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1.
Int J Gynecol Cancer ; 32(5): 619-625, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35288460

RESUMO

OBJECTIVES: Benign leiomyomas are the most common uterine tumors. In contrast, uterine leiomyosarcomas are malignancies with a poor prognosis due to difficulties in early diagnosis and inappropriate surgical treatment. Most often they are diagnosed incidentally after surgery performed for treatment of leiomyoma. As the appropriate surgical treatment is crucial for survival of the patient, there is a high demand to predict leiomyosarcoma pre-operatively. Available scoring systems to discriminate leiomyoma from leiomyosarcoma are based on retrospective studies with limited numbers of patients and are not implemented in routine clinical practice. METHODS: The aim of our study was to evaluate a recently published score-the pre-operative leiomyosarcoma (pLMS) score-to determine whether it would have been predictive of leiomyosarcoma in 177 patients from the NOGGO-REGSA study, a German register of histologically proven gynecological sarcoma detected during routine clinical investigation. RESULTS: The threshold of the pLMS score for 'leiomyosarcoma not probable' (< -3) failed for 7.5% of the patients and the threshold 'indicator for leiomyosarcoma' (>+1) was true for 39.1% of the patients. 53.4% of the patients were attributed to the group 'additional investigations are recommended' (-3 to +1). The most relevant parameters in our analysis were suspicious sonography and rapid growth, but neither have been quantitatively defined. CONCLUSION: In our validation cohort, the pLMS score seems not to be a reliable tool to predict leiomyosarcoma and therefore we do not recommend its clinical implementation to identify leiomyosarcoma.


Assuntos
Leiomioma , Leiomiossarcoma , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/patologia , Leiomioma/cirurgia , Leiomiossarcoma/patologia , Sistema de Registros , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
2.
Br J Cancer ; 126(9): 1346-1354, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35058591

RESUMO

BACKGROUND: Sarcomas are rare cancers of high heterogeneity. Health-Related Quality of Life (HRQoL) has been shown to be a prognostic factor for survival in other cancer entities but it is unclear whether this applies to sarcoma patients. PATIENTS AND METHODS: HRQoL was prospectively assessed in adult sarcoma patients from 2017 to 2020 in 39 German recruiting sites using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Vital status was ascertained over the course of 1 year. HRQoL domains were analysed by multivariable cox-regressions including clinical and socio-economic risk factors. RESULTS: Of 1102 patients, 126 (11.4%) died during follow-up. The hazard ratio (HR) for global health was 0.73 per 10-point increase (95% confidence interval (CI) 0.64-0.85). HR for the HRQoL-summary score was 0.74 (CI 0.64-0.85) and for physical functioning 0.82 (CI 0.74-0.89). There was also evidence that fatigue (HR 1.17, CI 1.10-1.25), appetite loss (HR 1.15, CI 1.09-1.21) and pain (HR 1.14, CI 1.08-1.20) are prognostic factors for survival. CONCLUSION: Our study adds sarcoma-specific evidence to the existing data about cancer survival in general. Clinicians and care-givers should be aware of the relations between HRQoL and survival probability and include HRQoL in routine assessment.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Prognóstico , Qualidade de Vida , Inquéritos e Questionários
3.
Eur J Surg Oncol ; 48(3): 518-525, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34688512

RESUMO

Fat-containing tumors are very commonly found in daily practice with benign lipoma accounting for the majority of superficial tumors. Overlap in imaging findings between benign and intermediate or malignant fat-containing tumor is common. Guidelines recommend a core needle biopsy (CNB) for all deep tumors, and superficial tumors over 3 cm. However, specific strategy for diagnosis and referral to a sarcoma center should be applied on adipocytic tumors. The aim of this consensus statement is to provide a specific algorithm for adipocytic tumors, to discriminate patients who do require a CNB for preoperative diagnosis from those who can simply undergo active surveillance or a simple excision.

