Omar Al-Muderis

Significant clinical benefit of first-line palliative chemotherapy in advanced soft-tissue sarcoma - Retrospective analysis and identification of prognostic factors in 488 patients

The efficacy of palliative chemotherapy was investigated in a large group of patients with advanced soft‐tissue sarcomas (STS) treated on routine palliative protocols.

Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis

BACKGROUND Aggressive fibromatosis (AF) or desmoid tumour is a monoclonal proliferation which is locally invasive but does not metastasize. If local treatment fails to control the disease, systemic treatment with anti-oestrogens, non-steroidal anti-inflammatory drugs (NSAIDs) or chemotherapy can be used. Recent reports indicate that pegylated liposomal doxorubicin (PLD) is effective. METHODS Twelve patients with AF received PLD between February 2006 and May 2009. PLD was administered intravenously (iv) at 50mg/m(2) over 1h every 4 weeks. RESULTS The female/male ratio was 11:1 and median age at presentation was 29 years (range 3-53). Objective response (PR) was achieved in 4 (36%) of 11 patients. In one case ongoing shrinkage of the tumour was observed for over 12 months and partial remission was achieved at 14 months after the completion of treatment. Seven patients achieved stable disease. One patient is currently undergoing chemotherapy. Clinical benefit in terms of pain relief, improved mobility or cosmesis was observed in 11 patients. Nine patients (75%) had no evidence of progression at the end of this follow-up period and disease control has ranged from 7 to 39 months with a median of 14 months. The most severe toxicities observed were palmar-plantar erythema (4) and mucositis (3). In 6 cases (55%) toxicity resulted in dose reduction. CONCLUSION This is the largest series of patients with AF receiving PLD reported to date. PLD as a single agent therapy has acceptable toxicity and highly promising activity in unresectable AF and may provide long-term clinical benefit in some patients.

Radiofrequency ablation is a feasible therapeutic option in the multi modality management of sarcoma

The role of radiofrequency ablation (RFA) in metastatic sarcoma is not well defined. The aim of this study was to evaluate the efficacy and safety of RFA in a series of sarcoma patients. A retrospective search of a prospectively maintained database identified 13 gastrointestinal stromal tumour (GIST) patients and 12 with other histological subtypes treated with RFA. All the GIST patients received RFA for metastatic disease in the liver: 12 of these responded to the first RFA procedure and one achieved stable disease. Two GIST patients received RFA on two occasions to separate lesions within the liver and both responded to the second RFA procedure. Of the other subtypes: 7 underwent RFA to liver lesions, 5 of these responded to RFA, one progressed and 1 was not assessable for response at the time of analysis. All 5 patients with lung metastases achieved a response following their first RFA procedure. RFA was effective and well tolerated in this series of sarcoma patients. RFA may have a role in patients with GIST who have progression in a single metastasis but stable disease elsewhere. Further larger studies are required to better define the role of this technique in this patient population.

Advanced aggressive fibromatosis: Effective palliation with chemotherapy

Abstract Background. Aggressive fibromatosis (AF) is a locally invasive proliferative disease. The mainstay of treatment is surgery. Chemotherapy may be considered in inoperable AF following failure of hormonal therapy and/or NSAIDs. Material and methods. We conducted a retrospective search of the prospectively maintained Royal Marsden Hospital Sarcoma Unit database to identify patients with AF treated with chemotherapy between 1987 and 2009. Results. Thirty-nine patients, thirty one females and eight males, received one or more lines of chemotherapy. The most frequently employed chemotherapy regimens were methotrexate/vinblastine [MTX/VBL] (18) and pegylated liposomal doxorubicin [PLD] (14). MTX/VBL was administered weekly or every two weeks at MTX 50 mg and VBL 10 mg. Treatment duration ranged from three weeks to one year with a median of 4.5 months. Partial response (PR) was observed in 11% of cases, disease stabilisation (SD) in 60% and progressive disease (PD) in 22%. Time to progression ranged from one month to sixteen years. The main toxicities reported were mucositis (4), peripheral neuropathy (3), vomiting (3), and neutropenia (3). PLD was administered at 40–50 mg/m2 every four weeks, for up to six cycles. PR was achieved in 33% and in the remainder the disease was stable with no progression during treatment. Three (25%) patients have so far progressed after treatment. Symptomatic benefit, especially pain relief, was reported in 86% (12/14) of cases. Main toxicities included palmar plantar erythema (5) and mucositis (4). Discussion. MTX/VBL remains a useful combination but PLD is emerging as a well tolerated and effective systemic therapy in advanced AF.

Clinical Activity and Tolerability of a 14-Day Infusional Ifosfamide Schedule in Soft-Tissue Sarcoma

Background. Soft-tissue sarcomas (STS) are a heterogeneous group of diseases with lack of effective treatments in most cases. Previous data suggest that continuous infusional ifosfamide regimens might improve cytotoxicity and tolerability compared to standard schedules. Methods. We retrospectively report the outcome of 35 patients affected by STS treated with a 14-day infusional ifosfamide regimen (1000 mg/m2/day) in our institution. Predictive factors for toxicity were also explored. Results. Median age was 53 years. There were 16 males and 19 females. Classification by histology was dedifferentiated liposarcoma (DDLPS): 22 (62.8%), synovial sarcoma: 7 (20%), myxoid/round-cell liposarcoma: 3 (8.5%), and others: 3 (8.5%). Overall, 7 patients (20%) achieved partial response (PR) and 10 patients (29%) achieved stable disease (SD). DDLPS showed special sensitivity: 5 patients (22.7%) had PR, 7 patients (31.8%) had SD, and disease control rate was 54.5%. Median progression-free survival and overall survival were 4.2 and 11.2 months, respectively. The most common toxicities were fatigue, nausea, and vomiting (all grades: 85.7%, 83%, and 54.3%, resp.). Neither hypoalbuminaemia nor gender was found to predict toxicity, although encephalopathy predominantly affected females. Conclusion. Ifosfamide administered as a 14-day continuous infusion is a safe regimen in STS with notable activity in DDLPS.

