diagnosis of second primary tumor and long-term survival after single initial triple endoscopy in...

HEAD AND NECK

Diagnosis of second primary tumor and long-term survivalafter single initial triple endoscopy in patients with head and neckcancer

Antonio Vitor Martins Priante • Jefferson Luiz Gross •

Claudia Zitron Sztokfisz • Ines Nobuko Nishimoto •

Luiz Paulo Kowalski

Received: 12 August 2013 / Accepted: 7 October 2013

� Springer-Verlag Berlin Heidelberg 2013

Abstract Patients with squamous cell carcinoma of the

upper aerodigestive tract (UADT) have a high risk of

developing second primary tumors (SPTs). Most of the

studies concerning triple endoscopy (laryngoscopy, diges-

tive tract endoscopy and bronchoscopy) describe the fre-

quency and stage of the SPT, but not its impact on survival.

This study is a matched pair analysis that included patients

with squamous cell carcinoma of the UADT who were

subjected to a triple endoscopy before the first treatment,

matched with patients who did not undergo triple endos-

copy. One hundred and thirty-five patients were included in

each group. The diagnosis of an SPT was more frequent in

the initial triple endoscopy group than in the control group

(34 and 20 cases, respectively). In the initial triple endos-

copy group, 50.0 % of these tumors were diagnosed

simultaneously, whereas in the control, only 5.0 %. No

significant differences in the survival rates or in clinical

stage of the SPTs were found in the two groups. There was

no difference in the clinical stage of the SPT and the sur-

vival rates of the patient groups who underwent triple

endoscopy at the initial evaluation and those subjected to

only a routine evaluation and follow-up.

Keywords Squamous cell cancer/prognosis � Head

and neck cancer � Second primary tumor �Panendoscopy � Bronchoscopy � Endoscopy �Survival � Prognosis

Introduction

The patients with upper aerodigestive tract (UADT) squa-

mous cell carcinomas are generally smokers and have a

high risk of developing other cancers in the smoke-exposed

mucosa simultaneously or subsequently. The incidence of

multiple primary tumors in these patients can be as high as

27 %. Most of these tumors are located in the oral cavity,

pharynx, larynx, lungs or esophagus [1–14]. Pre-treatment

and follow-up triple endoscopy (laryngoscopy, digestive

tract endoscopy and bronchoscopy) have been proposed

with the aim of diagnosing premalignant lesions and early

stage asymptomatic invasive tumors [15–18]. However,

most reports describe only the frequency of the diagnoses

and not the effects on long-term survival of treating these

lesions [4, 12, 15–28]. Furthermore, triple endoscopy could

increase the treatment costs, particularly when performed

regularly and routinely. When performed before treatment,

the procedures could extend the time until the initiation of

treatment. In addition, digestive tract endoscopy and

bronchoscopy are usually performed under sedation, which

means that complications, although unusual, could occur

[29–32].

With the aim of reducing costs and testing the efficacy

of a single initial triple endoscopy, from 1994 to 2000, one

of the authors performed a prospective study of 142

A. V. M. Priante (&)

Department of Medicine, Taubate University, Taubate, Brazil

e-mail: [email protected]

J. L. Gross

Department of Thoracic Surgery, Hospital A. C. Camargo, Sao

Paulo, Brazil

C. Z. Sztokfisz

Department of Endoscopy Digestive, Hospital A. C. Camargo,

Sao Paulo, Brazil

I. N. Nishimoto � L. P. Kowalski

Department of Head and Neck Surgery and

Otorhinolaryngology, Hospital A. C. Camargo, Sao Paulo, Brazil

123

Eur Arch Otorhinolaryngol

DOI 10.1007/s00405-013-2768-6

patients subjected to a triple endoscopy as part of the pre-

treatment work-up. The patients under the care of other

surgeons in the department underwent similar diagnostic

and staging work-up and treatments, but without a triple

endoscopy.

The aim of this study was to evaluate the impact of an

initial pre-treatment plan using triple endoscopy for the

diagnosis of multiple primary tumors on the elapsed time to

the diagnosis and the clinical stage (CS) of second primary

tumors (SPTs) and finally, to analyze the survival rates of

patients with squamous cell carcinoma of the UADT

treated with a curative intention.

Methods

This study is a matched pair analysis that compared two

groups of patients (initial triple endoscopy group and

control group) with squamous cell carcinoma of the UADT

admitted for treatment at the Head and Neck and Otorhi-

nolaryngology Department of the AC Camargo Hospital.

The study was reviewed and approved by the Ethics

Committee.

