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.

Keywords::

• chemoselection
• concurrent chemoradiation
• induction chemotherapy
• larynx preservation
• salvage laryngectomy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Definitive concurrent chemoradiation is the standard of care for organ preservation in patients with locally advanced squamous cell carcinoma (SCC) of the larynx without large-volume T4 disease or tumor extension through the thyroid cartilage and with acceptable larynx function to warrant consideration of larynx preservation.

• • The functional benefits of organ preservation must be balanced against the considerable morbidity of salvage laryngectomy in those patients who experience local failure after primary chemoradiation.

• • A strategy of ‘chemoselection’, in which the response of the primary tumor after 1 cycle of induction cisplatin and 5-fluorouracil (PF) serves as an in vivo test to identify patients most likely to achieve cure with definitive chemoradiation, has been used extensively at the University of Michigan to select patients for organ preservation, achieving high rates of success.

• • Chemoselection has been extended to patients with extensive T4 larynx cancers not typically considered for organ preservation, with similar rates of successful larynx preservation and survival achieved compared with patients with T3 tumors.

• • Chemoselection does not appear to be a viable strategy for patients with squamous cell carcinoma of the oral cavity, for whom definitive surgery followed by adjuvant (chemo)radiation appears to yield superior outcomes. The role of chemoselection in the management of patients with locally advanced oropharyngeal cancer, for whom both definitive chemoradiation and primary surgery with adjuvant (chemo)radiation are both considered acceptable standards of care, remains to be more clearly defined.