Identification Of Actionable Genetic Targets In Primary Cardiac Sarcomas

Background: Primary cardiac tumors are extremely rare; most are myxomas with a benign prognosis. However, primary sarcomas are highly aggressive and treatment options are limited. Radical surgery is often not feasible and conventional therapies provide only modest results. Due to the rare nature of primary cardiac tumors, there are no proper randomized studies to guide treatment. Their complexity requires alternative approaches in order to improve treatment efficacy. Methods: We isolated DNA from 5 primary cardiac sarcomas; the quality of DNA from 3 of them was sufficient to perform high-resolution single nucleotide polymorphism (SNP) array analysis. Results: In the present study, molecular karyotyping revealed numerous segmental chromosomal alterations and amplifications affecting actionable genes that may be involved in disease initiation and/or progression. These include chromosomal break flanking AKT2 in undifferentiated pleomorphic rhabdomyosarcoma, chromosomal break in promoter of TERT, and gain of CDK4 and amplification of MDM2 in inflammatory myofibroblastic tumor. We detected segmental break flanking MOS in high-grade myxofibrosarcoma. In addition, the high number of chromosomal aberrations in high-grade myxofibrosarcoma may cause multiple tumor-specific epitopes, supporting the study of immunotherapy treatment in this type of aggressive tumor. Conclusion: Our results provide a genetic rationale that supports an alternative, personalized therapeutic management of primary cardiac sarcomas

Clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival in patients with locally advanced rectal cancer treated with neoadjuvant long-course oral fluoropyrimidine- and oxaliplatin-based chemoradiotherapy and total mesorectal excision: Can we move towards a more personalised approach?

