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.     

Role of alcohol and smoking in diagnostic delay of head and neck cancer patients

CONCLUSIONS: This study shows that heavy drinking is a risk factor for prolonged delay in presenting with head and neck cancer and for presenting with a large tumour in the head and neck region. Excessive smoking is only a risk factor for being diagnosed with a large tumour, although there is a weak association between smoking and prolonged diagnostic delay. OBJECTIVE: It is reasonable to assume that prolonged delay in presenting with head and neck cancer is associated with an advanced stage of cancer at diagnosis. In this study we analysed the effects of drinking and smoking habits on diagnostic delay and the T stage of the tumour at diagnosis. MATERIAL AND METHODS: A total of 427 patients with newly diagnosed head and neck carcinomas were eligible for this study. Of these, 306 (72%) actually participated: 134 (77%) with an oral tumour; 117 (69%) with a larynx tumour; and 55 (65%) with a pharynx tumour. Diagnostic delay was defined as a period of >30 days between the appearance of the first tumour-related symptoms and the first visit to a physician. T3 4 tumours were defined as advanced tumours. Drinking behaviour was classified into three types: light (0 2 drinks/day); moderate (3 4 drinks/day); and heavy ( >4 drinks/day). Smoking habits were classified into 4 types: never; stopped; light (0 20 cigarettes/day); and heavy (>20 cigarettes/day). RESULTS: Logistic regression showed that there were significantly more heavy than light drinkers [p = 0.04; odds ratio (OR) 1.8; 95% CI 1.0-3.1] in the delay group than in the non-delay group. Light smokers showed a tendency towards prolonged delay (p = 0.06; OR 2.2; 95% CI 1.0-5.0). Both heavy drinking (p = 0.01; OR 2.0; 95% CI 1.2-3.6) and heavy smoking (p = 0.03; OR 3.1; 95% CI 1.1-8.4) were risk factors for a patient to be diagnosed with a large tumour.     

Multiple carcinomas in the upper aerodigestive tract. 1. Oral cavity and oropharynx

BACKGROUND: During the last years an absolute increase of tumour incidence of squamous cell carcinoma as well as an increase in the occurrence of synchronous and metachronous multiple primaries in the upper aerodigestive tract can be observed. This study analyses the so-called "multi-centric cancerization" in patients with primary carcinoma of the oral cavity and the oropharynx. METHODS: During 2 observation periods of 5 years each, from 1985 to 1994, we retrospectively analyzed 235 patients with squamous cell carcinoma of the oral cavity and 232 patients with tumour localisation in the oropharynx. Besides age, sex, tumour localization, TNM-stage and grading, the risk factors tobacco and alcohol were added as causes for the development of multiple primaries. RESULTS: In the primary localisation of the oral cavity synchronous and metachronous double tumours increased from 7% to 17% besides the absolute increase in tumour incidence. In the oropharynx a total increase of second carcinomas from 3% to 20% was found. At the same time a growing abuse of tobacco and alcohol could be observed. CONCLUSIONS: Panendoscopy during pre-therapeutical staging should be obligatory. Regular oncological controls are mandatory, especially for younger patients with smaller tumours and good prognosis, but a high risk of second primaries. In the long run, prevention has to play a decisive role in the fight against second primary tumors of the upper aerodigestive tract. Possible improvements of early diagnosis, genetical examinations, information campaigns as well as research of carcinogenic environmental pollutants are of foremost interest to the clinician.     

