Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up

The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.     

Multiple primary malignancies in head and neck cancer

Multiple primary (MP) malignancies were found in 9.7% of 1961 patients with primary head and neck cancer diagnosed at The Johns Hopkins Hospital, Baltimore, during the years 1975 to 1985. The index tumors were divided into six main groups. Out of the 190 MP malignancies, 46.9% were synchronous and 53.1% were metachronous. Seventy-four percent of MP lesions were noted during the first year after diagnosis of the index primary tumor. Patients with an index tumor in the upper aerodigestive tract had a significantly increased risk of developing a second cancer in the head and neck area. This risk was 5.94 for the oral cavity, 6.98 for the pharynx, 3.57 for the larynx, and 7.02 for the esophagus. Patients with an index tumor in the salivary gland or the thyroid gland had, respectively, a 3.59 and a 7.38 higher risk than the general population of developing a second tumor. Efforts aimed at improving the survival of patients with head and neck cancer must incorporate strategies for the prevention, early detection, and treatment of MP neoplasms.     

Multiple primary carcinomas in patients with head and neck malignancies

BACKGROUND: Multiple primary tumors can lead to diagnostic and therapeutical problems. In this study we surveyed frequency, localisation, diagnostic, chronologic and therapeutic aspects of multiple primary carcinomas in patients with head and neck tumors. PATIENTS AND METHODS: The data of 843 patients from the tumor registry of the ENT-clinic Aachen were retrospectively studied. RESULTS: Larynx (41.87%) and oropharynx (12.57%) were the main localisation of the first primary neoplasma. In 65 patients (7.71%) multiple primary tumors were observed. 24.6% of these tumors occurred synchronously. Preferential localisation of a second tumor were lung (20%), oral cavity (15.3%) and larynx (13.8%). 28.57% of the metachronous tumors were observed after more than five years. In 46.15% clinical complaints led to the suspicion of a second tumor. Panendoscopy was the most reliable diagnostic procedure. The survival rate and time was significantly reduced in patients with synchronous tumors. 3-year survival rate was 15% compared to 81% in patients with metachronous tumor appearance (p < 0.0001). CONCLUSION: Patients with head and neck tumors have a high incidence of multiple primary malignomas varying from the region of the first presentation of a malignant tumor. Concepts comprising surgery provide the highest survival rates. Because of the high incidence of metachronous carcinomas after five years found in this study, the authors regard a prolonged follow-up period as necessary.     

Multiple malignancies in patients with primary carcinomas of the head and neck

Eight hundred and twenty-five patients with primary carcinomas of the head and neck area were studied. Of these, there were 54 individuals with multiple primary neoplasms. Synchronous lesions occurred in 19 patients while nonsynchronous lesions occurred in 35. The frequency of occurrence of second neoplasms was 6.5%, which nearly doubles that of previously recorded series. A conclusion which can be made from this study is that, as long as the carcinogenic agent (alcohol and/or tobacco) continues to be present, the patient will continue to be affected.     

Abrasive esophageal cytology for the oncological follow-up of patients with head and neck cancer.

OBJECTIVES: The occurrence of a second primary cancer in the esophagus in patients with head and neck squamous cell carcinoma is frequent and is associated with a poor prognosis. The aim of this study was to evaluate the yield of abrasive esophageal cytology as a means of screening for metachronous cancer of the upper aerodigestive tract. STUDY DESIGN: We retrospectively reviewed the results of abrasive esophageal cytology performed twice yearly for the screening of patients with prior head and neck cancer. METHODS: From 1987 to 1996, 320 patients treated for head and neck cancer underwent 1,673 abrasive cytology examinations of the esophagus during a mean follow-up period of 4 years. Cytological results were classified as negative, suspect, or positive for malignancy. RESULTS: Twenty-five patients without symptoms had one or more suspect or positive cytologic findings, leading to 29 endoscopic examinations. These revealed 20 premalignant or early malignant lesions of the esophagus (2 dysplasias, 18 squamous cell carcinomas), 2 glandular carcinomas, and 10 clinically unsuspected oral or pharyngeal carcinomas. In seven patients, positive cytological results were associated with clinically visible head and neck cancer. Of the 34 patients with suspect cytological results for malignancy, 10 had no evidence of tumor at endoscopy and 24 had no endoscopic examination because of refusal or because suspected cells were not found in additional examinations. Negative results on cytological examination were found for 254 patients throughout their follow-up, and none of them developed esophageal cancer during a mean follow-up period of 3 years. CONCLUSIONS: For patients with head and neck cancer, abrasive sponge cytology is useful for detecting esophageal cancer at an early stage. In addition, it may reveal unsuspected second primaries or recurrences in the head and neck region.     

