Current Management of Desmoid Tumors: A Review.

Importance: Desmoid tumor (DT) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Previously, surgery was the standard primary treatment modality; however, within the past decade, a paradigm shift toward less-invasive management has been introduced and an effort to harmonize the strategy among clinicians has been made. To update the 2020 global evidence-based consensus guideline on the management of patients with DT, the Desmoid Tumor Working Group convened a 1-day consensus meeting in Milan, Italy, on June 30, 2023, under the auspices of the European Reference Network on Rare Adult Solid Cancers and Sarcoma Patient Advocacy Global Network, the Desmoid Foundation Italy, and the Desmoid Tumor Research Foundation. The meeting brought together over 90 adult and pediatric sarcoma experts from different disciplines as well as patients and patient advocates from around the world. Observations: The 2023 update of the global evidence-based consensus guideline focused on the positioning of local therapies alongside surgery and radiotherapy in the treatment algorithm as well as the positioning of the newest class of medical agents, such as γ-secretase inhibitors. Literature searches of MEDLINE and Embase databases were performed for English-language randomized clinical trials (RCTs) of systemic therapies to obtain data to support the consensus recommendations. Of the 18 full-text articles retrieved, only 4 articles met the inclusion criteria. The 2023 consensus guideline is informed by a number of new aspects, including data for local ablative therapies such as cryotherapy; other indications for surgery; and the γ-secretase inhibitor nirogacestat, the first representative of the newest class of medical agents and first approved drug for DT. Management of DT is complex and should be carried out exclusively in designated DT referral centers equipped with a multidisciplinary tumor board. Selection of the appropriate strategy should consider DT-related symptoms, associated risks, tumor location, disease morbidities, available treatment options, and preferences of individual patients. Conclusions and Relevance: The therapeutic armamentarium of DT therapy is continually expanding. It is imperative to carefully select the management strategy for each patient with DT to optimize tumor control and enhance quality of life.

Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma.

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma.

PURPOSE: We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans. PATIENTS AND METHODS: We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion. RESULTS: Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response. CONCLUSIONS: Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649.

PDGFRß Signaling Cooperates with ß-Catenin to Modulate c-Abl and Biologic Behavior of Desmoid-Type Fibromatosis.

PURPOSE: This study sought to identify ß-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRß), affect these targets to alter natural history or treatment response in patients. EXPERIMENTAL DESIGN: In vitro experiments utilized primary desmoid cell lines to examine regulation of ß-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies. RESULTS: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a ß-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRß signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRß and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRß/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment. CONCLUSIONS: The ß-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients.

MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors.

Murine double minute 2 (MDM2, gene name MDM2) is an oncogene that mainly codes for a protein that acts as an E3 ubiquitin ligase, which targets the tumor suppressor protein p53 for degradation. Overexpression of MDM2 regulates the p53 protein levels by binding to it and promoting its degradation by the 26S proteasome. This leads to the inhibition of p53's ability to regulate cell cycle progression and apoptosis, allowing for uncontrolled cell growth, and can contribute to the development of soft-tissue tumors. The application of cellular stress leads to changes in the binding of MDM2 to p53, which prevents MDM2 from degrading p53. This results in an increase in p53 levels, which triggers either cell cycle arrest or apoptosis. Inhibiting the function of MDM2 has been identified as a potential therapeutic strategy for treating these types of tumors. By blocking the activity of MDM2, p53 function can be restored, potentially leading to tumor cell death and inhibiting the growth of tumors. However, further research is needed to fully understand the implications of MDM2 inhibition for the treatment of soft-tissue tumors and to determine the safety and efficacy of these therapies in clinical trials. An overview of key milestones and potential uses of MDM2 research is presented in this review.

A Phase II Study of Epacadostat and Pembrolizumab in Patients with Advanced Sarcoma.

