Impact of second primary tumors on survival in head and neck cancer: an analysis of 2,063 cases

Objective/Hypothesis: To investigate the impact of second primary tumors on prognosis for patients with head and neck squamous cell carcinoma (HNSCC). Study Design: Prospectively recorded data on HNSCC patients treated at an academic tertiary referral center. Methods: An analysis of 2,063 patients treated over a 15 year period for tumors of the upper aerodigestive tract, with a minimum follow‐up of 10 years. Results: A total of 351 (17%) patients developed a second primary, mean time to diagnosis of the second tumor being more than 4 years from the date of the initial tumor. Median overall survival from the date of the first tumor among patients who later developed a second primary was 6 years versus 3 years among all other patients (P < .05). During the first 6 years after treatment of the initial tumor, cancer specific survival was better in the second primary group. After diagnosis of a second primary tumor, median survival was 12 months. A positive correlation was found between second primaries and stage I/II primary disease, low patient age, and initial tumors of the larynx and oral cavity. Conclusions: The group of patients with the highest risk of a second primary tumor was younger patients with limited initial tumors. A high proportion of patients who later developed a second primary were complete responders after treatment of the first tumor. However, prognosis was poor after the actual diagnosis of the second primary tumor.     

Synchronous multiple primary lesions of the upper aerodigestive system.

Multiple primary lesions were initially thought to be rare occurrences; however, recent numerous series show the incidence to vary from 1% to 11%. These reports generally refer to lesions that develop subsequently to diagnosis and treatment of the initial lesion, and the results of these studies reflect improved follow-up, treatment, and possibly a true increase in frequency. In the search for synchronously developing primary lesions, it was decided to perform panendoscopies on all cases of cancer of the upper aerodigestive tract, irrespective of size or situation or whether they were amenable to evaluation under local anesthesia. These panendoscopies were performed on 162 consecutive cases with a diagnosis of 15 synchronous second primary lesions, ie, an incidence of 9.2%. For this reason, as much time and effort as possible should be devoted to detecting the synchronous second primary lesion as the later developing lesion, and panendoscopy has proved invaluable in achieving this.     

Multiple synchronous carcinoma of the aero-digestive tract

Multiple carcinoma of the upper aerodigestive tract is an increasingly recognized problem, and a concept of 'field cancerization' has been proposed to explain this phenomena. The initial assessment of a patient with an isolated aerodigestive carcinoma must be extensive so as not to miss any synchronous lesions, and may include radiography and endoscopy. Treatment cannot be standardised but must be tailored to suit individual problems and because of the high incidence of metachronous tumours, follow-up must be both thorough and 'lifelong'. A case of three primary synchronous squamous carcinomas of the upper aerodigestive tract is presented. The relevant literature is reviewed.     

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 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 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.     

Incidence of multiple tumors in the upper aerodigestive tract. Routine panendoscopy?

The incidence of multiple squamous cell carcinomas in the upper aerodigestive tract of 589 patients is presented and discussed. Multiple synchronous tumors had been found in 1.83% of patients in 1980-1984. Since the end of 1984 in most cases routine praetherapeutic panendoscopy was performed. 15.6% of these patients with panendoscopy had multiple synchronous primary tumors. The mouth and oropharynx were found to be high risk primary areas and the larynx a low risk area, concerning synchronous tumors in other localizations. The incidence of second primaries in the bronchi and especially in the oesophagus justifies routine praetherapeutic panendoscopy of which our technique is described.     

Tonsil carcinoma — treatment results

Epidermoid carcinoma of the tonsil region is one of the most common malignancies of the upper aerodigestive tract, equal in frequency to laryngeal carcinoma at the University of Cincinnati Medical Center. This paper reviews the authors' experience in treating these lesions with a combination of 5000 rads preoperatively followed by composite resection. The overall two-year crude survival is 56%. A 60% two-year survival for T₃ lesions compares favorably with other series for treatment of T₃ lesions.     

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.     

Early detection of premalignant lesions and oral cancer

Cancers of the oral cavity account for approximately 3% of malignancies diagnosed annually in the United States. As with other upper aerodigestive tract cancers, 5-year survival rates for oral cavity cancers decrease with delayed diagnosis. Cancers of the oral cavity are thought to progress from premalignant/precancerous lesions, beginning as hyperplastic tissue and developing into invasive squamous cell carcinoma. Despite the general accessibility of the oral cavity during physical examination, many malignancies are not diagnosed until late stages of disease. To prevent malignant transformation of these oral precursor lesions, multiple screening and detection techniques have been developed to address this problem.     