Paraneoplastic syndromes in patients with primary head and neck cancer

Paraneoplastic syndromes represent the clinical manifestations of the indirect and remote effects produced by tumor metabolites or other products. The clinical spectrum of the various paraneoplastic syndromes related to primary malignancies of the head and neck region is presented. A review of the literature on paraneoplastic syndromes in patients with primary head and neck cancer was carried out. Paraneoplastic syndromes related to primary malignancies of the head and neck region can be categorized as: endocrine, cutaneous or dermatologic, hematologic, neurologic, osteoarticular or rheumatologic, ocular syndromes. Sometimes, paraneoplastic syndromes can be more serious than the consequences of the primary tumor itself and can precede, follow or be concurrent to the diagnosis of a malignancy; moreover, they can dominate the clinical picture and thus lead to errors with respect to the origin and type of the primary tumor. Physicians who deal with cancer-associated syndromes should be able to differentiate the paraneoplastic syndromes from the benign disorders that mimic them. Patients with a suspected paraneoplastic disorder should undergo a complete panel of laboratory studies, in addition to imaging studies and endoscopy. Identification of paraneoplastic syndromes allow the clinician to make an early diagnosis and to provide adequate treatment of tumors, with a favorable oncologic outcome and improved life expectancy for the patient. These syndromes can follow the clinical course of the tumor and thus be useful for monitoring its evolution.     

The dilemma of follow-up in head and neck cancer patients

The aims of tumor follow-up in head and neck cancer patients are (1) evaluation of therapeutic efficacy, (2) management of impairments, (3) detection of new tumor manifestations, and (4) psychosocial care. In general standardized 5-year-protocols are used for all such patients. However, it is questionable whether a rigid follow-up schedule is optimal for a very heterogeneous tumor population. Therefore 603 patients with sqamous cell carcinoma of the oral cavity, pharynx or larynx, or with cervical metastasis from an unknown primary site (CUP syndrome), who had been diagnosed and treated curatively by an operation with or without radiotherapy (n = 523) or just by radio(chemo)therapy (n = 80) between 1985 and 1994, and who had been followed-up regularly according to a standardized plan, were worked-up retrospectively. Data were evaluated for the manifestation and prognosis of curable new tumor manifestations as well as for tumor-specific factors likely to select groups which should be followed more or less intensively. Within a 5-year follow-up period new tumor growth was detected in 152/603 (25%) patients: 79 local and 31 regional recurrences, 18 systemic metastases and 24 second primary cancers. Where follow-up was extended beyond the 5th year, 168/603 (28%) patients presented a new tumor manifestation. One hundred and sixteen of the 152 (28%) patients had another operation with or without radiotherapy or had radio(chemo)therapy alone. So far 18/116 (14%) patients have survived their new tumor manifestation for more than 5 years and 30/116 for more than 2 years. Tumor-specific data on the initial tumors (T stage, N stage, site) did not indicate the risk of a new tumor manifestation, but 87% of patients who survived their new tumor manifestation for more than 2 years initially had T1 or T2 tumors and only 30% initially had N+ necks. Occurrence of distant metastasis or a second primary outside the head and neck region limited survival to ≤ 2 years after detection. In terms of survival, follow-up efforts should therefore concentrate on detection of locoregional recurrence, particularly if an option for further curative local therapy exists. The limited success of detection of new tumor manifestations in terms of survival does not justify a reduction in tumor-follow-up examinations, since the benefit of the other efforts cannot be determined from survival figures. Received: 29 January 2001 / Accepted: 8 February 2001     

Multiple primary malignancies in patients with malignant tumours of the nasal cavities and paranasal sinuses

The incidence of multiple primary malignancies (MPM) was analysed in 1297 patients with malignant tumours of the nasal cavities and paranasal sinuses. The patients were followed for a minimum of six years or until death. The incidence of MPM was 3.4 per cent (44/1297) which is lower in patients with malignant tumours of other regions in the upper aerodigestive tract. Five of the 44 patients had second malignancies within previously irradiated areas. There was a difference between the proportion of histologies occurring in irradiated tissues compared with the overall 1297 patients. This finding suggests that radiotherapy may induce a second cancer.     

