RESUMO
Sarcomas are a rare and highly diverse group of malignancies of mesenchymal origin. While sarcomas are generally considered resistant to immunotherapy, recent studies indicate subtype-specific differences in clinical response to checkpoint inhibitors (CPIs) that are associated with distinct immune phenotypes present in sarcoma subtypes. Oncolytic viruses (OVs) are designed to selectively infect and kill tumor cells and induce intratumoral immune infiltration, enhancing immunogenicity and thereby sensitizing tumors to immunotherapy. Herein we review the accumulated clinical data evaluating OVs in sarcoma. Small numbers of patients with sarcoma were enrolled in early-stage OV trials as part of larger solid tumor cohorts demonstrating safety but providing limited insight into the biological effects due to the low patient numbers and lack of histologic grouping. Several recent studies have investigated talimogene laherparepvec (T-VEC), an approved oncolytic herpes simplex virus (HSV-1), in combination therapy regimens in sarcoma patient cohorts. These studies have shown promising responses in heavily pre-treated and immunotherapy-resistant patients associated with increased intratumoral immune infiltration. As new and more potent OVs enter the clinical arena, prospective evaluation in subtype-specific cohorts with correlative studies to define biomarkers of response will be critical to advancing this promising approach for sarcoma therapy.
RESUMO
BACKGROUND: Radiation-associated soft tissue sarcomas (RA-STS) are rare complications of patients receiving radiation therapy (RT) and are generally associated with a poor prognosis. Most of the literature surrounding RA-STS of the chest is centered on angiosarcoma. Therefore, we aim to document the management and outcome of patients with non-angiosarcoma RA-STS of the chest. METHODS: We reviewed 17 patients (all female, median age 65 years) diagnosed with RA-STS. The most common primary malignancy was breast carcinoma (n = 15), with a median RT dose of 57.9 Gy. All patients underwent surgical resection; five patients (29%) received radiotherapy; and five patients (29%) received peri-operative chemotherapy. RESULTS: The 5-year local recurrence and metastatic-free survival were 61% and 60%, while the 5-year disease-specific survival was 53%. Local recurrence was associated with death due to disease (HR 9.06, p = 0.01). Complications occurred in nine of patients, most commonly due to a wound complication (n = 7). At the most recent follow-up, the median Musculoskeletal Tumor Society Score was 63%. CONCLUSION: RA-STS involving the chest wall are aggressive tumors with a high risk of local relapse and death due to disease. Local recurrence was associated with death due to disease; as such, we recommend aggressive surgical management with evaluation for adjuvant therapies.
Assuntos
Recidiva Local de Neoplasia , Sarcoma , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Sarcoma/radioterapia , Sarcoma/patologia , Sarcoma/mortalidade , Sarcoma/terapia , Sarcoma/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/mortalidade , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/cirurgia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Adulto , Neoplasias Torácicas/radioterapia , Neoplasias Torácicas/patologia , Neoplasias Torácicas/mortalidade , Parede Torácica/patologia , Parede Torácica/efeitos da radiação , Seguimentos , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapiaRESUMO
Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.
