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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 3  |  Page : 1160-1163

Brain metastasis from nonnasopharyngeal head and neck squamous cell carcinoma: A case series and review of literature


1 Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Radiation Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
3 Department of Radiotherapy, Navoday Cancer Hospital and Research Centre, Bhopal, Madhya Pradesh, India

Date of Web Publication4-Jan-2017

Correspondence Address:
Sarbani Ghosh-Laskar
Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.184525

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 > Abstract 

Background: Brain metastasis from primary head and neck squamous cell carcinoma (HNSCC) is infrequent and probably under-reported thereby leading to paucity of information.
Methods: Archives of two institutes in India were studied from 2005 to 2013 and relevant information regarding patient demographics, treatment details, and follow-up was obtained for patients having brain metastasis (BM) from HNSCC. Data were analyzed using SPSS software version 20 (IBM Corporation, NY, USA).
Results: Metastasis to the brain was detected in 17 patients with an HNSCC primary. The median age for diagnosis of index primary was 55 years (range (R) - 32–71 years) with 88% (15/17) being male. Oral cavity was the most common site of primary disease with 35% (6/17) followed by larynx (24%), oropharynx (18%), and hypopharynx (18%). The median stage at presentation was IVA (47%) and two (12%) were metastatic to the brain at presentation. Human papillomavirus analysis was not available for any of the patients. Neurological symptoms were complained of in 94% patients. The median BM-free-interval was 15 months (R - 1–67 months, SE ± 5.2). While 88% had multiple brain metastases, 82% also had extracranial metastasis and in 53% of patients, the index primary was not controlled. The median overall survival of all patients after the development of BM was 2 months (R - 0.5–6 months, SE ± 0.4).
Conclusion: BM in HNSCC is mostly multiple, associated with extracranial metastasis and can occur in patients without locoregional relapse or residual disease and carries a dismal outcome.

Keywords: Brain metastasis, head and neck cancer, radiotherapy, squamous cell carcinoma


How to cite this article:
Ghosh-Laskar S, Agarwal JP, Yathiraj PH, Tanawade P, Panday R, Gupta T, Budrukkar A, Murthy V. Brain metastasis from nonnasopharyngeal head and neck squamous cell carcinoma: A case series and review of literature. J Can Res Ther 2016;12:1160-3

How to cite this URL:
Ghosh-Laskar S, Agarwal JP, Yathiraj PH, Tanawade P, Panday R, Gupta T, Budrukkar A, Murthy V. Brain metastasis from nonnasopharyngeal head and neck squamous cell carcinoma: A case series and review of literature. J Can Res Ther [serial online] 2016 [cited 2017 Jul 26];12:1160-3. Available from: http://www.cancerjournal.net/text.asp?2016/12/3/1160/184525


 > Introduction Top


Brain metastasis (BM) is a debilitating medical condition with dismal outcomes with median survival ranging from 7.1 to 2.3 months for recursive partitioning analysis Class I–III patients.[1] Head and neck squamous cell carcinomas (HNSCC) are notorious for locoregional recurrences with the incidence of distant metastasis being 10–30% in clinical series and 47% in autopsy series.[2],[3] Areas of common sites of metastasis from a primary in the head and neck region include lung, liver, and bone, with brain being a rare site of metastasis. The incidence of intracranial metastases is only about 0.4% overall, and 2–8% for those patients who already have distant spread to the lungs or other extracranial sites.[4] Here, we present a series of patients with HNSCCs with BM. Success in achieving local and regional control is shifting patterns of failure and changing the natural history of HNSCC. Patients seemingly cured of their disease based on complete tumor eradication in the head and neck are at risk of succumbing to metastatic spread to distant and sometimes unusual sites.[5]


 > Methods Top


In this study, from two institutes in the country, archives were studied from 2005 to 2013 for HNSCC with brain metastases; the medical records were reviewed to confirm the origin of the primary tumor. The various other clinical parameters including tumor stage at diagnosis, histopathological report, treatment, time of onset of BM, performance status, and clinical outcome were analyzed. Analysis was performed using SPSS software version 20 (IBM Corporation, NY, USA).