During the period from November 3, 1994 to September

11, 2000, 142 patients referred to one physician of the

Head and Neck Surgery and Otorhinolaryngology Depart-

ment were selected for triple endoscopy (the initial triple

endoscopy group). All these patients were interviewed and

socio-demographic, clinical, pathological and therapeutic

information was prospectively collected. The inclusion

criteria of the initial triple endoscopy group were patients

with histologically confirmed primary squamous cell car-

cinoma of the oral cavity (excluding the lips and salivary

glands), pharynx (excluding the nasopharynx) and larynx,

previously untreated, without symptoms of an SPT, with

clinical conditions to be treated with curative intent by

surgery and/or radiotherapy (Karnofsky performance status

greater than 60) and older than 18 years. The exclusion

criteria included patients who came to the hospital only for

confirmation of the diagnosis and/or for a second opinion,

patients with other previously diagnosed malignancies, the

existence of severe chronic diseases (cardiac, pulmonary,

neurological, renal or systemic) that would prevent the

indication of the treatment considered optimal, those that

could have an unfavorable short-term evolution (e.g., pre-

sence of distant metastases, unresectable stage IV tumors in

patients with severely compromised clinical condition),

difficulties with follow-up and refusal to participate as a

volunteer.

The patients were subjected to nasopharyngolaryngos-

copy using a flexible Olympus� ENF T3 laryngoscope

under local anesthesia in the outpatient clinic. In cases of

larynx or hypopharynx tumors, microlaryngoscopy under

general anesthesia was also performed prior to surgery.

Bronchoscopy and upper digestive tract endoscopy using

flexible Olympus� models BF1T30 and GIF XQ20,

respectively, were performed in the outpatient clinic, under

topical anesthesia and sedation.

For comparison with the patients who underwent triple

endoscopy, the patients in the control group did not

undergo triple endoscopy but had the same eligibility cri-

teria described above. Matching was performed for gender,

age, primary tumor location, CS and treatment modality.

The CS of the primary tumor and the SPT was revised

based on the registered data in the records and according to

the American Joint Committee on Cancer (AJCC) criteria

[33]. Warren and Gates criteria [34] were used for the

diagnosis of the SPTs. The SPTs were classified as

simultaneous when diagnosed on the work-up date for

primary tumor staging, synchronous when diagnosed

within 6 months, and metachronous when diagnosed after

6-month follow-up.

Statistical analysis was performed using SPSS 10.0 for

Windows software. To compare the cases of the triple

endoscopy group with those of the control group, the Chi-

square test was used for the categorical variables and

Student’s t test or the Mann–Whitney U test was used for

the quantitative variables. The survival probability for

both groups was estimated using the Kaplan–Meier

method, and the log-rank test was used to compare the

groups. The overall survival was the time period between

the initial treatment and death related to any cause or

when the last objective information was recorded. Simi-

larly, the cancer-specific survival time was the period

between the initial treatment and death due to cancer or

when the information from the last objective follow-up

was recorded. For the post-SPT survival, the time

between the date of diagnosis of an SPT and the date of

death or the last record of objective information was

considered. Multivariable Cox proportional hazards

regression was used to determine the independent prog-

nostic factors and to estimate the risk of death in patients

diagnosed with SPTs. Statistical significance was set as

p values \0.05.

Results

A group of 142 patients was selected to undergo triple

endoscopy; however, seven were excluded. In four cases, a

primary tumor extension had obstructed the pathway of the

bronchoscope and/or upper digestive tract endoscope, and

in three cases, distant metastases were diagnosed during the

initial staging.

135 cases and 135 controls are described in Table 1. In

the initial triple endoscopy group, the registered number of


123

ex-smokers, ex-drinkers and a positive familial history of

cancer were more frequent (Table 1).

The follow-up period ranged from less than

1–155 months in the initial triple endoscopy group (median

24 months) and from less than 1–238 months in the control

group (median 22 months) (p = 0.864). During these

periods, 34 cases (25.2 %) of SPT were identified in the

initial triple endoscopy group and 20 cases (14.7 %) were

identified in the control group. In the initial triple endos-

copy group, 16 cases (47.1 %) were diagnosed during the

pre-treatment work-up and one (2.9 %) was diagnosed

during the surgical treatment of the primary tumor

(simultaneous tumors). In the other 17 cases, the SPT

diagnosis was given after 6-month follow-up

(metachronous tumors). In the control group, only one case

(5.0 %) was classified as a simultaneous tumor; in contrast,

19 (95.0 %) were metachronous. In both groups, most of

the SPTs occurred in the UADT, followed by the esopha-

gus and the lungs (Table 2).