4.
AJR Am J Roentgenol ; 218(4): 659-669, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34668385

RESUMO

BACKGROUND. CT-based criteria for assessing the gastrointestinal stromal tumor (GIST) response to tyrosine kinase inhibitor (TKI) therapy are limited in part because tumor attenuation is influenced by treatment-related changes including hemorrhage and calcification. The iodine concentration may be less impacted by such changes. OBJECTIVE. The purpose of this study was to determine whether the dual-energy CT (DECT) vital iodine tumor burden (TB) allows improved differentiation between treatment responders and nonresponders among patients with metastatic GIST who are undergoing TKI therapy compared with established CT and PET/CT criteria. METHODS. An anthropomorphic phantom with spherical inserts mimicking GIST lesions of varying iodine concentrations and having nonenhancing central necrotic cores underwent DECT to determine a threshold iodine concentration. Forty patients (25 women and 15 men; median age, 57 years) who were treated with TKI for metastatic GIST were retrospectively evaluated. Patients underwent baseline and follow-up DECT and FDG PET/CT. Response assessment was performed using RECIST 1.1, modified Choi (mChoi) criteria, vascular tumor burden (VTB) criteria, DECT vital iodine TB criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria. DECT vital iodine TB criteria used the same percentage changes as RECIST 1.1 response categories. Progression-free survival was compared between responders and nonresponders for each response criterion by use of Cox proportional hazard ratios and Harrell C-indexes (i.e., concordance indexes). RESULTS. The phantom experiment identified a threshold of 0.5 mg/mL to differentiate vital from nonvital tissue. With use of the DECT vital iodine TB, median progression-free survival was significantly different between responders and nonresponders (623 vs 104 days; p < .001).. For nonresponders versus responders, the hazard ratio for disease progression for DECT vital iodine TB was 6.9 versus 7.6 for EORTC PET criteria, 3.3 for VTB criteria, 2.3 for RECIST 1.1, and 2.1 for mChoi criteria. The C-index was 0.74 for EORTC PET criteria, 0.73 for DECT vital iodine TB criteria, 0.67 for VTB criteria, 0.61 for RECIST 1.1, and 0.58 for mChoi criteria. The C-index was significantly greater for DECT vital iodine TB criteria than for RECIST 1.1 (p = .02) and mChoi criteria (p = .002), but it was not different from that for VTB and EORTC PET criteria (p > .05). CONCLUSION. DECT vital iodine TB criteria showed performance comparable to that of EORTC PET criteria and outperformed RECIST 1.1 and mChoi criteria for response assessment of metastatic GIST treated with TKI therapy. CLINICAL IMPACT. DECT vital iodine TB could help guide early management decisions in patients receiving TKI therapy.


Assuntos
Tumores do Estroma Gastrointestinal , Iodo , Segunda Neoplasia Primária , Feminino , Fluordesoxiglucose F18 , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
5.
Clin Cancer Res ; 28(8): 1672-1679, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-34615721

RESUMO

PURPOSE: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort. EXPERIMENTAL DESIGN: Data from 185 patients were retrospectively collected in 23 European GIST reference centers. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Univariate and multivariate unweighted and weighted Cox proportional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival. RESULTS: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79-2.28]. The variables consistently associated with worse survival outcomes were high mitotic index and nongastric tumor location. CONCLUSIONS: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Éxons/genética , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Mutação , Recidiva Local de Neoplasia/tratamento farmacológico , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos
6.
Support Care Cancer ; 30(1): 187-196, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34247310

RESUMO

PURPOSE: Cancer patients have been shown to frequently suffer from financial burden before, during, and after treatment. However, the financial toxicity of patients with sarcoma has seldom been assessed. Therefore, the aim of this study was to evaluate whether financial toxicity is a problem for sarcoma patients in Germany and identify associated risk factors. METHODS: Patients for this analysis were obtained from a multicenter prospective cohort study conducted in Germany. Using the financial difficulties scale of the EORTC QLQ-C30, financial toxicity was considered to be present if the score exceeded a pre-defined threshold for clinical importance. Comparisons to an age- and sex-matched norm population were performed. A multivariate logistic regression using stepwise backward selection was used to identify factors associated with financial toxicity. RESULTS: We included 1103 sarcoma patients treated in 39 centers and clinics; 498 (44.7%) patients reported financial toxicity. Sarcoma patients had 2.5 times the odds of reporting financial difficulties compared to an age- and sex-matched norm population. Patient age < 40 and > 52.5 years, higher education status, higher income, and disease progression (compared to patients with complete remission) were associated with lower odds of reporting financial toxicity. Receiving a disability pension, being currently on sick leave, and having a disability pass were statistically significantly associated with higher odds of reporting financial toxicity. CONCLUSION: Financial toxicity is present in about half of German sarcoma patients, making it a relevant quality of life topic for patients and decision-makers.


