RAD51C and MYST3 Mutations in a Case of Desmoid-Type Fibromatosis With No Mutation in CTNNB1 or APC.

Most cases of desmoid-type fibromatosis (DTF) exhibit a mutation in APC or CTNNB1. We report a case of mesenteric DTF in which no mutation in APC or CTNNB1 was found, but a germline variant of uncertain significance (VUS) in RAD51C and a subclonal mutation in MYST3 were identified. Whether these genetic changes are important in DTF in this case, or whether genetically conventional DTF cells were present at a density below detection is unknown; it will be of interest to see results in further studies of wild-type APC/CTNNB1 cases.

Multifocal Desmoid-Type Fibromatosis: Case Series and Potential Relationship to Neuronal Spread.

Multifocal desmoid-type fibromatosis (DTF) is very rare and usually regional. We report three cases that initially appeared to be multifocal, but subsequent detailed imaging revealed unsuspected tracking along nerves in two cases. This neural spread is reminiscent of neuromuscular choristoma (NMC), a rare developmental lesion in which mature skeletal muscle cells, or rarely smooth muscle cells, infiltrate and enlarge peripheral nerves. NMC is frequently associated with DTF. These two cases suggest that DTF spread along nerves and appeared as distinct multifocal lesions while actually being contiguous. The third case was felt to represent true multifocal tumor development, possibly due to tumor seeding at the time of chest surgery. The relationship of DTF to NMC is discussed.

The Midwest Sarcoma Trials Partnership: Bridging Academic and Community Networks in a Collaborative Approach to Sarcoma.

The treatment of sarcoma necessitates a collaborative approach, given its rarity and complex management. At a single institution, multidisciplinary teams of specialists determine and execute treatment plans involving surgical, radiation, and medical management. Treatment guidelines for systemic therapies in advanced or nonresectable soft tissue sarcoma have advanced in recent years as new immunotherapies and targeted therapies become available. Collaboration between institutions is necessary to facilitate accrual to clinical trials. Here, we describe the success of the Midwest Sarcoma Trials Partnership (MWSTP) in creating a network encompassing large academic centers and local community sites. We propose a new model utilizing online platforms to expand the reach of clinical expertise for the treatment of advanced soft tissue sarcoma.

Patched Homolog 1 (PTCH1) Mutation in a CIC-Rearranged Sarcoma: Lack of Response to the Smoothened (SMO) Vismodegib.

Next-generation sequencing (NGS) to identify potential targets is becoming a common approach to refractory tumors. We describe a patient with a CIC-DUX4 sarcoma that harbored a patched homolog 1 (PTCH1) mutation, a mutation not previously reported in so-called Ewing family tumors. PTCH1 is part of the hedgehog signaling pathway. Basal cell carcinomas (BCC) commonly have PTCH1 mutations, and those with PTCH1 mutations are often responsive to therapy with the hedgehog pathway inhibitor vismodegib. The effect of any mutation in a gene important in cell growth and division is likely dependent upon the background biochemistry of the cell. In the current case, vismodegib was not effective. This case is the first report of a PTCH1 mutation in an Ewing family tumor and demonstrates that the utility of targeting a potential mutation may depend upon many factors, including other mutations in the signaling pathway, and importantly, also the background biochemistry of the malignant cell that may prevent effective treatment targeting.

Biclonal Desmoid-Type Fibromatosis With Two Beta-Catenin Mutations: Evidence for the Recruitment of Normal Myofibroblasts.

Sporadic aggressive fibromatosis, or desmoid-type fibromatosis, is characterized by oncogenic mutations in CTNNB1. The clonal cell is a myofibroblast-like cell, and it has been hypothesized that the recruitment of normal myofibroblasts could contribute significantly to the tumor. We describe a case in which a CTNNB1 p.T41A mutation was present at a mutant allele frequency of 30%, suggesting that a significant proportion of the tumor myofibroblasts may have been recruited from normal precursor pools. In addition, a small subclone with a p.S45F mutation (allele frequency of 2%) was identified in the tumor. This case provides additional evidence that myofibroblasts recruited by a tumor from a normal precursor pool contribute significantly to the tumor; such recruitment could impact response to treatment and long-term outcomes.