Fundamentos: La radioterapia (RT) neoadyuvante previa a la cirugía, ya sea la radioterapia de duración corta (RTDC) como la radioterapia de duración larga combinada con quimioterapia (QT) basada en 5-FU (QRTLD), es usada de forma rutinaria en el manejo del cáncer de recto localmente avanzado, con beneficios consistentes en el riesgo de recidiva local. Desafortunadamente, no se han podido demostrar mejorías en la supervivencia, especialmente en los casos tratados con cirugía radical en forma de una escisión mesorectal total (EMT). El riesgo de sobretratar a algunos pacientes y los posibles efectos secundarios a largo plazo han provocado a su vez dudas sobre el manejo con RT neoadyuvante, especialmente con QRTLD, en todos los pacientes con cáncer de recto localmente avanzado independientemente de su riesgo basal de recidiva local. Material y métodos: Revisión retrospectiva de una base prospectiva de pacientes con cáncer de recto cT3-T4 y/o cN+, tratados entre 1999 y 2014 con QRTLD basada en fluoropirimidinas orales y (en un 65%) oxaliplatino, seguido de EMT y QT adyuvante basada en 5-FU. Evaluamos factores pronóstico clínicos, radiológicos y patológicos para un mayor riesgo de recidiva local y de metástasis a distancia y una menor supervivencia libre de progresión (SLP) y supervivencia global (SG). Resultados: 203 pacientes fueron analizados. El riesgo de progresión precoz fue bajo y la mayor parte de pacientes procedieron a cirugía; hubo una EMT satisfactoria en el 89.7%. La tasa de infraestadiaje fue del 70.4% y el porcentaje de respuestas completas patológicas fue del 14.9%. No hubo ningún beneficio con la adición de oxaliplatino a la QRTLD. La tasa de recidivas locales fue del 8.3%. Los factores de riesgo para la recidiva local y para las metástasis a distancia fueron, con un valor variable para las dos situaciones, una EMT no exitosa, la calidad insuficiente del mesorecto, una resección R2, afectación del margen circunferencial radial (MCR) y del margen distal, no infraestadiaje, tumores pobremente diferenciados, regresión tumoral moderada o mínima, invasión perineural, afectación patológica linfática y una gran carga tumoral linfática. Los factores pronóstico clásicos como el estadio ypT ó ypN tuvieron mayor importancia que la regresión tumoral patológica. En el análisis multivariante, la afectación del MCR y la invasión perineural mantuvieron la significación. La cumplimentación de la QT adyuvante fue pobre, especialmente en los pacientes ancianos; menos de la mitad recibieron la dosis completa prevista. La SLP y SG a 5 y 10 años fue del 71.4% y 54.9% y del 75.4% y 62.4%, respectivamente. Los pacientes ancianos tuvieron una peor SLP y SG; ello estaba ligado a un aumento de las toxicidades graves no previsibles y una menor cumplimentación de la QRTLD y de la QT adyuvante. Los tumores mucinosos mostraron una respuesta muy pobre a la QRTLD. Factores significativos en el análisis multivariante para SLP y SG fueron una mayor edad, afectación del MRC, una EMT no exitosa y una gran carga tumoral linfática. Conclusiones: El pronóstico de los pacientes con un cancer de recto está determinado por dos factores competitivos: el riesgo de recidiva local y el de las metástasis a distancia. La identificación de los pacientes con un riesgo muy bajo de recidiva local, en donde el beneficio de la RT sea escaso depende de una exquisita estadificación con RMN y de un equipo quirúrgico especializado en la EMT. Un MRC libre y una EMT exitosa son los factores más importantes; los tumores rectales bajos y la carga linfática son también importantes. La QRTLD debería ser usada en los pacientes con una fascia mesorectal afecta clínica. El papel de la QT adyuvante es controvertido, aunque la cumplimentación es pobre. La QT neoadyuvante es una opción atractiva, especialmente en los pacientes con un mayor riesgo de metástasis a distancia. Por el contrario, otras opciones menos agresivas y mejor toleradas, como la RTCD, deberían ser usadas en pacientes ancianos o frágiles.Background: Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy (SCRT) and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction of the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and of the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRT. Material and methods: Retrospective review of a prospective base of patients with cT3-T4 and/or N+ rectal cancer treated at our Institution between 1999 and 2014 with LCRCT and oral fluoropyrimidines and (in 65% of patients) oxaliplatin, followed by TME and adjuvant 5-FU-based chemotherapy. We report clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival endpoints (disease-free survival (DFS) and overall survival (OS)) Results: 203 patients were analysed. The risk of early progression was small and most proceeded to surgery; a TME was done in 89.7%. The downstaging rate was 70.4% and the pathological complete response rate was 14.9%. No benefit was seen with the addition of oxaliplatin to LCRCT. Local relapse rate was 8.3%. Risk factors for local relapse and distant metastases were, to a varying degree for each situation, an unsuccessful TME, the unsatisfactory quality of the mesorectum, an R2 resection, involvement of the circumferential (CRM) and distal margins, no downstaging, poorly differentiated tumours, moderate or minimal regression, perineural invasion, pathological lymph node invasion and heavy lymph node burden. Classical pathological data such as ypT and ypN stage were better prognostic factors than tumour regression grading. In the multivariate analysis, CRM and perineural invasion retained their prognostic value. Compliance to adjuvant chemotherapy was poor, especially in elderly patients; less than half of patients received the full intended dose. 5- and 10-year DFS and OS were 71.4% and 54.9% and 75.4% and 62.4%, respectively. Elderly patients had an overall worse survival compared to younger patients; this was linked to higher unexpected toxicity and a lower compliance with LCRCT and adjuvant chemotherapy. Mucinous tumours showed a very poor response to LCRCT. Significant factors in the multivariate analysis for OS and DFS were older age, CRM involvement, an unsuccessful TME and a heavy lymph node burden. Conclusions: The prognosis of patients with locally advanced rectal cancer is determined by two competing factors: the risk of local relapse and the risk of distant metastases. The identification of patients with an extremely low risk of local relapse where radiotherapy would presumably offer little benefit is based on the premise of an exquisite imaging staging with MRI, supplemented with EUS, and a surgical team specialized in the TME procedure. A free CRM and a successful TME procedure are the most important factors; lower rectal tumours and a heavy lymph node burden are also important. In patients with invasion of the mesorectal fascia in the MRI, LCRCT should be used in order to lower the risk of a positive CRM. The role of adjuvant chemotherapy remains surprisingly undefined, although the compliance rates are poor in all published trials. Neoadjuvant chemotherapy is a possible option, especially in patients with a higher risk of distant metastases. On the other hand, other, better tolerated, options such as SCRT should be used in elderly or frail patients

Clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival in patients with locally advanced rectal cancer treated with neoadjuvant long-course oral fluoropyrimidine- and oxaliplatin-based chemoradiotherapy and total mesorectal excision: Can we move towards a more personalised approach?

