G. Bertola

Preoperative chemo-radiation therapy for localised retroperitoneal sarcoma: A phase I-II study from the Italian Sarcoma Group

BACKGROUND To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS). METHODS Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC_∗II_2004_003. FINDINGS Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120 mm (interquartile (IQ) range=82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06). INTERPRETATION The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone. FUNDING This is a pure academic trial. No funding sources contributed to it.

Metastatic angiosarcoma of the spleen. A case report and treatment approach

We report a case of a 28-year-old man with angiosarcoma of the spleen and liver metastases. The aim of this paper is to underline the importance of planned splenectomy in these patients even if they have metastatic disease, and to propose an intensive chemotherapy regimen consisting of anthracyclines, ifosfamide and mesna with G-CSF support.

Improved outcome with multimodal treatment and imatinib rechallenge in advanced GIST

Dear Editor: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the digestive tract. Surgery and imatinib are the recommended treatments for advanced highrisk GIST. However, even in most patients showing an initial response, imatinib resistance is developed within a few years. After progression, current therapeutic options include the switch to other tyrosine kinase inhibitors (TKI) or surgical debulking. We here report long-term survival in a metastatic GIST patient treated with reiterated multimodal therapeutic approaches and as a fourth-line treatment, imatinib rechallenge. Molecular analysis of the tumors provided a framework for interpretation of the pattern of response observed. A 52-year-old man was referred to surgical intervention for an abdominal mass in January 2003. Surgery revealed a major (15 cm) intestinal tumor, together with other smaller peritoneal nodules, which were also resected. At pathological evaluation, the lesions displayed a spindle cell morphology, were CD117 (KIT) positive, CD34 positive, desmin negative, focally positive for smooth muscle actin and S100, and negative for cytokeratins, consistent with a diagnosis of metastatic, high-risk GIST. Six months later, the patient relapsed and underwent a II surgery with complete resection (R0) of a mass of 12 cm at the right iliac fossa, pathologically confirmed as GIST. Adjuvant imatinib (400 mg/day) was administered for 24 months, without evidence of recurrence. Eight months after imatinib discontinuation, a CT scan revealed a mass of 6 cm at the right iliac fossa and multiple peritoneal nodules without clinical symptoms. Imatinib was therefore resumed at the same dose. Radiological assessment showed an initial response, but 14 months later, disease progression was observed. Patient then underwent curative III surgery (R0) for a major mass (8 cm) proximal to the rectum and multiple peritoneal and omental nodules of smaller size. After surgery, imatinib was continued at 400 mg/day until, 8 months later, disease recurrence was documented by CT scan with a larger pararectal mass and multiple small peritoneal nodules. Patient was again subjected to tumor debulking (IV surgery) with microscopic residual disease (R=1). Patient resumed imatinib at a higher dose (800 mg/day). Due to disease progression, after 3 months, he was switched to sunitinib (50 mg/day), reducing the dosage (37.5 mg/day) after the first cycle because of poor tolerance. Treatment was continued for 15 months until pelvic progression was detected. For his third line treatment, the patient was enrolled in a clinical trial evaluating nilotinib efficacy in patients with unresectable/metastatic GIST and refractory to imatinib and/ or sunitinib. Nilotinib was given at 800 mg/day for 2 months, until CT scan showed abdominal progression. Surgical Gianmaria Miolo and Elena Torrisi contributed equally to this work.

Primary extragenital endometrial stromal sarcoma of the lung: First reported case and review of literature

BackgroundEndometrial stromal sarcomas arising in extrauterine and extraovarian sites, in the absence of a primary uterine lesion are quite rare, especially in the absence of endometriosis. They usually present as an abdominal or pelvic mass lesion.Case presentationIn 2007, a 45-year-old woman underwent total hysterectomy for in situ squamous cell carcinoma of the cervix. In 2014, an upper left pulmonary lobectomy was performed for a mass, which was provisionally diagnosed as primary carcinosarcoma of the lung. A second histological revision of the lung surgical specimen was performed in the Pathology Unit of our Institute. After extensive immunohistochemical analyses, the preferred diagnosis was spindle-cell sarcoma, consistent with high-grade extragenital endometrial stromal sarcoma (EESS). A review of all slides of the hysterectomy specimen confirms the original diagnosis: no evidence of stromal tumor was found. Afterwards, the patient developed multiple and metachronous pulmonary lesions and a scapular soft tissue mass, which showed the same morphophenotypic features of the first lung mass. The patient was treated with antiblastic therapy, surgical resection and radioablation, when appropriate. To date, the patient has no signs or symptoms.ConclusionsThe authors present the first case of primary EESS arising in the lung with no association with endometriosis published to date. Detailed clinical history and follow-up are also described. Moreover, extensive literature review is reported, along with differential diagnoses, immunohistochemical and molecular findings, pathogenetic hypotheses and treatment options. The knowledge of EESS potential extrauterine location and of its peculiar morphophenotypic aspects are required for a correct diagnosis, and for choosing the most suitable treatment.

OC-0521: IORT after gross total resection combined with EBRT in extremity soft tissue sarcoma: a pooled analysis

treatment thereafter, their prognosis has been improving. We analyzed the results of our 18-year experience. Materials and Methods: Between 1993 and April 2011 48 patients (68 times) were treated. Their age ranged from 46 to 86 with a median of 64. There were 20 male patients and 28 females. Seventeen patients were unable to walk before IORT, while the remaining 31 were ambulant. IORT was given with proper energy electron beam from posteriorly shielding the spinal cord with lead of proper thickness. The doses of IORT ranged from 16Gy to 26Gy with a median of 20Gy. Ten patients received IORT more than once (2 to 6 times). External beam radiation therapy was administered in 29 patients, of which 1 received preoperatively (24Gy), 20 received postoperatively (20~40Gy, median 35.5Gy). All patients received thyroid stimulating hormone suppression therapy. Radioactive iodines (Iodine-131) were administered in 29 patients. Median follow-up period was 33 months. Results: Among 17 patients who had been unable to walk 15 became able to walk following IORT, while the remaining 2 died soon after the treatment (response: not evaluable). Overall median survival time of overall patients was 38 months. Threeand 5-year overall survival rates were 51% and 33%, respectively. Symptomatic recurrence was observed in 6 cases (14%). Conclusions: Well-differentiated thyroid cancer patients carried quite favorable prognoses considering their status prior to IORT. From our experience, aggressive treatment was justified since more than half of the patients survived 3 years and about one third of the patients survived 5 years. Furthermore, only small portion of the patients suffered from symptomatic recurrence. Our methods were very promising both for quantity and quality of life in the treatment of spinal metastases from well-differentiated thyroid cancer.

Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer: 10-years median follow-up

Highlights • We report the long-term results of addiction of gefitinib to preoperative chemoradiotherapy in locally advanced rectal cancer.• We wanted to see if the hight rate of pCR, already shown in previous studies, influenced survival outcomes.• The first promising results have not been confirmed by a significant improvement in outcomes.

OC-0540: IOERT after gross total resection combined with EBRT in extremity sarcoma: a pooled analysis

ESTRO 35 2016 _____________________________________________________________________________________________________ Material and Methods: Using the National Cancer Data Base, we identified stage II seminoma patients treated with orchiectomy and either RT or MACT diagnosed from 19982012. Separately for stage IIA and IIB, factors affecting treatment modality (RT vs. MACT) were studied using a parsimonious multivariable logistic regression model. Propensity scores for treatment decision were incorporated into a multivariable Cox regression analysis of overall survival.