Elsevier

Oral Oncology

Volume 122, November 2021, 105585
Oral Oncology

Brachytherapy and non-cancer mortality in patients with oral cavity and oropharynx SCCs

https://doi.org/10.1016/j.oraloncology.2021.105585Get rights and content

Highlights

  • Oral cavity/oropharynx subsites have the highest non-cancer mortality.

  • Brachytherapy correlates strongly with improvement in non-cancer survival.

  • Brachytherapy impact strongest on non-cancer survival in oropharynx cancer.

  • Benefit most pronounced in individuals with smoking history.

Abstract

Background

Oral cavity and oropharyngeal squamous cell cancers (OC-OPSCC) display high cancer-specific mortality and increased non-cancer mortality. We examined cause of death in patients treated for OC-OPSCC with brachytherapy, chemotherapy, external beam radiation, surgery, or combination of modalities. We hypothesized that brachytherapy does not increase non-cancer mortality comparably with external beam radiation.

Methods

A database was constructed from institutional tumor registry and electronic medical record data from all patients with first OC-OPSCC diagnosis at our institution between 2000 and 2010, excluding patients with a second primary cancer at diagnosis. The primary outcome was association between treatment modality and non-cancer mortality.

Results

Of 693 eligible patients, 460 were deceased; 84 from primary malignancy and 96 from a non-primary cancer cause, including 24 with a second primary cancer. 193 patients received brachytherapy. Cox proportional hazards regression was performed on treatment regimen, stratified by AJCC stage, race, and sex. Age, smoking history, and alcohol had HRs for death of 1.05 (p < 0.005), 1.37 (p = 0.106), and 2.24 (p < 0.005), respectively, while brachytherapy had a 0.53 HR (p < 0.005) for death. Non-smoking OPC patients had an 88% 5-year OS, suggesting these were largely HPV-driven cancers. In smoking OPC patients, 5-year OS was 61%. Non-cancer mortality HR of 0.36 for brachytherapy-treated patients.

Conclusion

We report non-cancer mortality from a cohort of curatively treated OC-OPSCC and show a significant correlation between brachytherapy and non-cancer survival, independent of remission status. The impact of brachytherapy in OPC was strongest in smokers.

Introduction

Oral cavity and oropharyngeal squamous cell cancers (OC-OPSCC) have traditionally carried a poor prognosis due to high recurrence rates, combined with high rates of second primary malignancy. Each year, more than a half of million persons are diagnosed with OC-OPSCC worldwide and at the time of diagnosis, most patients have locally advanced disease and are treated with curative surgical or non-surgical therapy [1]. Surgical resection is followed by risk-based postoperative radiation or chemoradiation [2]. Definitive radiation or chemoradiation are employed for unresectable tumors, for organ or function preservation, and in patients who are not surgical candidates [3], [4], [5]. Intensive multimodality therapy leads to acute and chronic toxicity [6] and may be associated with increased non-cancer mortality [7]. The emergence of Human Papillomavirus (HPV)-associated OPSCC, in a group of patients with lower median age, lesser tobacco exposure, fewer co-morbidities, and much greater radiosensitivity (and thus a much higher cure rate), has highlighted the importance of quantifying and characterizing such late sequelae, and identifying treatment approaches to minimize late sequelae and non-cancer mortality.

Non-cancer mortality includes treatment-associated acute or late complications from toxicity, second primary tumors and underlying comorbidities including cardiac and respiratory illness [8], [9]. Furthermore, the population demographics of patients with OC-OPSCC include high rates of tobacco and alcohol use, leading to high rates of competing causes of mortality among a subset of OC-OPSCC [3], [10], [11]. Aspiration, mucositis, dysphagia, and subsequent infections are among the unique late sequelae of chemoradiotherapy and surgery for head and neck cancers [12], [13], [14]. Recent studies have examined causes of mortality in patients with head and neck cancers and highlighted the impact of pre-existing and post-treatment comorbidities on death [11], [15].

Brachytherapy, or internal radiotherapy, has been used as early as the 1920s as a treatment modality for cancer and involves the implantation of radioactive isotopes directly into the tumor (interstitial) or surrounding tumor bed (intracavitary) as low dose rate (LDR), high dose rate (HDR) or permanent implants [16], [17]. The anatomical location and complexity of head and neck cancers are well-suited for local delivery of radiation via brachytherapy [18], [19]. Despite the common practice of increasing doses of adjuvant radiation for high-risk head and neck SCC in hopes of improving local–regional control, a recent study using the National Cancer Database suggested that higher doses did not have a survival benefit [20].

In our large, single institution study, we examine the cause of death in patients with head and neck cancers treated with a heterogeneous combination of surgery and chemoradiotherapy and associated co-morbidities contributing to non-cancer mortality, with a specific emphasis on the effects of brachytherapy on non-cancer mortality.

Section snippets

Patient selection and data collection

For this study, institutional review board approval was obtained. We retrospectively compiled a database through the XXXX Tumor Registry and the electronic medical record (EMR) of all adult patients who received a first treatment or diagnosis for a first OC-OPSCC diagnosis at XXXX between the years of 2000 and 2010, permitting long-term information on disease recurrence, second cancers, and non-cancer deaths whether from competing causes of mortality or resulting from late sequelae of

Results

Of 693 eligible patients, 460 (66%) were deceased. Eighty-four died of their primary malignancy. Baseline characteristics of the patients are shown in Table 1. There were no significant differences in demographics, disease status, and smoking/alcohol history between patients who received brachytherapy and those who did not. Among those receiving brachytherapy, 56.5% had a specified dose and isotope; of these, 54.1% received interstitial LDR with palladium-103 (17.55–38.92 mCi in 18–50 seeds)

Discussion

We report non-cancer mortality from an extensively annotated cohort of curatively treated OC-OPSCC at a single large academic institution over a decade. Our results demonstrate a significant correlation between receipt of brachytherapy and non-cancer survival, independent of remission status.

Brachytherapy has been used as sole therapy in early-stage disease, an adjuvant therapy after surgery, EBRT or induction chemotherapy, and rarely as the sole therapeutic modality for inoperable cancers.

Conclusion

We found a significant correlation between brachytherapy and non-cancer survival among individuals with curatively treated OC-OPSCC independent of remission status which was more pronounced amongst individuals who had a smoking history.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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