The enigma cloaking a bunch of malignant cells known as a sarcoma has existed since before the first radiation therapy treatment in 1896. And it seems like the more molecular and histologic details we learn as technology and research advance, the more mysteries we uncover. Perhaps inappropriately lumped together under one pseudonym, sarcomas are typically managed surgically, with perioperative radiation used to facilitate better surgical outcomes (ie, margin-negative resections or sterilization of the surgical bed).

However, the number of pathways one can follow on the NCCN guidelines provides just a glimpse into the breadth of caveats to this thinking. Desmoid tumors, for example, are like a bear you don’t want to poke. Observe at a distance, if at all possible. Meanwhile, clear cell sarcomas mandate aggressive local (and sometimes systemic) therapies. And low-grade liposarcomas are on par with low-risk prostate cancer; sometimes doing nothing is best.

When radiation comes into play, questions revolve largely around timing. Preoperative radiation affords a potential lower total radiation dose, shorter treatment course, smaller field, less late radiation toxicity, better extremity function, ease-of-target delineation, and improved resectability, among other theoretical benefits. In contrast, postoperative radiation can allow for definitive pathology review and fewer wound-healing complications, at the cost of larger radiation fields and arguably worse local control. Essentially, neoadjuvant radiation comes with more acute complications while adjuvant radiation carries more delayed complications.

The difficulty we face with sarcoma is that the data are inherently dirty. It’s hard to get enough numbers – especially for individual histologies – to create a study that has enough power to demonstrate potential survival benefits of radiation.

Timing of radiation, on top of dose and fractionation considerations, is further complicated by determining whether radiation is even appropriate for certain histologies. With such variety and vastly different prognoses and responses to therapy, the waters quickly become muddied. We don’t currently have clear data to suggest an overall survival benefit with radiation.

The difficulty we face is that the data are inherently dirty. It’s hard to get enough numbers – especially for individual histologies – to create a study that has enough power to demonstrate potential survival benefits of radiation. And so, we are stuck with a smattering of data points that give us a general idea of what we should do, but certainly don’t instill us with unfaltering confidence in our treatment. Then again, can we really be unfaltering in the world of oncology, where our target never fails to surprise us with more mutations, adaptations, and escape tactics? As with any type of cancer, we must consider the data, weigh the risks and benefits, and look closely at our patient.