Panendoscopy and synchronous second primary tumors in head and neck cancer patients

Endoscopy techniques are used to diagnose and to determine the extent and exact location of malignancies in the head and neck region, bronchial tree and esophagus. Panendoscopy is used to find the primary tumor in the case of metastatic disease from unknown primaries or to detect a simultaneous second primary tumor at the time of diagnosis of a malignancy in the upper aerodigestive tract (UADT). The value of panendoscopy has been debated lately because of the relatively small proportion of malignant findings and because of the lack of convincing data concerning its effect on survival rates. However, despite the relatively low proportion of positive findings, their significance is often crucial for the individual patient. The significant number of late metachronous, second primaries, especially in the lungs, also emphasizes the importance of follow-up endoscopies. This study consists of 203 consecutive patients with squamous cell cancer (SCC) of the upper aerodigestive tract who underwent panendoscopy in Turku University Central Hospital as part of the initial diagnostic workup from 1992–1999. Eight patients with synchronous second primaries were found to represent a prevalence of 3.9%, and in addition, 19 patients with metachronous tumors were diagnosed. In the case reports we illustrate the importance of some of these findings.     

The increase in incidence of cancer of the tongue in the Nordic countries continues into the twenty-first century

Conclusions This study shows that heavy drinking is a risk factor for prolonged delay in presenting with head and neck cancer and for presenting with a large tumour in the head and neck region. Excessive smoking is only a risk factor for being diagnosed with a large tumour, although there is a weak association between smoking and prolonged diagnostic delay.

Objective It is reasonable to assume that prolonged delay in presenting with head and neck cancer is associated with an advanced stage of cancer at diagnosis. In this study we analysed the effects of drinking and smoking habits on diagnostic delay and the T stage of the tumour at diagnosis.

Material and methods A total of 427 patients with newly diagnosed head and neck carcinomas were eligible for this study. Of these, 306 (72%) actually participated: 134 (77%) with an oral tumour; 117 (69%) with a larynx tumour; and 55 (65%) with a pharynx tumour. Diagnostic delay was defined as a period of >30 days between the appearance of the first tumour-related symptoms and the first visit to a physician. T3–4 tumours were defined as advanced tumours. Drinking behaviour was classified into three types: light (0–2 drinks/day); moderate (3–4 drinks/day); and heavy (>4 drinks/day). Smoking habits were classified into 4 types: never; stopped; light (0–20 cigarettes/day); and heavy (>20 cigarettes/day).

Results Logistic regression showed that there were significantly more heavy than light drinkers [p=0.04; odds ratio (OR) 1.8; 95% CI 1.0–3.1] in the delay group than in the non-delay group. Light smokers showed a tendency towards prolonged delay (p=0.06; OR 2.2; 95% CI 1.0–5.0). Both heavy drinking (p=0.01; OR 2.0; 95% CI 1.2–3.6) and heavy smoking (p=0.03; OR 3.1; 95% CI 1.1–8.4) were risk factors for a patient to be diagnosed with a large tumour.     

Metachronous adenocarcinoma of the maxillary sinuses: a rare entity

Malignant tumours of the nasal cavities and paranasal sinuses are uncommon. They constitute less than one per cent of all tumours and less than three per cent of head and neck tumours. Although multiple primary carcinomas of the aerodigestive tract are commonly reported, metachronous maxillary sinus carcinomas are rare. To date, all of these cases reported are of squamous cell origin. The incidence of metachronous maxillary carcinoma involving both sinuses is in the range of 1.4 per cent amongst patients with maxillary carcinoma. We present the first reported case, to our knowledge, of a patient with metachronous adenocarcinoma of the maxillary sinus.     

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.     

Malignant tumours in patients with non-invasive squamous cell lesions of the vocal cords

The concept of 'field cancerization' is applicable throughout the upper aerodigestive tract, oesophagus and lung. The material for this study consisted of 232 patients with hyperplasia, keratosis with or without dysplasia, and carcinoma in situ of the vocal cords. The overall risk for these patients with non-invasive squamous cell lesions of the vocal cords to have or to develop an independent, primary malignant tumour was 12.9% (30/232). Carcinomas of the head and neck, lung or oesophagus were diagnosed in 8.2% (19/232) of the patients. Patients with hyperplasia, keratosis, dysplasia and carcinoma in situ of the vocal cords should be carefully followed-up, not only as progression to invasive carcinoma may occur many years after the initial diagnosis, but also as there is a high incidence of independent primary tumours, especially of the multicentric type.     