Fundamentos: La radioterapia (RT) neoadyuvante previa a la cirugía, ya sea la radioterapia de duración corta (RTDC) como la radioterapia de duración larga combinada con quimioterapia (QT) basada en 5-FU (QRTLD), es usada de forma rutinaria en el manejo del cáncer de recto localmente avanzado, con beneficios consistentes en el riesgo de recidiva local. Desafortunadamente, no se han podido demostrar mejorías en la supervivencia, especialmente en los casos tratados con cirugía radical en forma de una escisión mesorectal total (EMT). El riesgo de sobretratar a algunos pacientes y los posibles efectos secundarios a largo plazo han provocado a su vez dudas sobre el manejo con RT neoadyuvante, especialmente con QRTLD, en todos los pacientes con cáncer de recto localmente avanzado independientemente de su riesgo basal de recidiva local. Material y métodos: Revisión retrospectiva de una base prospectiva de pacientes con cáncer de recto cT3-T4 y/o cN+, tratados entre 1999 y 2014 con QRTLD basada en fluoropirimidinas orales y (en un 65%) oxaliplatino, seguido de EMT y QT adyuvante basada en 5-FU. Evaluamos factores pronóstico clínicos, radiológicos y patológicos para un mayor riesgo de recidiva local y de metástasis a distancia y una menor supervivencia libre de progresión (SLP) y supervivencia global (SG). Resultados: 203 pacientes fueron analizados. El riesgo de progresión precoz fue bajo y la mayor parte de pacientes procedieron a cirugía; hubo una EMT satisfactoria en el 89.7%. La tasa de infraestadiaje fue del 70.4% y el porcentaje de respuestas completas patológicas fue del 14.9%. No hubo ningún beneficio con la adición de oxaliplatino a la QRTLD. La tasa de recidivas locales fue del 8.3%. Los factores de riesgo para la recidiva local y para las metástasis a distancia fueron, con un valor variable para las dos situaciones, una EMT no exitosa, la calidad insuficiente del mesorecto, una resección R2, afectación del margen circunferencial radial (MCR) y del margen distal, no infraestadiaje, tumores pobremente diferenciados, regresión tumoral moderada o mínima, invasión perineural, afectación patológica linfática y una gran carga tumoral linfática. Los factores pronóstico clásicos como el estadio ypT ó ypN tuvieron mayor importancia que la regresión tumoral patológica. En el análisis multivariante, la afectación del MCR y la invasión perineural mantuvieron la significación. La cumplimentación de la QT adyuvante fue pobre, especialmente en los pacientes ancianos; menos de la mitad recibieron la dosis completa prevista. La SLP y SG a 5 y 10 años fue del 71.4% y 54.9% y del 75.4% y 62.4%, respectivamente. Los pacientes ancianos tuvieron una peor SLP y SG; ello estaba ligado a un aumento de las toxicidades graves no previsibles y una menor cumplimentación de la QRTLD y de la QT adyuvante. Los tumores mucinosos mostraron una respuesta muy pobre a la QRTLD. Factores significativos en el análisis multivariante para SLP y SG fueron una mayor edad, afectación del MRC, una EMT no exitosa y una gran carga tumoral linfática. Conclusiones: El pronóstico de los pacientes con un cancer de recto está determinado por dos factores competitivos: el riesgo de recidiva local y el de las metástasis a distancia. La identificación de los pacientes con un riesgo muy bajo de recidiva local, en donde el beneficio de la RT sea escaso depende de una exquisita estadificación con RMN y de un equipo quirúrgico especializado en la EMT. Un MRC libre y una EMT exitosa son los factores más importantes; los tumores rectales bajos y la carga linfática son también importantes. La QRTLD debería ser usada en los pacientes con una fascia mesorectal afecta clínica. El papel de la QT adyuvante es controvertido, aunque la cumplimentación es pobre. La QT neoadyuvante es una opción atractiva, especialmente en los pacientes con un mayor riesgo de metástasis a distancia. Por el contrario, otras opciones menos agresivas y mejor toleradas, como la RTCD, deberían ser usadas en pacientes ancianos o frágiles.Background: Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy (SCRT) and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction of the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and of the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRT. Material and methods: Retrospective review of a prospective base of patients with cT3-T4 and/or N+ rectal cancer treated at our Institution between 1999 and 2014 with LCRCT and oral fluoropyrimidines and (in 65% of patients) oxaliplatin, followed by TME and adjuvant 5-FU-based chemotherapy. We report clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival endpoints (disease-free survival (DFS) and overall survival (OS)) Results: 203 patients were analysed. The risk of early progression was small and most proceeded to surgery; a TME was done in 89.7%. The downstaging rate was 70.4% and the pathological complete response rate was 14.9%. No benefit was seen with the addition of oxaliplatin to LCRCT. Local relapse rate was 8.3%. Risk factors for local relapse and distant metastases were, to a varying degree for each situation, an unsuccessful TME, the unsatisfactory quality of the mesorectum, an R2 resection, involvement of the circumferential (CRM) and distal margins, no downstaging, poorly differentiated tumours, moderate or minimal regression, perineural invasion, pathological lymph node invasion and heavy lymph node burden. Classical pathological data such as ypT and ypN stage were better prognostic factors than tumour regression grading. In the multivariate analysis, CRM and perineural invasion retained their prognostic value. Compliance to adjuvant chemotherapy was poor, especially in elderly patients; less than half of patients received the full intended dose. 5- and 10-year DFS and OS were 71.4% and 54.9% and 75.4% and 62.4%, respectively. Elderly patients had an overall worse survival compared to younger patients; this was linked to higher unexpected toxicity and a lower compliance with LCRCT and adjuvant chemotherapy. Mucinous tumours showed a very poor response to LCRCT. Significant factors in the multivariate analysis for OS and DFS were older age, CRM involvement, an unsuccessful TME and a heavy lymph node burden. Conclusions: The prognosis of patients with locally advanced rectal cancer is determined by two competing factors: the risk of local relapse and the risk of distant metastases. The identification of patients with an extremely low risk of local relapse where radiotherapy would presumably offer little benefit is based on the premise of an exquisite imaging staging with MRI, supplemented with EUS, and a surgical team specialized in the TME procedure. A free CRM and a successful TME procedure are the most important factors; lower rectal tumours and a heavy lymph node burden are also important. In patients with invasion of the mesorectal fascia in the MRI, LCRCT should be used in order to lower the risk of a positive CRM. The role of adjuvant chemotherapy remains surprisingly undefined, although the compliance rates are poor in all published trials. Neoadjuvant chemotherapy is a possible option, especially in patients with a higher risk of distant metastases. On the other hand, other, better tolerated, options such as SCRT should be used in elderly or frail patients

Clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival in patients with locally advanced rectal cancer treated with neoadjuvant long-course oral fluoropyrimidine- and oxaliplatin-based chemoradiotherapy and total mesorectal excision: Can we move towards a more personalised approach? /

Fundamentos: La radioterapia (RT) neoadyuvante previa a la cirugía, ya sea la radioterapia de duración corta (RTDC) como la radioterapia de duración larga combinada con quimioterapia (QT) basada en 5-FU (QRTLD), es usada de forma rutinaria en el manejo del cáncer de recto localmente avanzado, con beneficios consistentes en el riesgo de recidiva local. Desafortunadamente, no se han podido demostrar mejorías en la supervivencia, especialmente en los casos tratados con cirugía radical en forma de una escisión mesorectal total (EMT). El riesgo de sobretratar a algunos pacientes y los posibles efectos secundarios a largo plazo han provocado a su vez dudas sobre el manejo con RT neoadyuvante, especialmente con QRTLD, en todos los pacientes con cáncer de recto localmente avanzado independientemente de su riesgo basal de recidiva local. Material y métodos: Revisión retrospectiva de una base prospectiva de pacientes con cáncer de recto cT3-T4 y/o cN+, tratados entre 1999 y 2014 con QRTLD basada en fluoropirimidinas orales y (en un 65%) oxaliplatino, seguido de EMT y QT adyuvante basada en 5-FU. Evaluamos factores pronóstico clínicos, radiológicos y patológicos para un mayor riesgo de recidiva local y de metástasis a distancia y una menor supervivencia libre de progresión (SLP) y supervivencia global (SG). Resultados: 203 pacientes fueron analizados. El riesgo de progresión precoz fue bajo y la mayor parte de pacientes procedieron a cirugía; hubo una EMT satisfactoria en el 89.7%. La tasa de infraestadiaje fue del 70.4% y el porcentaje de respuestas completas patológicas fue del 14.9%. No hubo ningún beneficio con la adición de oxaliplatino a la QRTLD. La tasa de recidivas locales fue del 8.3%. Los factores de riesgo para la recidiva local y para las metástasis a distancia fueron, con un valor variable para las dos situaciones, una EMT no exitosa, la calidad insuficiente del mesorecto, una resección R2, afectación del margen circunferencial radial (MCR) y del margen distal, no infraestadiaje, tumores pobremente diferenciados, regresión tumoral moderada o mínima, invasión perineural, afectación patológica linfática y una gran carga tumoral linfática. Los factores pronóstico clásicos como el estadio ypT ó ypN tuvieron mayor importancia que la regresión tumoral patológica. En el análisis multivariante, la afectación del MCR y la invasión perineural mantuvieron la significación. La cumplimentación de la QT adyuvante fue pobre, especialmente en los pacientes ancianos; menos de la mitad recibieron la dosis completa prevista. La SLP y SG a 5 y 10 años fue del 71.4% y 54.9% y del 75.4% y 62.4%, respectivamente. Los pacientes ancianos tuvieron una peor SLP y SG; ello estaba ligado a un aumento de las toxicidades graves no previsibles y una menor cumplimentación de la QRTLD y de la QT adyuvante. Los tumores mucinosos mostraron una respuesta muy pobre a la QRTLD. Factores significativos en el análisis multivariante para SLP y SG fueron una mayor edad, afectación del MRC, una EMT no exitosa y una gran carga tumoral linfática. Conclusiones: El pronóstico de los pacientes con un cancer de recto está determinado por dos factores competitivos: el riesgo de recidiva local y el de las metástasis a distancia. La identificación de los pacientes con un riesgo muy bajo de recidiva local, en donde el beneficio de la RT sea escaso depende de una exquisita estadificación con RMN y de un equipo quirúrgico especializado en la EMT. Un MRC libre y una EMT exitosa son los factores más