12. Research questions – Soft Tissue Sarcoma

It is necessary to review the extent to which the guideline contents are applied and what influence this has on patient care.

The guideline group therefore strongly advocates the establishment of evaluation­programs of guideline application. What barriers can be identified to the establishment of the S3 guideline? In particular, the members of the steering group and patient representatives are happy to provide advice on the design of evaluation studies. This includes health economic analyses of the various primary therapy procedures.

There is a need for research on the care of geriatric patients, especially with regard to the offer of therapy standards and time delays in treatment, e.g., due to limited mobility for coordination or implementation of therapy. The possibilities of video communication should be evaluated in this partly also vulnerable patient group. The guideline group also sees a need for research in the analysis of treatment indications, since this patient group is usually excluded from registration studies.

The guideline group advocates studies to ensure the evaluation of biopsies (size, number, localization in the tumor of punch biopsies).

Histologic markers to assess the aggressiveness of sarcomas in relation to clinical parameters (e.g., sarculator) could be an important pillar for indicationsto adjuvant systemic therapies, see also below in other contexts.

In particular, the value of early application of a next generation sequencing panel (NGS) versus staged (immuno)histologic diagnostics represents an important concern, including both temporal relation to therapy as well as economic and availability aspects.

The guideline group sees a therapeutic need for research especially in neoadjuvant therapy with regard to the question of the value of neoadjuvant chemotherapy and the combination of chemotherapy and surgery also in the metastatic situation.

There is an urgent need for research in better defining patients who are at high risk for systemic tumor recurrence and thus may benefit from adjuvant systemic (chemo)therapy. This includes both a validation of prognostic nomograms in Germany (e.g. Sarculator) but also of significantly improved follow-up data from clinical cancer registries.

Soft tissue sarcoma therapy has been able to expand its portfolio in recent years. However, the development of different chemotherapy regimens could not lead to a prognostic leap in these entities. The lack of specific therapies clearly underlines the need for new forms of treatment. The transition of differential molecular diagnostics to specific therapies is a relevant focus of clinical research and should be expanded.

Consequently, there is a need for research in improving first-line therapy in metastatic soft tissue sarcoma. In second-line and follow-up therapy, it is important to investigate and optimize the sequencing of these therapies. In addition, sarcoma type-specific therapies can be further differentiated to develop new therapies.

There is a need for research in clarifying the development of sarcomas, both through genetic conditions (neurofibromatosis, Li-Fraumeni syndrome – see Australian KINDRED study). The rate of clarification of genetic risk factors to date is not yet within the desirable range.

Also iatrogenic factors (postradiogenic angiosarcoma after breast carcinoma, visceral sarcoma after whole body radiotherapy) have not yet been sufficiently investigated with regard to frequency and mechanisms of development, e.g. on the combined influence of chemotherapy and radiotherapy.

There is also a need for research on the problem of field carcinogenesis of dedifferentiated liposarcomas of the retroperitoneum, for which environmental influences in the development are also conceivable (e.g. lipotrophic chemicals).