Nasopharyngeal Cancer Management Presentation

1. Nasopharyngeal Carcinoma
Management
Achille Manirakiza, MD
Ocean Road Cancer Institute

2. Outline
• Case
• Early disease
• Intermediate Disease
• Advanced Disease
• Recurrent/Metastatic Disease
• Radiation Therapy Planning
• Back to the case

3. Case
• 54 year old male patient – presenting with left
eye disturbance, earache and facial pain – for
10 months;
• P/E – remarkable for left eye movements
disturbed in all directions;
• MRI – revealed a lesion in the fossa of
Rosenmuller, invading the sphenoid/ethmoid
sinus, left cavernous sinus > orbital apex; no
evidence of nodal disease

4. Case, cont’d
• Endoscopy – biopsy taken; Results:
Non keratinizing undifferentiated NPC; EBV
detected as Positive;
• Remainder of clinical exam – Normal, no
metastases found

5. MRI Images

6. EARLY DISEASE (T1N0M0)
INTERMEDIATE DISEASE (T1-2N1M0, T2N0M0)
ADVANCED DISEASE (STAGE III, IV A & IV B)
RECURRENT & METASTATIC DISEASE

7. Is there a role of surgery in the
treatment of early disease NPC?
Approach Authors Concerns/Findings
Through the nose Halsted Post-operative scarring+
deformity
Through the upper jaw Langenbeck No much value/line of
approach too high
Through the mouth Doyle, Wilson Some value found – worst
post-op cosmesis
Wilson, 1950

8. Fallen out in favor of…
Study group Location Local control
findings
Overall survival
Sanguinetti, 1997 MDACC LC-5: 71%
LC-10: 66%
LC-20:66%
OS-5: 48%
OS-10: 34%
OS-20: 18%
Johansen, 1992 Denmark LC -5: 54% OS: Stg I/II: 60%
OS: Stg III: 49%
OS: Stg IV: 27%
Lee, 1993 Hong Kong Local failure free
Rate: 61%
OS – 43%

9. Standard of care
N = 2687
5-y Failure free rates
Local : 85%;
Nodal: 94%;
Distant: 81%
5-y Progression
Free Survival
63%
Overall Survival (per stage)
I – 90%
II – 83%
III – 63%
IV – 58%
Stage I: 7%
Stage II: 41%
Stage III: 25%
Stage IV: 28%
RT ALONE – 66 Gy
Lee AW, 2005

10. What is the best RT technique?
N= 616
IMRT
(306)
LC – 5: 90.5%
OS – 5: 79.6%
LC – 5: 84.7%
OS – 5: 67.1%
2D – CRT
(310)
Lee AW, 2014

11. Neck management
N = 301
Upper Neck
Irradiation
N = 153
3- y OS = 89.5%
3- y RFS = 89.8%
3- y MFS = 91.7%
3- y OS = 87.4%
3- y RFS = 89.3%
3- y MFS = 90.9%
Whole Neck
Irradiation
N= 148
Li JG, 2013
Omission of lower neck RT in N0 does not
decrease the rate of lower neck control

13. EARLY DISEASE (T1N0M0)
INTERMEDIATE DISEASE (T1-2N1M0, T2N0M0)
ADVANCED DISEASE (STAGE III, IV A & IV B)
RECURRENT & METASTATIC DISEASE

14. Standard of care
N = 230
Arm 2:
CCRT – 116
RT + Weekly Cisplatin – 30
mg/m2
PFS: 77.8% Vs
87.9% (p=0.017)
OS: 85.8% Vs
94.5 % (p=0.007)
Arm 1:
RT - 114

15. CISPLATIN: ONCE WEEKLY OR THREE WEEKLY?

16. Little dose with little impact
NN= 300
Weekly
cisplatin
30mg/m2
(150)
LRC: 58.5 Vs
73.1*%
(p=0.014)
Toxicity (G3-4):
71.6 Vs 84.6*%
(p=0.006)Cisplatin q3
weekly
100mg/m2
(150)
PFS: 17.7 mo
Vs 28.6* vs
(p=0.21)
Noronha V, 2018
* 3- weekly cisplatin – better LRC but worse toxicity

18. EARLY DISEASE (T1N0M0)
INTERMEDIATE DISEASE (T1-2N1M0, T2N0M0)
ADVANCED DISEASE (STAGE III, IV A & IV B)
RECURRENT & METASTATIC DISEASE

19. Standard of care – INT 0099
N= 147;
Stage III& IV
RT alone = 67
(70/2/#)
3- y PFS: 24 Vs
69% (p<.001)
3 – y OS: 46%
Vs 76% (p <
0.01)
RT + iv
cisplatin
(100mg/m2) q
3 weekly
Al Sarraf, 1998

20. WHAT IS THE ROLE OF ADJUVANT
CHEMOTHERAPY?

21. MAC-NPC
Concurrent CRT +
Adjuvant Therapy
(HR: 0.65, 0.56-0.76)
Adjuvant chemotherapy
after RT alone
(HR: 0.87, 0.68-1.12)
CRT without Adjuvant
Therapy
(HR: 0.80, 0.70-0.93)
Induction chemotherapy
(HR: 0.96, 0.80-1.16)
19 trials, 4806
patients
Blanchard, 2015

22. ROLE OF INDUCTION THERAPY?

23. TPF got the best of NPC
OutcomesArmsEnrollment
N = 480,
stage III-IV
Arm 1*:
TPF + CRT
3-y Failure Free
Survival: 80 Vs 72%
3- y OS: 92 Vs 86%
Arm 2: CRT
alone
Sun Y, 2016

