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 Table of Contents  
INVITED EDITORIAL
Year : 2021  |  Volume : 1  |  Issue : 1  |  Page : 6-7

Oligometastatic nasopharyngeal cancer: Intent and approach?


Department of Radiation Oncology, Head and Neck Disease Management Group, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission19-Nov-2021
Date of Acceptance20-Nov-2021
Date of Web Publication06-Jan-2022

Correspondence Address:
Prof. Sarbani Ghosh Laskar
Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai 400012, Maharashtra.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoc.bjoc_28_21

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How to cite this article:
Laskar SG, Kumar A, Sinha S. Oligometastatic nasopharyngeal cancer: Intent and approach?. Bengal J Cancer 2021;1:6-7

How to cite this URL:
Laskar SG, Kumar A, Sinha S. Oligometastatic nasopharyngeal cancer: Intent and approach?. Bengal J Cancer [serial online] 2021 [cited 2022 Jan 28];1:6-7. Available from: http://www.bengaljcancer.org/text.asp?2021/1/1/6/335062



The incidence of distant metastasis in undifferentiated nasopharyngeal cancers (NPCs) is higher than other subsites in the head and neck region. Metastasis can either be synchronous (de novo) or metachronous in origin. The most commonly affected site is the bone, followed by the lungs and liver. Survival outcomes of metastatic NPCs (mNPCs) are divergent, depending upon the location, number of sites involved, and the volume of metastatic disease. However, the current American Joint Committee on Cancer (AJCC) staging for NPC does not differentiate between limited and disseminated metastasis.[1]

The concept of oligometastasis was proposed by Hellman and Weichselbaum in 1995. This entity is considered an intermediate state between locoregional and disseminated systemic disease. Different definitions of oligometastasis have been proposed for various cancers. However, the consensus definition is five or fewer sites of metastatic disease.[2] Oligometastatic cancers are considered to have superior outcomes as compared to widely metastatic cancers. Concurrent with increasing interest in the treatment and design of protocols for oligo metastases at other sites, there is growing in mNPCs. In a recent retrospective review of 157 patients with mNPC, patients with single-organ disease with less than six discrete lesions had a significantly better median overall survival (OS) of 24.8 months as compared to 12.8 months in patients with disseminated disease.[3]

On the basis of several retrospective analyses in NPC and other sites patients with oligometastatic disease may be potentially curable. Yet, there seems to be no consensus on the optimal management or approach. The role of local therapy for the locoregional disease and the metastatic foci is also a topic of debate. However, two nonhead and neck region randomized trials, the SABR-COMET and STAMPEDE, showed improved OS with local radiotherapy with limited metastatic burden in treatment naïve cancers.[4],[5] Though the patient numbers were small and the risk of toxicity remains a concern, the results support the existence of an oligometastatic state and a relatively better prognosis in patients with limited metastases.

Historically, de novo mNPCs have been treated with systemic chemotherapy alone. Several retrospective studies have evaluated the role of locoregional radiotherapy (LRRT) in mNPCs. In one of the largest series of 408 mNPCs by Chen et al.,[6] patients treated with LRRT and chemotherapy had more prolonged survival than with systemic therapy alone. Several other series have also shown improved survival outcomes with chemoradiation as compared to systemic chemotherapy alone. In a retrospective analysis of 821 patients of oligometastatic NPCs by Huang et al.,[7] systemic chemotherapy and sequential LRRT improved 3-year survival outcomes as compared to chemotherapy alone and radiotherapy-based treatment.

In 2020, a multicentric phase III randomized trial by You et al.[8] provided the first-level one evidence for the use of LRRT in mNPC. In this trial, de novo metastatic patients with partial/complete response following three cycles of induction chemotherapy with cisplatin and 5-fluorouracil (PF) showed an absolute OS benefit of 21.9% when treated with LRRT compared to chemotherapy alone. However, this trial had a mixed bag of patients with both limited and disseminated disease.

