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BACKGROUND: Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors are ultrarare soft-tissue tumors, traditionally treated with surgery. This study reviews the first results of using ipilimumab and nivolumab in the desmoid tumor cohort of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. METHODS: DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) that opened at 1,016 US sites. The primary endpoint included overall response rate (ORR) defined as confirmed complete (CR) and partial responses (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ≥6 months plus CR and PR) and toxicity. RESULTS: Sixteen evaluable patients (median age: 37) with desmoid tumors and a median of 1.5 prior therapies (with no prior exposure to immunotherapy) were analyzed. The tumors varied in location (eight abdomen, three lower limb, two upper limb, two pelvis, and one neck). ORR was 18.8% (3/16; 3 confirmed PR): 40% regression (PFS 30+ months), 83% regression (PFS 16 months) and 71% regression (PFS 8.4 months). Seven additional patients (43.8%) had prolonged SD over 6 months (PFS: 16.5, 22.4+, 22.6, 30.1, 38.2+, 48.3+ and 60.7+ months). Overall CBR was 62.5% (10/16). Median PFS was 19.4 months, with 6-month PFS of 73% and 1-year PFS of 67%. All patients were alive at 1 year; median OS was not assessable, as 13 patients were alive at analysis. Common adverse events included fatigue, nausea and hypothyroidism, with 50% experiencing grade 3-4 events. There were no grade 5 events. CONCLUSION: Treatment with ipilimumab and nivolumab in desmoid tumors yielded an ORR of 18.8% and a CBR of 62.5% with durable responses seen. This is the first prospective study exploring the efficacy of this combination in this rare disease. Ongoing studies aim to identify markers for response and resistance. Expanded trials are necessary. TRIAL REGISTRATION NUMBER: NCT02834013.
Assuntos
Antígeno CTLA-4 , Fibromatose Agressiva , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Antígeno CTLA-4/antagonistas & inibidores , Fibromatose Agressiva/tratamento farmacológico , Idoso , Adulto Jovem , Estudos Prospectivos , Ipilimumab/uso terapêutico , Ipilimumab/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Nivolumabe/uso terapêutico , Nivolumabe/farmacologia , AdolescenteRESUMO
BACKGROUND: In recent years, there has been a change in the therapeutic landscape of desmoid-type fibromatosis (DF). Watchful waiting is now preferred over initial local treatments such as surgery and radiotherapy. Systemic treatment is considered for progressive or symptomatic disease. The aim of this study is to review real-life data on the use of sorafenib in DF. METHODS: We established a retrospective dataset of patients treated with sorafenib in our centre, Ghent University Hospital, for progressive DF. Patient demographics, disease characteristics, response to therapy using Response Evaluation Criteria in Solid Tumours 1.1 criteria and toxicity according to CTCAE v5.0 were assessed. RESULTS: Eleven patients with DF were treated with sorafenib between 2020 and 2024. Median treatment duration was 20.4 months (95% confidence interval [CI], 10.0-NR). 36.4% achieved partial response, 54.5% stable disease and 9.1% progressive disease. For three patients, the treatment is ongoing. The median time to objective response rate is 15.0 months (95% CI, 8.8-NR). The majority (81.8%) experienced grade 2 toxicity, and one third of patients grade 3 toxicity (36.4%). The most common all-grade adverse event was skin toxicity (hand-foot syndrome, pruritus and rash) (90.9%). Nine patients (81.8%) needed dose reduction with a median time to first reduction of 1.1 months (95% CI, 0.5-NR). One patient stopped treatment due to toxicity. INTERPRETATION: Real-life data on the use of sorafenib in the treatment of DF is consistent with published data in clinical trial setting. Sorafenib is an effective treatment option for progressive DF although associated with significant toxicity and the need for rapid dose reduction.
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Antineoplásicos , Fibromatose Agressiva , Sorafenibe , Humanos , Sorafenibe/uso terapêutico , Sorafenibe/efeitos adversos , Feminino , Masculino , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Adulto Jovem , Resultado do TratamentoRESUMO
Presented are three casuistics of seemingly identical breast lesions which even by adopting advanced laboratory techniques may represent diagnostic challenge. Microscopic features of some bland spindle cell lesions of different histogenesis (epithelial or mesenchymal) are misleading and a potential source of unaware errors, which might affect optimal therapeutic strategy. In the setting of three diverse entities (low-grade spindle cell metaplastic carcinoma, desmoid fibromatosis and phyllodes tumor) is documented both demanding diagnostic algorithm and revealing molecular landscape on one side as well as evolving predictive/prognostic parameters on the other one. Close interdisciplinary cooperation is inevitable for accurate interpretation/understanding of revealed diagnostic facts which is required for adjustment of competent rational and individualized therapy.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Pessoa de Meia-Idade , Tumor Filoide/patologia , Tumor Filoide/diagnóstico , Adulto , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/patologiaRESUMO
PURPOSE: Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed. METHOD: Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation. RESULTS: From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8-89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. CONCLUSION: Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/ß-catenin, TGFß, IFN, and TNF pathways.