Assuntos
Glioblastoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Vírus do Sarampo/genética , Antígeno Carcinoembrionário/genética , Recidiva Local de Neoplasia/terapia , Vacina contra Sarampo , Microambiente TumoralRESUMO
BACKGROUND: Extraskeletal Ewing sarcoma are rare tumors within the Ewing sarcoma family. Initial staging studies for extraskeletal Ewing sarcoma historically have included imaging and bone marrow aspiration and biopsy (BMAB). However, recent studies on Ewing sarcoma of bone have questioned the utility of BMAB in the initial staging of patients, but no studies of which we are aware have evaluated the role of BMAB in extraskeletal Ewing sarcoma. We suspected that BMAB was of low diagnostic yield in patients with extraskeletal Ewing sarcoma and exposed patients to potential morbidity without an impact on their clinical course. QUESTION/PURPOSE: Is BMAB a useful test in the staging of extraskeletal Ewing sarcoma? METHODS: Between January 1996 and December 2021, our institution evaluated 109 patients with a listed diagnosis of extraskeletal Ewing sarcoma. Those patients were retrospectively reviewed for this study. Of those, we considered patients with biopsy-confirmed diagnosis of extraskeletal Ewing sarcoma. Biopsy was performed based on institutional protocols, with all diagnoses assigned by a board-certified pathologist. Based on that criteria, 96% (105 of 109) were eligible. An additional 18% (20 of 109) were excluded because records of their initial diagnostic and staging workup were not available. This left 78% (85 of 109) for analysis. Of those, 52% (44 of 85) were male. The average age was 32 ± 16 years. Primary tumor locations included extremities in 26% (22 of 85), paraspinal in 20% (17 of 85), chest in 19% (16 of 85), retroperitoneum in 13% (11 of 85), intraabdominal in 12% (10 of 85), intrapelvic in 7% (6 of 85), and head or neck in 4% (3 of 85). Initial diagnostic and staging information, including the use of PET-CT, bone scan, CT chest, and BMAB, was collected. Metastatic disease at the time of presentation or during follow-up was noted. The utility of BMAB was determined by the rate of positive tests in those undergoing BMAB during the initial staging process. Descriptive statistical analysis was sufficient to address the study question, and therefore no comparative statistics were performed. RESULTS: BMAB was obtained during the initial staging process in 64% (54 of 85) of patients. This BMAB was negative in all 54 patients, including those with known metastatic disease. CONCLUSION: Diagnosing metastatic disease in extraskeletal Ewing sarcoma is important as the presence of metastases at diagnosis adversely affects prognosis. The routine use of BMAB in the staging process of extraskeletal Ewing sarcoma is of low diagnostic yield. BMAB is unlikely to diagnose metastatic involvement even in patients with known metastases to bone. We do not have enough data to suggest whether other modalities, such as PET-CT, might be more useful. Similar studies should be pursued to determine the utility of the remainder of staging modalities in patients with extraskeletal Ewing sarcoma to elucidate the most efficient and effective staging protocol. LEVEL OF EVIDENCE: Level III, diagnostic study.
Assuntos
Neoplasias Ósseas , Sarcoma de Ewing , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/patologia , Neoplasias Ósseas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medula Óssea/patologia , Estudos Retrospectivos , Relevância Clínica , Biópsia , Tomografia Computadorizada por Raios X , Estadiamento de NeoplasiasRESUMO
PURPOSE: Extraskeletal Ewing sarcoma (EES), is a rare soft tissue sarcoma. Treatment for EES commonly involves chemotherapy and surgical resection (ST) or less commonly combined chemotherapy, surgery, and radiotherapy (ST + RT). The purpose of the current study was to evaluate our institutional experience treating EES. METHODS: We reviewed 36 (18 males:18 females) patients (mean age 30 years) with a nonretroperitoneal/visceral EES treated with either ST (n = 24, 67%) or ST + RT (n = 12, 33%). All patients were treated with chemotherapy, most commonly vincristine, doxorubicin, cyclophosphamide/ifosfamide and etoposide (VDC/IE, n = 23, 66%) Radiotherapy was mostly delivered preoperatively (n = 9). The mean follow-up was 8 years. RESULTS: The 10-year disease specific survival for patients was 78%, with no difference in the survival between patients in the ST versus the ST + RT groups (83% vs. 71%, p = 0.86). There was no difference in the 10-year local recurrence (91% vs. 100%, p = 0.29) or metastatic free survival (87% vs. 75%, p = 0.45) between the ST and ST + RT groups. CONCLUSION: The results of the current study highlight the ability to achieve excellent local control with chemotherapy and surgery for EES. We recommend for multidisciplinary management of patients with EES, including chemotherapy and surgery, with use of radiotherapy if there is concern for a potentially close margin of resection.
