Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

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.

Atypical Fibroxanthoma: Outcomes from a Large Single Institution Series.

BACKGROUND: Atypical fibroxanthomas (AFX) are rare malignant cutaneous neoplasms. Unfortunately, limited clinicopathologic and outcomes data on this cancer exists. OBJECTIVE: We report the clinical, pathologic, and treatment characteristics, as well as oncologic outcomes in this single-institution retrospective analysis. METHODS: This retrospective cohort study compiled clinical, pathologic, treatment, and outcome data for all patients with AFX on definitive excision diagnosed, evaluated, and treated primarily by surgical resection at a single institution between 2000-2020. Descriptive statistics evaluated clinical and pathologic characteristics. Kaplan-Meier method and Cox proportional-hazards models were used to evaluate overall survival and recurrence-free survival. RESULTS: 78 patients with AFX were identified. The majority were elderly, immunocompetent, Caucasian men. 85% of tumors were located on the head and neck. 63% of patients were correctly diagnosed only after complete resection of the index lesion. The median surgical margin was 1.0 cm. Overall, only 1.3% (1/78) of patients developed a local recurrence (RFS). No patients died of disease. CONCLUSION: This study suggests that resection margins of 1 cm achieve excellent local control with close to 99% RFS and 100% disease-specific survival.

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.

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.

NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare malignancies 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 Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

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.

Adrenal biopsy, as a diagnostic method, is associated with decreased overall survival in patients with T1/T2 adrenocortical carcinoma: A propensity score-matched analysis.

INTRODUCTION: The standard diagnosis for adrenocortical carcinoma (ACC) is clinical diagnosis (CD) based on radiographic and biochemical studies. Biopsy diagnosis (BD) is seldom required for the suspicion of secondary malignancy. We aim to study the impact of BD in the context of underlying T1/T2 ACC on overall survival (OS) compared with CD. METHODS: National Cancer Database (NCDB) for endocrine malignancies was utilized. Only patients with non-metastatic ACC, whose method of diagnosis and local disease extension were reported, and received a surgical adrenalectomy with curative intent were included. Patients were divided by disease stage into T1/T2, T3, and T4 groups. A propensity score match was applied to those with T1/T2 disease who received CD versus BD and the Kaplan-Meier method was used to compare OS. RESULTS: In total, 4000 patients with ACC were reported in the database, 1410 met selection criteria. Eight hundred and thirty patients had T1/T2, 365 had T3, and 162 had T4 ACC. Of patients with T1/T2 ACC, 742 (89.4%) received CD versus 88 (11.6%) with BD. A propensity score was calculated per a multivariable regression model with 79 patients matched from each group. Exact matching was applied for margin status and adjuvant therapies. Kaplan-Meier analysis showed a significant difference in median OS between CD versus BD patients in the matched data set (103.89 ± 15.65 vs. 54.93 ± 8.22 months; p = 0.001). In all comers, patients with T1/T2 ACC and BD had comparable median OS to that of patients with T3 ACC (52.21 ± 9.69 vs. 36.01 ± 3.33 months; p = 0.446). CONCLUSION: BD in T1/T2 ACC could be associated with disease upstaging and worse OS outcomes.

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

BACKGROUND: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). METHODS: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. RESULTS: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. CONCLUSIONS: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.

NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?

BACKGROUND: Approximately 30% of patients with clinically localized Merkel cell carcinoma (MCC) show nodal involvement on sentinel lymph node biopsy (SLNB). Optimal management of SLNB-positive disease has not been defined. This study compared outcomes after completion lymphadenectomy (CLND), radiation, and combined CLND plus radiation after a positive SLNB. METHODS: All patients treated at a single institution for SLNB-positive MCC (1998-2015) were retrospectively evaluated, with examination of patient demographics, clinicopathologic characteristics, outcomes, and regional toxicity. RESULTS: The study identified 71 evaluable patients with SLNB-positive disease. The median age of these patients was 76 years, and 76.1% were men. Of the 71 patients, 11 (15.5%) underwent CLND, 40 (56.3%) received radiation, and 20 (28.2%) underwent CLND plus postoperative radiation. Lymphovascular invasion was significantly more common in the radiation-alone cohort (p = 0.04). For the three cohorts, the median percentages of nodal involvement were respectively 2, 10, and 30% (p = 0.06). After a median follow-up period of 22.3 months, four patients had recurrence in their regional nodal basin (3 radiation-alone patients and 1 CLND + radiation patient). The three cohorts did not differ significantly in the development of distant metastases (p = 0.68) or overall survival (p = 0.72). Six patients experienced surgical-site infections (2 CLND and 4 CLND + radiation patients), and three patients experienced symptomatic lymphedema (1 CLND patient and 2 CLND + radiation patients). CONCLUSIONS: Regional failure was infrequent (≤ 10%) regardless of treatment, and morbidity appeared to be low with all approaches. Given that multiple treatment approaches can be successful in treating micrometastatic MCC, future efforts should be directed at refining criteria for allocating patients to a specific method, or possibly no further nodal basin treatment, in an effort to maximize regional control at the lowest cost and morbidity.

Management of intussusception in patients with melanoma.

BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

BACKGROUND: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure. METHODS: All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed. RESULTS: A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76 years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1 cm, 36 patients (15%) had a margin of 1.1-1.9 cm, and 135 patients (56.2%) had a margin of 2 cm or more. The median follow-up period was 21 months. The LR rate was 2.9% for a margin of 1 cm, 2.8% for a margin of 1.1-1.9 cm, and 5.2% for a margin of 2 cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1 cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2 cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1 cm, 66.2% for a margin of 1.1-1.9 cm, and 91.8% for a margin of 2 cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2 cm or more (p = 0.006). CONCLUSIONS: A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

Soft Tissue Sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

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 STS 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 tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Current principles of surgery for retroperitoneal sarcomas.

Surgery for primary retroperitoneal sarcomas (RPS) often requires a technically challenging, en bloc multivisceral resection to optimize outcomes. Surgery may also be appropriate for patients with localized recurrent RPS. Anatomic considerations and tumor biology driven by histologic subtype may guide the extent of resection in patients with RPS. This review provides an overview of the current surgical principles for primary and recurrent RPS.

Isolated Limb Infusion: A Single-Center Experience with Over 200 Infusions.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive technique for delivering regional chemotherapy to an extremity for patients with locally advanced cutaneous malignancies and sarcoma. METHODS: A single-institution, prospectively collected database was analyzed for intention-to-treat with ILI. RESULTS: From 2007 to 2016, 163 patients underwent 205 procedures (201 were successfully completed), and four malignancies were treated: melanoma (72.1% of all ILIs), sarcoma (23.4%), squamous cell carcinoma (SCC; 2.0%) and Merkel cell carcinoma (MCC; 2.5%). A median grade II regional Wieberdink toxicity score was observed, with 88.1% of patients experiencing grade II or less. Median follow-up was 21.8 months, and overall response rate (ORR) was 59.0% for melanoma, 48.9% for sarcoma, 50.0% for SCC, and 60.0% for MCC. A significant difference (p = 0.04) between upper (76.9%) and lower extremity (55.1%) ORR was observed in patients with melanoma. When comparing responders with nonresponders, patients with melanoma had significantly longer in-field progression-free survival (IPFS; 14.1 vs. 3.2 months, p < 0.001), distant metastatic-free survival (DMFS; not reached vs. 25.8 months, p = 0.006), and overall survival (OS; 56.0 vs. 26.7 months, p = 0.0004). Sarcoma responders had a significantly longer IPFS (13.0 vs. 2.7 months, p < 0.0001), but no significant distant metastatic or OS advantage. Over a median follow-up of 19.3 months, sarcoma patients had an overall limb salvage rate of 68.4%. CONCLUSION: ILI is a well-tolerated procedure for patients with locally advanced melanoma, sarcoma, and other cutaneous malignancies. ILI responders had a significantly longer time to IPFS, while melanoma responders also had a DMFS and OS advantage.

Myoepithelial carcinoma with RB1 mutation: remarkable chemosensitivity to carcinoma of unknown origin therapy.

BACKGROUND: Myoepithelial carcinoma of soft tissue is a rare, malignant neoplasm that is morphologically and immunophenotypically similar to its counterpart in salivary gland. It demonstrates myoepithelial differentiation, possessing both epithelial and myogenic characteristics. Thought to be chemotherapy insensitive, the optimal treatment regimen of this tumor has yet to be established and only a select few cases in the literature discuss treatment efficacy in detail. CASE PRESENTATION: Here we present a case of a young adult with metastatic myoepithelial carcinoma with an initial excellent response to systemic therapy utilizing carboplatin and paclitaxel with continued complete response after 3 years. The patient also underwent complete surgical excision and received adjuvant radiation to the primary site of disease. Exome sequencing revealed an inactivating mutation in RB1 which we believe to be the first such mutation to be reported in this cancer type. CONCLUSIONS: Given increasing evidence suggesting RB1 loss is associated with responsiveness to conventional chemotherapies, particularly platinum-based regimens, we hypothesize that this genetic feature predisposed chemosensitivity in our patient's tumor.

Is a Wider Margin (2 cm vs. 1 cm) for a 1.01-2.0 mm Melanoma Necessary?

BACKGROUND: The current NCCN recommendation for resection margins in patients with melanomas between 1.01 and 2 mm deep is a 1-2 cm radial margin. We sought to determine whether margin width had an impact on local recurrence (LR), disease-specific survival (DSS), and type of wound closure. METHODS: Melanomas measuring 1.01-2.0 mm were evaluated at a single institution between 2008 and 2013. All patients had a 1 or 2 cm margin. RESULTS: We identified 965 patients who had a 1 cm (n = 302, 31.3 %) or 2 cm margin (n = 663, 68.7 %). Median age was 64 years, and 592 (61.3 %) were male; 32.5 and 48.7 % of head and neck and extremity patients had a 1 cm margin versus 18.9 % of trunk patients (p < 0.001). LR was 2.0 and  2.1 % for a 1 and 2 cm margin, respectively (p = not significant). Five-year DSS was 87 % for a 1 cm margin and 85 % for a 2 cm margin (p = not significant). Breslow thickness, melanoma on the head and neck, lymphovascular invasion, and sentinel lymph node biopsy (SLNB) status significantly predicted LR on univariate analysis; however, only location and SLNB status were associated with LR on multivariate analysis. Margin width was not significant for LR or DSS. Wider margins were associated with more frequent graft or flap use only on the head and neck (p = 0.025). CONCLUSIONS: Our data show that selectively using a narrower margin of 1 cm did not increase the risk of LR or decrease DSS. Avoiding a 2 cm margin may decrease the need for graft/flap use on the head and neck.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

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.