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Fibromatose Agressiva , Mutação , Transcriptoma , beta Catenina , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/metabolismo , Adolescente , Prognóstico , Adulto Jovem , Idoso , Estudos Retrospectivos , Criança , Idoso de 80 Anos ou mais , beta Catenina/genética , beta Catenina/metabolismo , Pré-Escolar , Lactente , Biomarcadores Tumorais/genética , Neoplasias Abdominais/genética , Neoplasias Abdominais/patologia , Neoplasias Abdominais/mortalidade , Perfilação da Expressão Gênica , Neoplasias Torácicas/genética , Neoplasias Torácicas/patologia , Neoplasias Torácicas/mortalidadeRESUMO
ABSTRACT: Extra-abdominal desmoid fibromatosis arising from the oesophagus and the contemporaneous traction diverticula due to an oesophageal tumour is extremely rare. We present this complex situation in a 2-year-old girl which posed a surgical challenge requiring simultaneous management of multiple pathologies. Surgery addressed both the entities and the presence of the diverticulum facilitated achieving negative surgical margins.
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Divertículo Esofágico , Neoplasias Esofágicas , Fibromatose Agressiva , Humanos , Feminino , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/diagnóstico , Pré-Escolar , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/diagnóstico , Divertículo Esofágico/cirurgia , Divertículo Esofágico/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
RATIONALE: Aggressive fibromatosis (AF) is a fibroblastic/myofibroblastic tumor known for its locally aggressive properties. Intra-abdominal AF primarily occurs in the small intestine mesentery, ileocolic mesocolon, omentum, retroperitoneum, and pelvis, and rarely originates from the intestinal wall. Here, we report a rare case of small bowel obstruction caused by duodenum-derived AF with ß-catenin (CTNNB1) T41A mutation. PATIENT CONCERNS: A 35-year-old male had a 4-month history of abdominal pain, nausea, and vomiting, which gradually worsened over time. DIAGNOSES: Based on the results of CT examination, histopathology and Sanger sequencing, the patient was diagnosed with small bowel obstruction caused by duodenum-derived AF. INTERVENTIONS: Due to the extensive adhesion between the tumor and surrounding tissue, it is extremely challenging to completely remove the tumor through surgical resection with negative margins in this case. In order not to damage the function of surrounding vital organs, gastrojejunostomy was performed to relieve the symptoms of small bowel obstruction. OUTCOMES: The patient experienced a successful recovery. It is important to note that this patient is still at risk of local recurrence and requires regular follow-up. LESSONS: The best treatment should be taken based on the individual patient to relieve symptoms and improve quality of life. Moreover, histopathology plays a crucial role in diagnosing and differentiating duodenum-derived AF. The detection of mutations in exon 3 of the CTNNB1 has become strong evidence for diagnosing duodenum-derived AF.
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Fibromatose Agressiva , Obstrução Intestinal , Mutação , beta Catenina , Humanos , Masculino , Adulto , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/genética , Obstrução Intestinal/diagnóstico , beta Catenina/genética , Fibromatose Agressiva/genética , Fibromatose Agressiva/complicações , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/cirurgia , Intestino Delgado/patologia , Neoplasias Duodenais/genética , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/complicações , Neoplasias Duodenais/diagnósticoRESUMO
Objective: To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). Methods: The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing. Results: The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve (n=4), brachial plexus (n=2) or multiple nerves (n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of ß-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions: NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.