Five SPTs in the initial triple endoscopy group were

diagnosed during the physical examination, three in the

oropharynx and two in the mouth. The diagnosis of SPT

was reached in 3.68 of every 100 physical examinations.

Nasopharyngolaryngoscopy allowed for the diagnosis of

three SPTs (2.2 diagnoses per 100 exams), two in the

hypopharynx and one in the larynx. Bronchoscopy allowed

for the diagnosis of two SPTs (1.47 diagnoses per 100

examinations), one SPT of the lung and another of the

hypopharynx, that was classified as T1 and was not identified

in nasopharyngolaryngoscopy. Digestive tract endoscopy

identified six SPTs (4.44 diagnoses per 100 exams), five in

the esophagus and one in the stomach. Then, using triple

endoscopy, 11 SPTs were diagnosed, yielding a rate of 8.15

diagnoses per 100 triple endoscopies performed.

Table 3 shows the comparison between the main char-

acteristics of the SPTs in both groups. Using the informa-

tion in the medical records, 27 SPTs in the initial triple

endoscopy group (79.4 %) and 19 in the control group

(95.0 %) could be classified by CS. In comparing the SPTs

rated CS 0, I and II with those rated CS III and IV, no

significant differences were found between the groups

(p = 0.685).

In the initial triple endoscopy group, the 5-year overall

survival was 36.3 % (median 24 months) and that of the

Table 1 Socio-demographic and clinical characteristics in initial

triple endoscopy and control group

Variables Categories Initial triple

endoscopy

Control p

Number

(%)

Number

(%)

Gender Male 121 (89.6) 121 (89.6) [0.999b

Female 14 (10.4) 14 (10.3)

Age (years) Minimum/maximum 33/82 33/78 0.497c

Mean/median 58.3/59 57.5/57

Race Caucasian 112 (83.0) 112 (83.0) [0.999b

Noncaucasian 23 (17.0) 23 (17.0)

Smoking

statusaNever 6 (4.4) 10 (7.5) 0.016b

Current 99 (73.4) 110 (82.7)

Former 30 (22.2) 13 (9.8)

Alcohol usea None 7 (5.2) 41 (30.8) \0.001b

Current 71 (52.6) 77 (57.9)

Former 57 (42.2) 15 (11.3)

Cancer

familiar

historya

Yes 54 (40.0) 38 (28.6) 0.049b

No 81 (60.0) 95 (71.4)

Primary

tumor

site

Mouth 61 (45.2) 60 (44.4) 0.994b

Oropharynx 35 (25.9) 36 (26.7)

Larynx 25 (18.5) 24 (17.8)

Hypopharynx 14 (10.4) 15 (11.1)

Primary tumor

clinical stage

I 13 (9.6) 11 (8.1) 0.915b

II 14 (10.4) 17 (12.6)

III 37 (27.4) 32 (23.7)

IVa 54 (40.0) 58 (43.0)

IVb 17 (12.6) 17 (12.6)

Primary tumor

treatment

Surgery 30 (22.2) 31 (23.0) 0.759b

RT 20 (14.8) 23 (17.0)

Surgery and RT 64 (47.4) 62 (45.9)

RT and QT 5 (3.7) 8 (5.9)

Surgery, RT and QT 16 (11.9) 11 (8.2)

RT radiotherapy, QT chemotherapya Missing information in two cases in the control groupb Chi-square testc Student’s t test

Table 2 Cases distribution according to the localization of the sec-

ond primary tumor

Localization Initial triple endoscopy Control

Number (%) Number (%)

Esophagus 7 (20.6) 5 (25.0)

Oropharynx 6 (17.7) 4 (20.0)

Mouth 4 (11.8) 3 (15.0)

Hypopharynx 4 (11.8) 2 (10.0)

Lung 3 (8.9) 3 (15.0)

Larynx 2 (5.9) 1 (5.0)

Paranasal sinus/Nasal cavity 2 (5.9)

Stomach 1 (2.9)

Thyroid 1 (2.9)

Leukemia 1 (2.9)

Bladder 1 (2.9)

Liver 1 (2.9)

Colon 1 (2.9)

Brain 1 (5.0)

Lip 1 (5.0)

Total 34 (100.0) 20 (100.0)


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control group was 35.2 % (median 23 months)

(p = 0.573). There was also no significant difference in the

cancer-specific survival of the two groups (p = 0.537); in

the initial triple endoscopy group, it was 41.8 % (median

30 months); and in the control group, it was 42.7 %

(median 29 months).

The 5-year post-SPT survival was similar in both

groups. In the initial triple endoscopy group, this value was

22.0 % (median 17.0 months), and in the control group, it

was 22.5 % (median 11.0 months) (p = 0.944).

