Long-term efficacy update of crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumour from EORTC trial 90101 CREATE.

PURPOSE: European Organisation for Research and Treatment of Cancer (EORTC) 90101 (CREATE) was a prospective, multicentric, non-randomised, open-label phase II basket trial to assess the efficacy and safety of crizotinib in patients with different types of cancers, including advanced inflammatory myofibroblastic tumour (IMT) with or without anaplastic lymphoma kinase (ALK) rearrangements. Here, we report updated results with long-term follow-up. PATIENTS/METHODS: After central reference pathology, eligible ALK-positive and ALK-negative patients with advanced/metastatic IMT deemed incurable with surgery, radiotherapy or systemic therapy received oral crizotinib 250 mg twice daily. The ALK status was assessed centrally using immunohistochemistry and fluorescence in situ hybridisation. The primary end-point was the proportion of patients who achieved an objective response (i.e. complete or partial response). If ≥6 ALK-positive patients achieved a confirmed response, the trial would be deemed successful. RESULTS: At data cut-off on 28th January 2021, we performed the final analysis of this trial. Of the 20 eligible and treated patients (19 of whom were evaluable for efficacy), with a median follow-up of 50 months, five were still on crizotinib treatment (4/12 ALK-positive and 1/8 ALK-negative patients). The updated objective response rate (ORR) was 66.7% (95% confidence interval [CI] 34.9-90.1%) in ALK-positive patients and 14.3% (95% CI 0.0-57.9%) in ALK-negative patients. In the ALK-positive and ALK-negative patients, the median progression-free survival was 18.0 months (95% CI 4.0-NE) and 14.3 months (95% CI 1.2-31.1), respectively; 3-year overall survival rates were 83.3% (95% CI 48.2-95.6) and 34.3% (95% CI 4.8-68.5). Safety results were consistent with previously reported data. CONCLUSION: These updated results confirm previous findings that crizotinib is effective, with durable responses, in patients with locally advanced or metastatic ALK-positive IMT. With further follow-up after the original primary analysis, the ORR increased, as patients derived long-term benefit and some responses converted from stable disease to partial responses. CLINICAL TRIAL NUMBER: EORTC 90101, NCT01524926.

[Clinical characteristics, diagnosis and treatment of pulmonary inflammatory myofibroblastic tumor in children].

Objective: To explore the clinical characteristics, diagnosis and treatment of pulmonary inflammatory myofibroblastic tumor in children. Methods: The clinical data of 13 patients with pulmonary inflammatory myofibroblastic tumor between October 2009 and October 2015 were retrospectively analyzed, including 9 boys and 4 girls aged 1 to 12 years 4 months (mean 4 years 9 months). Seven patients underwent total tumor resection, 4 had lobectomy, 1 had partial tumor resection and 1 had biopsy. The follow-up time ranged from 2 months to 6 years and 2 months. Results: Among the 13 patients, 9 were cured. Two patients lived with tumor. One of them had tumor which shrinked gradually and the other had stable disease. One patient with multiple lesions encountered recurrence after 3 operations and developed suspicious hepatic metastasis. One died during the operation because of airway mismanagement. Conclusions: Pulmonary inflammatory myofibroblastic tumor in children has rather good prognosis while a few cases have the potential of recurrence and canceration. Surgery is the primary therapeutic approach. Close post-operative follow up is necessary.

Inflammatory myofibroblastic tumors in childhood.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor of intermediate malignant potential that can occur anywhere in the body. Surgical resection is the principal treatment. We report on nine children diagnosed with IMT at our institution over a 10-year period. Presenting symptoms were reflective of tumor location. Complete surgical resection was curative. Local recurrence occurred in the presence of involved surgical margins. One patient with metastatic disease achieved long-term remission with chemotherapy alone. Severe inflammatory response and death occurred in one patient. The 3-year event free and overall survivals (OS) were 58 ± 20% and 89 ± 10% respectively.