24. EBV: Prognostic Marker
P
r
e
-
R
T
1
w
k
p
o
st
R
T
Lin N 2004

25. Could then treatment be framed
around EBV positivity?

26. EARLY DISEASE (T1N0M0)
INTERMEDIATE DISEASE (T1-2N1M0, T2N0M0)
ADVANCED DISEASE (STAGE III, IV A & IV B)
RECURRENT & METASTATIC DISEASE

27. Steps to take
• Thorough examination – with newer staging to
rule out synchronous metastases;
• Challenges remain – location of nasopharynx +
caution for RT dose given during primary
irradiation

28. Options
Options Details & Complications Outcomes
Re-irradiation 3D, IMRT, Brachytherapy
(Au seeds), SRS, etc
CN palsy, hearing loss,
palatal fibrosis
3-y PFS – 36%;
3- y OS – 64%
Salvage surgery Local recurrence +/-
isolated neck recurrence;
Nasopharyngectomy!
High rate ORN, aspiration
pneumonia, oropalatal
fistula
3- y OS – 60%

29. Metastatic disease - options
Options Details
Cytotoxic
chemotherapy
1st line: Gemcitabine + Cisplatin (better
than 5-FU + Cisplatin – increased PFS – 7
months but more hematologic toxicity
Molecular targeted
therapy
EGFR inhibition – cetuximab
VEGF – Sorafenib + Sunitinib (caution to
increased upper GI bleeding if prior RT)
Therapeutic EBV vaccination – being
studied
PDL-1 (immune checkpoint) inhibitor

30. RADIATION THERAPY PLANNING

31. Patient setup and data acquisition
• Supine position – chin elevated (neutral if
IMRT) but spine kept as straight as possible;
• Immobilize with a perspex shell/
thermoplastic mask;
• Mouth bite to depress the tongue away from
treated volume

32. Data Acquisition, ct’d
• If CT scan to be used – 3-5 mm slices starting
from the superior orbital ridge (including the
skull base) to aortic arch;
• IV contrast needed for cervical nodes
definition;
• If simulator to be used – use bony anatomy
with opposing lateral fields – neck nodes to be
delineated with wires

33. Techniques
• Techniques:
 IMRT/IGRT
 3D-CRT
 Conventional technique
• Energy selection
 Co60: 1.25 MeV
 LINAC: 4-6 MV

34. Clinical Field Marking
Border Details
Superior 2.5 cm from zygomatic arch/ extend to 5 cm from
zygomatic arch if intracranial extension; if CT available
– place at 2 cm above visible disease – including the SB
+ sphenoid sinus
Posterior Along the tip of the mastoid – or behind the posterior
most extent of cervical LN
Anterior Including a margin of 2 cm of most anterior disease –
while excluding as much oral cavity as possible;
posterior 1/3 of maxillary sinus
Inferior At the thyroid notch – above the arytenoids
Lower anterior
neck field
Matches with lateral portals – ends inferiorly at the
lower border of the clavicle

35. Treatment volumes
Target Volumes Details
Gross Tumor Volume Locate tumor + infiltration – Retropharyngeal node > 5mm and
cervical nodes > 10mm to be included in GTV; in case induction has
been used – GTV to take care of initial disease sites – fuse pre-
induction CT with planning CT. Treat at 70 Gy
Clinical Target Volume •CTV70: GTV + 5mm – for clinically apparent disease;
• CTV60: High risk areas – copy CTV70 and expand to areas of
possible spread of NPC;
•CTV50: add level IB, level II – IV + low level V; N0 disease – omit IB
bilaterally – N1 – contralateral IB can be omitted; Rarely – level IV
and lower level V can be omitted in case of WHO I – N0
Planning Target
Volume
Every CTV described above should have its own PTV

36. Dose - RT
• Initial field – 40-44 Gy in 20 – 22 fractions of 2
Gy each;
• Boost – 20-26 Gy delivered with spine
shielding:
* Lateral field: off cord, border drawn along
the anterior 2/3 of the vertebral bodies;
* Anterior field: midline block of 2cm wide -
adequate

37. Boost – Nasopharynx + Neck nodes
Boost field Details + field
Nasopharynx 4 field – 2 anterior fields + opposing lateral fields
* Preferred – opposing lateral fields, off cord
Posterior
Neck field
Abutting the posterior border of the lateral field
(used for boost) – energy selected – 9 MeV;
prescribed at 85% isodose

38. Ho’s technique
• Developed in 1960s in Hong Kong – and
extensive use over 3 decades;
• Different volume specification and patient
immobilization – arrangement done with bony
landmarks, ;
• Best used in centers without CT planning

39. Ho’s technique, details
Phases Details
Initial phase Flexed head position – 3 fields techniques: 2
lateral opposed + 1 lower anterior neck field;
lateral opposed irradiate up to level III; shield:
midline lower anterior neck field (all treatment),
eyes, posterior tongue, pituitary + brainstem
Treat at 40 Gy in 20 #
Boost Extended – 3 fields technique: pull up lower
border of lateral fields up to the angle of
mandible + anterior cervical facial field
Dose – 22.5 Gy in 9# -
Total – 62.5 Gy in 29#

40. Ho’s technique survival
Ho J, 1978

41. Complex Planning
• IMRT- best possible technique for NPC;
• Use 5-7 equally spaced beams – keeping in
check the OARs; 3 PTVs can be treated to
different doses in a single phase;
• SIB – dose: 65 Gy to PTV70; 60 Gy in PTV60;
50.4 Gy in PTV50 in 30 # given in 6 weeks

42. Example - Plan

43. Back to the case
• Received – 70Gy in 35# of 2 Gy per fraction +
Cisplatin q 3 weekly – 100 mg/m2;
• Follow-up at 18 months with clinical exam
(+CT)revealed no local recurrences; Repeat
MR – revealed lung metastasis;
• He was put on a regimen of GC and is still
doing well on follow-up visits