Heather Magnan

Characteristic imaging features of desmoplastic small round cell tumour

BackgroundDesmoplastic small round cell tumour (DSRCT) is a rare malignant neoplasm. Its radiological features have rarely been described.ObjectiveTo assess the CT parameters characteristic of DSRCT. We also report our experience with combined FDG PET/CT in staging and follow–up for DSRCT.Materials and methodsThe pretreatment diagnostic CT’s of 65 patients with DSRCT were evaluated. Pertinent imaging findings were catalogued, with histopathology or serial follow-up studies as reference standard. Combined FDG PET/CT examinations of 11 of these patients who underwent pretreatment imaging were also reviewed.ResultsSixty-two patients presented with primary intra-abdominal disease; three had primary extra-abdominal tumours at presentation. The most common imaging finding of patients with intra-abdominal DSRCT was multiple peritoneal soft tissue masses, with a dominant mass in the retrovesical or rectouterine location in more than half of the cases. Forty percent had metastatic disease to the liver, lungs, spleen or bones at diagnosis. FDG PET/CT accurately detected 97.4% of all DSRCT lesions.ConclusionDSRCT typically presents as a large abdominopelvic mass with widespread peritoneal involvement predominantly in young males. Familiarity with its radiological features can help guide diagnosis and treatment. Functional imaging with PET/CT offers advantage over anatomical imaging for accurate disease staging.

20-Year Experience With Intraoperative High-Dose-Rate Brachytherapy for Pediatric Sarcoma: Outcomes, Toxicity, and Practice Recommendations

PURPOSE To assess outcomes and toxicity of high-dose-rate intraoperative radiation therapy (HDR-IORT) in the management of pediatric sarcoma. METHODS AND MATERIALS Seventy-five pediatric patients underwent HDR-IORT for sarcoma from May 1993 to November 2013. The median age was 9 years old (36 patients were ≤ 6 years old). HDR-IORT was part of initial therapy in 37 patients (49%) and for recurrent disease in 38 patients (51%). Forty-one patients (55%) received HDR-IORT and postoperative external beam RT (PORT), and 22 patients (29%) were previously treated with external beam radiation therapy to the IORT site. Local control (LC), overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier methods. RESULTS At a median follow-up of 7.8 years for surviving patients, 5-year projected rates of LC, EFS, and OS were 63% (95% confidence interval [CI] 50%-76%), 33% (95% CI 21%-45%), and 43% (95% CI 30%-55%), with a median survival of 3.1 years. The 5-year LC, EFS, and OS rates for patients with recurrent disease were 46% (95% CI, 28%-64%), 30% (95% CI, 13%-46%), and 36% (95% CI, 18%-54%). Acute toxicity ≥ grade 3 occurred in 2 (2.5%) treatments; late toxicity ≥ grade 3 occurred in 4 (5.3%) patients 0.3-9.9 years after HDR-IORT. The incidence of toxicity ≥ grade 3 was not associated with HDR-IORT applicator size, HDR-IORT dose, prior RT or PORT, or prior or postoperative chemotherapy, but all toxicity ≥ grade 3 occurred in patients ≤ 6 years treated with HDR-IORT doses ≥ 12 Gy. CONCLUSIONS HDR-IORT is a well-tolerated component of multimodality therapy for pediatric sarcoma, allowing additional local treatment while reducing external beam exposure. Taking clinical considerations into account, doses between 8-12 Gy are appropriate for HDR-IORT in patients ≤ 6 years of age.

Thrombolytic therapy is effective in paroxysmal nocturnal hemoglobinuria: a series of nine patients and a review of the literature

Background Thrombosis is the major risk factor for death in patients with paroxysmal nocturnal hemoglobinuria. Previous case reports indicate that venous thrombosis in patients with paroxysmal nocturnal hemoglobinuria is amenable to thrombolysis. Design and Methods We reviewed the outcome of thrombolytic therapy for patients with paroxysmal nocturnal hemoglobinuria who had thromboses refractory to anticoagulation at our institutions. Results In this study of 41 patients who had at least one thrombotic event, we confirmed a very high incidence of recurrence despite anticoagulation. Nine patients with thrombosis were regarded as eligible for administration of intravenous tissue plasminogen activator, which was effective in reversing thrombi in all of 15 occasions in which it was given. Serious hemorrhagic complications developed in three cases. At last follow-up visit, of the nine patients treated, three had died, and six were in very good to excellent condition in terms of clinical outcome and radiological findings. The only patient in whom thrombolysis may have contributed to a fatal outcome also had complications of “heparin induced thrombocytopenia with thrombosis”, which we diagnosed in three additional patients. In our review of the literature, nine out of 15 patients treated with thrombolysis have had a good outcome. Conclusions Although it is associated with a significant but manageable risk of bleeding, systemic thrombolysis is a highly effective treatment for reversing venous thromboses in patients with paroxysmal nocturnal hemoglobinuria.

Myeloablative chemotherapy with autologous stem cell transplant for desmoplastic small round cell tumor.

Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days) + thiotepa (300 mg/m2/day for 3 days) ± topotecan (2 mg/m2/day for 5 days). All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant). 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm.

Is Methylene Diphosphonate Bone Scan Necessary for Initial Staging of Ewing Sarcoma if 18F-FDG PET/CT Is Performed?