Non-squamous malignancy in lymph nodes: the occult primary

The present study presents 105 patients seen at a head and neck specialist clinic with a neck gland which subsequently proved to be a non-squamous malignancy. Of the 105 patients, 50 patients were eventually found to have a tumour in the head and neck region, 30 to have a distant primary and in 25 no primary site was ever found. The majority of patients were diagnosed in the clinic after careful examination and most of the remainder were diagnosed during endoscopy/biopsy. Chest radiography was the most useful investigation for diagnosing primary tumours of the lung. The 5-year-survival for the whole group of 105 patients was 28% (95% CI 17–39). The 5-year-survival for the head and neck primary tumour group was 44% (95% CI 25–60). The median survival of patients with a distant primary tumour was only a 6 months, there was one 5-year-survivor. The median survival for those in whom the primary was never discovered was 18 months. However, a reasonable proportion of these patients survived, five being alive at 5 years. The difference between survival for the three groups was statistically significant (P < 0.001). The most common histological type was undifferentiated/anaplastic tumours (37 out of 105) and this was followed by adenocarcinoma (33 out of 105). There was a significant difference in the survival between these two groups (χ²= 2.02, d.f. = 1, P= NS). Multi-variate analysis suggested that survival was better in the older age group and was affected by histology (P= 0.0093, P= 0.0332 respectively). The present study suggests that the treatment of patients in whom the primary site is eventually found to be in the head and neck region is rewarding with the same survival as a similar group of patients with squamous cell carcinoma. Sixty of the group of 105 patients had excision biopsies of the neck node and this did not affect survival.     

Improved tumor site and contrast resolution in ultrasound diagnosis by using harmonic frequencies

BACKGROUND: The aim of new techniques in head and neck sonography is to increase the sensitivity and the specificity of the examination. With tissue harmonic imaging (THI) and contrast harmonic imaging (CHI) new techniques are available which allow increased contrast and resolution in head and neck sonography as well as a better detection of small blood vessels. METHODS: We studied whether these techniques improve sonographic detection of head and neck lymph nodes and primary tumours of the upper aerodigestive tract. RESULTS: The results indicate that THI allows a better detection of cervical lymph nodes. Furthermore, intranodal structures and the borders of the lymph node can be better detected. Using CHI, typical patterns of vascularization can be seen, allowing a better interpretation of the node's tumour status. Primary tumours can be detected sufficiently well using conventional B-scan techniques although they are easier to detect with THI. Using CHI, many tumour vessels can be detected, but this does not increase the sensitivity of the sonographic examination. CONCLUSION: THI and CHI may increase the specificity of sonographic diagnostics of cervical lymph nodes but show no clinical benefit regarding the diagnostics of primary tumours of the upper aerodigestive tract.     

Teratomas of the head and neck in infancy and childhood

Teratomas of the head and neck make up only 9% of tumours occurring during childhood. They may occur within the upper aerodigestive tract or outside it in the neck. In either case they may present a life-threatening airway obstruction, which sometimes can occur at birth. We report the case of a child who presented at birth with a mass in the left submandibular region, and who subsequently developed a tumour at the upper pole of the left tonsil. Both lesions were teratomas with a similar histological composition. The significance of this is discussed in terms of the theories that have been previously advanced to explain the development of teratomas. Both tumours have been removed and the child remains well and free of recurrence.     

Tobacco- and alcohol-associated cancer risk of the upper respiratory and digestive tract

A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in the ENT Departments of the University hospitals of Heidelberg and Giessen (FRG) provided information on the role of chronic tobacco and alcohol consumption as risk factors in 200 patients and 800 control subjects (4:1 matched design).--Only 4.5% of the tumour patients were non-smokers in contrast to 29.5% in the control group. The average tobacco and alcohol consumption in the patients was more than twice that high than in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer.--It could be demonstrated that tobacco as well as alcohol increased the risk for head and neck cancer, in a dose-dependent fashion, as separate risk factors. In heavy smokers (greater than 60 pack years) a relative risk of 23.4 (alcohol-adjusted) was calculated. For heavy drinkers (greater than 100 g ethanol/day) a relative risk of 21.4 (tobacco-adjusted) was documented. Combined alcohol and tobacco consumption showed a synergistic effect and increased the cancer risk more in an multiplicative than in an additive manner: A daily ethanol consumption of more than 75 g/day combined with more than 50 pack years caused a risk value of 146.2.     

