had spread to deep layers of the skin or lymph nodes that can guide surgeons to the cancer when the tumor cannot be felt. We evaluated a marker that reflects radar signals that has been studied in breast surgery but not in melanoma. The marker was placed in the tumor before surgery and was located during surgery using a handheld probe, guiding the surgeon to the correct location. An advantage of the radar-reflecting marker we studied is that since it is safe to stay in the body, it can be placed ahead of the use of cancer medications and can keep track of the tumor as it responds to treatment. In a review of 23 surgeries in which the radar-reflecting marker was used, there was one case where the marker migrated away from the tumor and one case where the marker was not able to be located. Monitoring or alternative definitive treatment was provided in each of these cases. Overall, we found the marker to be an effective tumor localization tool for surgeons and safe for patients. Other marker options available are unable or less suitable to be placed a long time in advance of surgery due to either technical or safety reasons, so the radar-reflecting marker is especially useful when it is placed in a tumor ahead of medical treatment leading up to planned surgical treatment.

Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients.

BACKGROUND: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a promising immunotherapeutic approach for patients with advanced solid tumors. While numerous advances have been made, the contribution of neoantigen-specific CD4+T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. METHODS: We analyzed infused TIL products from metastatic melanoma patients previously treated with ACT for the presence of neoantigen-specific T cells. TILs were enriched on reactivity to neoantigen peptides derived and prioritized from patient sample-directed mutanome analysis. Enriched TILs were further investigated to establish the clonal neoantigen response with respect to function, transcriptomics, and persistence following ACT. RESULTS: We discovered that neoantigen-specific TIL clones were predominantly CD4+ T cells and were present in both therapeutic responders and non-responders. CD4+ TIL demonstrated an effector T cell response with cytotoxicity toward autologous tumor in a major histocompatibility complex class II-dependent manner. These results were validated by paired TCR and single cell RNA sequencing, which elucidated transcriptomic profiles distinct to neoantigen-specific CD4+ TIL. CONCLUSIONS: Despite methods which often focus on CD8+T cells, our study supports the importance of prospective identification of neoantigen-specific CD4+ T cells within TIL products as they are a potent source of tumor-specific effectors. We further advocate for the inclusion of neoantigen-specific CD4+ TIL in future ACT protocols as a strategy to improve antitumor immunity.

Grade of Primary Cutaneous Leiomyosarcoma Dictates Risk for Metastatic Spread and Disease-Specific Mortality.

BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.

Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells.

Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine, and spermine. These metabolites play critical roles in activation-induced T cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eukaryotic translation initiation factor 5A (eIF5A). Here, we demonstrated that the glutamine/polyamine/hypusine axis controlled the expression of CD69, an important regulator of tissue-resident memory T cells (Trm). Inhibition of this circuit augmented the development of Trm cells ex vivo and in vivo in the BM, a well-established niche for Trm cells. Furthermore, blocking the polyamine/hypusine axis augmented CD69 expression as well as IFN-γ and TNF-α production in (a) human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes and (b) human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate Trm cells for therapeutic benefit.

A Malignant Glomus Tumor of the Liver Harboring MIR143-NOTCH2 Rearrangement: From Diagnosis to Management.

A primary malignant glomus tumor of the liver is extremely rare and diagnostically challenging. We present an exceptional case of such with a diagnosis confirmed by MIR143-NOTCH2 rearrangement. The case was successfully managed with neoadjuvant chemotherapy followed by surgery. This report highlights the utilization of molecular analysis to aid in the diagnosis of rare soft tissue malignancies and supports a multimodality approach to the treatment of large, high-grade malignant glomus tumors.

Combination Nivolumab, CD137 Agonism, and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

PURPOSE: Metastatic melanoma is a tumor amenable to immunotherapy in part due to the presence of antigen-specific tumor-infiltrating lymphocytes (TIL). These T cells can be activated and expanded for adoptive cell transfer (ACT), which has resulted in relatively high rates of clinical responses. Similarly, immune checkpoint inhibitors, specifically programmed cell death protein 1 (PD-1) blocking antibodies, augment antitumor immunity and increase the influx of T cells into tumors. Thus, we hypothesized that addition of PD-1 inhibition may improve the outcomes for patients undergoing ACT with TILs. PATIENTS AND METHODS: Patients with stage III/IV metastatic melanoma with unresectable disease who were anti-PD-1 treatment-naïve were enrolled. TILs were generated in the presence of anti-4-1BB antibody in vitro and expanded for ACT. Patients in cohort 1 received TIL infusion followed by nivolumab. Patients in cohort 2 also received nivolumab prior to surgical harvest and during TIL production. RESULTS: A total of 11 patients were enrolled, all of whom were evaluated for response, and nine completed ACT. Predominantly CD8+ TILs were successfully expanded from all ACT-treated patients and were tumor reactive in vitro. The trial met its safety endpoint, as there were no protocol-defined dose-limiting toxicity events. The objective response rate was 36%, and median progression-free survival was 5 months. Two nonresponders who developed new metastatic lesions were analyzed to determine potential mechanisms of therapeutic resistance, which included clonal divergence and intrinsic TIL dysfunction. CONCLUSIONS: Combination therapy with TILs and nivolumab was safe and feasible for patients with metastatic melanoma and provides important insights for future therapeutic developments in ACT with TILs.