OBJECTIVE The purpose of this study was to determine whether methylene diphosphonate (MDP) bone scans are necessary during initial staging in patients with Ewing sarcoma (ES) in whom (18)F-FDG PET/CT is performed. MATERIALS AND METHODS A retrospective review was performed of patients who underwent FDG PET/CT and MDP bone scan before treatment of newly diagnosed ES from January 2004 to November 2012. Studies were reviewed to document suspected primary and metastatic malignancy. Pathology and imaging follow-up were used to determine the presence or absence of disease at suspected sites. RESULTS Sixty patients were identified in whom FDG PET/CT and MDP bone scans were performed before treatment of newly diagnosed ES. Forty-four primary malignancies had a lytic CT appearance, three were sclerotic, and 13 involved only soft tissue. In 11 of 12 patients with osseous metastases, these were detected on PET/CT, with the one false-negative occurring in a sclerotic primary tumor; in nine of 12 patients with osseous metastases, these were detected on MDP bone scan, with the three false-negatives occurring in patients with lytic primary tumors. Only one of 13 patients with a soft-tissue primary malignancy had bone metastases on both bone scan and PET/CT. PET/CT also showed that eight patients had lung metastases and three patients had lymph node metastases, which were not evident on MDP bone scan. CONCLUSION When ES is lytic, MDP bone scan does not add to staging performed by FDG PET/CT; thus, MDP bone scanning may be omitted. However, when ES is sclerotic, MDP bone scan may detect osseous metastases not detected by FDG PET/CT.

Desmoplastic small round cell tumor 20 years after its discovery.

Desmoplastic small round cell tumor (DSRCT) was proposed as a distinct disease entity by William L Gerald and Juan Rosai in 1991. Over 850 patients have been reported in the medical literature. A specific translocation, t(11;22)(p13;q12), is seen in almost all cases, juxtaposing the EWS gene to the WT1 tumor suppressor gene. DSRCT is composed of nests of small round cells with polyphenotypic differentiation, typically a mixture of epithelial, mesenchymal and neural features, surrounded by a prominent desmoplastic stroma. DSRCT has a predilection for adolescent and young adult males, and primarily involves the abdominal cavity and pelvis. Survival is low despite their initial response to multimodal treatment. Most patients relapse with disseminated disease that is unresponsive to further therapy.

Noninvasive imaging with thallium-201 scintigraphy may not correlate with survival in patients with osteosarcoma.

Histologic response to preoperative chemotherapy is a strong prognostic factor for osteosarcoma (OS). Thallium‐201 (Tl‐201) scintigraphic response to initial chemotherapy has previously been described as a predictor of histologic response. In the current study, the authors re‐examined a series of patients studied using Tl‐201 scintigraphy to determine the correlation between changes observed on Tl‐201 scintigraphy and event‐free survival (EFS).

Ifosfamide dose‐intensification for patients with metastatic Ewing sarcoma

Outcomes for patients with metastatic Ewing sarcoma (ES) remain poor. We investigated whether the intensification of ifosfamide improved survival for patients with metastatic ES.

Positron emission tomography for response assessment in desmoplastic small round cell tumor.

Background: Desmoplastic small round cell tumors (DSRCT) typically have a large stromal component and often are extensively disseminated in the peritoneal cavity at diagnosis. These factors contribute to difficulty in quantifying response to chemotherapy using RECIST or WHO criteria. This study compares the overall disease response to chemotherapy by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) in patients with DSRCT. Methods: We conducted a retrospective chart review of 7 patients with DSRCT who were imaged by FDG-PET and CT at diagnosis and after 3 cycles of chemotherapy. Response to chemotherapy was graded according to EORTC metabolic response guidelines and RECIST. Results: All tumors demonstrated some decrease in SUVmax (51%±21%) and longest diameter (23%±8%) with chemotherapy. The best response achieved by FDG-PET was a partial response in 6 patients and by CT was a partial response in 1 patient. Measured response was concordant between the 2 modalities in 2 patients. Conclusions: In this small series response measurement by FDG-PET did not always correlate with response measurement by CT. A greater decrease in metabolic activity as compared with size was seen in all patients. Further studies are needed to define the role of FDG-PET in assessing early response of DSRCT to chemotherapy.

Ewing sarcoma in adults treated with modern radiotherapy techniques.

BACKGROUND AND PURPOSE To evaluate local control and survival outcomes in adults with Ewing sarcoma (ES) treated with radiotherapy (RT). MATERIAL AND METHODS Retrospective review of all 109 patients age ⩾18 treated for ES with RT to the primary site at Memorial Sloan Kettering Cancer Center between 1990 and 2011. RT was used as the definitive local control modality in 44% of patients, preoperatively for 6%, and postoperatively for 50%. RESULTS Median age at diagnosis was 27years (range, 18-67). The 5-year local failure (LF) was 18%. Differences in LF were not identified when evaluated by modality of local control (RT versus combined surgery and RT), RT dose, fractionation, and RT technique. However, margin status at time of resection significantly predicted LF. The 5-year event-free survival and overall survival rates were 44% and 66% for patients with localized disease, compared with 16% and 26% for metastatic disease (p=0.0005 and 0.0002). Tumor size, histopathologic response to chemotherapy, and treatment on or according to a protocol were also significantly associated with survival. CONCLUSIONS This series of adults treated with modern chemotherapy and RT had prognostic factors and outcomes similar to adolescents with ES. All adults with ES should be treated with an aggressive, multidisciplinary approach.