Assuntos
Estresse Financeiro , Sarcoma , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Sarcoma/epidemiologia , Inquéritos e Questionários , Sobreviventes
7.
Cancers (Basel) ; 13(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34830814

RESUMO

BACKGROUND: The aim of this study was to investigate diagnostic accuracy, safety and histologic results of ultrasound guided core needle biopsy (CNB) in patients with soft tissue lesions (STL) at a tertiary referral center. METHODS: A retrospective analysis of all consecutive patients undergoing ultrasound guided CNB for STL at our sarcoma outpatient service between January 2015 and August 2020 was performed. RESULTS: A total of 392 patients were identified. Main histologic entities were sarcomas, lipomas and desmoid tumors. Biopsy was performed in an outpatient setting in 87.6% of the cases. Conclusive biopsies were obtained in 88.5% of the cases. In patients who underwent surgical resection after CNB, the concordance of dignity, tumor entity and histopathological grading between biopsy and resection specimen were 97.2%, 92.7% and 92.5% respectively. The risk of inconclusive CNB was highest in intraabdominal or retroperitoneal tumors (19.5%) and lowest in lesions at the lower extremity (4.4%). Major complications after CNB occurred in three cases (0.8%). No case of biopsy tract seeding was observed during the study period. CONCLUSIONS: Ultrasound guided CNB for STL at first presentation in a dedicated surgical outpatient setting is a safe procedure and yields a high diagnostic accuracy.

8.
PLoS One ; 16(11): e0258896, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34731178

RESUMO

PURPOSE: Thoracic surgeons are currently asked to resect smaller and deeper lesions which are difficult to detect thoracoscopically. The growing number of those lesions arises both from lung cancer screening programs and from follow-up of extrathoracic malignancies. This study analyzed the routine use of a CT-aided thoracoscopic approach to small pulmonary nodules in the hybrid theatre and the resulting changes in the treatment pathway. METHODS: 50 patients were retrospectively included. The clinical indication for histological diagnosis was suspected metastasis in 46 patients. Technically, the radiological distance between the periphery of the lesion and the visceral pleura had to exceed the maximum diameter of the lesion for the patient to be included. A spiral wire was placed using intraoperative CT-based laser navigation to guide the thoracoscopic resection. RESULTS: The mean diameter of the lesions was 8.4 mm (SD 4.27 mm). 29.4 minutes (SD 28.5) were required on average for the wire placement and 42.3 minutes (SD 20.1) for the resection of the lesion. Histopathology confirmed the expected diagnosis in 30 of 52 lesions. In the remaining 22 lesions, 9 cases of primary lung cancer were detected while 12 patients showed a benign disease. CONCLUSION: Computer tomography assisted thoracoscopic surgery (CATS) enabled successful resection in all cases with minimal morbidity. The histological diagnosis led to a treatment change in 42% of the patients. The hybrid-CATS technique provides good access to deeply located small pulmonary nodules and could be particularly valuable in the emerging setting of lung cancer screening.


Assuntos
Nódulos Pulmonares Múltiplos/cirurgia , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Assistida por Computador , Cirurgia Torácica Vídeoassistida , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Metástase Neoplásica , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Tomografia Computadorizada por Raios X
9.
Biology (Basel) ; 10(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34356494