Prospective Trial of Neutrophil/Lymphocyte Ratio and Other Blood Counts as Biomarkers of Survival among Patients with High-Grade Soft Tissue Sarcomas Treated with Pegylated Liposomal Doxorubicin and Ifosfamide.

Several studies have reported an association between levels of circulating blood cells, in particular the neutrophil to lymphocyte ratio (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) and outcomes in patients with cancer. In the current study, the association between lymphocyte, neutrophil, monocyte, and platelet counts and survival was examined in a prospective trial of preoperative pegylated-liposomal doxorubicin and ifosfamide for high-grade soft-tissue sarcomas. A statistically significant association between overall survival, but not progression free-survival, was observed with the ANC/ALC ratio at a cutoff value of ≥2 and a statistically significant trend using a cutoff of ≥5. Our results suggest that a balance between the lymphocyte count and the number of circulating myeloid cells that can suppress lymphocyte function may be predictive of survival in patients with soft-tissue sarcomas. Future research should therefore examine the role of lymphocyte-myeloid cell balance in sarcoma biology.

Prospective Trial of Monocyte Count as a Biomarker of Hand-Foot Syndrome Among Patients With Soft Tissue Sarcomas Treated With Pegylated Liposomal Doxorubicin and Ifosfamide.

Pegylated liposomal doxorubicin (PLD) is widely used and can be used for prolonged periods, with the limiting toxicity usually being hand-foot syndrome (HFS). The pharmacokinetics of PLD is variable between patients, leading to variability in the risk of developing HFS. Dosing based on body surface area does not decrease variability in PLD clearance; thus, other predictive markers could be useful. The peripheral blood absolute monocyte count (AMC) has been suggested as a possible marker of both reticuloendothelial system function and PLD pharmacokinetics. The present study examined the AMC as a potential predictive biomarker in a prospective trial of pre-operative PLD combined with ifosfamide in soft tissue sarcomas (STSs). While our results suggest a relationship between pre-treatment AMC and PLD-induced HFS, the association did not reach statistical significance. The clinical utility of the AMC as a predictor of PLD-induced HFS appears limited, at least when given with ifosfamide.

Pregnancy outcomes related to the treatment of sarcomas with anthracyclines and/or ifosfamide during pregnancy.

BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas. PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples. RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 ± 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 ± 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016). CONCLUSION: In this multi-institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study.

A Novel Tongue-Based Tumor With an RREB1-MRTFB Fusion: Variant Rhabdomyosarcoma or Aggressive Variant of Ectomesenchymal Chondromyxoid Tumor.

The presence of a FOXO1 fusion in a tumor is one of the most important prognostic factors in rhabdomyosarcoma. Most histologically defined alveolar rhabdomyosarcomas bear a FOXO1 fusion. We discuss a case that was initially thought to be a rhabdomyosarcoma but was later discovered to have an RREB1-MRTFB fusion. This fusion has never been reported in rhabdomyosarcoma but typically characterizes ectomesenchymal chondromyxoid tumor (ECT), a neoplasm with typically rather benign behavior. In this article, the authors discussed whether this patient's aggressive presentation represents a variation of ECT or an unusual case of rhabdomyosarcoma.

Multiple malignant tumors in a patient with familial chordoma, a case report.

BACKGROUND: Chordoma is a rare bone tumor that is typically resistant to chemotherapy and is associated with genetic abnormalities of the T-box transcription factor T (TBXT) gene, which encodes the transcription factor brachyury. Brachyury is felt to be a major contributor to the development of chordomas. CASE PRESENTATION: We describe a 67-year-old woman who developed an undifferentiated pleomorphic sarcoma in her thigh. Despite treatment with standard chemotherapy regimens, she had a rapidly progressive course of disease with pulmonary metastases and passed away 8 months from diagnosis with pulmonary complications. Her medical history was remarkable in that she had a spheno-occipital chordoma at age 39 and later developed multiple other tumors throughout her life including Hodgkin lymphoma and squamous cell carcinoma and basal cell carcinoma of the skin. She had a family history of chordoma and her family underwent extensive genetic study in the past and were found to have a duplication of the TBXT gene. CONCLUSIONS: Brachyury has been found to associate with tumor progression, treatment resistance, and metastasis in various epithelial cancers, and it might play roles in tumorigenesis and aggressiveness in this patient with multiple rare tumors and germ line duplication of the TBXT gene. Targeting this molecule may be useful for some malignancies.