Does the time-point of relapse influence outcome in pediatric rhabdomyosarcomas?

BACKGROUND: Childhood rhabdomyosarcoma (RMS), a soft tissue malignant tumor of skeletal muscle origin, accounts for approximately 3.5% of the cases of cancer among children 0-14 years and 2% of the cases among adolescents and young adults 15-19 years of age. PROCEDURE: We evaluated survival (SUR) after first relapse depending on the time to relapse (TTR) in RMSs of childhood and adolescence. Early, intermediate, and late relapsing patients were evaluated for prognostic risk factors. RESULTS: Two hundred thirty-four patients with RMS enrolled in the German sarcoma trial CWS-81, CWS-86, CWS-91, and CWS-96 met selection criteria. Of the 234 patients, 35%, 32%, and 33% relapsed within 6 (early), 6-12 (intermediate), and more than 12 (late) months respectively after the end of primary therapy. Four-year SUR was 12%, 21%, and 41% for early, intermediate, and late relapse respectively (P < 0.001). Four-year SUR after local relapse was 18% (early), 38% (intermediate), and 49% (late). Embryonal RMS showed four year SUR of 16%, 30%, and 46% (P < 0.001) whereas alveolar histology showed four year SUR of 8%, 6%, and 23% (P < 0.01) for early, intermediate, and late relapse respectively. CONCLUSION: TTR has significant influence on prognosis in relapsed RMS. It influences SUR independent of other features such as type of relapse, histology, tumor site, primary treatment time or irradiation in primary treatment.

Tissue factor expression correlates with disease-specific survival in patients with node-negative muscle-invasive bladder cancer.

Tissue factor (TF), a transmembrane glycoprotein responsible for initiating the extrinsic pathway of blood coagulation plays a key role in cancer growth, metastasis and angiogenesis. Various studies have demonstrated the prognostic potential of TF expression in several cancers. However, its role in bladder cancer is unclear. This study evaluated the prognostic potential of TF expression in muscle-invasive bladder tumors from patients treated with radical cystectomies. Immunohistochemical staining using a monoclonal antibody (mAb) anti-TF was carried out on sections of tissue microarray blocks containing cores of muscle-invasive bladder tumors (4 cores/tumor) from 218 patients. The intensity of the staining was evaluated on a scale from 0 to 3 by two independent observers who were both unaware of the clinicopathological characteristics of the samples. TF was expressed in 77.6% of tumors, independently from baseline characteristics (age, gender, stage and grade) as assessed using the chi(2) and Student t tests. During follow-up (median: 2.6 years), 45.4% of the patients died from the progression of their cancer. Kaplan-Meier survival showed that among the 103 patients with node-negative (N0) transitional cell carcinoma (TCC), those with TF-positive tumors had shorter bladder cancer-specific survival (p = 0.0276). Moreover, multivariate Cox regression analysis showed they had a 3.15-fold greater risk of dying from bladder cancer (95% CI: 1.1-9.0; p = 0.032). In conclusion, TF expression was an independent predictor of disease-specific survival in N0 muscle-invasive TCCs treated by radical cystectomy and therefore, might help identify patients at higher risk of disease progression. These patients could potentially benefit from adjuvant chemotherapy.

The role of liver transplantation in the management of paediatric liver tumours.

In recent years, considerable progress has been made in the treatment of children with hepatoblastoma largely due to effective pre-operative chemotherapy. Total hepatectomy and liver transplantation has emerged as an effective treatment for the small proportion of children with unresectable hepatoblastoma limited to the liver. A 5-year survival of 70% can be achieved in such cases. In contrast, the results of liver transplantation in children with hepatocellular cancer remain poor because these tumours are usually advanced with evidence of major vascular invasion and/or extrahepatic spread at the time of presentation. An exception is those children in whom the hepatocellular carcinoma is detected during surveillance of chronic liver disease - they typically have smaller tumours and frequently have a good prognosis after liver transplantation. The role of liver transplantation in children with other primary hepatic malignancies remains uncertain because experience is very limited. Liver transplantation is rarely needed in the management of children with benign liver tumours but, if other treatments have failed, it can be a life-saving intervention.