Conventional anthracycline-based chemotherapy has limited efficacy in solitary fibrous tumour.

ferentiation from haemangiopericytomas. The two entities share many morphological and clinical similarities, so for years the terms SFT and haemangiopericytoma were used interchangeably. According to the WHO classifi cation [1], however, there are distinct histological characteristics for each subtype and they should no longer be considered part of the same spectrum. It is now acknowledged that in the majority of studies published to date tumours classifi ed as haemangiopericytoma were in fact SFT. To the Editor,

Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewings sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7%) achieved disease control. Median duration of response was 11 months (95% CI: 9–13). On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1%) patients who failed to respond to first-line therapy achieved disease control. Eight (2.1%) patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months). On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

Role of palliative chemotherapy in advanced epithelioid sarcoma.

BackgroundEpithelioid sarcoma is a rare soft tissue sarcoma subtype. The response of this disease to chemotherapy is not well described. The aim of this study was to investigate the response rate and progression-free survival in a series of epithelioid sarcoma patients treated with chemotherapy at a single referral center. MethodsA retrospective search of a prospectively maintained database was made to identify epithelioid sarcoma patients treated with chemotherapy between 1990 and 2009. Radiological response and histological diagnosis were re-reviewed for this study. ResultsTwenty-one epithelioid sarcoma patients treated with chemotherapy were identified; follow-up data on palliative chemotherapy was available on 20 of these patients. The median age was 36.5 years (range, 17.4 to 64.8 y) and the male/female ratio was 19:2. Ten patients (50%) were treated with single-agent anthracycline, 9 patients (45%) were treated with a combination therapy (anthracycline and ifosfamide), and 1 patient received trabectedin (5%). Three patients achieved a partial response, 12 had stable disease, and 5 progressed. The median progression-free survival was 29 weeks (95% confidence interval [CI]: 23-35). Seven and 3 patients received second-line and third-line palliative chemotherapy, respectively. The median overall survival from commencing palliative chemotherapy in our series was 51 weeks (95% confidence interval; 29-73). ConclusionsSystemic chemotherapy provides satisfactory palliation in patients with epithelioid sarcoma. However, this is an aggressive disease, responses to chemotherapy are of short duration and there is a need for more effective novel therapies in the treatment of this condition.

Angiosarcoma of the face and scalp: Effective systemic treatment in the older patient

BACKGROUND Angiosarcoma of the face and scalp, though rare, frequently affects older people and the prognosis is poor. Due to its rarity, optimal management of advanced disease with chemotherapy has been difficult to define. OBJECTIVE This is a retrospective review of patients treated at the Royal Marsden Hospital (RMH), looking at chemotherapy regimens, toxicity profile and treatment outcome in this elderly population over the last 20years. MATERIALS AND METHODS Detailed clinical-pathologic data were collected on patients treated for head and neck angiosarcoma at RMH between 1992 and 2011. RESULTS Thirteen patients (median age: 79years) were eligible for analysis. The majority (92.3%) received taxanes with a response rate of 83.3% and median progression-free survival (PFS) of 7months. Although the main toxicities were lethargy and peripheral neuropathy, a median number of 6 cycles of paclitaxel were administered. Doxorubicin was used in 57% of patients (median number of cycles: 3) with a response rate of 50% (median PFS: 3months). Cardiotoxicity occurred in 2 out of 7 cases and led to discontinuation of treatment. Overall, 57.1% of patients received chemotherapy at least 2 lines of chemotherapy. There were no deaths attributable to systemic treatment. CONCLUSIONS Advanced angiosarcoma of face and scalp can be controlled with multiple lines of chemotherapy, consisting primarily of taxanes as well as anthracyclines. Old age should not preclude systemic therapy although safety and quality of life issues deserve careful consideration.

Poor treatment outcomes with palliative gemcitabine and docetaxel chemotherapy in advanced and metastatic synovial sarcoma

The outcome for patients with unresectable or metastatic soft tissue sarcoma remains poor with few treatment options. Synovial sarcoma is a rare type of sarcoma, predominantly affecting adolescents and young adults. Following failure of first-line anthracycline-based chemotherapy, several salvage options are available. We reviewed the safety and efficacy of gemcitabine/docetaxel chemotherapy in two tertiary oncology centres. We identified patients treated with gemcitabine/docetaxel between 2004 and 2016 in a UK and a US oncology centre using retrospective pharmacy and medical records. Treatment response, toxicity and outcome data were collected. Twenty one patients were treated with gemcitabine/docetaxel, the majority as a second- or third-line treatment for metastatic disease. The response rate was 5% with a median progression-free survival of 2 months (95% CI 1.3–3.7). Toxicities reported were as expected for this chemotherapy combination. Treatment was not discontinued due to toxicity. Gemcitabine/docetaxel chemotherapy shows little efficacy in synovial sarcoma and should not be offered to this patient group outside a clinical trial context.