As the current tumour node metastasis staging for NPCs has a catch-all M1 classification, a recent study from China classified patients as M1a (a single site with a single lesion), M1b (a single site with multiple lesions), and M1c (multiple sites with multiple lesions). Median OS was 53.2, 25.8, and 18.9 months for a, b, and c. Local treatment of metastasis was performed by radiotherapy in 95% of the patients. Treatment of locoregional disease significantly improved survival as compared to systemic therapy alone. However, incorporation of local treatment of metastatic sites did not improve survival.[9]

Treatment of the metastatic foci is still a matter of contention and not well established by any randomized studies. In a Surveillance, Epidemiology and End Results (SEER) analysis of 679 patients with mNPC diagnosed between 1988 and 2012, 488 received radiation therapy to the primary or metastatic foci. After a median follow-up of 13 months, it was observed that radiotherapy to the primary and/or metastatic foci was associated with significantly improved OS and cancer specific survival in both univariate and multivariate analyses.[10] The other issue is that not all metastatic sites may be amenable to local treatment.

With the incorporation of multimodality imaging and availability of superior radiotherapy delivery and verification, stereotactic body radiotherapy (SBRT) in head and neck cancers is emerging and is currently being used mainly in the recurrent and metastatic setting. There are several ongoing trials, and the evidence for different sites is evolving. With more oligometastatic cancers being diagnosed with current imaging modalities, the role of SBRT can be explored in patients with limited metastatic burden, especially in areas of distant metastatic foci.

It is essential to classify mNPCs as limited (oligometastatic) or disseminated at presentation. There is definite evidence to support aggressive treatment protocols in oligometastatic NPC. However, the optimal combinations remain a topic of debate. Treatment of the locoregional disease following a good response to initial chemotherapy seems promising. However, the best approach to the metastatic sites and role of systemic therapy after initial systemic therapy remain contentious.

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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Toumi N, Ennouri S, Charfeddine I, Daoud J, Khanfir A. Prognostic factors in metastatic nasopharyngeal carcinoma. Braz J Otorhinolaryngol2020:S1808-8694(20)30092–6. doi: 10.1016/j.bjorl.2020.05.022.  Back to cited text no. 1
    
2.
Sun XS, Michel C, Babin E, De Raucourt D, Péchery A, Gherga E, et al. Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC. Future Oncol 2018;14:877-89.  Back to cited text no. 2
    
3.
Chee J, Liu X, Eu D, Loh T, Ho F, Wong LC, et al. Defining a cohort of oligometastatic nasopharyngeal carcinoma patients with improved clinical outcomes. Head Neck 2020;42:945-54.  Back to cited text no. 3
    
4.
Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomised, phase 2, open-label trial. Lancet 2019;393:2051-8.  Back to cited text no. 4
    
5.
Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomised controlled phase 3 trial. Lancet 2018;392:2353-66.  Back to cited text no. 5
    
6.
Chen MY, Jiang R, Guo L, Zou X, Liu Q, Sun R, et al. Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis. Chin J Cancer 2013;32:604-13.  Back to cited text no. 6
    
7.
Huang T, Su N, Zhang X, Ma S, Zhong G, Tian X, et al. Systemic chemotherapy and sequential locoregional radiotherapy in initially metastatic nasopharyngeal carcinoma: Retrospective analysis with 821 cases. Head Neck 2020;42:1970-80.  Back to cited text no. 7
    
8.
You R, Liu YP, Huang PY, Zou X, Sun R, He YX, et al. Efficacy and safety of locoregional radiotherapy with chemotherapy vs chemotherapy alone in de novo metastatic nasopharyngeal carcinoma: A multicenter phase 3 randomized clinical trial. JAMA Oncol 2020;6:1345-52.  Back to cited text no. 8
    
9.
Liao W, He J, Gou Q, Duan B, Liu L, Ai P, et al. Synchronous metastatic nasopharyngeal carcinoma: Characteristics and survival of patients adding definitive nasopharyngeal-neck radiotherapy to systematic chemotherapy. Cancer Manag Res 2020;12:10211-9.  Back to cited text no. 9
    
10.
Hu J, Kong L, Gao J, Hu W, Guan X, Lu JJ Use of radiation therapy in metastatic nasopharyngeal cancer improves survival: A SEER analysis. Sci Rep 2017;7:721.  Back to cited text no. 10
    




 

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