Competing Causes of Death and Second Primary Tumors in Patients with Locoregionally Advanced Head and Neck Cancer Treated with Chemoradiotherapy

Abstract

Purpose: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy.Experimental Design: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis.Results: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n ‫؍‬ 88; 1.5 years), treatmentassociated acute or late complications (n ‫؍‬ 30; 4 months), second primary tumors (n ‫؍‬ 18; 3.5 years), comorbidities (n ‫؍‬ 41; 1.9 years), and unknown (n ‫؍‬ 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n ‫؍‬ 13), followed by the esophagus (n ‫؍‬ 3) and head and neck (n ‫؍‬ 2)Conclusions: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.

Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer

“…Recently, many studies on locoregionally advanced SCCHN have been focusing on neoadjuvant chemotherapy (NAC) with a high complete response (CR) rate followed by definitive radiotherapy, or concurrent chemoradiotherapy showing to improve the survival rate and to preserve functions and organs (Pignon et al, 2000;Monnerat et al, 2002;Forastiere et al, 2003;Haddad et al, 2003). However, 20 -30% of advanced patients with a pathologically CR even after the recent aggressive treatment has been showing locoregionally recurrent and/or distant metastatic tumours (unpublished data in our institutes) resulting in the poor outcome nevertheless (Argiris et al, 2004;Brockstein et al, 2004;Cohen et al, 2004). Based on these results, more advanced multidisciplinary treatments should be indispensable in the aim of improving the poor outcome of patients with advanced SCCHN.…”

Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus

“…Mortality for pneumonia is reported to occur well beyond 30 days after the end of treatments and a high risk of infection is maintained for several months [6,12]. Indeed, it must be considered that the local damage and nutritional impairment last several months after the end of treatment [150], consequently the risk of infection remains higher well after the end of treatment.…”

“…In CRT trials the acute mortality is described in the range from 2% [5] to 9.3% [6]. Infection is one of the main causes of acute mortality [6,7].…”

“…(1) Infection-related mortality can be confounded with other potential causes of death or categorized as "due to an unknown cause" [6], as the recognition of sepsis requires an active search and finite criteria. Most importantly unexplained organ failure (renal, respiratory, cardiovascular, coagulation, multi-organ etc.)…”

“…(2) Organ damage due to the systemic inflammatory response is often misinterpreted as being related to the individual toxicities of the treatment. In a retrospective analysis of 394 patients enrolled in consecutive CRT phase II trials at the University of Chicago, 14 deaths were attributed to infection and eight cases of pneumonia were considered "comorbidities" [6]. In total, 22 deaths (5.6%) were certainly due to infectious complications.…”