In an attempt to identify subgroups in which the initial

triple endoscopy could be related to better survival, the

groups were stratified by site and the CS of the primary

tumor. No significant differences were found in the overall

survival of the subgroups according to the location of the

primary tumor. In those with primary tumors in the oral

cavity, the 5-year overall survival was 36.1 % (median

24 months) for the initial triple endoscopy group and

37.7 % (median 30 months) for the control group

(p = 0.535). For those with oropharyngeal primary tumors,

this value was 40.0 % (median 18 months) for the initial

triple endoscopy group and 26.3 % (median 17 months) for

the control group (p = 0.756). When the primary tumor

was located in the larynx, the 5-year overall survival was

44.0 % (median 36 months) for the initial triple endoscopy

group and 50.0 % (median 51 months) for the control

group (p = 0.525). Finally, in the case of hypopharyngeal

primary tumors, the overall survival at 5 years was only

14.3 % (median 17 months) for the initial triple endoscopy

group and 21.7 % (median 17 months) for the control

group (p = 0.710).

No significant differences were found in the survival

rates of members of the two groups according to the CS of

the primary tumors. When the primary tumors were CS I

and II, the 5-year overall survival in the initial triple

endoscopy group was 77.8 % (median 126 months) and

that of the control group 73.7 % (median 114 months)

(p = 0.978). When the primary tumors were classified as

CS III and IV, the 5-year overall survival in both of the

groups was 30.1 % (median 21 months in the triple

endoscopy group and 19 months in the control group)

(p = 0.549).

The 5- and 10-year overall survival and the post-SPT

survival of the 54 patients who developed an SPT are

shown in Table 4. Patients younger than 57 years with a

primary laryngeal tumor and primary tumors rated CS I and

II had better overall survival. The post-SPT survival was

better in patients younger than 57 years, those with an SPT

classified s CS 0, I or II and when surgery was the main

treatment. There were no significant differences in the

overall survival and post-SPT survival between the control

and the initial triple endoscopy group.

Multivariate analysis revealed that in the patients who

developed an SPT, the independent predictors of the

overall survival were age (older than 57 years, OR 2.02, CI

95 % 1.10–3.71) and the CS of the primary tumor (III and

IV, OR 2.14, 95 % CI 1.07–4.27). The variables related to

the post-SPT survival were age (older than 57 years, OR

2.14, 95 % CI 1.09–4.21) and the CS of the SPT (III and

IV, OR 2.37, 95 % CI 1.21–4.66) (Table 5).

Discussion

In this study, we compared two groups of patients with

UADT primary tumors, one (control group) including

patients who underwent the standard evaluation (clinical

history, physical examination, chest radiography and

computed tomography of the face and neck) and the other

(initial triple endoscopy group) including patients who

were subjected, in addition to the standard evaluation, to

triple endoscopy as part of the initial evaluation.

Table 3 Comparison between

the second primary tumors in

the initial triple endoscopy

group and in the control group

a Mann–Whitneyb Chi-square test

Variable Category Initial triple

endoscopy

Control p

Number (%) Number (%)

Follow-up (months) Minimum/Maximum 0/155 0/238 0.864a

Mean 50.0 51.1

Median 24 22

Second primary tumor Yes 34 (25.2) 20 (14.8) 0.033b

No 101 (74.8) 115 (85.2)

Second primary tumor Simultaneous 17 (50.0) 1 (5.0) \0.001b

Type Metachronous 17 (50.0) 19 (95.0)

Second primary tumor site Upper aerodigestive tract 18 (52.9) 11 (55.0) 0.370b

Esophagus/lung 10 (29.4) 8 (40.0)

Others 6 (17.7) 1 (5.0)

Second primary tumor clinical stage 0, I and II 14 (51.9) 11 (57.9) 0.685b

III and IV 13 (48.1) 8 (42.1)


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Several studies have suggested that performing peri-

odic triple endoscopies is beneficial [12, 20–24], partic-

ularly in relation to an SPT diagnosis. The main problems

with repetition of a triple endoscopy are the costs and

frequent compliance. Aiming to test the alternative of a

single triple endoscopy as part of the evolving initial

work-up evolution, one of us accomplished performed a

prospective evaluation of 135 consecutive eligible

patients. In an attempt to minimize the influence of other

prognostic factors, the groups included patients referred

for treatment at the same institution matched by gender

and age, and the location, CS and treatment of the pri-

mary tumor.