RESUMO

In the framework of the German Interdisciplinary Sarcoma Group GISG-04/NOPASS trial, we evaluated soft tissue sarcoma samples taken before and after neoadjuvant pazopanib therapy using histopathology and next generation sequencing (NGS) to find potential predictive biomarkers. We also aimed to improve the genetically based sarcoma classification and to elucidate additional potentially druggable mutations. In total, 30 tumor samples from 18 patients consisting of 12 pre-therapeutic biopsies and 18 resection specimens following neoadjuvant pazopanib therapy were available for analyses. NGS was performed with the Oncomine Focus Assay (Ion Torrent) covering 0.03 Mb of DNA and enabled the detection of genetic variants in 52 cancer-relevant genes. Pathological analysis showed significant regression (≥50%) after pazopanib treatment in only one undifferentiated (pleomorphic) sarcoma. NGS analyses revealed a very high frequency of CDK4 amplification (88%; 7/8) in the group of dedifferentiated liposarcoma. In addition, two potentially druggable mutations, a MAP2K1 missense mutation (E203K) and a BRAF missense mutation (V600E), were traceable in two undifferentiated (pleomorphic) sarcoma patients (11%; 2/18). Our findings demonstrate that NGS testing is a powerful technology helping to improve diagnostic accuracy and offering some patients the chance for personalized medicine even in a "mutation unlikely" cohort like STS.

10.
J Clin Oncol ; 39(28): 3128-3139, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343033

RESUMO

PURPOSE: Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V-mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS: VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS: Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION: Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Pirróis/administração & dosagem , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Triazinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Ásia , Austrália , Progressão da Doença , Esquema de Medicação , Europa (Continente) , Feminino , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , América do Norte , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/genética , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Pirróis/efeitos adversos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Fatores de Tempo , Triazinas/efeitos adversos
11.
Eur J Cancer Care (Engl) ; 30(6): e13484, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34342924

RESUMO

OBJECTIVE: We investigated the health-related quality of life (HRQoL) of patients with gastrointestinal stromal tumours (GIST). METHODS: In the multicentre PROSa study, the HRQoL of adult GIST patients was assessed between 2017 and 2019 using the European Organisation for Research and Treatment of Cancer HRQoL questionnaire (EORTC QLQ-C30). We performed group comparisons and multivariate linear regressions. RESULTS: Among 130 patients from 13 centres, the mean global HRQoL was 63.3 out of 100 points. Higher sores indicate better HRQoL. The highest restrictions were in emotional, social, role functioning, insomnia, fatigue, and pain. In multivariate linear regression, we found no significant differences between patients receiving tyrosine kinase inhibitor (TKI) treatment and those without TKI treatment as well as between patients treated with curative or with palliative intent. Patients who received multiple lines of TKI treatment had the most restrictions, notably in physical (unstandardized regression coefficient [B] = -15.7), role (B = -25.7), social (B = -18.4), and cognitive functioning (B = -19.7); fatigue (B = 15.93); general health (B = -14.23); and EORTC-sum score (B = -13.82) compared to all other patients. CONCLUSION: The highest HRQoL restrictions were in GIST patients receiving multiple lines of TKI therapy. Underlying causes need further investigation.


Assuntos
Tumores do Estroma Gastrointestinal , Qualidade de Vida , Adulto , Estudos Transversais , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Inquéritos e Questionários
12.
EJNMMI Radiopharm Chem ; 6(1): 22, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34228236

RESUMO

BACKGROUND: [68Ga]Ga-NeoB is a novel DOTA-coupled Gastrin Releasing Peptide Receptor (GRPR) antagonist with high affinity for GRPR and good in vivo stability. This study aimed at (1) the translation of preclinical results to the clinics and establish the preparation of [68Ga]Ga-NeoB using a GMP conform kit approach and a licensed 68Ge/68Ga generator and (2) to explore the application of [68Ga]Ga-NeoB in patients with gastrointestinal stromal tumors (GIST) before and/or after interventional treatment (selective internal radiotherapy, irreversible electroporation, microwave ablation). RESULTS: Validation of the production and quality control of [68Ga]Ga-NeoB for patient use had to be performed before starting the GMP production. Six independent batches of [68Ga]Ga-NeoB were produced, all met the quality and sterility criteria and yielded 712 ± 73 MBq of the radiotracer in a radiochemical purity of > 95% and a molar activity of 14.2 ± 1.5 GBq/µmol within 20 min synthesis time and additional 20 min quality control. Three patients (2 females, 1 male, 51-77 yrs. of age) with progressive gastrointestinal stromal tumor metastases in the liver or peritoneum not responsive to standard tyrosine kinase inhibitor therapy underwent both [68Ga]Ga-NeoB scans prior and after interventional therapy. Radiosynthesis of 68Ga-NeoB was performed using a kit approach under GMP conditions. No specific patient preparation such as fasting or hydration was required for [68Ga]Ga-NeoB PET/CT imaging. Contrast-enhanced PET/CT studies were performed. A delayed, second abdominal image after the administration of the of [68Ga]Ga-NeoB was acquired at 120 min post injection. CONCLUSIONS: A fully GMP compliant kit preparation of [68Ga]Ga-NeoB enabling the routine production of the tracer under GMP conditions was established for clinical routine PET/CT imaging of patients with metastatic GIST and proved to adequately visualize tumor deposits in the abdomen expressing GRPR. Patients could benefit from additional information derived from [68Ga]Ga-NeoB diagnosis to assess the presence of GRPR in the tumor tissue and monitor antitumor treatment.