Assuntos
Coristoma , Fibromatose Agressiva , Mutação , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Fibromatose Agressiva/metabolismo , Fibromatose Agressiva/cirurgia , Masculino , Feminino , Criança , Estudos Retrospectivos , Lactente , Adolescente , Pré-Escolar , Coristoma/patologia , Coristoma/genética , Adulto Jovem , Plexo Braquial/patologia , Plexo Braquial/cirurgia , Nervo Isquiático/patologiaRESUMO
RATIONALE: Desmoid tumor (DT) is a rare soft tissue tumor that can occur anywhere in the body. Abdominal wall DT presents unique clinical challenges due to its distinctive manifestations, treatment modalities, and the lack of biomarkers for diagnosis and recurrence prediction, making clinical decisions exceedingly complex. PATIENT CONCERNS: A 32-year-old female who underwent radical resection combined with patch reinforcement for rectus abdominis DT, successfully alleviating abdominal discomfort, with no recurrence during the 6-month follow-up after surgery. DIAGNOSES: Based on the imaging studies and medical history, the patient underwent radical surgical resection. Histopathology reveals that the tumor cells predominantly composed of proliferative fibroblasts with local collagen deposition. The lesional cells show positive staining for ß-catenin, indicating a diagnosis of DT. INTERVENTIONS: The patient underwent radical surgical resection with patch reinforcement to repair the abdominal wall defect. Pathology confirmed negative margins, achieving an R0 resection, and genetic testing identified a T41A mutation in CTNNB1. Consequently, no additional adjuvant therapy was administered postoperatively. OUTCOMES: The patient was discharged with the incision healing well after 3 days postoperation. Upon reexamination 6 months later, no recurrence or adverse complications were observed. LESSONS: Abdominal wall DT treatment requires personalized plans from multidisciplinary team discussions. Genetic testing plays a crucial role in identifying novel biomarkers for abdominal wall DT. We have once again demonstrated the significant clinical significance of CTNNB1 mutations in the diagnosis and progression of abdominal wall DT. Additionally, genes such as CCND1, CYP3A4, SLIT1, RRM1, STIM1, ESR2, UGT1A1, among others, may also be closely associated with the progression of abdominal wall DT. Future research should delve deeper into and systematically evaluate the precise impact of these genetic mutations on treatment selection and prognosis for abdominal wall DT, in order to better guide patient management and treatment decisions.
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Fibromatose Agressiva , Reto do Abdome , Humanos , Feminino , Adulto , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Reto do Abdome/cirurgia , beta Catenina/genética , Neoplasias Abdominais/cirurgia , Neoplasias Abdominais/genética , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/patologiaRESUMO
RATIONALE: Desmoid-type fibromatosis (DTF), also known as aggressive fibromatosis, is a rare neoplasm originating from the fascial or musculoaponeurotic tissues. While benign and characterized by slow growth, it exhibits local aggressiveness and lacks specific clinical characteristics. However, in a considerable percentage of patients, it could be asymptomatic and discovered by accident during routine clinical examinations. Only a few cases of DTF arising from the psoas major muscle have been reported in the medical literature. PATIENT CONCERNS: A 24-year-old male, asymptomatic and without significant personal or family medical history, was diagnosed with grade 2 hydronephrosis by abdominal ultrasonography during a routine physical examination. This diagnosis was made 15 days after undergoing uncomplicated open-heart surgery to repair an atrial septal defect. DIAGNOSIS: Intravenous pyelogram revealed hydronephrosis with dilation of the pelvicalyceal system. Ureteroscopy ruled out any intrinsic lesions of the ureter. Contrast-enhanced computed tomography identified a 3.5â ×â 2â ×â 5.2 cm mass in the retroperitoneum, closely associated with the psoas muscle and enveloping the ureter adjacent to the iliac artery. Postoperative pathological analysis confirmed a definitive diagnosis of sporadic DTF. INTERVENTIONS: The patient underwent exploratory abdominal surgery, during which the tumor was resected without any intraoperative complications. RESULTS: After close monitoring over a 5-year follow-up period, which included periodic physical examinations, magnetic resonance imaging, and ultrasonography, no local recurrence was detected. LESSONS: Achieving an accurate preoperative diagnosis presents a challenge in cases involving retroperitoneal tumors originating from the psoas major muscle and encasing the ureter. However, the insertion of a double J stent is deemed a crucial step in the surgical process, facilitating the dissection and isolation of the ureter from the tumor while preserving kidney function.
Assuntos
Fibromatose Agressiva , Hidronefrose , Achados Incidentais , Músculos Psoas , Humanos , Masculino , Hidronefrose/etiologia , Hidronefrose/cirurgia , Hidronefrose/diagnóstico , Hidronefrose/diagnóstico por imagem , Adulto Jovem , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/patologia , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/complicações , Fibromatose Agressiva/diagnóstico por imagem , Seguimentos , Ultrassonografia/métodos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Desmoid tumors are a rare and complex disease characterized by a great diversity in its forms, localizations, and prognosis. Both the disease and the treatment can have a significant impact on quality of life in patients. Given the complexity of the disease and its rarity, the literature on patients' experience with the disease scarce. The purpose of this study is to investigate illness representations and subjective experience in participants affected with desmoid tumors. METHODS: Telephonic semi-directive interviews were used in French patients over 18 years, diagnosed with desmoid tumor. Data were analyzed through a general inductive method to identify emergent general themes in participants' discourse. RESULTS: Participants (8 women, 7 men) in this study were aged between 27 and 71. The analysis revealed eight major themes relative to representations of illness and treatment, live with the illness, the impact of illness on relationships with others, the illness and medical pathways, and the identity changes caused by the illness. The two most salient themes were illness and treatment representations and life with the illness. Those themes were chosen for this study. CONCLUSIONS: The results provide new insights on representation of and experience with desmoid tumors in patients. It brings arguments for the necessity of development wider systematic study to explore those variables in a larger sample during all the illness pathway. Indeed, this population meets particular issues appealing for the development of a specific psychosocial support.