In relation to the data collection, the fact that the

patients in the initial triple endoscopy group participated in

a prospective research project for detecting SPT and have

always been examined by the same physician may, in part,

explain the five SPT simultaneous diagnosis made during

physical examination in this group. The incidence of SPT

increases with the follow-up time. Day and Blot [3]

reported a rate of SPT development of 3.7 % per year.

Panosetti et al. [6], found that 22 % of the diagnoses of

SPT occurred after the fifth year of follow-up. In this study,

the follow-up time of both groups was similar. However,

most SPT diagnoses in the study group were made simul-

taneously with the diagnoses of the primary tumor.

In three large series of cases, that of Chuang et al. [9]

with 99,257 patients, that of Haughey et al. [4] with 40,287

and that of Panosetti et al. [6] with 9,089, the incidences of

SPT were 10.9, 14.2 and 9.4 %, respectively. In our control

group, the incidence of SPT was similar to the series above

(14.8 %), whereas in the initial triple endoscopy group, it

was significantly higher (25.2 %). The incidence of SPT in

the initial triple endoscopy group, however, was similar to

that presented by other authors who used a triple endos-

copy in the evaluation of patients with squamous cell

Table 4 Overall and post-

second primary tumor survivals

rates

RT radiotherapy, QT

chemotherapya Log-rank testb Median cut (57 years)

Variables Categories Overall/post-second

primary tumor survival

(%)

pa

5 years 10 years

Gender Male 50.0/21.0 16.9/9.2 0.121/0.714

Female 75,0/50.0 75.0/50.0

Ageb B57 years 60.0/32.3 28.2/9.2 0.028/0.011

[57 years 22.2/8.7 13.0/8.7

Primary tumor site Mouth 59.1/24.8 22.5/9.3 0.004/0.070

Oropharynx 43.8/12.5 18.8/12.5

Larynx 77.8/55.6 44.4/27.8

Hypopharynx 14.3/0.0 0.0/0.0

Primary tumor T stage T1 and T2 61.9/18.7 45.5/18.7 0.154/0.661

T3 and T4 32.7/24.2 13.0/0.0

Primary tumor N stage N0 56.7/23.9 27.3/23.9 0.346/0.671

N1 57.1/14.3 14.3/0.0

N2 and N3 41.2/23.5 15.7/0.0

Primary tumor clinical stage I and II 75.0/24.8 36.5/24.8 0.037/0.175

III and IV 42.1/21.1 14.4/0.0

Primary tumor treatment Surgery and RT 37.9/20.7 8.3/5.7 0.058/0.364

Surgery 73.7/27.6 38.9/27.6

RTwith or without QT 50.0/0.0 33.3/0.0

Group Initial triple endoscopy 50.0/22.0 18.8/5.9 0.242/0.941

Control 55.5/22.5 28.0/22.5

Second primary tumor site Upper aerodigestive tract 51.7/24.9 20.7/10.0 0.274/0.273

Esophagus/lung 38.9/14.8 11.1/0.0

Others 85.7/28.6 57.1/28.6

Second primary tumor clinical stage 0, I and II 52.0/38.6 34.7/33.1 0.227/0.019

III and IV 47.6/4.8 9.5/0.0

Second primary tumor treatment Surgery 59.4/31.5 28.9/18.4 0.423/0.005

RT 41.2/11.8 11.8/0.0

Palliative care 50.0/0.0 25.0/0.0


123

carcinoma of the UADT, such as Weaver et al. [24] (20 %)

and McGuirt et al. [20] (17.3 %). This fact suggests that

there is a percentage of asymptomatic lesions, and these

lesions are potentially curable, but are not identified when

they are not investigated systematically. The death of

patients due to the first tumor and the possibility of treat-

ment of small lesions located in the field of radiotherapy,

not identified in the initial evaluation, could partly explain

the difference in the incidence of SPT when a systematic

search for an SPT is conducted.

Three SPTs were diagnosed by nasopharyngolaryngos-

copy, two by bronchoscopy and six by digestive tract

endoscopy. There are important variations in the rates of

diagnoses in reported in different studies. In some, such as

that of Davidson et al. [27], Kerawala et al. [28] and

Kesting et al. [17], digestive tract endoscopy reveal any

SPTs. Kerawala et al. [28] did not identify any SPTs using

bronchoscopy and in the study of Guardiola et al. [19],

laryngoscopy did not identify any SPT. In this study,

digestive tract endoscopy yielded the highest rate of diag-

noses (4.44 %). However, of the six patients in which the

SPT was diagnosed using digestive tract endoscopy, only

one survived longer than 5 years and did not die of cancer

(overall survival of 110 months and death due to bron-

chopneumonia). Of the other five patients, two died of the

residual disease after radiotherapy, two of distant metas-

tases and one due to a third primary tumor. Digestive tract

endoscopy is a promising examination, which, in addition

to allowing the diagnosis of SPTs, could provide a survival

advantage in a subgroup of patients, although this was not

demonstrated in this study.

