Background and Aims

To determine clinicopathologic characteristics and outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases.

Methods

Data was analyzed for 428 patients with newly diagnosed, metastatic RMS treated on COG studies from 1999-2013 (D9802, D9803, ARST0431, ARST08P1). Categorical variables were compared using Chi-square or Fisher’s exact tests. Five-year event-free survival (EFS) and overall survival (OS) were estimated using Kaplan Meier method and compared between groups (lung only metastases vs. other sites +/- lung) using the log-rank test.

Results

Compared to patients with other metastatic sites (n = 373, 87.1%), patients with lung-only metastases (n = 55, 12.9%) were more likely to be 1-9 years of age (58.2% vs. 30.8%, P < 0.0001), have embryonal histology (74.6% vs. 25.7%, P < 0.0001), have N0 disease (78.2% vs. 32.4%, P < 0.01), and have a smaller proportion of primary extremity tumors (7.3% vs. 27.1%, P < 0.0001). Compared to patients with other metastatic sites, patients with lung-only metastatic disease had an improved 5-yr EFS (48.1% vs. 18.8%, p < 0.0001) and 5-yr OS (64.1% vs. 26.9%, p<0.0001). Patients with lung-only metastases had higher 5-yr EFS and 5-yr OS compared to patients with a single site of metastases not involving lung (EFS: 48.1% vs. 31.2%; OS: 64.1% vs. 49.6%, P<0.0001). In patients with ERMS and lung-only metastatic disease, there was no significant difference in survival outcomes between patients ≥10 years of age and 1-9 years of age (5-yr EFS: 58.3% vs. 68.2%, 5-yr OS: 66.7% vs. 67.7%).

Conclusions

With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior 5-yr EFS and 5-yr OS regardless of age. Consideration should be given to including patients >10 years with ERMS and lung only metastases in the same group as those <10 years in future risk stratification algorithms.

Background and Aims

The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children’s Oncology Group (COG), European pediatric Soft Tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS) Soft Tissue Sarcoma Committees devoted to improving patient outcomes. The assessment and definition of margin status in childhood, adolescent and young adult non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) is controversial.

Methods

The INSTRuCT committee aimed to develop international consensus recommendations around surgical margin assessment and definition in NRSTS.

Results

Clinical staging for NRSTS should be established through multi-disciplinary input from oncologists, surgeons, pathologists, and radiation oncologists and include post-operative assessment using the The R grouping system. R0 stage should only be assigned when a complete en-bloc resection of the tumor has been accomplished without tumor rupture. Patients who undergo complete primary re-excision (PRE) <6 weeks following an initial incomplete primary resection are classified as R0(ir) stage. Authors propose to arbitrarily define “R0 margin” by the absence of tumor cells < 1 mm from the closest margin in any direction. The R0(ab) sub-classification includes a surgical margin that is an anatomic site boundary.

If the margin is < 5 mm (close margin), the tumor should be classified as R1(c). If tumor necrosis is present at the margin, this can be classified as R1(n). Tumors should be classified as R1(x) when margins cannot be defined in mm or are unknown.

The R2(a/b/c) sub-classification of gross residual tumor differentiates unresected tumor (a), unresectable tumor (b), and unknown/unspecified (c).

Conclusions

This consensus aims to establish an evidence-based framework to be used for common guidelines for future protocols. A standardized pathology report template, such as that provided by the College of American Pathologists (CAP), is recommended that includes the distance from the tumor to the inked margins in mm.

Background and Aims

Orbital Rhabdomyosarcoma (ORMS) commonly presents as low-risk (localized embryonal) disease with excellent 3-year outcomes reported by the Children’s Oncology Group (COG). Long-term follow-up of low-risk ORMS and outcomes of less-common subgroups of ORMS on COG trials have not been reported.

Methods

Patients with ORMS were identified on seven COG trials. Demographic information and disease characteristics were collected. Survival was determined for the following subgroups: 1) low-risk ORMS on D9602 and ARST0331, 2) resected (Group I/II) low-risk ORMS on D9602 and ARST0331 (including Group IIA who had a radiation dose reduction from 41.4 to 36 Gy beginning with D9602), 3) non-low-risk ORMS on D9802, D9803, ARST0431, ARST0531, and ARST08P1, and 4) recurrent disease in low-risk patients. Event-free Survival (EFS) and Overall Survival (OS) were estimated by the Kaplan-Meier method and reported with 95% confidence intervals.

Results

We identified 218 patients with ORMS: the majority were male (n=129, 59.17%) and age 1-9 years (n=159, 72.94%). Most tumors were embryonal/botryoid (n=169, 77.52%), under 5 cm (n=213, 97.71%), Group III (n=170, 77.98%), and without regional lymph node involvement (n=217, 99.5%). Thirteen of 26 tested were FOXO1 fusion-negative. For 192 patients on D9602 and ARST0331, 10-year EFS and OS were 85.49% (76.96%-94.02%) and 95.62% (90.75%-100%), respectively. Of these, 44 patients with resected low-risk ORMS (5 Group I, 39 Group IIA) had 10-year EFS and OS of 88.01% (72.59%-100%) and 97.62% (90%-100%), respectively. Twenty-six patients with non-low-risk ORMS had 5-year EFS and OS of 88.46% (75.61%-100%) and 95.83% (87.66%-100%), respectively. Of low-risk patients with recurrent disease, the 5-year OS from time of recurrence was 75% (50.5%-99.5%) for 12 patients on ARST0331 and 63.46% (29.84%-97.09%) for 13 patients on D9602.

Conclusions

Our results support a long-term favorable prognosis for patients with ORMS, including those with non-low-risk disease, and a significant proportion of patients with recurrent ORMS may achieve long-term survival.

Background and Aims

Outcome of patients with relapsed disease of localized rhabdomyosarcoma (RD RMS) remain poor despite intensive, multimodal treatment. The VIT (vincristine, irinotecan, temozolomide) combination is considered the new european standard treatment in patients with RD RMS after alkylating agent containing regimen in primary disease.

Methods

All patients with RD RMS registered in the European soft tissue sarcoma registry of the Cooperative Weichteilsarkom Studiengruppe (n=68; 2009–2018) were retrospectively analyzed regarding characteristics of relapse, treatment and outcome data.

Results

Patients had a relapse after first-line stratification in the low/standard risk (SR) group (n=2/16), high risk (HR) group (n=41) and very high risk (VHR) group (n=9) with the diagnosis of embryonal RMS (n=34), alveolar RMS (fusion positive, n=29) and spindle-cell RMS (n=5). Secondary treatment regimen consisted of adriamycin, carboplatin, cyclophsophamide, topotecan, trofosfamide, ifosfamide, vincristine, etoposide (ACCTTIVE, n=36), topotecan, etoposide, carboplatin, cyclophosphamide (TECC, n=12) or other (n=12). Resection was performed in 40/68 (59%) patients and/or radiation in 47/68 (69%). Initial risk stratification, pattern of relapse, time to relapse, best surgery ± radiotherapy and achievement of 2^nd complete remission were significant prognostic factors. The regimen ACCTTIVE was superior to TECC in the whole cohort, but not when adjusted for initial risk stratification. Overall 5-year EFS and OS was 26% and 31%, respectively. Patients with RD of SR group had a 5-year OS of 80%, HR patients of 20% and VHR patients with 13% (p=0.008).

Conclusions

Local control is mandatory for long-term survival in RD RMS. Second line CHT with ACCTTIVE is comparable to VIT in HR patients.