Resection is usually the most effective way of achieving local control, but:
- Surgery can only be used alone to achieve local control, if a planned radical excision is possible with negative margins for disease.
- Sometimes excision alone can be performed, but the surgery may result in significant "mutilation" and this may not be acceptable to the patient or family.
- If surgery is not possible with wide margins, then radiation therapy (RT) can be given before surgery to sterilize microscopic disease at the margins of the tumor.
- Surgery can be done after pre-operative RT with narrow margins to excise viable tumor in the center of the tumor mass.
- Post-operative RT can also be given. No significant differences have been found between pre and post-operative radiotherapy in terms of tumor control, but there are advantages and disadvantages for both approaches.
Some Differences between Pre and Post-operative RT:
PRE-OPERATIVE RT |
POST-OPERATIVE RT |
Easy to plan accurately as the tumor is still in place |
Much harder to plan as the tumor is gone, tumor bed is harder to identify and the entire extent of the post-surgical bed needs therapy |
Smaller RT treatment volume |
Larger RT treatment volume |
Pathology information not as good
|
Better pathology information |
In theory more effective as blood vessels have not been disrupted by surgery |
In theory deals with bulk of tumor immediately and that should improve efficacy of treatment |
Associated with significant risk of early wound healing delay (20% or so). |
Associated with significantly increased risk of fibrosis and scarring in the long term |
Criteria for therapy in the COG study ARST0332:
For this study (which is now closed to accrual), patients with non-RMS were stratified into different risk groups.
Low risk: Patients in the low risk group (those with resected non-RMS at diagnosis and no evidence of metastases) received post-operative RT alone when the tumor was high grade, less than or equal to 5cm in greatest dimension and the surgical margins were positive.
Intermediate risk: Patients in the intermediate risk group (those with resected non-RMS at diagnosis and no evidence of metastases), received post-operative adjuvant radiation therapy and chemotherapy regardless of margin status when the tumor was high-grade and larger than 5cm.
Patients in the intermediate risk group (those with unresected non-RMS at diagnosis and
no evidence of metastases) received pre-operative combined modality therapy regardless of tumor grade or size.
Patients with high-grade tumors measuring greater than 5cm and no evidence of metastatic disease received pre-operative combined modality therapy when delayed resection was planned.
High Risk: The high-risk group included patients with metastatic disease. Their primary site treatment followed the algorithm outlined for intermediate-risk patients without evidence of metastases. If the primary tumor was resected at diagnosis, post-operative RT was administered beginning at Week 4.
If the primary was deemed unresectable at diagnosis, pre-operative combined modality therapy was administered with RT beginning at Week 4. The goal of combined modality preoperative therapy was to make surgery feasible and improve the extent of resection.
RT Techniques:
The pre-operative dose in ARST0332 was 45 Gy in 180 cGy fractions. This dose was chosen to limit the morbidity of therapy, but there is some contention about whether this dose is as effective as 5040 cGy in 180 cGy fractions.
The post-operative dose was 55.8 Gy in 180 cGy fractions
- Gross tumor volume (GTV) = volume occupied at diagnosis by visible or palpable disease.
- Clinical target volume (CTV) = GTV and sites with potential occult tumor involvement
including lymph nodes adjacent to the GTV that may be clinically involved. - Planning target volume (PTV) = CTV surrounded by a geometric margin to account for variability in set-up, breathing or motion during treatment
In treating extremities, the volumes could be modified to avoid circumferential irradiation of extremity lymphatics and treatment across a joint.
ARST0332 in more detail:
This was the last COG study and is now closed to accrual: Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
The aim was to develop and determine the outcomes for a risk-based strategy comprising of different treatment arms (observation only, adjuvant radiation therapy (RT), or adjuvant and neo-adjuvant chemotherapy combined with RT and surgery) for young patients with non-RMS.
OUTLINE: This was a multicenter study. Patients were divided into 3 risk groups according to:
- Presence of metastatic disease (yes vs no)
- Status of prior surgery (resected vs unresected)
- Grade of tumor (low vs high)
- Size of primary tumor (≤ 5 cm vs > 5 cm)
Patients were assigned to different treatment regimens based on:
- Disease extent (non-metastatic vs metastatic)
- Tumor size (≤ 5 cm vs > 5 cm)
- Extent of resection of primary tumor (resected vs unresected)
- Extent of resection of metastases (complete or microscopic residual vs gross residual)
- Microscopic tumor margins (negative vs positive)
- Tumor grade (low vs high)
Group 1 = Low risk = non-metastatic and grossly resected disease, except high-grade tumor > 5 cm
- Patients with low-grade tumor with either negative or positive microscopic margins or high-grade tumor ≤ 5 cm (in maximum diameter) with negative microscopic margins were assigned to regimen A.
- Patients with high-grade tumor ≤ 5 cm (in maximum diameter) with positive microscopic margins were assigned to regimen B.
Regimen A (observation only): Patients underwent observation only
Regimen B (adjuvant RT): Beginning between 6-42 days after surgical resection, patients underwent a total of 31 fractions of adjuvant RT.
Group 2 = Intermediate risk = non-metastatic, resected or unresected disease
- Patients with grossly resected, high-grade tumor > 5 cm (in maximum diameter) were assigned to regimen C.
- Patients with unresected tumor were assigned to regimen D.
Regimen C (adjuvant chemoRT): Patients received ifosfamide IV over 3 hours on days 1-3 in weeks 1, 4, 7, 10, 13, and 16 and doxorubicin hydrochloride IV over 24 hours on days 1 and 2 in weeks 1, 4, 13, 16, and 19. Beginning in week 4, patients also underwent a total of 31 fractions of RT.
Regimen D (neoadjuvant chemoRT, surgery, and adjuvant chemotherapy with or without RT):
Neoadjuvant chemoRT and surgery: Patients received ifosfamide IV over 3 hours on days 1-3 in weeks 1, 4, 7, and 10 and doxorubicin hydrochloride IV over 24 hours on days 1 and 2 in weeks 1 and 4. Beginning in week 4, patients also underwent a total of 31 fractions of RT. Patients underwent surgical resection in week 13.
Adjuvant chemotherapy with or without RT: Patients received ifosfamide IV over 3 hours on days 1-3 in weeks 16 and 19 and doxorubicin hydrochloride IV over 24 hours on days 1 and 2 in weeks 16, 19, and 22. Beginning in week 16, patients achieving gross total resection with positive microscopic margins underwent a total of 6 fractions of adjuvant radiotherapy. Patients achieving less than total gross resection underwent a total of 11 fractions of adjuvant radiotherapy. Patients achieving total gross resection with negative microscopic margins did not receive adjuvant RT.
Group 3 = high risk = metastatic, resected, incompletely resected, or unresected disease:
- Patients with low-grade, all-sites resected tumor with either negative or positive microscopic margins were assigned to receive treatment as in group 1 regimen A.
- Patients with high-grade, grossly resected primary tumor, and metastatic disease were assigned to receive treatment as in group 2 regimen C.
- Patients with unresected, high-grade metastatic tumor were assigned to receive treatment as in group 2 regimen D.
