Annual Meeting Proceedings Part 1 - American Society of Clinical ...

650s Sarcoma
10080 General Poster Session (Board #52A), Sun, 8:00 AM-12:00 PM
Results of pulmonary metastasectomy for osteosarcoma in the pediatric
age group. Presenting Author: Bassam Redwan, Division of Thoracic
Surgery, University Hospital of Muenster, Muenster, Germany
Background: Despite multimodal treatment concepts and complete surgical
resection, prognosis in pediatric patients with pulmonary metastases from
osteosarcoma has remained limited due to frequent relapse of disease. We
investigated the results of an aggressive surgical approach. Methods: In a
retrospective study, procedures and outcomes of pulmonary metastasectomy
in the pediatric age group (up to 18 years) at our institution were
analyzed over a period of 10 years (1999-2009). Resection of the primary
osteogenic tumor and chemotherapy (CROSS-96-protocol and EURAMOS-
1-protocol) were performed prior to thoracic surgery. Results: Forty-five
pediatric patients (20 females) underwent pulmonary metastasectomies
via sternotomy or sequential anterolateral thoracotomy at a mean age of 14
(6 -18) years. At primary surgery, a mean number of 7.9 (1 – 53) palpable
suspicious lesions were resected per patient. Histo-pathological evaluation
revealed 3.7 (0 – 40) metastases per patient. Mean total duration of surgery
was 152 (46–323) minutes. Mean hospital stay was 10 days (3 – 33).
In-hospital and 30-day mortality was 0%. The overall survival at 1 and 5
years was 97.8% and 77.3%, respectively. Mean disease-free-survival was
12.2 (3.2-38.0) months. In 19 (42.2 %) patients recurrent pulmonary
metastases were detected and re-thoracotomies were required. Up to 7
procedures per patient were performed. Overall survival for patients
undergoing more than one surgical procedure for recurrent lung metastases
was not statistically different from survival in patients without relapse (p �
0.05). Survival was significantly better in patients initially presenting with
less than 10 metastases (85.3 % vs. 54.1 % at 5 years, p � 0.028).
Conclusions: Complete pulmonary metastasectomies are essential in pediatric
osteosarcoma patients with lung metastasis. Repeated resections for
recurrent relapses improve survival and may allow for long-term event-freesurvival.
10082 General Poster Session (Board #52C), Sun, 8:00 AM-12:00 PM
Multimodality treatment of pediatric and adult patients with Ewing sarcoma:
A single-institution experience. Presenting Author: David Lorente,
Medical Oncology Department, Valencia, Spain
Background: Treatment of Ewing sarcoma pts. usually follows pediatric
protocols, both in children and in adults. However, older patients fare
poorly in most series. We analyze our experience with the 2001 protocol of
the Spanish Society of Pediatric Oncology. Methods: Retrospective analysis.
Schema: 6 cycles (cy) of VIDE chemotherapy (CT: vincristine, ifosfamide,
etoposide, doxorrubicin). If no progression, local treatment (surgery
or RT) and consolidation adjusted to risk: VACx8 (vincristine, dactinomycin,
ciclophosphamyde) in standard-risk pts; if increased risk (axial,
complete response in lung metastases or non-pulmonary metastases)
VACx1, high-dose CT (busulphan-melphalan) and autologous transplant
(ATSP). Analysis: induction CT toxicity, pathological response rates,
consolidation treatment, disease-free (DFS) and overall survival (OS)
(Kaplan- Meier). Log-rank and Cox regression analysis of prognostic factors
in OS. Results: 35 patients (01.2003-05.2011). 60% male. Median age
16 y (r 7-57). Axial (43%), extremities (34%), extra-osseous (18%) and
ribs (9%). Metastases: 54% (lung 58%, bone 26%, others 12%). � 1
location: 29%. Induction CT: 83% received 6 cy. 6% early progressions
and 3% toxic deaths. 196 cycles of CT. Dose reduction (etoposide) in 60%.
Grade 3-4 toxicity: neutropenia 13%, anemia 14%, neutropenic fever
13%, diarrhoea-stomatitis 7%.Local treatment: surgery (49%), radiotherapy
(29%), none (22%). In 17 resections, � 90% necrosis in 53%.
Consolidation: VACx8 29%; VACx1-ATSP in 34%; 37% other treatments
(progression). No ATSP-related mortality. Median follow-up: 36 m ( 5-101
m). Median DFS 25 m (16-34 m). Median OS 28 m (15-41 m), 3-year OS
40%. Median time to progression 7 m (0.4-15 m). Median OS from
progression 7 m (0.4-15 m). Age � 15 years, a non-axial primary and no
extra-pulmonary metastases were favourable prognostic factors in the
univariate analysis. Conclusions: Induction CT with the VIDE regimen is
feasible in most patients, with a low risk of early progression. Hematological
toxicity is substantial but manageable. Adults patients have a worse
prognosis compared to pediatric patients. Unfortunately, survival after
progression is dismal.