Assuntos
Neoplasias Ósseas , Sarcoma de Ewing , Sarcoma , Adulto , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Doxorrubicina , Etoposídeo/uso terapêutico , Sarcoma/tratamento farmacológico , Sarcoma de Ewing/terapia , Sarcoma de Ewing/patologia , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Compared to other sarcomas, myxoid liposarcoma (ML) is known to be radiosensitive, with improved oncologic outcomes. Although these tumors "shrink" following radiotherapy, there is a paucity of data examining the degree of radiosensitivity and oncologic outcome. The purpose of the study was to evaluate pre- and postradiotherapy tumor volume to determine if size reduction impacts outcome. METHODS: We reviewed 62 patients with ML undergoing surgical resection combined with preoperative radiotherapy, with pre- and postradiotherapy MRI. This included 34 (55%) males, with a mean age of 47 ± 14 years. All tumors were deep to the fascia, and 12 (19%) patients had tumors with a >5% round-cell component. RESULTS: The mean volume reduction was 54% ± 29%. Compared to patients with >25% volume reduction, patients with reduction ≤25% had worse 10-year disease specific survival (86% vs. 37%, p < 0.01), in addition to an increased risk of metastatic disease (HR 4.63, p < 0.01) and death due to disease (HR 4.52, p < 0.01). CONCLUSION: Lack of volume reduction is a risk factor for metastatic disease and subsequent death due to disease in patients with extremity ML treated with combined preoperative radiotherapy and surgery. This data could be used to stratify patients for adjuvant therapies and follow-up intervals.
Assuntos
Lipossarcoma Mixoide , Lipossarcoma , Sarcoma , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Combinada , Extremidades/patologia , Lipossarcoma/patologia , Lipossarcoma Mixoide/radioterapia , Lipossarcoma Mixoide/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Radiation-associated angiosarcoma of the breast (RAASB) is a rare and aggressive malignancy occurring after radiation therapy as part of breast cancer treatment. RAASB usually presents several years after prior radiation and typically involves the skin with or without involvement of the parenchyma. Most RAASB are detected as cutaneous changes on physical exam. Herein, we present a unique case of a clinically occult RAASB diagnosed as non-mass enhancement on annual surveillance breast MRI.
RESUMO
BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas. PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples. RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 ± 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 ± 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016). CONCLUSION: In this multi-institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study.
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Ifosfamida/efeitos adversos , Lactente , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
Primary pulmonary artery sarcomas are rare tumors and are commonly misdiagnosed as pulmonary embolism. Primary pulmonary sarcomas demonstrate intraluminal growth into the vessel, rather than through the wall; require complete resection to enhance survival; and require complex surgical planning. The purpose of this case report is to describe an optimal team approach with multidisciplinary planning facilitated by a customized 3-dimensional model to guide intervention and enhance communication.
Assuntos
Neoplasias Pulmonares , Neoplasias de Tecido Vascular , Sarcoma , Neoplasias Vasculares , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Artéria Pulmonar/patologia , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Impressão Tridimensional , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/cirurgiaRESUMO
Musculoskeletal interventions are increasingly used with palliative and curative intent in the multidisciplinary treatment of oncology patients with bone and soft-tissue tumors. There is an unmet need for high-quality evidence to guide broader application and adoption of minimally invasive interventional technologies to treat these patients. Therefore, the Society of Interventional Radiology Foundation and the Society of Interventional Oncology collaborated to convene a research consensus panel to prioritize a research agenda addressing the gaps in the current evidence. This article summarizes the panel's proceedings and recommendations for future basic science and clinical investigation to chart the course for interventional oncology within the musculoskeletal system. Key questions that emerged addressed the effectiveness of ablation within specific patient populations, the effect of combination of ablation with radiotherapy and/or immunotherapy, and the potential of standardization of techniques, including modeling and monitoring, to improve the consistency and predictability of treatment outcomes.
Assuntos
Radiologia Intervencionista , Neoplasias de Tecidos Moles , Consenso , Humanos , Oncologia , Cuidados PaliativosRESUMO
Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm which typically originates from liver, lung, or bone. Due to the low incidence of disease, the most effective treatment is not easily studied and much of the information known about EHE has been learned through case reports and case series. In this case, we will present an uncommon form of primary soft tissue EHE with local recurrence, bone metastasis, and lymphangitic spread to the lungs leading to respiratory failure. Imaging of the chest was atypical for EHE with intraseptal thickening and hilar lymphadenopathy. Respiratory failure was progressive despite aggressive multimodal treatment. This case highlights an unusually aggressive recurrence and metastasis of primary soft tissue EHE with atypical pulmonary imaging findings.
