Activity of anthracycline- and ifosfamide-based chemotherapy in a series of patients affected by advanced myxofibrosarcoma

Background

We report on the activity of anthracycline-based and high-dose prolonged-infusion ifosfamide chemotherapy in a retrospective series of patients affected by advanced myxofibrosarcoma treated at Istituto Nazionale Tumori in Milan, Italy, and within the Italian Rare Cancer Network (RTR).

Methods

Advanced myxofibrosarcoma patients treated with anthracycline + ifosfamide and high-dose prolonged-infusion ifosfamide as a single agent from November 2001 to December 2016 were retrospectively reviewed. All pathological diagnosis were centrally reviewed by at least two expert pathologists. Response was evaluated by RECIST, and survival functions were computed.

Results

Among 34 advanced myxofibrosarcoma patients, 13 were treated with front-line anthracycline + ifosfamide chemotherapy (male/female = 6/7, median age 54 years, range 33–72). Overall best response was: 4 partial responses, 3 stable diseases and 6 progressive diseases, with a median progression-free survival of 4 months. Twenty-eight patients received second/further line high-dose prolonged-infusion ifosfamide (male/female = 17/11, median age 55 years, range 27–75 years). We observed 10 partial responses, 4 stable diseases and 14 progressive diseases, with a median progression-free survival of 4 months. Median overall survival was 12 months.

Conclusions

This retrospective analysis suggests that the combination of anthracyclines and ifosfamide is active in myxofibrosarcoma. In patients already treated with a combination of anthracyclines and ifosfamide, high-dose prolonged-infusion ifosfamide showed activity as well.

     

Prosthetic infections following total knee arthroplasty: a six-year prospective study (1997–2002)

This paper reports on a prospective observational study that evaluated the frequency of prosthetic infections after total knee arthroplasty. During a six-year observational period, 171 patients underwent knee arthroplasty. Single shot prophylaxis with teicoplanin was administered to all patients. Nine patients (5.3%) had a followup of less than four weeks; the remaining 162 had a follow-up of at least 12 weeks. Of these, 155 completed the 24-month observational period. In the end, three patients developed early prosthetic joint infection which produced infection rates of 1.85% and 1.93% when the follow-up was ≥12 weeks and ≥24 months, respectively. The mean time from surgery to infection was 54 days (range, 14–87). All three infections were caused by Staphylococcus aureus susceptible to methicillin. Fever, pain, effusion and secretion were present in all cases. In this cohort of patients, no cases of delayed infection were observed. Thorough reporting is the first step in reducing the incidence of post-surgical infective complications and can contribute to more productive prophylactic protocols.     

Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy

Background:

Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients.

Methods:

EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model.

Results:

Increasing IL8^T1 level associated with lower response probability at covariance analysis (P=0.010). Both IL8^T0 (P=0.019) and IL8^T1 (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8^T1 best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8^T1 level<80 pg ml⁻¹ portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level⩾80.

Conclusion:

IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.     

Front‐line window therapy with cisplatin in patients with primary disseminated Ewing sarcoma: A study by the Associazione Italiana di Ematologia ed Oncologia Pediatrica and Italian Sarcoma Group

The aim was to assess the activity of cisplatin (CDDP) in Ewing sarcoma (ES). The study consisted of front‐line window therapy with CDDP 120 mg/sqm every 3 weeks for two courses in children and young adults with primary disseminated ES. Response was assessed using the Response Evaluation Criteria in Solid Tumours criteria, and Simon's two‐stage design was applied. Twelve consecutive patients were enrolled in stage 1. Only one objective response was observed. Since the target response rate was not achieved, accrual was stopped and CDDP as a single agent in ES was judged unworthy of further assessment.     

The symptom interval in children and adolescents with soft tissue sarcomas

BACKGROUND:

In a series of 575 patients ≤21 years of age with soft tissue sarcomas (STSs), the authors investigated the association patterns between symptom interval (ie, the period between the onset of the first symptoms or signs of the disease and its definitive diagnosis) and patient/tumor characteristics or disease outcome (in terms of survival).

METHODS:

The analysis was based on multivariate models (linear for associations with patient/tumor characteristics and Cox's for survival).

RESULTS:

The symptom interval ranged between 1 week and 60 months (median, 2 months) and tended to be longer the older the patient (ie, the interval was longer in adolescents than in children) and the larger the tumor's size, and for tumors located at the extremities and for nonrhabdomyosarcoma STSs (as opposed to rhabdomyosarcomas). A longer symptom interval unfavorably influenced survival (P = .002), which was also significantly affected by the patient's age and the size and surgical stage of the tumor. A different pattern of association between symptom interval and survival emerged for different types of STS histology.

CONCLUSIONS:

Our study points to an independent prognostic effect of symptom interval that cannot be explained by its associations with other factors, such as patient's age or the site, size, stage, and histology of the tumor. Future studies should focus more on the possible causes of symptom interval in pediatric STS populations to enable corrective measures to be implemented to reduce the diagnostic delay. Cancer 2010. © 2010 American Cancer Society.