Spinal intradural extraosseous Ewing's sarcoma

Extraosseous Ewing's sarcoma (EES) involving the central nervous system is rare, but can be diagnosed and distinguished from other primitive neuroectodermal tumors (PNET) by identification of the chromosomal translocation (11;22)(q24;q12). We report EES arising from the spinal intradural extramedullary space, based on imaging, histopathological, and molecular data in two men, ages 50 and 60 years old and a review of the literature using PubMed (1970–2009). Reverse transcriptase polymerase chain reaction (RT-PCR) identified the fusion product FL1-EWS. Multimodal therapy, including radiation and alternating chemotherapy including vincristine, cyclophosphamide, doxorubicin and ifosfamide and etoposide led to local tumor control and an initial, favorable therapeutic response. No systemic involvement was seen from the time of diagnosis to the time of last follow-up (26 months) or death (4 years). This report confirms that EES is not confined to the earliest decades of life, and like its rare occurrence as an extra-axial meningeal based mass intracranially, can occasionally present as an intradural mass in the spinal canal without evidence of systemic tumor. Gross total resection followed by multimodal therapy may provide for extended progression free and overall survival

ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases

The increasing incidence of breast cancer brain metastases is a major clinical problem with its associated poor prognosis and limited treatment options. The long-acting topoisomerase-1 inhibitor, etirinotecan pegol, was designed to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Motivated by improved survival findings from subgroup analyses from the Phase III BEACON trial, this ongoing randomized, Phase III trial compares etirinotecan pegol to drugs commonly used for advanced breast cancer in patients with stable, treated breast cancer brain metastases who have been previously treated with an anthracycline, taxane and capecitabine. The primary end point is overall survival. Secondary end points include objective response rate, progression-free survival and time to CNS disease progression or recurrence in patients with/without CNS lesions present at study entry. Trial registration number: NCT02915744

Abstract P4-11-21: Dosimetric Comparison of Radiotherapy for Left Sided Breast Cancer: Breath-Hold Versus Free-Breathing

Abstract Background: Radiotherapy for left sided breast cancer potentially increases risk for late toxicity to the heart. The simple technique of breath-hold (BH) can be instituted in an attempt to reduce volume of lung and heart irradiated in tangential fields. We report on patients with left sided breast cancer that were planned both with conventional free-breathing (FB) and BH radiation techniques from a single institution. Methods: From 10/2006 to 5/2010, 20 patients with node-negative, early stage breast cancer underwent CT simulation for left sided breast cancer and were selected for analysis in this report. FB and BH CT scans were obtained and treatment plans using opposed tangential fields were created to compare various dosimetric indices. Results: BH plans resulted in lower doses to the heart (max dose 1774 vs. 4560cGy, P&amp;lt;0.0001; mean dose 175 vs. 296cGy, p=0.0178; V25 0 vs. 1.85%, P&amp;lt;0.0001; volume in tangential field 0 vs. 10.11cc p=0.0002) compared to FB. The ipsilateral lung received lower doses but a larger volume of lung was encompassed in the tangential fields (V20 13.32 vs. 20.32%, P&amp;lt;0.0001; mean dose 741 vs. 1025cGy, p=0.0003; volume in tangential field 198.8 vs. 256.8cc P&amp;lt;0.0001) compared to FB. Conclusions: Treatment of early stage left sided breast cancer with BH technique is a simple method for minimizing cardiac and ipsilateral lung dose. Long term follow-up is necessary to demonstrate if these dosimetric differences translate into clinically meaningful differences. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-21.</jats:p

Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer.

Unresectable chest wall recurrences of breast cancer (CWR) in heavily pretreated patients are especially difficult to treat. We hypothesised that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD), given with mild local hy

Abstract P4-15-05: Novel targeted therapy for breast cancer chest wall recurrence: Low temperature liposomal doxorubicin and mild local hyperthermia

Abstract Background: Unresectable breast cancer chest wall recurrence (CWR) following radiation is very difficult to treat and often responds poorly to standard chemotherapy. Symptoms include pain, reduced range of motion, disfigurement, and skin erosions with bleeding and infection. We hypothesized that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD, ThermoDox®), given with mild local hyperthermia (MLHT) would be a safe and effective targeted therapy. LTLD is given by iv infusion; it then localizes in CWR tumors due to their leaky vasculature. When heated to ≥ 39.5°C, LTLD releases a high concentration of the heat-enhanced cytotoxic doxorubicin. Methods: The results of 2 similarly-designed independent phase I trials were combined for analysis. Eligible patients had CWR progressing after radiation, hormone therapy, and chemotherapy. Subjects were to get up to 6 cycles of LTLD every 21-35 days, followed immediately by chest wall MLHT for 1 hour at 40°- 42°C. In Trial A, 18 subjects received LTLD at 20, 30, or 40 mg/m2; in Trial B, 11 subjects received LTLD at 40 or 50 mg/m2. The primary endpoint of each trial was to determine the maximum tolerated dose (MTD); secondary endpoints were local objective response and the pharmacokinetic (PK) and safety profiles of LTLD. Local response was assessed by serial photography and measurements of CWR. PK samples for total plasma doxorubicin and doxorubicinol were collected at Cycle 1 and Cycle 2 for both trials. Results: Twenty-nine subjects were enrolled and received ≥ 1 cycle (median 4, range 1-6). Median age was 57; 16 (55%) had triple negative disease and 13 (45%) had distant metastases. The median prior exposure to anthracylines was 256 mg/m2 and the median prior dose of radiation was 6,100 cGy. Thirteen subjects were evaluable for MTD in Trial A and 9 in Trial B. Trial B established a phase II dose of 50 mg/m2 recommended by a Data Safety Monitor Board, based on 1 of 6 subjects at the 50 mg/m2 dose level having a DLT (grade 3 hypokalaemia unrelated to study treatment). In Trial A, 2 of 7 subjects at 40 mg/m2 had a DLT (grade 4 neutropenia lasting &amp;gt; 5 days; grade 3 dehydration lasting 27 days). The Cmax concentrations between 18,400 to 20,700 ng/mL were consistent at an equal dose level (40 mg/m2) between trials. Altogether, 7 (24%) subjects developed reversible grade 3-4 neutropenia and 4 (14%) reversible grade 3-4 leukopenia. No cardiac toxicity or hand-foot syndrome was seen. One case of CW thermal burn (grade 3) and one case of radiation recall (grade 2) were reported. Five (17%) complete local responses and 9 (31%) partial local responses were seen. The rate of local response was 48% (14/29; 95% CI: 30%-66%). Seven of 29 subjects (24%) progressed outside the study treatment field. Conclusion: LTLD plus MLHT is a novel therapy that is safe and produces objective responses in heavily pretreated CWR patients with limited therapeutic options. The primary toxicity is reversible bone marrow suppression. A phase II trial is ongoing at the MTD (50 mg/m2). Future work should test thermally enhanced LTLD delivery in a less advanced, less heavily pretreated patient population. *Author note-M.W.D. and K.L.B. equally contributed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-15-05.</jats:p