The follow-up of patients with head and neck cancer: an analysis of 1,039 patients

In all cancer specialities, there has been much debate about the best follow-up regime. The provision of a service that meets high standards whilst being cost-effective is increasingly pertinent. The objectives of the study were to examine: whether routine follow-up facilitates early diagnosis and recurrence; whether there is a cohort of patients who require a more intensive follow-up regime; whether follow-up should be customised to individual patients. A total of 1,039 consecutive outpatient consultations were prospectively analysed in a multicentre study. All adult patients who had undergone multidisciplinary, multimodality management for head and neck cancer were included. The case mix was representative of all head and neck tumour sites and stages. Suspicion of recurrence was noted in 10% (n = 96/951) of patients seen routinely. This rose to 68% (n = 60/88) for the subset of patients who had requested an appointment. Most recurrences were found within the first follow-up year (n = 64/156, 54%). Only 0.3% (n = 3/1,039) of asymptomatic patients attending routine appointments were suspected of having a recurrence, and two (0.2%) were found to have an actual recurrence following investigation. Of the total number of patients reporting a new suspicious symptom, recurrence was suspected in 56% (n = 152/270). Patients thus had a 98.1% sensitivity to raising suspicion for a recurrence based on the reporting of new symptoms with a 99.6% negative predictive value. Our data show that the efficiency of the current follow-up regime at detecting suspected recurrence of head and neck cancer is low, suggesting the need for a customised, more focused follow-up regime, tailored to individual cases. Patient education and close relationships with clinicians and allied health-care professionals are essential for early diagnosis and management of cancer recurrence. Follow-up regimes within the first year should be most intensive as recurrence is most likely within this time, and it serves to alleviate patient anxiety in the early post-treatment period. More research needs to be carried out to investigate the role of patient self-reporting and surveillance of cancer recurrence.     

Multiple primary cancers of the head and neck

Multiple primary cancers of the head and neck are not always rare. We have experienced 30 cases of multiple primary cancers in the Department of Otolaryngology, Ehime University School of Medicine from 1976 to 1989. The incidence ranged from 3.6% to 8.9% with flexible criteria. The minimum was 14 of 393 cases of all index cancers, strictly conformed with Warren's definition. The maximum was 29 of 327 cases of index cancers on the mucosal surfaces, including a combination of both head and neck cancers. In view of organic specificity of the index cancers, the incidence was high in the larynx and oral cavity, low in the nasopharynx and maxillary sinus. The concept of "multicentric cancerization" was verified by the result that 60% of the additional cancers were head and neck, esophagus and lung. During following-up studies of oropharyngeal, hypopharyngeal and laryngeal cancers, we have to examine the esophagus periodically due to high risk of occurrence of cancer. To compare the data of multiple primary cancers of the head and neck between institutions, adequate and detailed criteria should be established.     

Treatment costs for patients with head and neck cancer.

A national health program is inevitable if medical care costs continue to soar as they have in recent years. Those of us treating patients with cancer of the head and neck are aware that the costs are high, but many are not aware of the actual figures involved. In this study, five typical head and neck cancer patients were selected, and the costs incurred by these patients were calcualted. Both direct and indirect medical expenses were considered and are presented. In addition, we report the representative costs of various treatment modalities. An awareness of medical care costs plus appropriate consideration of them in the planning and administration of treatment may help to reduce health care expenses. If we do not control these costs, the government undoubtedly will.     

Survival in second primary malignancies of patients with head and neck cancer

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.     

Immunoglobulin allotypes in head and neck cancer patients with multiple primary cancers

Immunoglobulin allotypes G1m, G2m, G3m, A2m and Km were determined in patients with a single head and neck cancer and in head and neck cancer patients with multiple primary tumours. Frequencies were compared with those of healthy controls. In all 39 patients with multiple primary tumours studied, Km(1) was absent vs. 82% and 75% absence in healthy controls and patients with a single head and neck cancer, respectively. This difference is highly significant. We conclude that head and neck cancer patients lacking the Km(1) are susceptible to the development of new cancers, and therefore should be screened thoroughly for more tumours.