Primary angiosarcoma of the spleen, a rare indication for splenectomy: a case report.

INTRODUCTION AND IMPORTANCE: Primary angiosarcoma of the spleen is a rare condition with a nonspecific clinical presentation and is associated with a poor prognosis. We describe two patients with primary splenic angiosarcoma successfully treated with splenectomy and adjuvant chemotherapy. CASE PRESENTATIONS: Case 1: A 50-year-old female presented with fatigue and left-sided rib, shoulder, and abdominal pain. A CT scan demonstrated a large splenic mass, and biopsy was diagnostic of angiosarcoma. An open en bloc resection of the spleen was performed, and pathologic examination confirmed high-grade angiosarcoma; the surgical margins were negative. The patient received pegylated liposomal doxorubicin (PLD) and ifosfamide; she demonstrated no evidence of recurrence with four years of follow-up. Case 2: A 70-year-old male presented with acute back pain. A CT scan demonstrated a splenic mass; biopsy was diagnostic of angiosarcoma. The patient underwent open splenectomy, and pathology revealed high-grade angiosarcoma; the surgical margins were positive. The patient received PLD and ifosfamide but presented three years later with metastatic tumor to the spine. The patient had a favorable tumor response to pembrolizumab. The patient's tumor burden remains stable at 5 years following splenectomy. CLINICAL DISCUSSION: Angiosarcoma of the spleen is a rare clinical entity and is often challenging to diagnose early. Moratality is high, especially in the case of metastasis or spontaneous rupture. CONCLUSION: Due to the rare nature of this tumor, optimal treatment is not known. Here, we show excellent response in two patients to surgery combined with adjuvant therapy.

Pegylated liposomal doxorubicin-induced renal toxicity in retroperitoneal liposarcoma: a case report and literature review.

Doxorubicin is one of the most active drugs for sarcoma. Pegylated liposomal doxorubicin (PLD) is a unique formulation of doxorubicin, which carries a more favorable toxicity profile in comparison with free doxorubicin. The main toxicity of PLD is hand-foot syndrome. Unlike free doxorubicin, PLD is unlikely to cause alopecia, nausea, myelosuppression, or cardiotoxicity. Additionally, no premedications are required. We describe the case of a 50-year-old man with advanced retroperitoneal liposarcoma who developed irreversible PLD-associated progressive renal failure requiring chronic hemodialysis due to a thrombotic microangiopathy. No cardiotoxicity was noted 84 months after he initiated PLD. This case describes a lesser known toxicity of PLD and may be a toxicity of long-term treatment with other liposomal drugs.

Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum.

STUDY DESIGN: This was a subanalysis of an international, multicenter, open-label study. OBJECTIVE: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992). SUMMARY OF BACKGROUND DATA: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine). METHODS: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). RESULTS: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). CONCLUSION: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2.

Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4.

The formation of 3D multicellular spheroids in the ascites fluid of ovarian cancer patients is an understudied component of the disease progression. Spheroids are less sensitive to chemotherapy, in part due to the protection afforded by their structure, but also due to their slower proliferation rate. Previous studies suggest that the cell adhesion molecule Nectin-4 plays a key role in the formation of ovarian cancer spheroids. In this study, we further examined the role of Nectin-4 at early time points in spheroid formation using real-time digital photography. Human NIH:OVCAR5 ovarian cancer cells formed aggregates within 8 h, which further contracted into compact spheroids over 24 h. In contrast, Nectin-4 knockdown cells did not form tightly compacted spheroids. Synthetic peptides derived from Nectin-4 were tested for their ability to alter spheroid formation in two ovarian cancer cell lines. Nectin-4 peptide 10 (N4-P10) had an immediate effect on disrupting ovarian cancer spheroid formation, which continued for over 24 h, while a scrambled version of the peptide had no effect. N4-P10 inhibited spheroid formation in a concentration-dependent manner and was not cytotoxic; suggesting that N4-P10 treatment could maintain the cancer cells as single cells which may be more sensitive to chemotherapy.