13.
Cancer Discov ; 11(11): 2780-2795, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112699

RESUMO

The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. SIGNIFICANCE: Rare cancers are difficult to treat; in particular, molecular pathogenesis-oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials.See related commentary by Eggermont et al., p. 2677.This article is highlighted in the In This Issue feature, p. 2659.


Assuntos
Neoplasias , Transcriptoma , Adulto , Perfilação da Expressão Gênica , Genômica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Sequenciamento Completo do Exoma
15.
J Thorac Dis ; 13(4): 2649-2660, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012614

RESUMO

BACKGROUND: Soft tissue sarcoma (STS) tend to metastasis to the lungs. Pulmonary metastasectomy seems to be a common practice always when plausible. The objective of this article was to review systematically the results of a literature search on pulmonary metastasectomy for STSs published in the last ten years and to offer a brief overview about the current practice as well. METHODS: Eight retrospective studies published in the period 2010-2020, which included patients with pulmonary metastases and metastasectomy were selected. Indication for surgery, survival rate and factors influencing survival were the primary outcomes, while further interesting findings in the studies were also collected and evaluated. RESULTS: Cumulative 1,004 patients participated in these studies. The most common histological types were leiomyosarcoma, malignant fibrous histiocytoma (MFH) and synovial sarcoma, being present together at 60% of the study population. Five-year survival was reported to be in the range from 20-58%, better survival going along with a fewer (preferably one) metastases, longer disease free interval (DFI) and R0 resection in most of the cases. CONCLUSIONS: Complete resection of the metastatic lesions seems to be the most effective treatment for long-term survival, or even achieving cure in selected patients. At selection of the patients amenable for surgery, a high probability of R0 resection, as well as a disease free period of at least 12 months should perhaps bear a higher specific value.

16.
Oncol Res Treat ; 44(6): 301-312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33887740

RESUMO

BACKGROUND: Data on institutional structures of sarcoma care in Germany are scarce. The utilization of an interdisciplinary tumor board (IDTB) is an essential part of modern cancer care. We investigated to which extent and when IDTB are used in sarcoma care. We hypothesized that IDTB before treatment initiation were used more often at certified cancer centers and at high-volume centers and that IDTB utilization increased over time. METHODS: From 2017 to 2020 we conducted a prospective cohort study, undertaking major efforts to include the whole spectrum of sarcoma treatment facilities. To analyze potential predictors of IDTB utilization, we calculated multivariable logistic regressions. RESULTS: Patients and survivors (n = 1,309) from 39 study centers (22 tertiary referral hospitals, 9 other hospitals, and 8 office-based practices) participated; 88.3% of the patients were discussed at some stage of their disease in an IDTB (56.1% before treatment, 78% after therapy, and 85.9% in metastatic disease). Hypotheses were confirmed regarding the utilization of IDTB in certified cancer centers (vs. all others: OR = 5.39; 95% CI 3.28-8.85) and the time of diagnosis (2018/2019 vs. until 2013: OR = 4.95; 95% CI 2.67-9.21). CONCLUSION: Our study adds to the evidence regarding the institutional structures of sarcoma care in Germany. Utilization of a tumor board before therapy seems to be in an implementation process that is making progress but is far from complete. Certification is a possible tool to accelerate this development.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Certificação , Alemanha , Humanos , Estudos Prospectivos
17.
Cancer ; 127(16): 2934-2942, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33910263

