Top Line: Ultra-hypofractionation is coming on the scene for early-stage laryngeal cancer.
The Study: In LT-SABR, five-fraction highly-conformal radiation to gross disease appeared to be safe and effective for small laryngeal targets in patients who were not actively smoking. We now have another iteration with a small prospective phase 1/2 trial where 33 patients received 3-fraction definitive radiation for cT1 glottic cancer. Cutting to the chase, it stopped accruing after 33 of 59 planned enrollees due to an 18% rate of necrosis. Let’s back up to understand the radiation volumes and delivery. The prescription was 36 Gy to the involved third(s) (i.e., segment) of the true cord and 30 Gy to the adjacent segments (note: the anterior commissure was considered a segment). Thyroid and cricoid cartilages were always excluded, and a planning margin of 3 mm was used in all directions except 5 mm craniocaudal for movement: patients were instructed not to swallow during simulation or treatments. All of that is to say we are talking about small treatment fields here. What’s more, the maximum dose was limited to 107%, so this is more like ultra-hypofractionation of the prostate where homogeneity still matters. Plus there was a goal to limit 0.1 cc of cartilage to ≤30 Gy, but this was sacrificed if needed for target coverage. Ultimately, there were four cases of soft tissue necrosis and two cases of cartilage necrosis at a median of 15 months. Once again, 2/2 chondronecrosis events occurred in active smokers and, interestingly, 2/4 mucosal necrosis events occurred in patients with recent COVID infections posing the question of interplay of radiation necrosis and infectious laryngitis. On the bright side, patient-reported voice outcomes mirrored that after fractionated radiation with improvement from pretreatment baseline by 6 months, and all 33 patients continued with local control at a median follow up of over 4 years. A final interesting thought from the authors is that such highly-conformal treatment “will not address areas of microscopic field cancerization and may not prevent second primary tumors” as potentially achieved with whole larynx treatment. And, in fact, one enrollee did develop a short interval out-of-field second primary laryngeal tumor.
TBL: Ultra-hypofractionated radiation for larynx cancer is very much a work in progress with the next iteration of trials hoping to strike a better balance between tumor control and toxicity…but in the meantime, more fractionated and more inclusive laryngeal treatment remains the standard radiation approach. | Sanguineti, Int J Radiat Oncol BIOl Phys 2024
The Study: In LT-SABR, five-fraction highly-conformal radiation to gross disease appeared to be safe and effective for small laryngeal targets in patients who were not actively smoking. We now have another iteration with a small prospective phase 1/2 trial where 33 patients received 3-fraction definitive radiation for cT1 glottic cancer. Cutting to the chase, it stopped accruing after 33 of 59 planned enrollees due to an 18% rate of necrosis. Let’s back up to understand the radiation volumes and delivery. The prescription was 36 Gy to the involved third(s) (i.e., segment) of the true cord and 30 Gy to the adjacent segments (note: the anterior commissure was considered a segment). Thyroid and cricoid cartilages were always excluded, and a planning margin of 3 mm was used in all directions except 5 mm craniocaudal for movement: patients were instructed not to swallow during simulation or treatments. All of that is to say we are talking about small treatment fields here. What’s more, the maximum dose was limited to 107%, so this is more like ultra-hypofractionation of the prostate where homogeneity still matters. Plus there was a goal to limit 0.1 cc of cartilage to ≤30 Gy, but this was sacrificed if needed for target coverage. Ultimately, there were four cases of soft tissue necrosis and two cases of cartilage necrosis at a median of 15 months. Once again, 2/2 chondronecrosis events occurred in active smokers and, interestingly, 2/4 mucosal necrosis events occurred in patients with recent COVID infections posing the question of interplay of radiation necrosis and infectious laryngitis. On the bright side, patient-reported voice outcomes mirrored that after fractionated radiation with improvement from pretreatment baseline by 6 months, and all 33 patients continued with local control at a median follow up of over 4 years. A final interesting thought from the authors is that such highly-conformal treatment “will not address areas of microscopic field cancerization and may not prevent second primary tumors” as potentially achieved with whole larynx treatment. And, in fact, one enrollee did develop a short interval out-of-field second primary laryngeal tumor.
TBL: Ultra-hypofractionated radiation for larynx cancer is very much a work in progress with the next iteration of trials hoping to strike a better balance between tumor control and toxicity…but in the meantime, more fractionated and more inclusive laryngeal treatment remains the standard radiation approach. | Sanguineti, Int J Radiat Oncol BIOl Phys 2024