One patient with an SPT diagnosed by nasopharyngo-

laryngoscopy is still alive after a 60-month follow-up. The

other two died: one due to local recurrence of the primary

tumor and another due to a third tumor in the cervical

esophagus. Two factors reinforce the utility of employing

nasopharyngolaryngoscopy in the initial evaluation of

patients with UADT tumors. The first is that this procedure

is also useful for evaluating the extension of the primary

tumor and the second is that, as reported by some authors

[7, 11, 13], the best survival rates post-SPT occurred when

the SPT was located in UADT.

The two patients with an SPT diagnosed by bronchos-

copy died due to the first tumor. The highest rates of

diagnosis of SPTs using bronchoscopy was reported by

McGuirt et al. [20]; however, in their study, two of the

three tumors identified using this type of examination had

been previously noted in chest radiography.

As reported in most studies [2–4, 7, 11, 13, 21, 22], in

both groups evaluated in this study, the most frequent

location of the SPT was the UADT mucosa, followed by

the esophagus and lung. Due to the heterogeneous loca-

tions and the difficulty of determining the CS of some of

the SPTs, only 42 of the 54 SPTs were grouped according

to the CS. No differences in the CS values in the initial

triple endoscopy and control group were discovered.

Comparing the survival of the two groups, no significant

differences were found in the overall and cancer-specific

survival.

Approximately 80 % of the patients included in this

study had primary tumors classified as CS III or IV. In 9

cases of the 11 SPTs diagnosed by initial triple endoscopy,

(81.8 %) the primary tumors were CS IV (one IVb). In

patients with advanced CS-graded UADT tumors, the

possibility of death due to the primary tumor is high. This

fact reflects the evolution of the SPTs diagnosed using an

initial triple endoscopy. Seven of the 11 patients (63.6 %)

died from the primary tumor, 2 (18.2 %), because of

multiple tumors, and 1 (9.1 %), because of bronchopneu-

monia. Only 1 (9.1 %) patient was disease-free at a

60-month follow-up. In the study of Guardiola et al. [19],

most of the deaths of SPT cases also occurred due to the

recurrence of the primary tumor.

Moreover, in patients with CS I and II tumors, as

demonstrated by the studies of Franchin et al. [35] and Lee

et al. [36], in patients with laryngeal tumors, the SPT may

be the main cause of death when the primary tumor is in its

early stage. In patients with tumors at an early CS,

Table 5 Multivariate analysis

of prognostic factors (patients

with second primary tumors) for

overall and post-second primary

tumor survival

a Median cut (57 years)

Variable Category OR crude (95 % CI) OR multivariate (95 % CI)

Overall survival

Agea B57 years 1.0 (reference) 1.0 (reference)

[57 years 1.94 (1.06–3.55) 2.02 (1.10–3.71)

Primary tumor clinical stage I and II 1.0 (reference) 1.0 (reference)

III and IV 2.05 (1.03–4.09) 2.14 (1.07–4.27)

Post-second primary tumor survival

Agea B57 years 1.0 (reference) 1.0 (reference)

[57 years 2.13 (1.16–3.92) 2.14 (1.09–4.21)

Second primary tumor clinical stage 0, I and II 1.0 (reference) 1.0 (reference)

III and IV 2.15 (1.11–4.17) 2.37 (1.21–4.66)


123

performing an initial triple endoscopy could affect their

survival.

Evaluation of the survival of 54 patients who developed

SPT and the 48 cases in which the SPT was located in an

area accessible to triple endoscopy, once again showed no

difference in the survival rates of the control and initial

triple endoscopy groups. In the multivariate analysis, age

and the CS of the SPT were identified as independent

predictors of survival post-SPTs. This information dem-

onstrated a group with a better survival rate (young people)

that may benefit even more from the early SPT diagnosis.

The results also show that to diagnose an SPT in an early

CS may improve the survival rate.

As previously mentioned, a relationship was not found

between the performing an initial triple endoscopy and

diagnosis of an SPT in an early CS. Positron emission

tomography (PET/CT) may be a promising method for the

early diagnosis of SPT. Haerle et al. [37] showed that PET/

CT allowed the diagnosis of SPT more frequently than did

triple endoscopy, although with a high number of false

positives. In a series of 589 patients with squamous cell

carcinoma of the UADT who underwent PET/CT, Strobel

et al. [38] diagnosed 56 SPTs in 44 patients, 55 % of them

at the initial CS.

