RESUMO
We present a case of an extremely rare type of soft-tissue sarcoma with an atypical clinical presentation. The patient, a female in her 20s with Li Fraumeni syndrome, had prior surgery for a large intra-abdominal tumour that was given the diagnosis of malignant myxoid spindle cell neoplasm. Her recurrence manifested as diffuse intra-abdominal sarcomatosis for which she ultimately underwent subtotal debulking with palliative intent. Final pathology rendered the diagnosis of myxoid pleomorphic liposarcoma, a newly described entity, distinct from the more common liposarcoma subtypes. The optimal treatment for this typically aggressive disease is currently unknown; until that is better defined, management should be carried out by sarcoma specialists.
Assuntos
Neoplasias Abdominais , Síndrome de Li-Fraumeni , Lipossarcoma Mixoide , Lipossarcoma , Neoplasias de Tecidos Moles , Humanos , Feminino , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Recidiva Local de Neoplasia , Lipossarcoma Mixoide/diagnóstico por imagem , Lipossarcoma Mixoide/cirurgiaRESUMO
Surgery is the cornerstone of treatment for retroperitoneal sarcoma (RPS). Surgery should be performed by a surgical oncologist with sub-specialization in this disease and in the context of a multidisciplinary team of sarcoma specialists. For primary RPS, the goal of surgery is to achieve the complete en bloc resection of the tumor along with involved organs and structures to maximize the clearance of the disease. The extent of resection also needs to consider the risk of complications. Unfortunately, the overarching challenge in primary RPS treatment is that even with optimal surgery, tumor recurrence occurs frequently. The pattern of recurrence after surgery (e.g., local versus distant) is strongly associated with the specific histologic type of RPS. Radiation and systemic therapy may improve outcomes in RPS and there is emerging data studying the benefit of non-surgical treatments in primary disease. Topics in need of further investigation include criteria for unresectability and management of locally recurrent disease. Moving forward, global collaboration among RPS specialists will be key for continuing to advance our understanding of this disease and find more effective treatments.
Assuntos
Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Recidiva Local de Neoplasia/patologia , Sarcoma/cirurgia , Sarcoma/patologia , Resultado do Tratamento , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologiaRESUMO
BACKGROUND: This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma. METHODS: Phase I endpoints-maximum tolerated dose in previously treated patients; Phase II endpoints-best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments-escalating doses of trabectedin (1.0, 1.2, 1.5 mg/m2) as continuous intravenous infusion over 24 h every 3 weeks, 1 mg/kg of ipilimumab given intravenously every 12 weeks, and 3 mg/kg of nivolumab given intravenously every 2 weeks; Phase II treatments-maximum tolerated dose of trabectedin and defined doses of ipilimumab and nivolumab. RESULTS: Phase I (n = 9)-the maximum tolerated dose of trabectedin was 1.2 mg/m2; Phase II (n = 79)-6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median progression-free survival, 6.7 months (CI 95%: 4.4-7.9), median overall survival, 24.6 months (CI 95%: 17.0-.); Grade 3/4 therapy-related adverse events (n = 92)-increased ALT (25%), fatigue (8.7%), increased AST (8.7%), decreased neutrophil count (5.4%) and anemia (4.6%). CONCLUSION: SAINT is a safe and effective first-line treatment for advanced soft tissue sarcoma.
RESUMO
Benign retroperitoneal tumors (BRT) represent a rare group of heterogeneous diseases. The literature lacks high-quality evidence about the optimal management of BRT, and most of the information available takes the form of case reports or case series. The aim of this review is to provide an overview of current management strategies for adult patients with BRT. A literature search using PubMed indexed articles was conducted and BRT were classified into five different biological subgroups: 1) lipomatous tumors, 2) smooth muscle tumors, 3) peripheral nerve sheath tumors, 4) myofibroblastic tumors, and 5) others. Tumors that are primarily pelvic in origin were excluded. Despite the significant heterogeneity of the disease, several generic considerations have emerged and can be applied to the management of BRT. Specifically, the risk of misdiagnosing a BRT with another pathology such as retroperitoneal sarcoma is notable. When encountered, suspected BRT should therefore be referred to a specialized sarcoma center. Multidisciplinary tumor boards, present at these centers, have a pivotal role in managing BRT. The decision of whether to offer surgery, nonsurgical treatment or a "watch-and-wait" approach should be made after multidisciplinary discussion, depending on tumor histology. Moving forward, collaborative research efforts dedicated to BRT remain crucial in gathering evidence and knowledge to further optimize patient care.