RESUMO
Primary pulmonary artery sarcoma (PPAS) is a rare malignancy that is commonly mistaken for pulmonary embolism due to similarities in clinical presentation and radiographic findings. Distinct radiographic findings to help differentiate between the two diseases are highlighted in the case presented. (1) Several nuances in various imaging modalities have been identified to help distinguish pulmonary artery sarcoma from pulmonary thromboembolic disease. (2) The wall eclipsing sign is considered pathognomonic for pulmonary artery sarcoma. (3) Positron emission tomography/computed tomography may help reduce time between diagnosis and treatment, which may ultimately prolong survival. (4) Providers should be well versed on the subtle differences on imaging to prevent future delays in diagnosis and treatment.
Assuntos
Embolia Pulmonar , Sarcoma , Neoplasias Vasculares , Diagnóstico Diferencial , Humanos , Imagem Multimodal , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Sarcoma/diagnóstico por imagem , Neoplasias Vasculares/diagnóstico por imagemRESUMO
Chromosome region maintenance protein 1 (CRM1) mediates protein export from the nucleus and is a new target for anticancer therapeutics. Broader application of KPT-330 (selinexor), a first-in-class CRM1 inhibitor recently approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, have been limited by substantial toxicity. We discovered that salicylates markedly enhance the antitumor activity of CRM1 inhibitors by extending the mechanisms of action beyond CRM1 inhibition. Using salicylates in combination enables targeting of a range of blood cancers with a much lower dose of selinexor, thereby potentially mitigating prohibitive clinical adverse effects. Choline salicylate (CS) with low-dose KPT-330 (K+CS) had potent, broad activity across high-risk hematological malignancies and solid-organ cancers ex vivo and in vivo. The K+CS combination was not toxic to nonmalignant cells as compared with malignant cells and was safe without inducing toxicity to normal organs in mice. Mechanistically, compared with KPT-330 alone, K+CS suppresses the expression of CRM1, Rad51, and thymidylate synthase proteins, leading to more efficient inhibition of CRM1-mediated nuclear export, impairment of DNA-damage repair, reduced pyrimidine synthesis, cell-cycle arrest in S-phase, and cell apoptosis. Moreover, the addition of poly (ADP-ribose) polymerase inhibitors further potentiates the K+CS antitumor effect. K+CS represents a new class of therapy for multiple types of blood cancers and will stimulate future investigations to exploit DNA-damage repair and nucleocytoplasmic transport for cancer therapy in general.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colina/análogos & derivados , Reparo do DNA/efeitos dos fármacos , Hidrazinas/farmacologia , Carioferinas/antagonistas & inibidores , Linfoma não Hodgkin/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Salicilatos/farmacologia , Triazóis/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Colina/administração & dosagem , Colina/efeitos adversos , Colina/farmacologia , Replicação do DNA/efeitos dos fármacos , DNA de Neoplasias/efeitos dos fármacos , Combinação de Medicamentos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Ftalazinas/administração & dosagem , Ftalazinas/farmacologia , Piperazinas/administração & dosagem , Piperazinas/farmacologia , Distribuição Aleatória , Salicilatos/administração & dosagem , Salicilatos/efeitos adversos , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína Exportina 1RESUMO
BACKGROUND: Earlier studies report a direct association between diseases of the skin-particularly those on the face-and depression. However, to our knowledge, such associations have not been examined in patients with non-squamous, non-basal call skin cancers. METHODS: The primary goal was to assess whether malignant skin disease-specifically on the face as opposed to other sites-was associated with depression. The medical records of patients with cutaneous cancer (either primary or metastatic but non-squamous, non-basal cell) were reviewed for the relevant data. RESULTS: One hundred and sixty-five patients were studied. Only 23 patients (14%) had metastases to the face, and 115 (70%) had a readily viewable skin cancer. Twenty-one patients (13%) developed depression after a diagnosis