Management of Nasopharyngeal

Carcinoma: Current
Practice and Future Perspective

Catatan Dameria Purba

Jakarta Pusat, 11 September - 14 Oktober 2017

• Nasopharyngeal carcinoma of the undifferentiated subtype
is endemic to southern China, and patient prognosis has
improved significantly over the past three decades because
of advances in disease management, diagnostic imaging,
radiotherapy technology, and broader application of
systemic therapy.

Abstract
• Advances in molecular technology have helped to decipher
the molecular pathogenesis of nasopharyngeal carcinoma as
well as its etiologic association with the Epstein-Barr virus.
This in turn has led to the discovery of novel biomarkers
and drug targets, rendering this cancer site a current
focus for new drug development.

Abstract
• This article reviews and appraises the key
literature on the current management of
nasopharyngeal carcinoma and future directions
in clinical research.

Abstract
• Nasopharyngeal carcinoma (NPC) of the undifferentiated
subtype remains endemic in southern China, with a peak
annual incidence approaching 30 per 100,000 persons.
• Overall prognosis has dramatically improved over the past
three decades because of advances in management

Introduction
• Current therapeutic decisions are based mainly on disease
stage.
• The general consensus is to treat stage I disease with RT
alone, stage II disease with RT with or without concurrent
chemotherapy (CRT), and stage III to IVB NPC with CRT.

Introduction
• Intensity-modulated RT (IMRT) is the current
standard of treatment for NPC.
• Randomized controlled trials comparing IMRT
with conventional twodimensional RT have shown a
significant reduction in the risk of permanent
xerostomia, especially in patients with early
disease as well as improvement in local control
with reduction of other treatment complications.

Advance in Radiotherapy
• To minimize the risk of geographic miss resulting from the
highly conformal dose distribution of IMRT, accuracy in
the delineation of gross tumor volume (GTV), appropriate
design of margins and clinical target volume, and precision
in RT delivery are important standards to maintain when
prescribing IMRT.
• Thorough pretreatment assessment incorporating
endoscopy, magnetic resonance imaging, and positron
emission tomography coupled with computed tomography
(CT), as well as fusion of images from different modalities
with the planning CT images, is fundamental.
• Although IMRT can achieve excellent 5-year local control
rates 90% forT3 disease, the corresponding rates forT4
disease still range from 74% to 80%
• Late toxicities, especially neurologic damage, are also more
common after RT for T3 to T4 NPC.
• The general principle is to administer the maximum tumor
dose within the tolerance of critical organs at risk.
• The target volume underdosed ( 65 Gy) is one of the most
significant factors affecting tumor control and overall
survival (OS).
• For large primary tumors abutting or infiltrating critical
structures, one common practice is to add induction
chemotherapy to shrink the tumor bulk for better dose
coverage during subsequent RT plus concurrent cisplatin
• The current practice is to prescribe a fairly uniform and
standardized dose level (approximately 70 Gy) to the whole
GTV. Another future perspective is to individualize the
radiation dose.
• With almost half of all patients presenting at an advanced
stage, of whom one third subsequently die as a result of
this cancer within 5 years of diagnosis
• To date, at least nine randomized studies have compared
concurrent CRT ( adjuvant chemotherapy) versus RT alone.
• These studies have reported a significant improvement in
event-free survival, and in some studies, an advantage in
OS has been observed, with hazard ratios (HRs; where
reported) for death ranging from 0.51 to 0.71 at 3 to 5
years of follow-up

CRT for Locoregionally

Advance Disease
• In a recently presented meta-analysis, in which patient-
based data on 4,798 patients with mostly stage III to
IVBNPC were analyzed, the addition of chemotherapy was
found to confer an absolute OS benefit of 6% at 5 years
and 8% at 10 years. The benefit was significant for OS
(HR, 0.79; 95% CI, 0.72 to 0.86), progression-free survival
(HR, 0.76; 95% CI, 0.70 to 0.82), locoregional control (HR,
0.74; 95% CI, 0.65 to 0.85), and distant control (HR, 0.68;
95% CI, 0.60 to 0.76).
• Chen et al42 randomly assigned 230 patients, ofwhom87%
had stage II and 13% had stage IIINP. They reported a
significant improvement in OS with CRT over RT alone.
• Su et al, where 198 patients with stage I to II NPC were
treated with IMRT alone, the 5-year distant metastasis–
free rates for T2N0, T1N1, and T2N1 disease were 98.8%,
100%, and 93.8%, respectively.
• Chemotherapy should be confined to patients
with high-risk stage II disease with N1
classification and/or parapharyngeal tumor
extension; studies investigating other risk
factors, such as tumor size and plasma EBV DNA
level, are also warranted in the future.
• Even with the best available treatment in modern practice,
retrospective reports of patients treated with IMRT over
the last decade have revealed the stark reality that 5% to
15% of patients will develop local failure, and 15% to 30%
will experience failure at distant sites
• Despite the varying success of surgery or reirradiation in
salvage therapy for highly selected patients with local
recurrence, a vast majority of cases of recurrent disease
are only amenable to palliative chemotherapy.

Management of Recurrence
and Development of New
Systemic Therapies
• In phase II studies of platinum-based doublets that are in
popular use today, the median OS rates in the first-line
setting ranged from a minimum of 11 to 28 months with
regimens containing paclitaxel, fluorouracil, gemcitabine, or
capecitabine
• It has long been proposed that the molecular pathogenesis
of EBV-associated NPC follows a stepwise progression. This
transformation consists of a series of seminal events,
which include EBVlatent infection, evasion of host immune
surveillance, loss of heterogeneity at specific chromosomal
regions, genetic mutations and activation of oncogenic
signaling pathways, and epigenetic silencing of tumor
suppresso genes.
• The precision of RT planning and delivery could potentially
be refined in individuals through the use of adaptive RT,
image-guided RT, and proton therapy.
• Likewise, with the discovery of new driver mutations,
putative tumor suppressor genes, and immunecheckpoint
targets in NPC, it is time to adopt a more systematic
approach to new drug development.
• The concept of individualized therapy also applies to the
optimal selection of patients for adjunctive chemotherapy
during RT, and multinational studies are now addressing the
role of adjuvant chemotherapy in subpopulations with
elevated plasma EBVDNA levels after RT.

Discussion
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