A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas.

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two median prior therapies received checkpoint inhibitors. Treatments included pembrolizumab in 47, nivolumab in 6, ipilimumab in 1, combination ipilimumab/nivolumab in 27, and other combination immunotherapies in 7 patients. Immunotherapy was discontinued in 54 patients-72.2% for progression, 16.7% for toxicity, and 11.1% for other reasons. Median progression-free survival (PFS) was 4.1 months and median overall survival was 19.1 months. One patient with undifferentiated pleomorphic sarcoma (UPS) achieved a CR, while 20 patients had a PR, including 7 UPS, 9 leiomyosarcoma (LMS), and 1 each with alveolar soft part sarcoma, fibroblastic sarcoma, sclerosing epithelioid fibrosarcoma, and myxofibrosarcoma. Forty-five percent (9 of 20) of LMS patients achieved a PR. Twenty-eight patients had SD. Our results confirm the activity and safety of anti-PD-1 therapy in metastatic STS. A notable response rate was observed in UPS and LMS subtypes. This study expands the knowledge base beyond what is currently available from clinical trials involving checkpoint inhibitors in metastatic STS.

Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

BACKGROUND: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB. METHODS: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, number NCT00680992, and has been completed. FINDINGS: Between Sept 9, 2008, and Feb 25, 2016, 532 patients were enrolled: 267 in cohort 1, 253 in cohort 2, and 12 in cohort 3. At data cutoff on Feb 24, 2017, median follow-up was 58·1 months (IQR 34·0-74·4) in the overall patient population, and 65·8 months (40·9-82·4) in cohort 1, 53·4 months (28·2-64·1) in cohort 2, and 76·4 months (61·2-76·5) in cohort 3. During the treatment phase, the most common grade 3 or worse adverse events were hypophosphataemia (24 [5%] of 526 patients), osteonecrosis of the jaw (17 [3%], pain in extremity (12 [2%]), and anaemia (11 [2%]). Serious adverse events were reported in 138 (26%) of 526 patients; the most common were osteonecrosis of the jaw (17 [3%]), anaemia (6 [1%]), bone giant cell tumour (6 [1%]), and back pain (5 [1%]). 28 (5%) patients had positively adjudicated osteonecrosis of the jaw, four (1%) had atypical femur fracture, and four (1%) had hypercalcaemia occurring 30 days after denosumab discontinuation. There were four cases (1%) of sarcomatous transformation, consistent with historical data. Ten (2%) treatment-emergent deaths occurred (two of which were considered treatment-related; bone sarcoma in cohort 2 and sarcoma in cohort 1). Median time to progression or recurrence for patients in cohort 1 during the first treatment phase was not reached (28 [11%] of 262 patients had progression or recurrence). 227 (92%; 95% CI 87-95) of 248 patients who received at least one dose of denosumab in cohort 2 had no surgery in the first 6 months of the study. INTERPRETATION: The types and frequencies of adverse events were consistent with the known safety profile of denosumab, which showed long-term disease control for patients with GCTB with unresectable and resectable tumours. Our results suggest that the overall risk to benefit ratio for denosumab treatment in patients with GCTB remains favourable. FUNDING: Amgen.

Development of cutaneous squamous cell carcinoma after prolonged exposure to pegylated liposomal doxorubicin and hand-foot syndrome: a newly recognized toxicity.

Pegylated liposomal doxorubicin (PLD) can be administered for prolonged periods with minimal toxicity. The risk of cutaneous squamous cell carcinoma (SCC) with this therapy has not been reported. We describe cutaneous SCC of the plantar foot in two patients exposed to high doses of PLD. A 50-year-old man with angiosarcoma received a total PLD dose of 1350 mg/m2 and developed cutaneous SCC of bilateral plantar feet. A 45-year-old woman with cutaneous T-cell lymphoma was treated with a total PLD dose of 1142 mg/m2 with subsequent diagnosis of cutaneous SCC of the right plantar foot. No risk factors for SCC of the plantar foot were identified in either patient. Cutaneous SCC is likely an unreported side effect of prolonged exposure to PLD. An extended duration of hand-foot syndrome from other anti-cancer drugs may also share this risk. Regular complete skin examination with early intervention for suspicious lesions is indicated in this patient population.