Assuntos
Braquiterapia , Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/terapia , Neoplasias Retroperitoneais/patologia , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/patologia , Terapia Combinada , Neoplasias de Tecidos Moles/cirurgiaRESUMO
Background: Complete resection (CR) serves as the standard of surgical treatment for retroperitoneal liposarcoma (RPLS). Unfortunately, even at referral centers, recurrence rates are high, and CR may not address multifocal diseases, which are a common phenomenon in RPLS. We sought to retrospectively compare the clinical outcomes of RPLS patients treated with total (ipsilateral) retroperitoneal lipectomy (TRL) and CR. Because TRL remove potentially multifocal tumors in the fat, patients may have a better prognosis than CR. Methods: Patients with primary/first-recurrent RPLS who had been treated at 5 referral centers were recruited from December 2014 to June 2018. Multivariable Cox regression analyses were conducted to determine the effects of demographic, operative, and clinicopathological variables on the following primary endpoints: local recurrence (LR), local recurrence-free survival (LRFS), and overall survival (OS). Results: A total of 134 patients were enrolled in this retrospective study, 53 of whom underwent TRL, and 81 of whom underwent CR. The 2 groups were comparable in terms of age, gender, presentation (primary vs. first-recurrent RPLS), number of tumors (unifocal vs. multifocal) at presentation, and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade. The TRL group had higher levels of preoperative hemoglobin (Hb) (13 vs. 12.5 g/dL; P=0.008) and a lower amount of intraoperative blood loss (400 vs. 500 mL; P=0.034), but there were no significant differences in the length of hospital stay (23 vs. 22 d; P=0.47) or complications (32 vs. 30; P=0.82) between the 2 groups. In a subset of patients with multifocal tumors at initial presentation, OS was more prolonged in those treated with TRL than those treated with CR (P=0.0272). Based on the multivariable analysis, primary liposarcoma and a low FNCLCC grade were associated with decreased LR and improved OS. Conclusions: TRL is a safe procedure that positively affects the OS of patients with multifocal RPLS. This novel strategy deserves further investigation in prospective studies.
RESUMO
Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcÔRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.
Assuntos
Omalizumab , Urticária , Animais , Anticorpos Monoclonais Humanizados , Regulação para Baixo , Humanos , Imunoglobulina E , Camundongos , Omalizumab/farmacologia , Omalizumab/uso terapêutico , Urticária/tratamento farmacológico , Urticária/genéticaRESUMO
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.
Assuntos
Produtos Biológicos , Lipossarcoma , Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/cirurgiaRESUMO
BACKGROUND: In extremity or trunk liposarcoma, the implications of a dedifferentiated (DD) component within a well-differentiated (WD) tumor are unclear. We evaluated outcomes after surgery and identified potential predictors of survival in these patients compared to those with an entirely WD tumor. METHODS: Retrospective data were collected for patients who underwent complete resection from 2009 to 2019. Cumulative incidences of local recurrence (LR) and distant metastasis (DM) were calculated, and overall survival (OS) was estimated. Associations between OS and clinicopathologic variables were evaluated by univariable models. RESULTS: A total of 210 patients with MDM2-verified tumors were studied, including 58 (27.6%) with DD. In primary disease, LR occurred only in DD and worse OS was observed versus WD (p < 0.001). In recurrent disease, the LR incidences were similar between WD and DD (p = 0.559); however, worse OS persisted in DD (p = 0.004). The incidence of DM was extremely low (3.8%) and limited to DD. Higher grade (p < 0.001) and DD size (p = 0.043), but not overall tumor size were associated with worse OS. CONCLUSIONS: In extremity or trunk liposarcoma, the presence of DD leads to significantly worse outcomes in both primary and recurrence diseases. Further study is needed to determine if these patients benefit from adjunct therapies (e.g., radiation).
