Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas
Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas
Currently, soft tissue sarcomas (STS) are preoperatively irradiated in a conventionally
 fractionated regimen of 25 x 2 Gy in five weeks. Recent radiobiological investigations,
 however, suggest sensitivity to (modest) hypofractionation. Within this study, patients will
 be randomized to receive either the conventional schedule of 25 x 2 Gy or a shorter
 preoperative regimen of 14 x 3 Gy, in the hypothesis that both the postoperative wound
 complication rate until 30 days after surgery, as well as the local control probability at
 two years are comparable in both arms.
Surgery is the cornerstone in the treatment of non-metastatic sarcomas. Whenever feasible the
 resection should include a free surgical margin providing a rim of uninvolved tissue
 surrounding the tumor. In most deep located tumors however, to preserve essential
 neurovascular and bone structures and thus to preserve function, the margins are often
 limited. High grade tumors are, even with wider margins, at higher risk of local failure.
 Radiotherapy can reduce this risk of local failure.

 Preoperative radiotherapy does increase the risk for early complications due to unavoidable
 irradiation of the normal tissues surrounding the sarcoma mass, particularly for lower
 extremity lesions (6-9).

 Preoperative radiotherapy aims to reduce tumor vitality prior to resection, theoretically
 allowing more conservative surgical therapy. Postoperative RT allows histological examination
 of the tumor specimen, especially the margins, aiding in further treatment planning; it may
 also be associated with fewer early wound complications. (10, 11).

 In preoperative radiotherapy, as compared to postoperative radiotherapy, lower doses (50
 versus 60 to 66 Gy) and smaller field sizes can be used, resulting in a reduced risk of late,
 often irreversible, complications. Consequently, preoperative RT is the preferred approach in
 many centers. Although the outcomes of combined RT and surgery are favorable, approximately
 15% of the patients may relapse locally and about 30-50% distantly (dependent upon, among
 others, age, histopathology, size and grade), stressing the need for further improvement.
 These improvements should not only be sought in the domain of oncological endpoints, but also
 in decreasing treatment burden. A reduction in treatment duration, maintaining local control
 rates without increasing the rates of postoperative wound complications would serve the
 latter endpoints. For this purpose, quality of life questionnaires as well as patient
 reported outcomes measurements could come of help.Modern radiobiological investigations
 suggest that, on average, intermediate to high-grade soft tissue sarcomas may have α/β
 ratio's substantially below 10 Gy, justifying clinical studies exploring the possibility of
 (modest) hypofractionation. Obviously, various subtype derived cell lines exhibit different
 characteristics but on average an α/β ratio of 5 Gy would be a reasonable denominator for
 sarcomas as a group. However, it is important not to exaggerate hypofractionation in a
 setting where patients still need to undergo surgery.
Inclusion Criteria:

 -  Histologically confirmed newly diagnosed intermediate to high grade soft tissue
 sarcoma localized to the extremities, trunk and chest wall or the head and neck area,
 for which the standard treatment is a combination of and radiotherapy and surgery
 (deep seated and/or > 5cm in largest tumor diameter and/or an anticipated close
 resection margin and/or grade II/III according to the FNCLCC definition);

 -  • Absence of regional and/or distant disease. Patients staged by at least a CT scan of
 the chest (. Staging may also be performed by FDG-PET scanning and or total body MRI
 scans. Patients with an uncertain metastatic status (e.g. small indifferent lung
 nodules) and patients with a low metastatic burden not precluding the application of
 both preoperative radiotherapy and definitive surgery, are allowed to participate;

 -  WHO Performance Status ≤ 2;

 -  Able and willing to undergo preoperative radiotherapy;

 -  Able and willing to undergo definitive surgery;

 -  Able and willing to comply with regular follow-up visits;

 -  Able and willing to complete patient reported outcome questionnaires (health-related
 quality of life and cost effectiveness);

 • Able and willing to undergo randomization;

 -  Age ≥ 18 years;

 -  Signed written informed consent

 Exclusion Criteria:

 -  Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or
 completely resected non-melanomatous skin carcinoma or successfully treated in situ
 carcinoma;

 -  Patients with recurrent sarcomas who underwent prior radiotherapy to the target lesion
 (if the primary sarcoma was managed by surgery only and no perioperative RT, patients
 are eligible);

 -  Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and
 adult), osteosarcomas;

 -  Any psychological, familial, sociological or geographical condition potentially
 hampering compliance with the study protocol and follow-up schedule; those conditions
 should be discussed with the patient before registration in the trial;

 -  Female patients who are pregnant;

 -  Intention to perform an isolated limb perfusion, instead of a tumor resection;

 -  Neoadjuvant chemotherapy to be scheduled between end of radiotherapy and definitive
 surgery (neoadjuvant chemotherapy before radiotherapy is allowed);