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.     

Squamous cell carcinoma of the sinonasal cavity arising as a second primary in individuals with head and neck cancer

OBJECTIVES/HYPOTHESIS: Second primary tumors occur frequently in patients with head and neck carcinoma. This may be caused by generalized exposure to carcinogens resulting in "field cancerization" or to the individuals' generalized susceptibility to cancer. The paranasal sinuses are not commonly included in the sites considered at risk for this process. We therefore sought to assess the overall risk of contracting a primary cancer in this region after having a tumor elsewhere in the upper aerodigestive tract. STUDY DESIGN: Retrospective. METHODS: Two thousand four hundred seventy-five patients with squamous cell carcinoma of the upper aerodigestive tract were analyzed using a tumor registry at a tertiary care institution. RESULTS: Five (0.2%) patients were identified as having a second primary in the sinonasal tract. The average interval between the index and second primary tumors was 28.4 (range 8-60) months. All five patients presented with symptoms typical of sinus inflammatory disease and had advanced sinus lesions at the time of diagnosis. These findings are typical of those with sinonasal carcinoma in that they present with nonspecific signs and symptoms and were diagnosed with locally advanced disease despite being in a surveillance program for their index cancer. CONCLUSIONS: Although uncommon, the data reported here support inclusion of the sinonasal tract in these surveillance programs. This could result in earlier detection and greater opportunity for curative intervention.     

Laparoscopic Gastrostomy Versus Open Gastrostomy in Head and Neck Cancer Patients

Alimentation in the surgically treated head and neck cancer patient frequently requires bypassing the upper aerodigestive tract. The laparoscopic gastrostomy fulfills this criterion. The authors compared 25 laparoscopic gastrostomies (group 1) with 18 open gastrostomies (group 2) performed on head and neck cancer patients. The length of operation, morbidity, mortality, and cost were evaluated. Operative time was significantly shorter in group 1 (40± 2 minutes) than in group 2 (56 ± 4 minutes), with P=.003. The major complication rate was 9% for group 1 and 11% for group 2. There was no procedure-related mortality in group 1, but 1 patient died in the immediate postoperative period in group 2. The cost was not significantly different. It is concluded that the laparoscopic gastrostomy is a safe and cost-effective alternative to open gastrostomy in this patient group.     

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.     

„Field cancerization“ im oberen Aerodigestivtrakt

The term "field cancerization" was coined by Slaughter in1953 when describing multifocal synchronous and metachronous carcinogenesis in the upper aerodigestive system. Patients suffering from head and neck cancer (HNC) have or develop a second esophageal squamous cell cancer (ESCC) or bronchial cancer (BC) in 5-14% of cases. When a second esophageal cancer occurs in a patient with HNC, the prognosis is generally determined by the ESCC, and, unfortunately, it is poor. Screening and surveillance by Lugol chromoesophagoscopy enable early detection and curative treatment of second esophageal neoplasias. Surveillance appears to result in a survival benefit for HNC patients. Vice versa, patients with ESCC or BC have a risk of about 10% for developing HNC. Periodic pharyngolaryngoscopy is recommended for curatively treated ESCC or BC patients. Patients with field cancerization should be surveilled by a multidisciplinary approach.     

Observing stage‐shifts in head and neck squamous cell carcinoma from initial clinical outpatient staging to definite clinical tumour board staging using radiological and endoscopical investigations: will less do?