Assuntos
Extremidades/patologia , Lipossarcoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retroperitoneais/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Feminino , Seguimentos , Humanos , Lipossarcoma/patologia , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in the evaluation of retroperitoneal sarcomas is poorly defined. We evaluated the correlation of maximum standardized uptake value (SUVmax) with pathologic tumor grade in the surgical specimen of primary retroperitoneal dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). METHODS: Patients with the above histological subtypes in three participating institutions with preoperative 18 F-FDG PET/CT scan and histopathological specimen available for review were included. The association between SUVmax and pathological grade was assessed. Correlation between SUVmax and relapse-free survival (RFS) and overall survival (OS) were also studied. RESULTS: Of the total 58 patients, final pathological subtype was DDLPS in 44 (75.9%) patients and LMS in 14 (24.1%) patients. The mean SUVmax was 8.7 with a median 7.1 (range, 2.2-33.9). The tumors were graded I, II, III in 6 (10.3%), 35 (60.3%), and 17 (29.3%) patients, respectively. There was an association of higher histological grade with higher SUVmax (rs = 0.40, p = .002). Increasing SUVmax was associated with worse RFS (p = .003) and OS (p = .003). CONCLUSION: There is a correlation between SUVmax and pathologic tumor grade; increasing SUVmax was associated with worse OS and RFS, providing a preoperative noninvasive surrogate marker of tumor grade and biological behavior.
Assuntos
Leiomiossarcoma/mortalidade , Lipossarcoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Retroperitoneais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/metabolismo , Seguimentos , Humanos , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/patologia , Leiomiossarcoma/cirurgia , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/patologia , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function. OBJECTIVES: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS. METHODS: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019. RESULTS: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery. CONCLUSION: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging.
Assuntos
Mesentério/patologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retroperitoneais/mortalidade , Sarcoma/mortalidade , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes. METHODS: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared. RESULTS: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma. CONCLUSIONS: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.
Assuntos
Neoplasias Retroperitoneais/tratamento farmacológico , Sarcoma/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Neoplasias Retroperitoneais/mortalidade , Estudos Retrospectivos , Sarcoma/mortalidadeRESUMO
ABSTRACT: Soft tissue sarcomas are a heterogenous group of malignant tumors that represent approximately 1% of adult malignancies. Although these tumors occur throughout the body, the majority involved the lower extremity. Management may involve amputation but more commonly often includes wide local resection by an oncologic surgeon and involvement of a plastic surgeon for reconstruction of larger and more complex defects. Postoperative wound complications are challenging for the surgeon and patient but also impact management of adjuvant chemotherapy and radiation therapy. To explore risk factors for wound complications, we reviewed our single-institution experience of lower-extremity soft tissue sarcomas from April 2009 to September 2016. We identified 127 patients for retrospective review and analysis. The proportion of patients with wound complications in the cohort was 43.3%. Most notably, compared with patients without wound complications, patients with wound complications had a higher proportion of immediate reconstruction (34.5% vs 15.3%; P = 0.05) and a marginally higher proportion who received neoadjuvant radiation (30.9% vs 16.7%; P = 0.06).
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , CicatrizaçãoRESUMO
PURPOSE: Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy. METHODS: We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed. RESULTS: Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes. CONCLUSION: PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Spindle cell carcinoma (SpC), also known as metaplastic carcinoma-spindle cell type, is a subtype of metaplastic carcinoma. Metaplastic carcinomas of the breast are rare but are thought to be more aggressive than invasive ductal carcinomas. Due to their rarity, there are few randomized trials that can inform any standardized approaches to treatment. Treatment is instead extrapolated from other types of breast cancer or metaplastic carcinomas of different locations. Here we present the first known case report of a patient with spindle cell carcinoma of the breast successfully treated with a standard sarcoma neoadjuvant regimen of doxorubicin, ifosfamide, and mesna (AIM) that resulted in >99% necrosis of the tumor and negative margins at the time of resection.