|Year : 2021 | Volume
| Issue : 1 | Page : 6-7
Oligometastatic nasopharyngeal cancer: Intent and approach?
Sarbani Ghosh Laskar, Anuj Kumar, Shwetabh Sinha
Department of Radiation Oncology, Head and Neck Disease Management Group, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
|Date of Submission||19-Nov-2021|
|Date of Acceptance||20-Nov-2021|
|Date of Web Publication||06-Jan-2022|
Prof. Sarbani Ghosh Laskar
Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai 400012, Maharashtra.
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Laskar SG, Kumar A, Sinha S. Oligometastatic nasopharyngeal cancer: Intent and approach?. Bengal J Cancer 2021;1:6-7
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.
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. 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.
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., 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., 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., 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. 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.
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. 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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Conflicts of interest
There are no conflicts of interest.
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