Presentation and outcomes of second primary malignancies (SPMs) in locally advanced oral cavity squamous carcinoma (LA-OSCC): Secondary analysis of a phase III randomised control trial (NCT00193843).

Background: Second Primary Malignancies (SPMs) are a common cause of morbidity and mortality in Head & Neck Squamous Carcinoma (HNSCC). Prospective data on incidence, outcomes and prognostic factors is sparse. The current publication summarizes data on 83 SPMs which developed on follow up among patients accrued on a Phase III Randomized Controlled Trial testing treatment intensification in Oral Cavity Squamous Carcinoma (OSCC).

Patients And Methods: Nine hundred patients of OSCC accrued between 2005-2013 were followed up as part of the trial protocol. Standard clinical criteria were used to determine SPM occurrence. Clinicopathological and demographic variables were summarized using descriptive statistics and analysed using measures of central tendency and dispersion. Outcomes of interest included Overall-Survival (OS) and Progression-Free-Survival (PFS) post SPM diagnosis and were analysed using the Kaplan-Meier method and factors of prognostic significance were compared using the log-rank test and multivariate analysis thereafter.

Results: The median follow-up of surviving patients was 95.9 months {(IQR) = 76.1-122.4 months}. A total of 83 SPMs were detected at a median time-to-occurrence of 48 months (IQR-20-87 months) (Cumulative Incidence -11 % at 5 years). The Head & Neck was the most common site of SPM. The 2-year Kaplan Meier estimates of OS and PFS post diagnosis of SPM were 30.3 % (95 %CI-20.9 %-43.9 %) and 21.6 % (95 %CI-13.8 %-34 %) respectively. Multivariate analysis revealed time-to-development of SPM more than 2 years and surgical management of SPM to be associated with superior PFS.

Conclusions: SPMs can cause major morbidity and mortality in OSCC survivors. Strategies need to be developed to gear towards early detection and aggressive salvage.