RESUMO

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. RESULTS: It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. CONCLUSIONS: Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Tecido Conjuntivo/patologia , Consenso , Humanos , Incidência , Estudos Prospectivos , Sarcoma/diagnóstico , Sarcoma/epidemiologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/epidemiologia
18.
Eur J Surg Oncol ; 47(8): 2173-2181, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33895019

RESUMO

BACKGROUND: Oesophageal gastrointestinal stromal tumours (GISTs) account for ≤1% of all GISTs. Consequently, evidence to guide clinical decision-making is limited. METHODS: Clinicopathological features and outcomes in patients with primary oesophageal GIST from seven European countries were collected retrospectively. RESULTS: Eighty-three patients were identified, and median follow up was 55.0 months. At diagnosis, 59.0% had localized disease, 25.3% locally advanced and 13.3% synchronous metastasis. A biopsy (Fine Needle aspiration n = 29, histological biopsy n = 31) was performed in 60 (72.3%) patients. The mitotic count was low (<5 mitoses/50 High Power Fields (HPF)) in 24 patients and high (≥5 mitoses/50 HPF) in 27 patients. Fifty-one (61.4%) patients underwent surgical or endoscopic resection. The most common reasons to not perform an immediate resection (n = 31) were; unresectable or metastasized GIST, performance status/comorbidity, patient refusal or ongoing neo-adjuvant therapy. The type of resections were enucleation (n = 11), segmental resection (n = 6) and oesophagectomy with gastric conduit reconstruction (n = 33), with median tumour size of 3.3 cm, 4.5 cm and 7.7 cm, respectively. In patients treated with enucleation 18.2% developed recurrent disease. The recurrence rate in patients treated with segmental resection was 16.7% and in patients undergoing oesophagectomy with gastric conduit reconstruction 36.4%. Larger tumours (≥4.0 cm) and high (>5/5hpf) mitotic count were associated with worse disease free survival. CONCLUSION: Based on the current study, enucleation can be recommended for oesophageal GIST smaller than 4 cm, while oesophagectomy should be preserved for larger tumours. Patients with larger tumours (>4 cm) and/or high mitotic count should be treated with adjuvant therapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/cirurgia , Esofagectomia , Esofagoscopia , Tumores do Estroma Gastrointestinal/cirurgia , Mesilato de Imatinib/uso terapêutico , Idoso , Fístula Anastomótica/epidemiologia , Biópsia por Agulha Fina , Quimioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Europa (Continente) , Feminino , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/secundário , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Índice Mitótico , Terapia Neoadjuvante , Metástase Neoplásica , Complicações Pós-Operatórias , Intervalo Livre de Progressão , Procedimentos Cirúrgicos Reconstrutivos , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral
19.
Cancers (Basel) ; 13(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799576

RESUMO

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7-15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

20.
Sci Rep ; 11(1): 6030, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727576

RESUMO

Carcinosarcoma of the urinary bladder is a very rare and aggressive subtype of bladder cancer with poor prognosis. Characteristically carcinosarcomas exhibit biphasic nature with both epithelial and mesenchymal differentiation. Limited information is available regarding its clinical features and appropriate treatments due to its rarity. Development of tumour models can further our understanding of bladder carcinosarcoma. We report establishment and characterization of the first-ever bladder carcinosarcoma cell line MaS-3. It is established by the outgrow method from 86 year-old caucasian male who underwent a radical pelvic resection after neoadjuvant radiotherapy. MaS-3 showed carcinosarcoma profile with high conformity with to the original tumour in terms of immunocytochemistry. Proteome analysis also aligned the MaS-3 cell line with the carcinosarcoma specimen rather than corresponding non-malignant tissue. Chemotherapy sensitivity testing revealed a great sensitivity of MaS-3 growth to 5-Fluorouracil, Gemcitabine and Cisplatin, with almost no impact of Irinotecan. Additionally, the suitability of MaS-3 for 3D in vitro experiments was also demonstrated. The newly established cell line MaS-3 shows typical characteristics of the tumour and may thus be a useful in vitro model system for studying the tumour biology and developing future of treatments of this rare but very aggressive entity.


Assuntos
Carcinossarcoma , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária , Carcinossarcoma/metabolismo , Carcinossarcoma/patologia , Humanos , Masculino , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
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