of cutaneous cancer (of note, the rate of missing data for depression was 37%). Only one patient with facial cutaneous cancer manifested depression, yielding an odds ratio for not developing depression (95% confidence interval (CI)) of 4.4 (0.5,35); p = 0.13. Depression appeared to occur more often in women (62% versus 43%), patients with a history of depression (52% versus 6%), and younger patients (median age with and without depression 55 years and 67 years, respectively). CONCLUSION: In contrast to other cutaneous diseases, no association was found between cutaneous cancer to the face and depression. Nonetheless, high rates of missing data underscore the need to focus on depression in patients with cutaneous cancers in the future.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma Basocelular/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pele , Neoplasias Cutâneas/epidemiologiaRESUMO
There are limited data regarding the surgical management of primary pulmonary artery sarcomas (PPAS) because of their rarity and complicated diagnostic history. The objective of this study was to analyze our institution's long-term surgical management outcomes for PPAS in the absence of a care pathway. From May 1997 to June 2013, 8 patients (mean age 60.6 ± 11.8 years; range, 40-73 years; 5 women and 3 men) underwent surgical intervention for PPAS at our institution. The most common computed tomography finding was a luminal filling defect obstructing the pulmonary artery (PA), without evidence of extraluminal extension. Three patients underwent debulking/pulmonary endarterectomy alone and 5 patients underwent a more radical resection with PA patch angioplasty, PA resection and reconstruction, pulmonary valve replacement, and unilateral pneumonectomy. The mean postoperative survival in this series was 3.8 ± 3.6 years (range, 1-11.9 years), with 2 radical surgical resection patients alive at 4.9 and 11.9 years, respectively. For those patients with incomplete resection, 3-dimensional (3D) models were created to demonstrate the advantage of a preoperative guide for a more complete resection and what it would entail. Six patients had local recurrences with mean disease-free interval of 14 ± 10.9 months (range, 2 months-2.5 years), and 2 patients with re-resections had an overall postoperative survival of 2.8 and 11.9 years, respectively. In our small cohort of PPAS, patients treated with radical surgical resection had better survival. The small number of PPAS cases in this series makes proving this association unlikely but warrants consideration.
Assuntos
Artéria Pulmonar , Sarcoma , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Impressão Tridimensional , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Resultado do TratamentoRESUMO
Measles virus (MV) Edmonston derivative strains are attractive vector platforms in vaccine development and oncolytic virotherapy. Helicobacter pylori heat shock protein A (HspA) is a bacterial heat shock chaperone with essential function as a Ni-ion scavenging protein. We generated and characterized the immunogenicity of an attenuated MV strain encoding the HspA transgene (MV-HspA). MV-HspA showed faster replication within 48 h of infection with >10-fold higher titers and faster accumulation of the MV proteins. It also demonstrated a superior tumor-killing effect in vitro against a variety of human solid tumor cell lines, including sarcoma, ovarian and breast cancer. Two intraperitoneal (i.p.) doses of 106 50% tissue culture infectious dose (TCID50) MV-HspA significantly improved survival in an ovarian cancer xenograft model: 63.5 days versus 27 days for the control group. The HspA transgene induced a humoral immune response in measles-permissive Ifnarko-CD46Ge transgenic mice. Eight of nine animals developed a long-term anti-HspA antibody response with titers of 1:400 to 1:12,800 without any negative impact on development of protective anti-MV immune memory. MV-HspA triggered an immunogenic cytopathic effect as measured by an HMGB1 assay. The absence of significant elevation of PD-L1 expression indicated that vector-encoded HspA could act as an immunomodulator on the immune check point axis. These data demonstrate that MV-HspA is a potent oncolytic agent and vaccine candidate for clinical translation in cancer treatment and immunoprophylaxis against H. pylori.