importantes; los tumores rectales bajos y la carga linfática son también importantes. La QRTLD debería ser usada en los pacientes con una fascia mesorectal afecta clínica. El papel de la QT adyuvante es controvertido, aunque la cumplimentación es pobre. La QT neoadyuvante es una opción atractiva, especialmente en los pacientes con un mayor riesgo de metástasis a distancia. Por el contrario, otras opciones menos agresivas y mejor toleradas, como la RTCD, deberían ser usadas en pacientes ancianos o frágiles.Background: Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy (SCRT) and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction of the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and of the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRT. Material and methods: Retrospective review of a prospective base of patients with cT3-T4 and/or N+ rectal cancer treated at our Institution between 1999 and 2014 with LCRCT and oral fluoropyrimidines and (in 65% of patients) oxaliplatin, followed by TME and adjuvant 5-FU-based chemotherapy. We report clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival endpoints (disease-free survival (DFS) and overall survival (OS)) Results: 203 patients were analysed. The risk of early progression was small and most proceeded to surgery; a TME was done in 89.7%. The downstaging rate was 70.4% and the pathological complete response rate was 14.9%. No benefit was seen with the addition of oxaliplatin to LCRCT. Local relapse rate was 8.3%. Risk factors for local relapse and distant metastases were, to a varying degree for each situation, an unsuccessful TME, the unsatisfactory quality of the mesorectum, an R2 resection, involvement of the circumferential (CRM) and distal margins, no downstaging, poorly differentiated tumours, moderate or minimal regression, perineural invasion, pathological lymph node invasion and heavy lymph node burden. Classical pathological data such as ypT and ypN stage were better prognostic factors than tumour regression grading. In the multivariate analysis, CRM and perineural invasion retained their prognostic value. Compliance to adjuvant chemotherapy was poor, especially in elderly patients; less than half of patients received the full intended dose. 5- and 10-year DFS and OS were 71.4% and 54.9% and 75.4% and 62.4%, respectively. Elderly patients had an overall worse survival compared to younger patients; this was linked to higher unexpected toxicity and a lower compliance with LCRCT and adjuvant chemotherapy. Mucinous tumours showed a very poor response to LCRCT. Significant factors in the multivariate analysis for OS and DFS were older age, CRM involvement, an unsuccessful TME and a heavy lymph node burden. Conclusions: The prognosis of patients with locally advanced rectal cancer is determined by two competing factors: the risk of local relapse and the risk of distant metastases. The identification of patients with an extremely low risk of local relapse where radiotherapy would presumably offer little benefit is based on the premise of an exquisite imaging staging with MRI, supplemented with EUS, and a surgical team specialized in the TME procedure. A free CRM and a successful TME procedure are the most important factors; lower rectal tumours and a heavy lymph node burden are also important. In patients with invasion of the mesorectal fascia in the MRI, LCRCT should be used in order to lower the risk of a positive CRM. The role of adjuvant chemotherapy remains surprisingly undefined, although the compliance rates are poor in all published trials. Neoadjuvant chemotherapy is a possible option, especially in patients with a higher risk of distant metastases. On the other hand, other, better tolerated, options such as SCRT should be used in elderly or frail patients