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Fibromatose Agressiva , Pesquisa Qualitativa , Qualidade de Vida , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fibromatose Agressiva/terapia , Fibromatose Agressiva/psicologia , Idoso , França , Adaptação Psicológica , Entrevistas como AssuntoRESUMO
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.
Assuntos
Fibromatose Agressiva , Humanos , Fibromatose Agressiva/terapia , Fibromatose Agressiva/patologia , Fibromatose Agressiva/tratamento farmacológicoRESUMO
ABSTRACT: Prostate-specific membrane antigen (PSMA) PET/CT is widely used in the evaluation of suspected metastasis for initial definitive therapy and suspected recurrence of prostate cancer. We outline a case report of a 62-year-old man with history of prostate cancer treated with surgery, salvage radiation, and hormonal therapy presenting with rising PSA levels. There was incidental detection of a PSMA-avid subcutaneous abdominal wall mass on PSMA PET/CT study, which was consistent with desmoid fibromatosis on an ultrasound-guided biopsy.
Assuntos
Parede Abdominal , Antígenos de Superfície , Glutamato Carboxipeptidase II , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Glutamato Carboxipeptidase II/metabolismo , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/patologia , Antígenos de Superfície/metabolismo , Fibromatose Agressiva/diagnóstico por imagem , Neoplasias Abdominais/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Nirogacestat is a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors. In the phase 3 DeFi study (NCT03785964) of nirogacestat, ovarian toxicity (OT) was identified as a safety signal among females of reproductive potential (FORP). This analysis further describes the incidence, presentation, and resolution of OT. METHODS: Patients were randomized to twice-daily oral nirogacestat (150 mg) or placebo, taken in continuous 28-day cycles. Investigator-identified OT in FORP was based on abnormal reproductive hormone values or perimenopausal symptoms (or both). Adverse event follow-up was conducted to assess OT resolution. Post hoc analyses included return of menstruation and return of follicle-stimulating hormone (FSH) to within normal limits (WNL) (≤20.4 mIU/mL). RESULTS: Of 92 randomized females, 73 in the safety population were FORP (n = 36 nirogacestat, n = 37 placebo). OT was identified in 75% (27 of 36) receiving nirogacestat and 0% (0 of 37) receiving placebo. As of October 24, 2022, investigators reported OT resolution in 78% (21 of 27) of patients, with median OT duration of 19.1 weeks. Off-treatment resolution was reported in all 11 patients (100%) who stopped nirogacestat treatment; of these, all nine with available menstruation information experienced return of menstruation and eight had FSH WNL at last reported assessment. Resolution was reported in 10 of 14 (71%) while on nirogacestat; of these, all 10 experienced return of menstruation and seven had FSH WNL. Two patients were lost to follow-up. CONCLUSION: Most FORP treated with nirogacestat experienced OT, with the majority resolving, including all who stopped treatment, suggesting that OT is transient.