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.     

Multiple primary cancers of oral cavity and pharynx

Multiple primary cancers were found in 23 of 68 patients (34%) with an index cancer in the oral cavity or pharyngeal area treated in our institute from June 1995 to July 1998. Four cases had triple primary cancers. All 68 cases underwent upper and lower gastrointestinal endoscopy as well as ultrasonography of the liver. Lung CT was performed in cases with abnormal findings on chest roentgenograms. Multiple cancers were found in 5 of 25 oral cavity cases (20%), 6 of 14 mesopharynx cases (43%) and 12 of 29 hypopharynx cases (41%). Nine of 23 cases (39%) were synchronous and 14 (61%) were metachronous. Eighteen of 27 (69%) secondary cancers occurred in the upper aerodigestive tract with an especially high incidence (22%) in the esophagus. Gastroendoscopy also revealed 7 neoplastic lesions, aside from cancers, with the total abnormal rate of 24% (24/68). Thus, gastroendoscopy is useful for the diagnosis of multiple primary cancers. The frequency of multiple primary cancers in males (33%) was not different from that in females (35%). The average age of multiple primary cancer patients (65.1 years) was a little higher than that of single cancer patient (62.7 years). Smoking or drinking was not related to the incidence of multiple cancers. The interval between the first and the second cancer in metachronous cancer cases was 25.5 months on average, and within 4 years in 71% (10/14) of the cases. This result suggests that close follow-up including endoscopy should be required for at least 4 years after treatment of oral or pharyngeal cancer. Radical treatment for each of the multiple cancer lesions was performed in 22 of 23 cases, and the mortality rate of multiple primary cancer cases was not significantly different from that of single cancer cases. Among 7 cases who died of disease, 5 cases died of distant metastasis, suggesting that control of distant metastasis is an important issue in the treatment of multiple primary cancers.     

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.     

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.     

Management of thyroid carcinoma invading the aerodigestive tract

Objectives: To evaluate approaches to thyroid carcinoma invading the aerodigestive tract, with particular attention to well-differentiated carcinomas. Study Design: Retrospective review of experience with thyroid carcinoma invading the aerodigestive tract over a 20-year period at a tertiary referral hospital. Methods: The medical records of all patients with a diagnosis of thyroid cancer treated at Emory University Hospital, Atlanta, Georgia, from 1977 through 1997 were reviewed. Multiple clinical variables were analyzed including treatment, development of recurrence, and survival. Survival and time to local recurrence were determined by Kaplan-Meier analysis, and statistical comparisons were made using log-rank analysis. Results: Five hundred thirty-six cases were identified; 28 patients (5.2%) were identified with invasive disease involving the aerodigestive tract. Histologic findings at the time of invasion included 15 well-differentiated (WD) carcinomas and 13 poorly differentiated (PD) carcinomas. Eight of the 28 patients (5 WD, 3 PD) underwent surgical resection of some portion of the aerodigestive tract with curative intent. Ten patients (8 WD, 2 PD) underwent incomplete resection with tumor left adjacent to aerodigestive tract structures. All patients undergoing incomplete resection developed local recurrence. Six required salvage resection, as opposed to no recurrences in WD carcinomas following complete resection (P = .01). Survival at 5 years for WD carcinomas undergoing complete resection versus initial incomplete resection was 100% versus 50%, respectively (P = .27). Conclusion: Review of our experience shows that complete resection of thyroid carcinoma invading the aerodigestive tract can offer prolonged palliation, improved local control, and the opportunity for cure in selected patients.     

Cyclin D1 and p53 overexpression predicts multiple primary malignant neoplasms of the hypopharynx and esophagus

BACKGROUND: Multiple primary upper aerodigestive tract carcinomas can occur in up to 15% of patients. We have shown previously that half of the patients with multiple upper aerodigestive tract squamous cell carcinomas are initially seen with synchronous tumors. Most metachronous squamous cell carcinomas become manifest within 3 years. OBJECTIVE: To examine the expression of 2 proteins-cyclin D1 and p53--in an attempt to predict the occurrence of multiple primary malignant neoplasms (MPs). MATERIALS AND METHODS: Monoclonal antibodies to cyclin D1 (DCS-6 [dilution, 1:50]. Novocastra Laboratories Ltd, Newcastle, England) and p53 (DO-7 [dilution, 1-100], Dako Corp, Carpinteria, Calif) proteins were used. Resection specimens from a total of 47 patients, 12 patients with MP and 35 patients with nonmultiple primary malignant neoplasms, were analyzed. Those in the nonmultiple primary malignant neoplasm group had longer than 3 years' follow-up to ascertain the absence of MP. RESULTS: Tumor overexpression of cyclin D1 was significantly associated with the development of MP (P<.01). Tumor overexpression of p53 was also frequent in patients with MP although statistical significance was not achieved. The combination of these 2 parameters was an even greater predictor of MP (P<.001). CONCLUSIONS: Overexpression of cyclin D1 and p53 proteins was highly correlated with the development of MP. Additional studies are necessary to confirm this finding. Immunohistochemical evaluation of primary squamous cell carcinomas for cyclin D1 and p53 overexpression may become an important fact of surgical pathologic reporting for primary upper aerodigestive tract squamous cell carcinomas.     