Heart Failure as First Sign of Development of Cardiac Metastases in a Patient with Diagnosis of Papillary Thyroid Carcinoma on Treatment with Tyrosine-Kinase Inhibitors: Differential Diagnoses and Clinical Management

Background: Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer. Patient: A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases. Results: After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels. Conclusions: We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation

A phase II trial of weekly nab-paclitaxel for progressive and symptomatic desmoid tumors.

Desmoid fibromatosis (DF) are mesenchymal neoplasms, with potential aggressive course and relevant clinical impact. New systemic therapy modalities are needed in this symptomatic/progressive population. In this multicenter, phase II trial (NCT03275818), patients with symptomatic/progressing DF received three cycles of weekly nab-paclitaxel. Brief pain inventory short form (BPI-SF) was collected at baseline and in every visit. MRI was performed every 3 months. Primary composite endpoint was RECIST 1.1 overall response rate (ORR) and/or clinical response (improvement ≥ 2 points in BPI-SF). If 40% of patients achieved clinical/radiological response, further investigation would be warranted. Toxicity, progression-free survival (PFS), pattern of response and its correlation with clinical best response and BPI, variation of physical function, and analgesic consumption were secondary endpoints. The translational research reported was not a pre-specified secondary outcome. Forty eligible patients started therapy, being 35 radiologically and clinically evaluable. The study achieved its primary endpoint, as 7(20%) patients obtained RECIST partial response, whereas 31(89%) experienced pain reduction of ≥2 points in BPI-SF worst pain. Therapy was well tolerated. With a median follow-up of 30(14-44) months, median 12 and 24-months PFS rates were 91%(CI 95%, 82-100) and 84%(CI 95%, 71-97). For clinical progression, 12 and 24-months PFS rates were 85% (CI 95%, 73-97) and 74% (CI 95%, 58-90) respectively. Short course of nab-paclitaxel is active, safe and achieves quick and durable responses in progressing/symptomatic DF patients

Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib.

Oncogenic KIT/PDGFRA signaling inhibition with imatinib achieves disease control in most patients with advanced/metastatic gastrointestinal stromal tumor (GIST), but resistance eventually develops after 20-24 months. Notably, a small subset of these patients obtain durable benefit from imatinib therapy. We analyzed clinical, pathological, and molecular characteristics and long-term outcomes in patients with metastatic GIST treated with continuous daily dosing of frontline imatinib in a cohort of patients benefiting for ≥5 years. A control group was obtained from the national Spanish Group for Sarcoma Research database and used as comparator. Sixty-four imatinib long-term responders (LTRs) and 70 control cases were identified. Compared with controls, LTRs at baseline had better performance status (PS) 0-1 (100% vs. 81%), lower mitotic count (median, 8 vs. 15), and tumor burden (number of metastases, 3 vs. 7). KIT exon 11 was the only region found mutated in LTRs. LTRs achieved 34% complete responses and a median progression-free survival of 11 years, compared with 4% and 2 years, respectively, in the control cohort. Prognostic factors that independently predicted long-term benefit with imatinib were PS, number of metastases prior to imatinib, and response to imatinib. Fifteen LTR patients developed new side effects attributable to imatinib after ≥5 years of continuous treatment. No resistance mutations were found in metastatic samples from three patients progressing on imatinib. GISTs in LTRs are a distinctive entity with less aggressive behavior and marked sensitivity to KIT inhibition. Patients reaching 5 or more years on imatinib have a higher chance of remaining progression free over time. This work demonstrates that clinical and inherent tumor characteristics define a subset of patients with gastrointestinal stromal tumor (GIST) with increased likelihood to achieve durable response to first-line imatinib therapy. Patients reaching ≥5 years on imatinib have a greater chance of remaining progression free over time, although the disease is unlikely to be cured. Imatinib is well tolerated for >5 years, and emergent toxicities are overall manageable. Resistance to imatinib emerging in patients with GISTs after long-term imatinib treatment does not involve polyclonal expansion of KIT secondary mutations