Assuntos
Fibromatose Agressiva , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Fibromatose Agressiva/tratamento farmacológico , Ovário/efeitos dos fármacos , Adulto Jovem , Método Duplo-Cego , Hormônio Foliculoestimulante , Idoso , AdolescenteRESUMO
BACKGROUND: Sorafenib and pazopanib, two tyrosine kinase inhibitors (TKI), are widely used in patients with progressive symptomatic desmoid tumors (DT). Limited real-word data is available on long-term outcomes of patients who progressed on, stopped, or continued TKIs. METHODS: Patients diagnosed with DTs and treated with sorafenib or pazopanib between 2011 and 2022 at 11 institutions were reviewed. Patient history, response to therapy and toxicity were recorded. Statistical analyses utilized Kaplan-Meier and log-rank tests. RESULTS: 142 patients with DT treated with sorafenib (n = 126, 88.7 %) or pazopanib (n = 16, 11.3 %) were analyzed. The median treatment duration was 10.8 months (range: 0.07- 73.9). The overall response rate and the disease control rate were 26.0 % and 95.1 %, respectively. The median tumor shrinkage was - 8.5 % (range -100.0 %- +72.5 %). Among responders, the median time to an objective response was 15.2 months (range: 1.1 to 33.1). The 1-year and 2-year progression-free survival rates were 82 % and 80 %. Dose reductions were necessary in 34 (23.9 %) patients. Grade 3 or higher adverse events were reported in 36 (25.4 %) patients. On the last follow-up, 55 (38.7 %) patients continued treatment. Treatment discontinuation (n = 85, 59.9 %) was mainly for toxicity (n = 35, 45.9 %) or radiological or clinical progression (n = 30, 35.3 %). For the entire cohort, 36 (25.4 %) patients required subsequent treatment. In the 32 responders, only 1 (3.1 %) patient required a subsequent treatment. In patients who discontinued TKI, 25 (44.6 %) with stable disease received subsequent treatment compared to 0 (0.0 %) of responders. CONCLUSION: This retrospective study represents the largest cohort of DT patients treated with sorafenib or pazopanib to date. Discontinuation of treatment in responders is safe. The optimal treatment duration in patients with stable disease remains to be defined.
Assuntos
Fibromatose Agressiva , Indazóis , Pirimidinas , Sorafenibe , Sulfonamidas , Humanos , Sorafenibe/uso terapêutico , Sorafenibe/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Masculino , Feminino , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/patologia , Adolescente , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do TratamentoRESUMO
A man in his 50s who presented an abnormal shadow on chest X-ray was diagnosed with posterior mediastinal tumor that had grown compared to the previous chest X-ray. Computed tomography showed a 5.7×3.9 cm solid mass with a smooth surface in the posterior mediastinum. A neurogenic tumor was suspected, and the mediastinal tumor was resected through thoracotomy because it was strongly adherent. The postoperative course was good, and he was discharged from the hospital on postoperative day 3. Contrary to preoperative expectations, the tumor was pathologically diagnosed as a desmoid tumor. After 6 months postoperatively without any complications, no recurrence was observed.
Assuntos
Fibromatose Agressiva , Neoplasias do Mediastino , Humanos , Masculino , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/diagnóstico por imagem , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/diagnóstico por imagem , Pessoa de Meia-Idade , Toracotomia , Tomografia Computadorizada por Raios XAssuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Conduta Expectante , Fibromatose Agressiva/diagnóstico por imagemAssuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Fibromatose Agressiva/diagnóstico por imagem , Valor Preditivo dos Testes , Conduta Expectante , Fibromatose Abdominal/diagnóstico por imagemRESUMO
Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.
Assuntos
Fibroma , beta Catenina , Humanos , beta Catenina/genética , Fibroma/genética , Fibroma/patologia , Masculino , Feminino , Mutação , Pessoa de Meia-Idade , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Adulto , Síndrome de Gardner/genética , Síndrome de Gardner/patologia , Mutação em Linhagem GerminativaRESUMO
INTRODUCTION: APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers. AREAS COVERED: The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices. EXPERT OPINION: FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
Assuntos
Polipose Adenomatosa do Colo , Colectomia , Qualidade de Vida , Humanos , Polipose Adenomatosa do Colo/terapia , Polipose Adenomatosa do Colo/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Equipe de Assistência ao Paciente , Medicina de Precisão , Fenótipo , Genótipo , Fibromatose Agressiva/terapia , Fibromatose Agressiva/patologiaRESUMO
PURPOSE OF REVIEW: This article discusses the evolving approaches to desmoid tumors management, shedding light on recent developments. RECENT FINDINGS: Active surveillance has become the primary approach for managing primary peripheral desmoid tumors. This strategy was initially based on evidence from retrospective studies. Roughly 50% of cases managed with active surveillance show spontaneous stabilization or regression. Recent prospective trials conducted in Italy, The Netherlands, and France (2022-2023) confirm the efficacy of active surveillance, revealing 3-year progression-free survival rates ranging from 53.4 to 58%. For the patients under active surveillance, decisions regarding treatment are based on significant tumor growth or progressive symptoms. Moreover, three contemporary randomized trials investigated medical treatments for progressive or recurrent desmoid tumors. Sorafenib, pazopanib, and nirogacestat demonstrated clinical activity, as evidenced by favorable progression-free survival and objective response rates. SUMMARY: Active surveillance has solidified its position as the primary management approach for desmoid tumors, validated by three robust prospective studies. Three recent randomized trials explored medical treatment for progressive or recurrent desmoid tumors, revealing promising clinical activities.