 > Results Top


Patient demographics

Between the years 2005–2013, a total of 63,738 cases were registered in the two institutes. Seventeen cases of BM from an HNSCC primary were identified, amounting to an incidence of 0.03% in our series. The median age of the cohort was 55 years (range (R) - 32–71 years) with 88% (15/17) being male. Of the 16 (94%) patients in whom habits were known, 14 (88%) had a history of tobacco chewing or smoking or alcohol consumption. Oral cavity was the most common site of primary disease with 35% (6/17) with larynx 24% (4/17), hypopharynx and oropharynx being 18% (3/17) each. The predominant histological subtype was moderately differentiated SCC (53%), while 41% were poorly differentiated, two of which were sarcomatoid variant. The median T and N staging of our series was T3 and N2. The median stage at presentation was stage IVA (AJCC, 2002) with two cases being metastatic at presentation [Table 1]. Among the 14 (88%) patients with metastasis to neck nodes, 57% (8/14) were having metastases at multiple levels. Low neck nodes (supraclavicular) were involved in three patients (21%). Human papillomavirus (HPV) analysis was not available for our series of patients.
Table 1: Clinical features for patients with metastatic HNSCC to the brain in current series

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Treatment details

Except for the two patients who presented with distant metastases, all others were treated with curative intent according to their stage and institutional policy [Table 1]. Among the seven (41%) who were operated for the diagnosed HNSCC, 2/7 (29%) had perineural invasion. All patients treated radically received radiotherapy to the primary site – either adjuvant or definitive. Systemic therapy was administered in 76% (13/17); two neoadjuvant and rest concomitantly. Resection of intracranial metastasis was performed in none. All patients received palliative whole brain radiotherapy after developing brain metastases out of which only one could not finish her planned dose of radiotherapy.

Details of metastases

All patients except one developed neurological symptoms for which they were investigated with neuro-imaging, either computed tomography or magnetic resonance imaging or PET-CT [Figure 1]. Single intracranial metastasis was detected in two patients (12%) as seen in [Figure 2]. Extracranial metastases were also detected in 14 (82%) patients [Figure 1]; commonly pulmonary (12/14), osseous (2/14), and hepatic and supra-renal (one each). Among patients with only cranial metastasis, none had solitary BM. Both patients with single BM were also harboring extracranial metastases. The index primary was controlled in 47%; the rest had either local or regional disease at the time of detection of BM [Figure 3]. The median Karnofsky performance scale (KPS) was 60 (R - 30–90) with the median recursive partitioning analysis (RPA) Class being III. The median BM free interval defined as the time interval from the completion of treatment of the index tumor to the diagnosis of BM was 15 months (R - 1–67 months, SE ± 5.2). This excludes the two patients who presented with brain metastases upfront. The median overall survival of all patients after the development of BM was 2 months (R - 0.5–6 months, SE ± 0.4).
Figure 1: 18F-FDG-PETCT showing recurrence at tracheostomy site, brain and bone metastasis- case 5

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Figure 2: CT scan brain at the time of diagnosis of metastasis

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Figure 3: Cytology proven local recurrence seen in a patient at the time of Brain metastasis

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 > Discussion Top


HNSCC is the 2nd most common malignancy in India, accounting for 22.7% of all malignancies in males and 6.1% of all malignancies in females. Oral cavity forms nearly half the HNSCC malignancies.[6] BM in HNSCC is an infrequent phenomenon and probably under-reported. The incidence of BM of 0.03% from our series also might be an under-reported phenomenon due to the majority of cases being referred outside for treatment, many of whom will be followed up at the referral center. However, a single institute's experience reported an incidence of 0.25%.[4] Autopsy series too have differed in incidence - Peltier et al. showed no BM among the 17% distant metastasis in their series while Posner and Chernik showed the incidence to be around 6%.[7],[8]

The two possible mechanisms of spread to the brain are hematogenous and perineural invasion of the tumor with retrograde intracranial deposits. It is speculated that a tumor with perineural invasion leads to intracranial metastasis by seeding the intrafunicular spaces of the nerves which has a direct communication with the subarachnoid spaces.[9]

Males constitute 88% of the patients in our study; a similar finding to the predominant male incidence reported by Bulut et al. (82%).[10] The median age at diagnosis of the index primary was 55 years; similar to a European study of 55 years.[11] Oral cavity was found to be the most common site associated with BM, possibly due to close proximity to multiple cranial nerves and dense lymphovascular channels. This might be due to the higher incidence of oral cavity malignancies seen in India. Moreover, HPV-induced malignancies have a different natural history with an altered pattern of distant spread.[11] Though, we could not determine HPV positivity among our patients, the relatively young age at presentation (cases 4, 6, and 12) and predominant oral cavity and oropharyngeal malignancies in our series cannot exclude the possibility of HPV-positive malignancies.