Early percutaneous endoscopic gastrostomy nutrition in head and neck cancer patients

Objective Many head and neck cancer patients suffer from poor nutrition. Nutrition is a problem during and after therapy, especially when it consists of extensive surgery, intensive (chemo)radiotherapy or their combination. Additional enteral nutrition has been provided by means of either nasogastric tube feeding, surgical gastrostomy, radiologic percutaneous gastrostomy or percutaneous endoscopic gastrostomy (PEG). Because of the straightforward, easy technique involved and its low complication rate, PEG has become established as the primary route of nutrition in these patients. Previously, the aim of assisted enteral nutrition was to compensate for already existing malnutrition; nowadays, an additional purpose is to diminish or prevent the development of malnutrition. The main objective of this study was to evaluate the safety of pre-treatment PEG in a sample of patients with an upper aerodigestive tract area malignancy treated in a tertiary referral centre.

Material and methods A total of 79 patients with an upper aerodigestive tract area malignancy were treated with a total of 80 PEGs during the period 1997–2001.

Results Most of the PEGs (62/80; 77.5%) were performed by an otolaryngologist. An open gastrostomy was needed in five cases because of unsuccessful gastroscopy due to oesophageal stricture (n=4) or severe trismus (n=1). Both acute and late complications were minor and the respective complication rates (1/80; 1.3% and 12/80; 15%) were low. In addition, all complications were easily managed and did not seriously affect the actual treatment.

Conclusions A major advantage of having the PEG performed by the otorhinolaryngologist was the possibility to combine it easily with other necessary procedures, such as panendoscopy, tracheostomy and additional biopsy. In addition, the timing of the procedure was easy to schedule.     

Amyloidosis of the upper aerodigestive tract

OBJECTIVES/HYPOTHESIS: To delineate the clinical and pathologic characteristics of upper aerodigestive tract amyloidosis with particular attention to laryngeal amyloidosis. STUDY DESIGN: Retrospective chart review of patients with amyloidosis of Thomas Jefferson University and its affiliated hospitals. MATERIAL AND METHODS: The charts of 16 patients with upper aerodigestive tract amyloidosis identified from the databases of the Thomas Jefferson University pathology department were reviewed and included in the study. RESULTS: Sixteen patients (9 male and 7 female, with an average age of 49.8 years) with upper aerodigestive tract amyloidosis were identified. The most common site of amyloid involvement was the larynx. Consequently, patients most commonly presented with hoarseness (14 of 16). All patients underwent surgical removal of the amyloid deposits. Fourteen patients had primary localized amyloidosis. Two experienced systemic involvement. Seven of the 16 patients developed recurrences requiring further treatment. CONCLUSIONS: Amyloidosis of the upper aerodigestive tract generally behaves as a benign, localized condition treatable by surgical resection. Regular follow-up with laryngoscopy is indicated for early diagnosis of recurrence, and multiple surgical procedures may be required to control symptoms.     

Narrow-Band Imaging in oncologic otorhinolaryngology: State of the art

ObjectivesTo describe the diagnostic performance of Narrow Band Imaging (NBI) combined with White Light Imaging (WLI) in the diagnosis of mucosal lesions at each location of the upper aerodigestive tract, for detection of primary tumor in case of carcinoma of unknown primary, for determination of intraoperative resection margins, and to describe its main diagnostic pitfalls.Material and methodsA PubMed search was carried out according to the PRISMA method.ResultsFour hundred and seventy-seven articles published between 2007 and 2020 were identified, 133 of which met the study inclusion criteria and were assessed.ConclusionThe current literature seems to support the use of NBI in diagnosis and/or follow-up of (pre-)malignant head & neck tumors, and in the determination of intraoperative resection margins.