Surgical Considerations for Tumor Tissue Procurement to Obtain Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy.

ABSTRACT: Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), an investigational cellular therapy, has demonstrated antitumor efficacy in patients with advanced solid tumors, including melanoma. Tumor-infiltrating lymphocyte cell therapy involves surgical resection of a patient's tumor, ex vivo TIL expansion under conditions that overcome immunosuppressive responses elicited by the tumor and the tumor microenvironment, administration of a lymphodepleting regimen, and infusion of the final TIL cell therapy product back into the patient followed by interleukin 2 administration to support T-cell activity. The surgeon plays a central role in patient identification and tumor selection-steps that are critical for successful outcomes of TIL cell therapy. Commercialization of TIL cell therapy and its broader access to patients will require education and collaboration among surgeons, oncologists, and cellular therapists. This review highlights the unique role that surgeons will play in the implementation of TIL cell therapy and serves as a contemporary report of best practices for patient selection and tumor resection methods.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3-29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer.

Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization.

BACKGROUND: Soft-tissue sarcomas (STS) are heterogeneous with variable response to radiation therapy (RT). Utilizing the radiosensitivity index (RSI) we estimated the radiobiologic ratio of lethal to sublethal damage (α/ß), genomic-adjusted radiation dose(GARD), and in-turn a biological effective radiation dose (BED). METHODS: Two independent cohorts of patients with soft-tissue sarcoma were identified. The first cohort included 217 genomically-profiled samples from our institutional prospective tissue collection protocol; RSI was calculated for these samples, which were then used to dichotomize the population as either highly radioresistant (HRR) or conventionally radioresistant (CRR). In addition, RSI was used to calculate α/ß ratio and GARD, providing ideal dosing based on sarcoma genomic radiosensitivity. A second cohort comprising 399 non-metastatic-STS patients treated with neoadjuvant RT and surgery was used to validate our findings. RESULTS: Based on the RSI of the sample cohort, 84% would historically be considered radioresistant. We identified a HRR subset that had a significant difference in the RSI, and clinically a lower tumor response to radiation (2.4% vs. 19.4%), 5-year locoregional-control (76.5% vs. 90.8%), and lower estimated α/ß (3.29 vs. 5.98), when compared to CRR sarcoma. Using GARD, the dose required to optimize outcome in the HRR subset is a BEDα/ß=3.29 of 97 Gy. CONCLUSIONS: We demonstrate that on a genomic scale, that although STS is radioresistant overall, they are heterogeneous in terms of radiosensitivity. We validated this clinically and estimated an α/ß ratio and dosing that would optimize outcome, personalizing dose.

Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors.

BACKGROUND: Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients. METHODS: In this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA). RESULTS: In this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11b+Gr-1+ cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α. CONCLUSIONS: These results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer.

Management of Primary Retroperitoneal Sarcoma (RPS) in the Adult: An Updated Consensus Approach from the Transatlantic Australasian RPS Working Group.

BACKGROUND: Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document. METHODS: The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation. RESULTS: Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies. CONCLUSIONS: Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.

Expansion of tumor-infiltrating lymphocytes (TIL) from penile cancer patients.

Penile cancer is a rare but highly lethal cancer, and therapeutic options for patients presenting with lymph nodal disease are very limited. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) was shown to provide durable objective response in patients with metastatic melanoma and TIL have been expanded from solid tumors at rates between 70 and 90% depending on the specific diagnosis. We evaluated whether TIL could be expanded from surgical specimens of patients with penile cancer. Tumor samples from metastatic lymph nodes obtained at the time of inguinal lymph node dissection were collected, minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. The phenotype of expanded TILs was assessed by flow cytometry and their anti-tumor reactivity was assessed by IFN-γ ELISA. TIL were expanded from 11 out of 12 (91.6%) samples of metastatic lymph nodes. Expanded TIL were predominantly CD3+ (mean 67.5%, SD 19.4%) with a mean of 46.8% CD8+ T cells (SD 21.1%). Five out of 11 samples (45.4%) from expanded TIL secreted IFN-γ in response to autologous tumor. TIL expansion and phenotype of expanded T cell lymphocytes were independent of previous HPV infection and treatment with neoadjuvant chemotherapy. This is the first report demonstrating successful expansion of tumor-reactive TIL from penile cancer patients, which support development of ACT strategies using TIL for the treatment of advanced and recurrent penile cancer.

Expanded Tumor-infiltrating Lymphocytes From Soft Tissue Sarcoma Have Tumor-specific Function.

Adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TILs) can generate durable clinical responses in patients with metastatic melanoma and ongoing trials are evaluating efficacy in other advanced solid tumors. The aim of this study was to develop methods for the expansion of tumor-reactive TIL from resected soft tissue sarcoma to a degree required for the ACT. From 2015 to 2018, 70 patients were consented to an institutional review board-approved protocol, and fresh surgical specimens were taken directly from the operating room to the laboratory. Fragments of the tumor (1 mm3) or fresh tumor digest were placed in culture for a period of 4 weeks. Successfully propagated TIL from these cultures were collected and analyzed by flow cytometry. TIL were cocultured with autologous tumor and function was assessed by measurement of interferon-γ in the supernatant by enzyme-linked immunosorbent assay. Initial TIL cultures were further expanded using a rapid expansion protocol. Nearly all specimens generated an initial TIL culture (91% fragment method, 100% digest method). The phenotype of the TIL indicated a predominant CD3+ population after culture (43% fragment, 52% digest) and TIL were responsive to the autologous tumor (56% fragment, 40% digest). The cultured TIL expanded to a degree required for clinical use following rapid expansion protocol (median: 490-fold fragment, 403-fold digest). The data demonstrate the feasibility of TIL culture from fresh soft tissue sarcoma. The derived TIL have tumor-specific reactivity and can be expanded to clinically relevant numbers. An active ACT clinical trial using the methods described in this report is now approved for patients with metastatic soft tissue sarcoma.

Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood interleukin-6 and ferritin levels were each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumors, IFN signaling is associated with the expression of multiple checkpoint ligands, including programmed cell death-ligand 1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, which also gives rise to expression of immune checkpoint ligands.

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

BACKGROUND: Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT® is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported. METHODS: We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT® from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts. RESULTS: Ten SAVI SCOUT®-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT® facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14 months, only one patient recurred locally 7.5 months after SAVI SCOUT®-localized resection, requiring re-resection. CONCLUSION: SAVI SCOUT® technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.

Intrapelvic melanocytic schwannoma resection with computer-assisted navigation.

Melanocytic schwannoma is a rare nerve tumor characterized by melanin-producing neoplastic Schwann cells. Wide surgical resection is the management of choice for this tumor; however, anatomical location and proximity to nerve roots can make locating this tumor and the surgical resection challenging. Here we describe the case of 49-year-old male with a melanocytic schwannoma in the presacral area adjacent to the second sacral nerve root that was managed by wide resection aided by computer-assisted navigation due to the difficulty in identifying its location intraoperatively. The utilization of computer-assisted navigation improves accuracy and precision through the creation of a virtual continuous tridimensional map, particularly useful when oftentimes tumor margins may seem equivocal and further resection would compromise the patient's functionality. The value of computer-assisted navigation for soft tissue tumor resections in orthopedic oncology is still in its infancy, though, in certain scenarios it may advance the technique for some soft tissue resections.

Tumor grade may be used to select patients with multifocal hepatocellular carcinoma for resection.

BACKGROUND: While resection is a recommended treatment for patients with stage 1 hepatocellular carcinoma (HCC), it remains controversial for multifocal disease. We sought to identify patients with multifocal HCC with survival after resection similar to patients with clinical stage 1 HCC. METHODS: The National Cancer Database was queried to identify patients that underwent resection for HCC. RESULTS: In this study, 2990 patients with a single tumor, and 1087 patients with multifocal disease confined to one lobe underwent resection. In the multifocal cohort, patients with clinical stage 3 (HR 1.54, CI 1.31-1.81, p < 0.0001) or 4 (HR 2.27, CI 1.57-3.29, p < 0.0001) disease, and those with moderately-differentiated (HR 1.32, CI 1.06-1.64, p = 0.012) or poorly differentiated/undifferentiated tumors (HR 1.53, CI 1.20-1.95, p = 0.0006) were associated with worse overall survival (OS). There was no difference in OS between patients with well-differentiated clinical stage 2 multifocal HCC and those with all grades of clinical stage 1 HCC (median of 84.8 (CI 66.3-107.2) vs 76.2 months (CI 71.2-81.3), respectively, p = 0.356). CONCLUSIONS: Patients with well-differentiated, clinical stage 2 multifocal HCC confined to one lobe experience similar OS following hepatic resection to patients with clinical stage 1 disease. These findings may impact the management of select patients with multifocal HCC.