KEY POINTS
- This systematic review included 35 studies of non-metastatic anal squamous cell carcinoma: 4 phase I or II trials, 13 retrospective cohort studies, and 18 case series. Twenty-nine studies evaluated photon radiotherapy and six evaluated proton therapy.
- Bone marrow-sparing strategies used computed tomography-defined pelvic bone marrow or functional imaging-defined active bone marrow. Selective sparing reduced pelvic bone marrow V10–20 by 0–47% and active bone marrow V3–45 by 2–14%, generally without compromising target coverage.
- Low-to-intermediate dose exposure was most consistently associated with acute hematologic toxicity. The lumbosacral spine was the strongest regional predictor, with proposed planning goals of V10 <85% and V20 <65%for both pelvic bone marrow and the lumbosacral spine.
- Across studies, grade 3–4 hematologic toxicity ranged from 25–71% with bone marrow-sparing intensity-modulated radiotherapy and 14–86% without marrow-sparing, with substantial heterogeneity in populations, chemotherapy, endpoints, and assessment timing.
- Proton therapy produced larger pelvic marrow dose reductions than photon techniques, but comparative studies did not demonstrate consistent clinical mitigation of neutropenia or lymphopenia.
CLINICAL TAKEAWAY
Bone marrow avoidance is a reasonable planning objective during definitive chemoradiotherapy for anal cancer, particularly for low-to-intermediate doses to the pelvic marrow and lumbosacral spine, provided target coverage remains the priority. However, the evidence is heterogeneous and does not establish that dosimetric sparing consistently reduces clinically meaningful hematologic toxicity; the findings support prospective validation rather than a practice-changing conclusion.