Cranial-only metastasis was reported in 18% of our series as against 3% and 38% from two different studies.[4],[12] The wide variety is attributable to the low incidence of BM in HNSCC. There were no cases of stage I/II tumors seen in our series as against 2/13 (15%) in a European series.[4] Regional lymph nodes are the first echelon of spread in head and neck cancers, and distant metastasis is suspected in bulky nodal diseases – N2+ or N3. In our series, 53% patients had bulky nodal disease at presentation which is similar to another series where 62% had >N2 disease.[4] Moderate to poorly differentiated carcinoma was seen in 94% (16/17) of the patients. Among the seven (41%) who were operated, 2/7 (29%) had perineural invasion. de Bree et al. reported 85% incidence of multiple BM, which is similar to our study of 88%.[4] A comparative analysis of the type of metastasis and the locoregional recurrence of disease revealed that distant metastasis does not strongly correlate with locoregional recurrence [Table 2].
Table 2: Comparison with Loco.regional control and type of metastasis

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The median BM free survival in our study was 15 months (mean - 19.3 months). This parameter was similar to the available literature on HNSCC with BM, barring one study by Ruzevic et al. (mean - 45) [Table 3].[11] The median KPS was 60 and the median RPA was Class III. The median OS of 2 months after diagnosis of BM was lower than the reported literature. This is attributable to the fact that four patients were lost to follow-up and two were alive at last follow-up. This is the major critic of this paper – lack of precise information on overall survival of all the patients and the absence of HPV analysis among the patients.
Table 3: Review of cases of HNSCC with brain metastasis in available literature with current study

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Our work is the first known series from the Indian subcontinent, where HNSCC is among the foremost malignancies. Albeit a rare occurrence, BM must be suspected in any patient with neurological symptoms and signs. Brain metastases from HNSCC primary are mostly multiple, associated with extracranial metastasis and can equally occur in patients without locoregional relapse or residual disease and carry a dismal prognosis. These series show a similar pattern of spread to the brain as reported in Western populations. The role of HPV in this unusual pattern of distant spread is yet to be defined in our population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 1997;37:745-51.  Back to cited text no. 1
    
2.
Merino OR, Lindberg RD, Fletcher GH. An analysis of distant metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 1977;40:145-51.  Back to cited text no. 2
    
3.
Kotwall C, Sako K, Razack MS, Rao U, Bakamjian V, Shedd DP. Metastatic patterns in squamous cell cancer of the head and neck. Am J Surg 1987;154:439-42.  Back to cited text no. 3
    
4.
de Bree R, Mehta DM, Snow GB, Quak JJ. Intracranial metastases in patients with squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg 2001;124:217-21.  Back to cited text no. 4
    
5.
Müller S, Khuri FR, Kono SA, Beitler JJ, Shin DM, Saba NF. HPV positive squamous cell carcinoma of the oropharynx. Are we observing an unusual pattern of metastases? Head Neck Pathol 2012;6:336-44.  Back to cited text no. 5
    
6.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. http://globocan.iarc.fr [Last accessed on 2015 Aug 01].  Back to cited text no. 6
    
7.
Peltier LF, Thomas LB, Barclay TH, Kremen AJ. The incidence of distant metastases among patients dying with head and neck cancers: An analysis of 200 autopsies. Surgery 1951;30:827-33.  Back to cited text no. 7
    
8.
Posner JB, Chernik NL. Intracranial metastases from systemic cancer. Adv Neurol 1978;19:579-92.  Back to cited text no. 8
    
9.
Djalilian HR, Tekin M, Hall WA, Adams GL. Metastatic head and neck squamous cell carcinoma to the brain. Auris Nasus Larynx 2002;29:47-54.  Back to cited text no. 9
    
10.
Bulut OC, Lindel K, Hauswald H, Brandt R, Klauschen F, Wolf J, et al. Clinical and molecular characteristics of HNSCC patients with brain metastases: A retrospective study. Eur Arch Otorhinolaryngol 2014;271:1715-22.  Back to cited text no. 10
    
11.
Ruzevick J, Olivi A, Westra WH. Metastatic squamous cell carcinoma to the brain: An unrecognized pattern of distant spread in patients with HPV-related head and neck cancer. J Neurooncol 2013;112:449-54.  Back to cited text no. 11
    
12.
Pickren JW, Lopez G, Tsukada Y, Lane WW. Brain metastases: An autopsy study. Cancer Treat Symptoms 1983;2:295-313.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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