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)

Sarbani Ghosh Laskar; Sahil Sood; Abhishek Chatterjee; Shwetabh Sinha; Shilpi Sharma; Devendra Chaukar; Jai Prakash Agarwal; Tejpal Gupta; Ashwini Budrukkar; Vedang Murthy; Monali Swain; Anuj Kumar; Samarpita Mohanty; Pankaj Chaturvedi; Prathamesh Pai; Gouri Pantvaidya; Anuja Deshmukh; Deepa Nair; Sudhir Nair; Vidisha Tuljapurkar; Mandar Deshpande; Amit Joshi; Vanita Noronha; Kumar Prabhash; Anil K Dcruz

doi:10.1016/j.radonc.2025.110944

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)

Radiother Oncol. 2025 May 21:209:110944. doi: 10.1016/j.radonc.2025.110944. Online ahead of print.

Authors

Sarbani Ghosh Laskar¹, Sahil Sood², Abhishek Chatterjee², Shwetabh Sinha², Shilpi Sharma³, Devendra Chaukar⁴, Jai Prakash Agarwal², Tejpal Gupta², Ashwini Budrukkar², Vedang Murthy², Monali Swain², Anuj Kumar², Samarpita Mohanty², Pankaj Chaturvedi², Prathamesh Pai⁵, Gouri Pantvaidya², Anuja Deshmukh², Deepa Nair², Sudhir Nair², Vidisha Tuljapurkar², Mandar Deshpande⁶, Amit Joshi², Vanita Noronha², Kumar Prabhash², Anil K Dcruz⁷

Affiliations

¹ Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India. Electronic address: sarbanilaskar@gmail.com.
² Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.
³ Narayana Superspeciality Hospital, Gurugram, India.
⁴ Nanavati Max Super Speciality Hospital, Mumbai, India.
⁵ Punyashlok Ahilyadevi Holkar Head & Neck Cancer Institute of India, Mumbai, India.
⁶ Kokilaben Dhirubhai Ambani Hospital, Mumbai, India.
⁷ Apollo Cancer Centre, Mumbai, India.

PMID: 40409369
DOI: 10.1016/j.radonc.2025.110944

Abstract

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.

Keywords: Head neck cancer; Oral cavity cancer; Radiotherapy; Second primary cancer.