Clinical Characteristics, Treatments, and Prognosis of Patients with Multiple Primary Carcinoma of Head and Neck

Clinical Characteristics, Treatments, and Prognosis of Patients with Multiple Primary Carcinoma of Head and Neck

Multiple primary carcinoma (MPC), also known as secondary primary carcinoma, refers to the occurrence of two or more malignant tumors in the same organ or different organs of a patient. MPC is classified into two categories: synchronous MPC, where the time between diagnoses is six months or less, and metachronous MPC, where the time between diagnoses exceeds six months. Clinically, MPC is often misdiagnosed as the recurrence or metastasis of a malignant tumor. Accurate diagnosis and active treatment are crucial for patients with head and neck MPC.

This study was conducted over a 10-year period, from January 2008 to August 2018, at the Chinese People’s Liberation Army General Hospital. A total of 246 patients (145 males and 101 females) with MPC of the head and neck were included in the study. Among these, 66 patients had synchronous MPC, and 180 had metachronous MPC. The mean age of the patients was 56.6 years, ranging from 19 to 93 years.

The classification of MPC is based on the theory of regional cancer, which divides MPC into field cancerization of the head and neck (FCHN) and non-field cancerization of the head and neck (NFCHN). The inclusion and exclusion criteria for the study were based on Warren and Gates’ diagnostic criteria for MPC. Inclusion criteria required that each tumor must be malignant, each tumor must be solitary or have a tumor margin distance from normal tissue of more than 2 cm, and in the same area, the pathological types of tumors must be different. Exclusion criteria included cases where the pathological diagnosis was non-malignant or where there was recurrence or metastasis of the primary tumors.

All patients underwent a series of diagnostic examinations, including magnetic resonance imaging (MRI) of the primary site, ultrasound examination of cervical and superior clavicle lymph nodes and abdominal organs, fibronasopharyngoscopy, esophageal barium meal angiography, chest computed tomography (CT), and bone scan examinations. Additionally, 79 patients received whole-body positron emission tomography-CT (PET-CT) examinations.

Based on the treatment methods, patients were divided into three groups: synchronous FCHN patient group (time between diagnoses ≤6 months), synchronous NFCHN patient group (time between diagnoses ≤6 months), and metachronous patient group (time between diagnoses >6 months). In the synchronous FCHN patient group, 34 patients were given the most sensitive treatment according to clinical staging. In the synchronous NFCHN patient group, 32 patients were treated first for the life-threatening tumor sites with serious lesions. In the metachronous patient group, 180 patients received standard treatment plans according to international guidelines or expert consensus.

Follow-up was conducted mainly through outpatient reviews and telephone calls, with the last follow-up conducted in November 2018. Statistical analysis was performed using SPSS version 22. For categorical data, the Chi-square test was used for comparison. Survival rates were assessed using the Kaplan-Meier method. The log-rank test and the Cox proportional hazards model were used to identify prognostic factors independently associated with survival.

The follow-up period ranged from 3.0 to 127.0 months, with a median of 77.5 months. After follow-up, 60 patients had died, 21 patients were lost to follow-up, and 165 patients survived. Among these, the synchronous MPC group had 19 deaths and three patients lost to follow-up, while the metachronous MPC group had 41 deaths and 18 patients lost to follow-up. The 3-year and 5-year overall survival (OS) rates for the 246 patients were 89.91% and 83.82%, respectively. The 3-year and 5-year progression-free survival (PFS) rates were 87.40% and 79.71%, respectively.

The most common combination of cancers was hypopharyngeal carcinoma associated with esophageal cancer, which also had the lowest 3-year and 5-year OS rates (78.71% and 66.9%, respectively). The second most common combination was thyroid cancer associated with breast cancer, which had the highest OS rates (both 100%). The 3-year and 5-year OS rates for synchronous MPC patients were 71.71% and 63.36%, respectively, compared with 95.39% and 89.76% for metachronous MPC patients (P < 0.0001). The 3-year and 5-year PFS rates for synchronous MPC patients were 70.98% and 64.93%, respectively, compared with 92.57% and 84.38% for metachronous MPC patients (P = 0.0012). The 3-year and 5-year OS rates for FCHN patients were 83.45% and 76.66%, respectively, compared with 93.55% and 89.73% for NFCHN patients (P = 0.0014).

Single-factor analysis showed that gender, smoking, alcohol consumption, interval time, and the site of the first primary cancer were all factors affecting the survival of patients with MPC of the head and neck (all P < 0.05). Log-rank test and Cox proportional hazards model analysis showed that interval length was an independent risk factor (odds ratio = 0.500, 95% confidence interval, 0.389–0.644; P < 0.05).

For long-surviving patients with head and neck carcinoma, regular imaging and head and neck check-ups are crucial for the early detection of metachronous MPC. For patients with hypopharyngeal or esophageal cancer, cross-screening is required. Additionally, pathological biopsy is recommended for patients with head and neck tumors when other tumors are found outside the primary site.

With the improvement of tumor diagnosis and treatment, the incidence of MPC is rising and has become a focus of clinical and basic research. Cancer patients should be regularly reviewed and screened for potential tumors of other pathological types in the predisposed sites.

doi.org/10.1097/CM9.0000000000000632

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