As in the other studies [12, 20, 21, 23, 24], an initial

triple endoscopy allowed for more SPT diagnoses, but no

significant differences in the CS of the SPTs and no impact

on survival rates were observed. Therefore, there are no

advantages to routinely perform a single initial triple

endoscopy for SPT diagnosis.

Acknowledgments The author thanks Ms. Adrienne Beecker and

Larissa Fernanda Silva Holtz for their help in grammar review. This

study was funded by Grants 93/3248/8 from the Fundacao de Amparo

a Pesquisa do Estado de Sao Paulo.

Conflict of interest There were no conflicts of interest in this study.

References

1. Franco EL, Kowalski LP, Kanda JL (1991) Risk factors for

second cancers of the upper respiratory and digestive systems: a

case-control study. J Clin Epidemiol 44:615–625

2. Leon X, Quer M, Diez S, Orus C, Lopez-Pousa A, Burgues J

(1999) Second neoplasm in patients with head and neck cancer.

Head Neck 21:204–210

3. Day GL, Blot WJ (1992) Second primary tumors in patients with

oral cancer. Cancer 70:14–19

4. Haughey BH, Gates GA, Arfken CL, Harvey J (1992) Meta-

analysis of second malignant tumors in head and neck cancer: the

case for an endoscopic screening protocol. Ann Otol Rhinol

Laryngol 101:105–112

5. Lin K, Patel SG, Chu PY, Matsuo JM, Singh B, Wong RJ et al

(2005) Second primary malignancy of the aerodigestive tract in

patients treated for cancer of the oral cavity and larynx. Head

Neck 27:1042–1048

6. Panosetti E, Luboinski B, Mamelle G, Richard JM (1989) Mul-

tiple synchronous and metachronous cancers of the upper aero-

digestive tract: a nine-year study. Laryngoscope 99:1267–1273

7. Jones AS, Morar P, Phillips DE, Field JK, Husband D, Helliwell

TR (1995) Second primary tumors in patients with head and neck

squamous cell carcinoma. Cancer 75:1343–1353

8. Gonzalez-Garcıa R, Naval-Gıas L, Roman-Romero L, Sastre-

Perez J, Rodrıguez-Campo FJ (2009) Local recurrences and

second primary tumors from squamous cell carcinoma of the oral

cavity: a retrospective analytic study of 500 patients. Head Neck

31:1168–1180

9. Chuang SC, Scelo G, Tonita JM, Tamaro S, Jonasson JG, Kliewer

EV et al (2008) Risk of second primary cancer among patients

with head and neck cancers: a pooled analysis of 13 cancer

registries. Int J Cancer 123:2390–2396

10. Leon X, del Prado Venegas M, Orus C, Lopez M, Garcıa J, Quer M

(2009) Influence of the persistence of tobacco and alcohol use in the

appearance of second neoplasm in patients with a head and neck

cancer. A case-control study. Cancer Causes Control 20:645–652

11. Rennemo E, Zatterstrom U, Boysen M (2008) Impact of second

primary tumors on survival in head and neck cancer: an analysis

of 2,063 cases. Laryngoscope 118:1350–1356

12. Gluckman JL (1979) Synchronous multiple primary lesions of the

upper aerodigestive system. Arch Otolaryngol 105:597–598

13. Priante AVM, Carvalho AL, Kowalski LP (2010) Second primary

tumor in patients with upper aerodigestive tract cancer. Braz J

Otorhinolaryngol 76:251–256

14. Slaughter DP, Southwick HW, Smejkal W (1953) ‘‘Field cancer-

ization’’ in oral stratified squamous epithelium. Cancer 6:963–968

15. Tincani AJ, Brandalise N, Altemani A, Scanavini RC, Valerio JB,

Lage HT et al (2000) Diagnosis of superficial esophageal cancer

and dysplasia using endoscopic screening with a 2 % lugol dye

solution in patients with head and neck cancer. Head Neck

22:170–174

16. Hashimoto CL, Iriya K, Baba ER, Navarro-Rodriguez T, Zerbini

MC, Eisig JN et al (2005) Lugol’s dye spray chromoendoscopy

establishes early diagnosis of esophageal cancer in patients with

primary head and neck cancer. Am J Gastroenterol 100:275–282

17. Kesting MR, Schurr C, Robitzky L, Steinstraesser L, Nieberler

M, Baurecht H et al (2009) Results of esophagogastroduodeno-

scopy in patients with oral squamous cell carcinoma—value of