RESUMO
Objective. We explore the clinicopathologic features of Ewing sarcoma (ES) presenting in older adulthood. Methods. Cases of molecularly confirmed ES arising in patients aged ≥40 years were evaluated. Results. Fifty patients were identified (33 males/17 females; 41-86 years). The majority of tumors (41) arose at extraskeletal sites, while 9 were bone primaries. Twenty-eight cases showed nested architecture, while the remaining cases showed sheet-like growth. Tumor cytology was categorized as conventional (n = 39), crushed (n = 5), clear cell (n = 4), rhabdoid (n = 3), and epithelioid (n = 2). Fifty percent had necrosis, while rosettes were noted in 1 case. Immunostains performed ranged from 1 to 28 (median = 10). Follow-up (n = 43, 1-147 months) revealed 15 patients with metastasis. Conclusion. Although rare, ES should be considered in the differential diagnosis for round cell malignancies in older adult patients. In this cohort, ES is most often extraskeletal, and may show unusual morphologic features, closely simulating more common neoplasms in this age group.
Assuntos
Neoplasias Ósseas/diagnóstico , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Osso e Ossos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Perioperative radiation therapy (RT) has been associated with reduced local recurrence in patients with retroperitoneal sarcomas (RPS); however, selection criteria remain unclear. We hypothesized that perioperative RT would improve survival in patients with RPS and would be associated with pathological factors. The National Cancer Database (NCDB) from 2004 to 2012 was reviewed for patients with nonmetastatic RPS undergoing curative intent resection. Tumor size was dichotomized at 15 cm based on 8th edition American Joint Committee on Cancer (AJCC) staging. Patients with the highest comorbidity score were excluded. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards modeling analyzed overall survival (OS). Multivariable logistic regression modeled margin positivity. A total of 2,264 patients were included; 727 patients (32.1%) had perioperative radiation in whom 203 (9.0%) had radiation preoperatively. Median (IQR) RPS size was 17.5 [11.0-27.0] cm. Histopathology was high grade in 1048 patients (43.7%). Multivariable analysis revealed that perioperative radiation was independently associated with decreased mortality (HR 0.72, 95% confidence intervals (CIs) 0.62-0.84, p < 0.001), and preoperative RT was associated with reduced margin positivity (HR 0.72, 95% CI 0.53-0.97, p=0.032). Stratified survival analysis showed that radiation was associated with prolonged median OS for RPS that were high-grade (64.3 vs. 43.6 months, p < 0.001), less than 15 cm (104.1 vs. 84.2 months, p=0.007), and leiomyosarcomatous (104.8 vs. 61.8 months, p < 0.001). Perioperative radiation is independently associated with decreased mortality in patients with high-grade, less than 15 cm, and leiomyosarcomatous tumors. Preoperative radiation is independently associated with margin-negative resection. These data support the selective use of perioperative radiation in the multidisciplinary management of RPS.
RESUMO
BACKGROUND: Myoepithelioma of the soft tissues is a rare entity and little is known about how best to manage locally recurrent and high-grade disease. Here, we retrospectively examined outcomes of surgery, chemotherapy, and radiation therapy (RT) for treatment of low-grade and high-grade myoepithelioma of soft tissues. METHODS: We reviewed 20 cases of myoepithelioma of soft tissues seen at Mayo Clinic between 1994 and 2014. The effect of histologic grade and therapies received on relapse and survival were assessed. RESULTS: We identified 13 patients with low-grade disease and 7 patients with high-grade disease. We found that low-grade disease was frequently effectively managed with surgical resection alone, whereas high-grade disease frequently metastasized and was often fatal. The 5-year event-free survival was 88% (confidence interval, 46%-98%) for low-grade disease versus 36% (confidence interval, 7%-75%; P=0.04) for high-grade disease. The relapse rate in low-grade disease was 29% at 5 years versus 64% (P=0.04) in high-grade disease. No significant responses to chemotherapy were noted, however, excellent responses to perioperative RT were seen. CONCLUSIONS: Surgery continues as the primary modality of treatment for myoepithelioma of soft tissues. Our study did not show a clear benefit of chemotherapy in the metastatic disease setting, but supports the use of perioperative RT in the management of high-grade disease; further investigation is warranted.