Histopathological features and clinical course of the gastrointestinal stromal tumors.

BACKGROUND/AIMS: C-kit expression is a sensitive marker for a specific group of mesenchymal tumors of the gastrointestinal tract, gastrointestinal stromal tumors, the histogenesis and prognosis of which are uncertain. METHODOLOGY: We have investigated the expression of c-kit by immunohistochemical analysis (APAAP method) in 12 out of 13 cases of mesenchymal gastrointestinal neoplasms operated from January 1991 to December 1998, in which the follow-up data were fully available. Furthermore, the c-kit expression was correlated both with the expression of vimentin, CD34 and the mitotic rate, and with the expression of muscle (muscle-specific actin-HHF35 and desmin) or neural (neuron-specific enolase) differentiation markers. RESULTS: C-kit was expressed in all 12 cases (100%). Two different patterns of expression were observed: cytoplasmic in 7 (58.3%) cases and nuclear in 3 (25%) cases; in 2 (16.7%) cases both cytoplasmic and nuclear immunostaining was detected. Three (60%) out of the five cases showing a nuclear c-kit expression were also neuron-specific enolase positive, whereas none of the cases showing an exclusively cytoplasmic c-kit expression was neuron-specific enolase positive. The correlation between the two patterns of c-kit expression and the follow-up data have shown a trend towards a better prognosis in gastrointestinal stromal tumors with a nuclear c-kit immunostaining and neuron-specific enolase positivity, but the relatively low number of cases does not allow us to draw conclusions. In gastrointestinal stromal tumors the mitotic rate (> 2 x 10 HPF vs. < 2 x 10 HPF) is related with statistically significant differences (P < 0.05) to the 5-year survival (0% vs. 80%, respectively). CONCLUSIONS: These findings, together with the already known c-kit nuclear immunostaining in normal adrenal medullary cells, suggest that a nuclear c-kit expression in gastrointestinal stromal tumors is consistent with a neural differentiation. In this study the mitotic rate has demonstrated a significant influence on the prognosis of gastrointestinal stromal tumors.

Metástasis musculares de miembros superiores e inferiores de adenocarcinoma gástrico de células en "anillo de sello" / Muscular metastases of the upper and lower limbs from gastric signet ring cell adenocarcinoma

Presentamos un caso de metástasis de adenocarcinoma gástrico de células en "anillo de sello" en la musculatura de los miembros inferiores y superiores (aductores, bíceps femoral, vasto interno izquierdo, obturador derecho, bíceps izquierdo y radiales derechos).Es un hecho infrecuente y su aparición puede ser explicada por fenómenos inmunológicos. Los síntomas y las exploraciones complementarias (RM) no son específicas, por tanto toda lesión de partes blandas en la evolución de un paciente intervenido de adenocarcinoma gástrico debe de ser biopsiada (AU)

[DNA flow cytometry in smooth muscle tumors of the gastrointestinal tract].

DNA ploidy of 45 smooth muscle tumors of the G.I. tract was determined by flow cytometry and correlated with clinical features and prognosis. The sites of the tumors were: esophagus (1), stomach (24), small intestine (12), large intestine (6), liver (1) and pancreas (1). The histologic type was leiomyoma in 14, leiomyosarcoma in 29, and leiomyoblastoma in 2. DNA aneuploidy was more frequent in leiomyosarcoma (17/29) than leiomyoma (5/14), but the difference was not statistically significant. One leiomyoblastoma was diploid and the other was aneuploid. No patients with leiomyoma died. In patients with leiomyosarcomas, 5-year survival was significantly poorer in those with aneuploid tumors (38%) than in those with diploid tumors (83%). There was no correlation between DNA ploidy and clinico-pathological features of tumors. The present study disclosed that DNA ploidy is a prognostic variable, independent of other variables.