Cardiotoxicity Monitoring in Patients Treated with Tyrosine Kinase Inhibitors.

Tyrosine kinase inhibitors (TKIs) can cause cardiotoxicity, and some suggest routine monitoring of cardiac function during TKI use. We describe two cases of TKI-induced heart failure (HF) that suggest the utility of monitoring with laboratory tests is questionable. One patient developed HF 5 days after starting pazopanib. The other developed HF while receiving 25 mg per day sunitinib, and had previously received a higher dose (50 mg per day) with no symptoms of cardiotoxicy. In addition, she later received 5 cycles of sunitinib (25 mg per day) without developing an abnormal left ventricular ejection fraction (LVEF) value by echocardiography or cardiac symptoms. Although the LVEF is commonly performed to monitor TKI cardiotoxicity, evidence for its predictive utility is limited. These cases raise questions regarding the practical utility of sequential measurement of LVEF in adults treated with TKIs. We suggest a simple daily activity such as stair climbing to monitor exercise tolerance.

Effect of chemotherapy on cancer stem cells and tumor-associated macrophages in a prospective study of preoperative chemotherapy in soft tissue sarcoma.

BACKGROUND: Cancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells. METHODS: This study examined the expression of the putative cancer stem cell markers ALDH1, CD44, and CD133; the angiogenesis marker CD31; and the macrophage marker CD68 in soft tissue sarcomas (STS) before and after 4 cycles of chemotherapy with doxorubicin and ifosfamide in 31 patients with high-grade soft tissue sarcoma in a prospective clinical trial. RESULTS: None of the markers clearly identified CSCs in STS samples. Macrophages represented a prominent component in viable tumor areas in pre-treatment STS biopsies, ranging from < 5 to > 50%. Furthermore, macrophages expressed CD44 and ALDH1. Macrophage density correlated with baseline maximum standardized uptake value (SUVmax) on fluoro-deoxyglucose positron emission tomography (PET) imaging. Pre-chemotherapy CD68 staining correlated positively with the baseline SUVmax, and negatively with the percent of viable tumor cells in post-chemotherapy resection samples. In particular, cases with more CD68-positive cells at biopsy had fewer viable tumor cells at resection, suggesting a better response to chemotherapy. CONCLUSIONS: In conclusion, ALDH1, CD44, and CD133 are not likely to be useful markers of CSCs in STS. However, our observation of infiltrating macrophages in STS specimens indicates that these immune cells may contribute significantly to STS biology and response to chemotherapy, and could provide a potential target of therapy. Future studies should investigate macrophage contribution to STS pathophysiology by cytokine signaling.

Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure.

BACKGROUND: Doxorubicin is one of the most active drugs available for the treatment of sarcoma. Pegylated-liposomal doxorubicin (PLD) is a formulation of doxorubicin in which the doxorubicin is encapsulated in liposomes coated with methoxypoly (ethylene glycol); this formulation results in decreased uptake by the reticuloendothelial system, higher concentrations of drug in tumor, and less toxicity, including reduced cardiotoxicity, nausea, alopecia, and myelosuppression. No premedication is necessary. While PLD has a better toxicity profile than free doxorubicin, there is no consensus on the relative efficacy of PLD and free doxorubicin in sarcoma. CASE PRESENTATION: In this report, we describe a patient with high-grade metastatic soft tissue sarcoma with rapid recurrence after adjuvant treatment with free doxorubicin, cisplatin, ifosfamide, and dacarbazine. Second-line treatment with PLD resulted in long-term disease remission during a 20-year follow-up period. Mucositis and hand-foot syndrome were controlled by adjustment of dose and treatment interval. CONCLUSIONS: This case illustrates the curative potential of PLD after failure of free doxorubicin and the absence of long term cardiotoxicity with PLD. As with all drugs, individual adjustment of dose and treatment interval is important.