Clin. Otolaryngol. 2011, 36 , 352–360 Objectives: Staging head and neck squamous cell carcinoma usually is initiated in the outpatient department (OPD) using patient history and physical examination. To reach consensus on stage and therapy, imaging and panendoscopy are more or less routinely applied as additional staging tests. Staging results from the outpatient department were evaluated for tumour and neck stage. We investigated in which situations additional staging tests are needed. Design: Prospective cohort study. Setting: Head and Neck Oncology Group, University Medical Centre. Participants: Of 341 patients, initial staging results from the outpatient department were compared with the ultimate staging results from the tumour board review, which provides the basis for decisions on therapy. Main outcome measures: Tumour stage and neck stage migrations during this staging tract. Results: In staging head and neck tumours are squamous cell carcinomas, additional staging tests like imaging and/or panendoscopy remain necessary to evaluate the primary tumour stage. Average accuracies of T‐staging in oral cavity, pharynx and larynx only amount to 71%, 47% and 61%, respectively. For T1N0 and T2N0 oral cavity tumours, neck assessment in the outpatient department was accurate in 100% (95% CI: 91–100%) and 93% (95% CI: 80–98%), respectively. In the larynx group, this was 100% (95% CI: 91–100%) and 97% (95% CI: 86–100%), respectively. Conclusions: For oral cavity and laryngeal tumours staged as T1‐2N0 in the outpatient department, we concluded that the outpatient department staging is highly predictive of the final pre‐treatment staging. In these cases, computer tomography and/or MRI remain a necessity but additional ultrasound with or without fine needle aspiration cytology can be omitted. In our institution, this would have resulted in a 46% reduction in ultrasound procedures. If T‐stage is upgraded during imaging or panendoscopy, additional staging tests for N‐stage should still be considered.     

Current concepts in the management of a second malignancy of the lung in patients with head and neck cancer

Simultaneous, synchronous, and metachronous presentation of lung malignancies when treating head and neck squamous cell cancers is one of the most difficult challenges in head and neck surgery. However, good (> 40%) 5-year survival can be obtained when proper screening techniques, patient selection, and therapy are combined. Because of the complexity of the head and neck resection and reconstruction and the multiple surgical and medical services used to diagnose and treat this clinical entity, a comprehensive review of the current literature is provided. The clinically pertinent meanings of simultaneous, synchronous, and metachronous second malignancy of the lung are presented. A review of the current literature is presented that divides second lung malignancy into two groups: second primary and metastasis. The incidence of a second lung malignancy is identified. The tools used in the screening of high-risk patients and the role of the new diagnostic studies such as positron emission tomography and positron emission tomography CT scans are reviewed. Finally, the current literature on patient selection and surgical therapy is used to put forth a clinical pathway followed at the authors' institution for the treatment of these patients.     

Photodynamic therapy with meta-tetrahydroxyphenylchlorin (Foscan<Superscript>®</Superscript>) in the management of squamous cell carcinoma of the head and neck: experience with 35 patients

Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin and mucosa. After the injection of a photosensitising agent, the tumour area is exposed to non-thermal laser light. This causes a phototoxic reaction, producing oxygen radicals that destroy tumour cells. From November 2003 to July 2007, a total of 35 patients with recurrent squamous cell carcinoma or secondary tumours of the head and neck region were treated with PDT at the German Armed Forces Hospital in Ulm. These patients had failed or found unsuitable for other treatments. Meta-tetrahydroxyphenylchlorin (mTHPC), known under the trade name of Foscan^®, was used as the photosensitising agent. Local control was achieved in 21 patients (60%) and partial remission in 10 patients (28.5%). Four patients (11.5%) did not respond to PDT treatment. The mean duration of overall survival was 401.45 (±321.2) days, median was 356 after the completion of treatment. The mean duration of recurrence-free survival was 327.7 (±131.1) days, median was 181 for patients with complete remission. None of the patient developed serious complications. Photodynamic therapy is an important treatment option for patients who present with recurrent carcinoma or secondary tumours of the upper aerodigestive tract and who have failed or unsuitable for other treatments. Due to the excellent treatment results that have been achieved so far, PDT may in the future also play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx.