GUIDELINE SUMMARY (Fig. 1)
PM-RMS represents a very challenging site to treat with local failure
remaining the dominant form of failure. Definitive chemoradiation is the
preferred treatment approach for PM-RMS, with the goal of maximizing
cure while minimizing loss of form and function. Radiation timing,
volumes, and techniques have evolved greatly over the last 50 years with
this goal in mind.
Imaging with MRI of the head neck is critical in PM-RMS to assess the
extent of disease (including any possible intracranial extension),
evaluate response, and fuse for accurate radiation planning. Although
radiotherapy was previously delivered earlier for those with high-risk
parameningeal features, the timing of primary site radiotherapy for
localized PM-RMS is now similar to other sites at week 13 (and up to
week 20-22 in the metastatic setting). The recommended radiation dose
for PM-RMS is 50.4 Gy in 28 fractions, with a boost to 55.8 - 59.4 Gy
allowed for unfavorable features. To account for the response to
chemotherapy prior to radiation, the pre-chemotherapy extent of disease
can be treated to 36 Gy - 41.4 Gy, with a boost to the macroscopic
residual disease present at the time of radiation planning to the final
dose. Radiation target volumes have reduced drastically over time, with
the goal of enhancing the therapeutic ratio, from prior craniospinal
irradiation to now conformal treatment of the tumor with a 1-1.5cm
margin. Although prophylactic nodal irradiation is not recommended, for
patients with clinical or pathologic involvement of nodes, a dose of
36-41.4 Gy over 20-23 fractions (with gross disease to 50.4 Gy) is
recommended to the involved nodal chain or site. To minimize toxicity
and dose to the many critical organs at risk in the head and neck,
highly conformal techniques like IMRT or proton therapy must be
utilized, with proton therapy specifically encouraged whenever feasible
to minimize normal tissue toxicity. Despite advancements in volumes and
technology, morbidity of local therapy with radiation to the head and
neck remains significant, including cosmetic defects, endocrinopathies,
impaired vision and hearing, dental complications, and second cancers.
Given the locally infiltrative nature and difficulty with obtaining
negative margins, the role of surgical resection is often limited to
initial biopsy and for local therapy in the relapsed setting. However,
constant re-evaluation of the optimal treatment approach for patients
with PM-RMS is necessary. Overall, we recommend a multi-disciplinary
approach for treatment of PM-RMS, with the primary goal of maximizing
cure while maintaining form and function.
ACKNOWLEDGMENTS
We would like to thank Suzi Birz for her organizational and
administrative expertise. The International Soft Tissue Sarcoma
Consortium and the Pediatric Cancer Data Commons are supported in part
by Cancer Research Foundation, Children’s Research Foundation, Comer
Development Board, Kick Cancer, King Baudouin Foundation, Rally
Foundation for Childhood Cancer Research, Seattle Children’s Foundation
from Kat’s Crew Guild through the Sarcoma Research Fund, St. Baldrick’s
Foundation, and The Andrew McDonough B+ Foundation. This work is made
possible through the efforts of Children’s Oncology Group, Cooperative
Weichteilsarkom Studiengruppe der GPOH, The European paediatric Soft
tissue sarcoma Study Group, MMT Malignant Mesenchymal Tumour Committee,
and STSC AIEOP Italian Soft Tissue Sarcoma Committee.
CONFLICT OF INTEREST STATEMENT:
DC, SH, AS, BT, SW have no relevant conflicts to disclose. HM
acknowledges the support of the NIHR Biomedical Research Centre at The
Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.
JB acknowledges a research grant from Asco/Pfizer.
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