endoscopic screening: 10-year experience. J Oral Maxillofac

Surg 67:1649–1655

18. Kesting MR, Robitzky L, Al-Benna S, Steinstraesser L, Baurecht

H, Wolff KD et al (2009) Bronchoscopy screening in primary

oral squamous cell carcinoma: a 10-year experience. Br J Oral

Maxillofac Surg 47:279–283

19. Guardiola E, Pivot X, Dassonville O, Poissonnet G, Marcy PY,

Otto J et al (2004) Is routine triple endoscopy for head and neck

carcinoma patients necessary in light of a negative chest com-

puted tomography scan? Cancer 101:2028–2033

20. McGuirt WF, Matthews B, Koufman JA (1982) Multiple simul-

taneous tumors in patients with head and neck cancer: a pro-

spective, sequential panendoscopy study. Cancer 50:1195–1199

21. Leipzig B, Zellmer JE, Klug D (1985) The role of endoscopy in

evaluating patients with head and neck cancer. A multi-institu-

tional prospective study. Arch Otolaryngol 111:589–594

22. Stoeckli SJ, Zimmermann R, Schmid S (2001) Role of routine

panendoscopy in cancer of the upper aerodigestive tract. Oto-

laryngol Head Neck Surg 124:208–212

23. Hujala K, Sipila J, Grenman R (2005) Panendoscopy and syn-

chronous second primary tumors in head and neck cancer

patients. Eur Arch Otorhinolaryngol 262:17–20

24. Weaver A, Fleming SM, Knechtges TC, Smith D (1979) Triple

endoscopy: a neglected essential in head and neck cancer. Sur-

gery 86:493–496


123

25. Shaha A, Hoover E, Marti J, Krespi Y (1988) Is routine triple

endoscopy cost-effective in head and neck cancer? Am J Surg

155:750–753

26. Hordijk GJ, Bruggink T, Ravasz LA (1989) Panendoscopy: a

valuable procedure? Otolaryngol Head Neck Surg 101:426–428

27. Davidson J, Gilbert R, Irish J, Witterick I, Brown D, Birt D et al

(2000) The role of panendoscopy in the management of mucosal

head and neck malignancy—a prospective evaluation. Head Neck

22:449–455

28. Kerawala CJ, Bisase B, Lee J (2009) Panendoscopy and simul-

taneous primary tumours in patients presenting with early carci-

noma of the mobile tongue. Br J Oral Maxillofac Surg 47:363–365

29. Colt HG, Matsuo T (2001) Hospital charges attributable to

bronchoscopy-related complications in outpatients. Respiration

68:67–72

30. Ginzburg L, Greenwald D, Cohen J (2007) Complications of

endoscopy. Gastrointest Endosc Clin N Am 17:405–432

31. Soni A, Sampliner RE, Sonnenberg A (2000) Screening for high-

grade dysplasia in gastroesophageal reflux disease: is it cost-

effective? Am J Gastroenterol 95:2086–2093

32. Gupta N, Bansal A, Wani SB, Gaddam S, Rastogi A, Sharma P

(2011) Endoscopy for upper GI cancer screening in the general

population: a cost-utility analysis. Gastrointest Endosc 74:610–624

33. American Joint Committee on Cancer (2002) AJCC cancer

staging manual, 6th edn. Springer, New York

34. Warren S, Gates O (1932) Multiple primary malignant tumors: a

survey of the literature and a statistical study. Am J Cancer

16:1358–1403

35. Franchin G, Minatel E, Gobitti C, Talamini R, Vaccher E, Sartor

G et al (2003) Radiotherapy for patients with early-stage glottic

carcinoma: univariate and multivariate analyses in a group of

consecutive, unselected patients. Cancer 98:765–772

36. Lee JH, Machtay M, McKenna MG, Weinstein GS, Markiewicz

DA, Krisch RE et al (2001) Radiotherapy with 6-megavolt pho-

tons for early glottic carcinoma: potential impact of extension to

the posterior vocal cord. Am J Otolaryngol 22:43–54

37. Haerle SK, Strobel K, Hany TF, Sidler D, Stoeckli SJ (2010)

(18)F-FDG-PET/CT versus panendoscopy for the detection of

synchronous second primary tumors in patients with head and

neck squamous cell carcinoma. Head Neck 32:319–325

38. Strobel K, Haerle SK, Stoeckli SJ, Schrank M, Soyka JD, Veit-

Haibach P et al (2009) Head and neck squamous cell carcinoma

(HNSCC)—detection of synchronous primaries with (18)F-FDG-

PET/CT. Eur J Nucl Med Mol Imaging 36:919–927


123

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