PURPOSE: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor, proposed to shift the tumor microenvironment toward an immune-stimulated state, showed early promise in melanoma but has not been studied in sarcoma. This study combined epacadostat with pembrolizumab, which has modest activity in select sarcoma subtypes. PATIENTS AND METHODS: This phase II study enrolled patients with advanced sarcoma into five cohorts including (i) undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma, (ii) liposarcoma (LPS), (iii) leiomyosarcoma (LMS), (iv) vascular sarcoma, including angiosarcoma and epithelioid hemangioendothelioma (EHE), and (v) other subtypes. Patients received epacadostat 100 mg twice daily plus pembrolizumab at 200 mg/dose every 3 weeks. The primary endpoint was best objective response rate (ORR), defined as complete response (CR) and partial response (PR), at 24 weeks by RECIST v.1.1. RESULTS: Thirty patients were enrolled [60% male; median age 54 years (range, 24-78)]. The best ORR at 24 weeks was 3.3% [PR, n = 1 (leiomyosarcoma); two-sided 95% CI, 0.1%-17.2%]. The median PFS was 7.6 weeks (two-sided 95% CI, 6.9-26.7). Treatment was well tolerated. Grade 3 treatment-related adverse events occurred in 23% (n = 7) of patients. In paired pre- and post-treatment tumor samples, no association was found between treatment and PD-L1 or IDO1 tumor expression or IDO-pathway-related gene expression by RNA sequencing. No significant changes in serum tryptophan or kynurenine levels were observed after baseline. CONCLUSIONS: Combination epacadostat and pembrolizumab was well tolerated and showed limited antitumor activity in sarcoma. Correlative analyses suggested that inadequate IDO1 inhibition was achieved.

Sentinel Lymph Node Biopsy for Extremity and Truncal Soft Tissue Sarcomas: A Systematic Review of the Literature.

BACKGROUND: Regional lymph node metastasis (RLNM) occurs infrequently in patients with soft tissue sarcoma (STS), although certain STS subtypes have a higher propensity for RLNM. The identification of RLNM has significant implications for staging and prognosis; however, the precise impact of node-positive disease on patient survival remains a topic of controversy. Although the benefits of sentinel lymph node biopsy (SLNB) are well documented in patients with melanoma and breast cancer, whether this procedure offers a benefit in STS is controversial. METHODS: A systematic literature search was performed and articles reviewed to determine if SLNB in patients with extremity/truncal STS impacts disease-free or overall survival. RESULTS: Six studies were included. Rates of sentinel lymph node positivity were heterogeneous (range 4.3-50%). The impact of SLNB on patient outcomes remains unclear. The overall quality of available evidence was low, as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system. CONCLUSIONS: The literature addressing the impact of nodal basin evaluation on the staging and management of patients with extremity/truncal STS is confounded by heterogeneous patient cohorts and clinical practices. Multicenter prospective studies are warranted to determine the true incidence of RLNM and whether SLNB could benefit patients with clinically occult RLNM at diagnosis.

The Evolving Management of Desmoid Fibromatosis.

Desmoid fibromatosis is a rare disease caused by genetic alterations that activate ß-catenin. The tumors were previously treated with aggressive surgeries but do not metastasize and may regress spontaneously. For these reasons, in the absence of symptoms and when growth would not induce significant complications, active observation is considered first-line therapy. When intervention is required, surgery can be considered based on anatomy and risk of postoperative recurrence, but increasingly nonoperative therapies such as liposomal doxorubicin or sorafenib are prescribed. Cryoablation, chemoembolization, and high-intensity focused ultrasound can also be used to obtain local control in selected patients.

Feasibility of Preoperative Dose-Painting Intensity Modulated Radiation Therapy (IMRT) for Borderline-Resectable Primary Retroperitoneal Sarcoma.

PURPOSE: The role of radiation therapy (RT) in resectable retroperitoneal sarcoma (RPS) remains controversial; however, preoperative RT may play an important role in borderline-resectable (at risk of R2 resection) disease. We evaluated the outcome of such patients treated with preoperative dose-painting IMRT followed by planned resection. METHODS: Between January 2001 and December 2017, 30 patients with borderline-resectable primary nonmetastatic RPS (after multidisciplinary review) received preoperative dose-painting IMRT in this retrospective cohort study. RESULTS: Median follow-up for all patients was 32 months. Median dose to the whole tumor/high-risk margin was 50.4 Gy/60.2 Gy. Sixteen patients were female, 24 were >50 years. Median tumor size was 9.2 cm. After RT, 6 did not have surgery. Of the 24 who were explored, 20 underwent complete gross resection. During RT, 7 of 30 patients developed acute grade 2+ toxicities: 5 fatigue, 1 nausea and vomiting, and 1 cystitis. RT was completed in 29 of 30 patients. Postoperatively, 12 of 20 patients developed grade 2+ complications: 2 gastropathy, 5 intraabdominal collections requiring drainage, 1 retroperitoneal bleed, and 3 delayed wound healing. Late grade 2+ toxicity was observed in 3 of 20 patients: 1 lymphedema with recurrent cellulitis, 1 chronic diarrhea, 1 gastrointestinal bleeding from anastomosis requiring transfusions, and 2 renal insufficiency. In those who underwent complete gross resection (n = 20, median follow-up 47 months), the 5-year local control was 57%, and overall survival was 46%. DISCUSSION: Preoperative dose-painting IMRT given to borderline-resectable RPS rendered 67% of patients resectable, provided a 5-year local control rate of 57%, which is similar to those with resectable disease, and had an acceptable morbidity profile.

Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets.

The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analysis of 2,138 sarcomas representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations are in cell cycle control and TP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations include TERT amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varies between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response.

Management of Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genomically complex tumors commonly diagnosed in the extremities or trunk of elderly patients. They likely represent a spectrum of disease differentiated by myxoid stroma and curvilinear vessels observed in MFS but not in UPS. Limb-sparing surgery is the standard of care although the infiltrative nature of MFS mandates wider resection margins than are necessary for UPS. UPS are conversely associated with high risks of distal recurrence, often prompting recommendations for adjuvant chemotherapy. In both histologies, anthracycline-based therapies or gemcitabine and docetaxel are used to manage advanced disease; immunotherapy may be of benefit in a subset of patients.

Transarterial Chemoembolization with Doxorubicin Eluting Beads for Extra-Abdominal Desmoid Tumors: Initial Experience.

PURPOSE: To evaluate the feasibility, efficacy, and safety of doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) as an alternative local treatment for extra-abdominal desmoid tumors (DTs). METHODS: Eleven adult female patients (mean age = 40.1 years) with symptomatic, progressively enlarging extra-abdominal DTs were determined ineligible for cryoablation after failing observation or systemic therapy and treated with a single session doxorubicin DEB-TACE. Six rectus sheath, one chest wall, three axilla, and one upper extremity DTs were included. The median follow-up was 155.0 ± 52.3 days. Treatment response was assessed by MRIs and maximum visual analog scale (VAS). RESULTS: All procedures were technically successful without immediate complications. The average size of treated DT was 161.8 ml (range: 28.3-420.0 ml). The mean doxorubicin dose was 13.3 mg/m2. All patients experienced skin changes which improved over time without treatments. No higher-grade adverse events were observed. Initial one-month follow-up MRI demonstrated partial to near-complete tumor necrosis, ranging from 1.4 to 97.6% (mean: 36.4%). Additional follow-up revealed a further reduction of overall tumor volume (mean: - 38.1%, p < 0.0001) and maximum VAS (mean: - 2.6, p = 0.0026) in 10 out of 11 patients (90.9%). After the first month, the residual tumors exhibited continued volume reduction in 10 out of 11 patients (mean: - 16.5%, p = 0.0230). There was also a significant decrease of T2 signal intensity within residual tumor on the latest follow-up (mean: - 29.6%, p = 0.0217), suggesting a reduction in tumor cellularity. CONCLUSION: DEB-TACE may be a safe and effective local treatment alternative in DT patients.

Phase Ib Trial of the Combination of Imatinib and Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumors.

PURPOSE: This phase Ib trial was designed to evaluate the safety and early efficacy signal of the combination of imatinib and binimetinib in patients with imatinib-resistant advanced gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: This trial used a standard 3 + 3 design to determine the recommended phase II dose (RP2D). Additional patients were enrolled on an expansion cohort at the RP2D enriching for succinate dehydrogenase (SDH)-deficient GISTs to explore potential efficacy. RESULTS: The trial enrolled nine patients in the dose-escalation cohort and 14 in the dose-expansion cohort including six with SDH-deficient GISTs. Imatinib 400 mg daily with binimetinib 45 mg twice daily was established as the RP2D. Dose-limiting toxicity (DLT) was asymptomatic grade 4 creatinine phosphokinase (CPK) elevation. The most common non-DLT grade 3/4 toxicity was asymptomatic CPK elevation (69.6%). Other common ≥grade 2 toxicities included peripheral edema (17.4%), acneiform rash (21.7%), anemia (30.4%), hypophosphatemia (39.1%), and aspartate aminotransferase (AST) increase (17.4%). Two serious adverse events occurred (grade 2 dropped head syndrome and grade 3 central retinal vein occlusion). No unexpected toxicities were observed. Limited clinical activity was observed in KIT-mutant GIST. For SDH-deficient GISTs, one of five had confirmed RECIST1.1 partial response (PR). The median progression-free survival (mPFS) in patients with SDH-deficient GIST was 45.1 months [95% confidence interval (CI), 15.8-not estimable (NE)]; the median overall survival (mOS) was not reached (95% CI, 31.6 months-NE). One patient with a refractory metastatic SDH-deficient GIST had an exceptional pathologic response and durable clinical benefit. CONCLUSIONS: The combination of imatinib and binimetinib is safe with manageable toxicity and has encouraging activity in SDH-deficient but not imatinib-refractory KIT/PDGFRA-mutant GISTs. The observed clinical benefits provide a motivation for a larger trial of the combination strategy in SDH-deficient GISTs.

