Chemoselection: a paradigm for optimization of organ preservation in locally advanced larynx cancer

Abstract

Definitive chemoradiation (CRT) and laryngectomy followed by postoperative radiotherapy (RT) are both considered standard-of-care options for the management of advanced laryngeal cancer. While organ preservation with chemoradiotherapy is often the preferred up-front approach for appropriately selected candidates, the functional benefits of organ preservation must be carefully balanced against the considerable morbidity of salvage laryngectomy in patients who fail primary chemoradiation. Up-front identification of patients who are likely to require surgical salvage, therefore, is an important aim of any organ preserving approach in order to minimize morbidity while maximizing organ preservation. To this end, a strategy of 'chemoselection', using the primary tumor's response after 1 cycle of induction chemotherapy as an in vivo method of selecting responders for definitive chemoradiation while reserving primary surgical management for non-responders, has been employed extensively at our institution. The rationale, treatment results and future directions of this approach are discussed.

Figure 1

Disease-Free Survival by Response to Induction Chemotherapy in the Veterans Affairs Larynx Trial [15]. Patients with a complete response (CR) after 2 cycles of induction PF achieved superior disease-free survival compared to those who requires 3 cycles for a CR or who did not achieve a CR.

Figure 2

Schema for the Larynx Preservation Chemoselection Protocol Used at the University of Michigan [31,33]

Figure 3

Contrast enhanced CT images of a 74 year old male with T4 N1 M0 squamous cell carcinoma of the right glottic larynx treated successfully with chemoselection. (A) CT demonstrates tumor invasion through the anterior aspect of the thyroid cartilage at the time of diagnosis. (B) Three weeks after a single induction cycle of cisplatin-fluorouracil, repeat CT scan demonstrated greater than 50% tumor response, and he went on to receive radiotherapy to 70 Gy concurrent with cisplatin 100 mg/m² every 3 weeks. (C) He remains free of disease at 2 years after completion of chemoradiation.

Figure 4

Contrast enhanced CT of a 62 year old male with T4 N2b M0 squamous carcinoma of the left supraglottic larynx treated successfully with chemoselection. (A) Contrast enhanced CT scan at time of diagnosis demonstrates an aggressive appearing left supraglottic mass with erosion through the left lateral aspect of the thyroid cartilage. (B) Three weeks after a single induction cycle of cisplatin-fluorouracil, a greater than 50% tumor response was achieved. (C) CT at 6 months after completion of chemoradiation demonstrated residual left supraglottic tissue fullness attributable to post-radiotherapy change without evidence of residual disease, confirmed on endoscopic examination. The patient remains disease free 2 years after completion of therapy.