10081 General Poster Session (Board #52B), Sun, 8:00 AM-12:00 PM
EURAMOS-1 study: Recruitment, characteristics, and initial treatment of
more than 2,000 patients (pts) with high-grade osteosarcoma. Presenting
Author: Jeremy Whelan, University College Hospital, London, United
Kingdom
Background: EURAMOS is a transAtlantic collaboration formed to improve
survival in osteosarcoma by conducting RCTs in a clinically relevant
timeframe. EURAMOS-1, the largest study conducted in this rare cancer,
has completed accrual. It includes two randomized comparisons investigating
treatment optimization on the basis of histological response to
neoadjuvant chemotherapy. Methods: Pts �40yrs with resectable, high
grade extremity or axial osteosarcoma were eligible for registration. All were
planned for 2 cycles of neoadjuvant methotrexate, doxorubicin, cisplatin
(MAP) then surgical resection of the primary tumour. Pts with complete
macroscopic resection and no disease progression were eligible for randomization:
[i] “good responders”, �10% viable tumor, MAP �/- 18m
maintenance pegylated interferon; [ii] “poor responders”, �10% viable
tumor, MAP vs MAPIE (MAP � ifosfamide, etoposide). Target sample size
was ~1,260 pts randomized requiring ~2000 pts registered estimating a
non-randomization rate of 30-35%. Results: From Apr 2005 to Dec 2011,
2,260 pts were registered and 1,332 randomized from 17 countries, 320
sites: median age 14yrs (IQR 11-17); 59% male; 50% femoral site; 23%
definite/possible metastases; 92% conventional osteosarcoma (diagnostic
biopsy). At Sep 2011 planned IDMC review, neoadjuvant treatment data
were known for 2024 pts; 1926 (95%) completed 2 cycles pre-operative
MAP with 3 treatment related deaths. 59% pts were randomized; nonconsent
was the most frequent reason for non-randomization. Relative to
expected age-specific incidence (UK NCIN 1979-2007) there was apparent
under recruiting of older pts: females �15yrs and all pts �19yrs, with
greater under recruitment of females than males �35yrs. Pts 20-29yrs
were less likely to be randomized than those aged 5-19 and �30 yrs, 52%
vs 57-62%. Conclusions: EURAMOS-1 demonstrates that large RCTs are
feasible in rare cancers with inter-continental collaboration and is a model
for future trials. Neoadjuvant MAP was safe in a geographically diverse
cohort. Improving clinical trial access and randomization rates for young
people is still required. Multiple funders detailed at bit.ly/ymUR9w.
10083 General Poster Session (Board #52D), Sun, 8:00 AM-12:00 PM
A retrospective safety analysis of adult patients treated with high-dose
methotrexate for osteosarcoma in Stockholm, Sweden. Presenting Author:
Daniel Alm, Oncology, Stockholm, Sweden
Background: Patients with osteosarcoma are routinely treated with pre- and
post-operative chemotherapy that includes high-dose methotrexate. The
treatment is associated with a risk of severe renal and hepatic toxicity.
Methods: All patients with osteosarcoma that had received at least one cycle
of high-dose methotrexate at the adult oncology department, Karolinska
University Hospital were retrospectively identified. Treatment toxicity,
including hematologic, renal, hepatic toxicity, infections and oral mucositis
were registered and graded according to CTCAE v 4.0. A possible
relationship between methotrexate blood concentration and toxicity was
investigated. Results: Sixteen eligible patients that had received a total of
103 cycles of high-dose methotrexate were identified. Ten patients
experienced a severe hepatic toxicity, (Grade 3, n�5 and Grade 4, n�5).
Grade 3 renal toxicity was seen in one patient and although reversible, it led
to treatment interruption. Reversible, grade 2 elavation of serum creatinine
occured in 5 cases. Four grade 3 infections were seen in 2 patients and 8
patients had at least one occurrence of Grade 3 oral mucositis. Thrombocytopenia
was a common event (Grade 3, n�5 and Grade 4, n�2) but no
severe bleeding complications were observed. One patient died as a result
of multi-organ failure two days after methotrexate administration. Methotrexate
blood concentration at 24 hours from administration could predict
for renal toxicity (p�0.005, by chi-square test), but not for other toxicity.
Conclusions: High-dose methotrexate in adult patients with osteosarcoma
was frequently associated with severe, however reversible toxicity.
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