A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma.

PURPOSE: Because the Hedgehog and Notch pathways are often overexpressed in mesenchymal malignancies, we evaluated the efficacy of concurrent inhibition of Notch and Hedgehog signaling using the gamma-secretase inhibitor (GSI) RO4929097 and the smoothened antagonist vismodegib in unresectable or metastatic sarcoma. PATIENTS AND METHODS: In this investigator-initiated trial, phase Ib used standard 3+3 dose escalation in which patients first received vismodegib once daily for 21 days, followed by the combination of RO4929097 concurrently with vismodegib in 21-day cycles. In phase II, patients were randomized to RO4929097 alone or in combination with vismodegib. RESULTS: Nine patients were treated in phase Ib with no dose-limiting toxicities. RO4929097 at 15 mg daily in combination with 150 mg daily of vismodegib was declared the recommended phase II dose. Most adverse events were grade ≤ 2. In phase II (closed early due to discontinuation of RO4929097 evaluation), 34 patients were randomized to RO4929097 alone and 33 to RO4929097 plus vismodegib. RO4929097 did not interfere with the steady-state concentration of vismodegib, while vismodegib reduced the plasma concentration of RO492909. No patients had an objective response. Neither progression-free nor overall survival differed significantly between treatment arms. Paired tumor biopsies from a subset of patients demonstrated inhibition of cleaved Notch. CONCLUSIONS: The combination of RO4929097 plus vismodegib was generally well tolerated. Although accrual to this study was not completed, vismodegib did not meaningfully enhance the clinical efficacy of RO4929097 in an unplanned analysis. GSIs and GSIs plus vismodegib can inhibit intratumoral Notch and downstream phosphorylated Akt signaling.

Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor.

PURPOSE: Dual targeting of the gastrointestinal stromal tumor (GIST) lineage-specific master regulators, ETV1 and KIT, by MEK and KIT inhibitors were synergistic preclinically and may enhance clinical efficacy. This trial was designed to test the efficacy and safety of imatinib plus binimetinib in first-line treatment of GIST. METHODS: In this trial (NCT01991379), treatment-naive adult patients with confirmed advanced GISTs received imatinib (400 mg once daily) plus binimetinib (30 mg twice daily), 28-day cycles. The primary end point was RECIST1.1 best objective response rate (ORR; complete response plus partial response [PR]). The study was designed to detect a 20% improvement in the ORR over imatinib alone (unacceptable rate of 45%; acceptable rate of 65%), using an exact binomial test, one-sided type I error of 0.08 and type II error of 0.1, and a planned sample size of 44 patients. Confirmed PR or complete response in > 24 patients are considered positive. Secondary end points included Choi and European Organisation for Research and Treatment of Cancer Response Rate, progression-free survival (PFS), overall survival (OS), pathologic responses, and toxicity. RESULTS: Between September 15, 2014, and November 15, 2020, 29 of 42 evaluable patients with advanced GIST had confirmed RECIST1.1 PR. The best ORR was 69.0% (two-sided 95% CI, 52.9 to 82.4). Thirty-nine of 41 (95.1%) had Choi PR approximately 8 weeks. Median PFS was 29.9 months (95% CI, 24.2 to not estimable); median OS was not reached (95% CI, 50.4 to not estimable). Five of eight patients with locally advanced disease underwent surgery after treatment and achieved significant pathologic response (≥ 90% treatment effect). There were no unexpected toxicities. Grade 3 and 4 toxicity included asymptomatic creatinine phosphokinase elevation (79.1%), hypophosphatemia (14.0%), neutrophil decrease (9.3%), maculopapular rash (7.0%), and anemia (7.0%). CONCLUSION: The study met the primary end point. The combination of imatinib and binimetinib is effective with manageable toxicity and warrants further evaluation in direct comparison with imatinib in frontline treatment of GIST.

Radiation Therapy in Primary Soft Tissue Sarcoma of the Superficial Trunk.

PURPOSE: Despite anatomical differences, truncal soft tissue sarcomas (STS) often are grouped with extremity sarcomas. We evaluated the clinical outcome of patients with truncal STS who underwent gross total resection (GTR) and radiation therapy (RT), with special emphasis on those treated with intensity modulated radiation therapy (IMRT). METHODS: From January 1, 2001 to December 31, 2018, 64 patients received GTR and RT, where 48 patients were male, 35 patients were aged ≤ 60 years, and 48 patients had tumors ≤ 10 cm. Sixty-two tumors were high grade, 36 were in the chest wall, 7 in the abdominal wall, and 21 were paraspinal. During surgery, 7 received mesh reconstruction, and 6 received flap closure. R0 resection was achieved in 53 patients. Thirteen patients received chemotherapy. RESULTS: With a median follow-up of 57 months, the 5-year actuarial local control (LC) was 71%. In the IMRT subset (50/64, 78%), the 5-year LC for the chest/abdominal wall was 84%, and 69% for the paraspinal subsite. Grade 2+ radiation dermatitis was seen in 21 of 64 (33%) patients, 5 of 64 (8%) developed noninfectious wound complications, 5 of 64 (8%) developed infectious wound complications, and 1 of 64 (2%) developed grade 2 chest wall pain. No additional grade 2+ late toxicity was observed. CONCLUSIONS: Based on this study, achieving LC in truncal STS treated with GTR and RT remains challenging even with IMRT (5-year LC: 78%). While the use of IMRT was more promising for tumors of the chest/abdominal wall with 5-year LC of 84%, it was 69% for those located in the paraspinal subsite, indicating a need for further improvement.

Percutaneous Cryoablation Provides Disease Control for Extra-Abdominal Desmoid-Type Fibromatosis Comparable with Surgical Resection.

PURPOSE: The aim of this study was to determine outcomes and prognostic factors for patients with primary and locally recurrent extra-abdominal desmoid tumors who underwent percutaneous cryoablation, and to compare with patients treated with surgery. METHODS: Group characteristics were compared using Fisher's exact test, and propensity score matching was performed using the nearest-neighbor approach. Kaplan-Meier and log-rank analyses were used to evaluate the variation in first local recurrence and disease control, while multivariate Cox regression was used to identify factors associated with first local recurrence. All statistical tests were two-sided and a p-value of 0.05 was considered statistically significant. RESULTS: Twenty-two cryoablation patients were matched with 33 surgical patients (n = 55). Median follow-up after cryoablation was 16.3 months versus 14.9 months after surgery. Two-year local recurrence-free survival (LRFS) was 59% after cryoablation and 71% after surgery, and median LRFS was 26.6 months after cryoablation but was not reached after surgery. Two-year disease control for all patients was 85%, however median disease control was not reached in either the cryoablation or surgery groups. There was no significant difference in LRFS or disease control between matched cryoablation and surgical patients. No local recurrences occurred after the first cryoablation in patients with zero or one of the following risk factors: tumor size > 5 cm, age ≤ 25 years, or locally recurrent disease. All patients with two or more of these risk factors recurred locally after the first cryoablation. CONCLUSION: Percutaneous cryoablation of primary and locally recurrent extra-abdominal desmoid tumors provides freedom from first local recurrence and long-term disease control comparable with surgery.

Pseudoaneurysm within a desmoid tumor in an extremity: report of 2 cases.

Desmoid tumor is considered a benign neoplasm, yet substantial morbidity can result from local invasion of structures adjacent to the tumor or from complications related to its treatment. We report two patients with extremity desmoid tumor who were each found at MRI to have an unsuspected pseudoaneurysm within their tumor after prior treatments (surgery and systemic therapy in one, surgery alone in the other). Such a pseudoaneurysm probably results from weakening of an arterial wall by adjacent desmoid tumor, as well as from local trauma. Due to the potential risk for life-threatening rupture of a pseudoaneurysm, one patient underwent surgical repair and the other, coil embolization. To our knowledge the presence of pseudoaneurysm has been reported within a few cases of abdominal desmoid tumor but not within an extremity desmoid tumor. This diagnosis has not been reported to have been made at MRI, either.