2. Tumor related
TNM staging: most important prognostic factor.
• advanced T-category: associated with worse local control and overall
survival;
• advanced N-category: increased risk of distant metastasis and worse
survival.
• M1 stage: poor prognosis
Histopathology: nonkeratinizing and undifferentiated carcinomas more
radiosensitive and offer better prognosis than keratinizing SCC.
Plasma EBV DNA - higher pretreatment levels – poor prognosis.
Prognostic Factors
3. Patient related
Age: better prognosis younger patients
Ethnicity: no prognostic difference patients
Gender : not significant
Performance status, weight loss & anaemia before treatment :not
significant in pts. treated definitively
Diagnosis & treatment related
Treatment delay > 8 weeks after diagnosis or extending break during RT
adversely effect outcome
Treatment strategy & techniques: use of Chemo RT & IMRT improves
tt. outcome compared to conventional therapy
Tumor regression during RT: not significant
*Lin JC 2009:prognostic factors in NPC
4. Nasopharyngeal carcinoma is different from other H&N cancers in termsof:
Geographic & ethnic distribution (MORE IN SOUTH EAST ASIA)
Association with Epstein–Barr virus (EBV)
Aggressive natural behaviour
High predilection for distant metastases
Challenges in management:
Detection is difficult: silent deep seated location.
Treatment is difficult: anatomical proximity to critical structures.
Role of surgery is limited to biopsy and salvage.
Fortunately, this cancer is highly radiosensitive and chemosensitive;
However, the therapeutic margin is narrow, and the most conformal and
precise radiotherapy is demanded
UNIQUE FEATURES OF NASOPHARYNGEAL CANCER
6. Rx recommendations
STAGE RECOMMENDED Rx
I • RT alone
II-IVB • CCRT (70/2Gy + cisplatin 100mg/m2 on day 1,21,42) --------adj
chemo(cisplatin/5FU x 3c)
• Neck dissection for persistent or recurrent nodes
• Neoadj chemo (platinum/5FU +/- taxane) is under
IV C • Platinum based chemo
• If CR---- definitive RT
• or
• Palliative RT to metastatic nodes.
Local
recurrence
• Re-radiation with IMRT, SRS, brachytherapy or surgery.
7. Role of surgery
• Due to deep location of nasopharynx, and anatomic
proximity to critical structures, radical surgery is
typically not used.
• Limited to
Biopsy for histological confirmation
Neck dissections for persistently enlarged lymph nodes
Nasopharyngectomy in persistent or recurrent disease
9. Impact Of Dose
High dose is needed for NPC tumor despite its radiosensitivity.
The general recommendation is : 70 Gy to the gross tumor @1.8-2 Gy /#.
50-60 Gy to potential risk sites @ 1.8-2 Gy /#.
Retrospective studies shown that T1-2 tumors had good local control rateof 90-
100% for >70 Gy, compared to 80% for 66 to 70 Gy.
However, local control for patients with T3-4 tumors remained<55%, even with
total dose >70 Gy.
Higher doses did not significantly improve outcomes in T3-4 tumors.
These observations suggested that, besides consideration of the prescribed dose,
the problem of sufficient coverage has to be overcome foradvanced tumors.
10. Impact of time & fractionation
• Prolongation of treatment significantly jeopardizes local control.
• Benefit of accelerated fractionation is uncertain (no benefit in
local control, increased toxicities).
• Retrospective study by Lee et al. in 1,008 patients with T1 tumours
irradiated by four different fractionation schedules demonstrated that
total dose was the most important radiation factor (p = .01).
• Dose per fraction did not affect local control; however, it was a
significant risk factor for temporal lobe necrosis.
• Therefore, a fractional dose of >2-2.12 Gy should be avoided.
12. Role of Radiation Therapy: Treatment of Choice
• Historically, RT alone was used, and resulted in
• SURVIVAL:
• Early-stage (I-II) outcomes were good, with 5-year DFS 75-95%
and OS 70-80%
• For advanced-stage (III-IV) 5-year DFS was ~50%, and OS only
10-40%
• AT PRESENT :
• Early stage disease (Stage I) :continues to be managed with RT
alone
• Advanced stage disease (Stage II-IV) - CCRT
17. The potential benefit of IMRT for NPC
• Improve the local control especially for concave
shape tumors
• Reduce the post-irradiation complications
• Reduce the rate of distant metastasis by improving the
local control
• The intensity of the radiation beams can be modulated to
deliver a high dose to the tumor with a superior target
volume coverage while significantly limiting the dose
to surrounding normal structures.
18. TECHNIQUES OF IMRT:
EWF
Extended whole field
SF
Split field
Total target volume is encompassed
in the IMRT plan
Target volume superior to vocal cords
– IMRT
Lower neck – CONVENTIONAL low
anterior neck field.
Unnecessary dose to NORMAL
GLOTTIC LARYNX
Dose to the vacal cords is minimal
Shielding with CERROBEND BLOCK or
MLC
LOW NECK IN LOW RISK NODAL INV:
54Gy at 1.64/#
50Gy at 1.8Gy/#
19. IMRT Target Delineation for
Nasopharyngeal Carcinoma
CTV STRUCTURE (lee et al…RTOG 0615)
CTV1 GTV + >/= 5mm margin
Reduced to as low as 1mm when close to critical structures.
CONSIDER 10mm IF ECE+
70/2.12 Gy
CTV2 • CTV70 + >/= 5mm margin (as low as 1mm near critical
structures)
• Entire nasopharynx
• Posterior ethmoid sinus
• Base of skull (ovale, rotundum, lacerum, petrous tip)
• Pterygoid fossa
• Parapharyngeal spaces
• Sphenoid sinus- inferior ½ if T1-2, whole if T3-4
• Posterior nasal cavity(at least 5mm from choanae)
• Posterior maxillary sinus(at least 5 mm from posterior
wall)
• Cavernous sinus (T3,T4, involved side only)
• Clivus (1/3rd if no invasion, whole if invasion)
• High risk nodal levels(all bilaterally)
Level II,III ,Va, RP.
VIIb + I/L one level below the involved levels.
56-59.4/1.8 Gy
CTV3 • LEVEL VIb and Vb
• OMIT IF N0 OR N1 BASED SOLELY ON RPLN inv.
54/1.6 Gy
20.
21.
22.
23. LEVEL IB:
Bilateral IB can be SPARED – NODE NEGATIVE
(since normal structures gets significant radiation doses- floor of mouth,
mandible, upper pharyngeal mucosa above the hyoid.)
IS INCLUDED IF structures that drain to level Ib as first level of LN
for eg- oral cavity, anterior half of nasal cavity + level II with ECE.
24. DOSE CONSTRAINTS (based on memorial sloan kettering cancer center)
CRITICAL STRUCTURES or
Brainstem
Optic nerve
Optic chiasm
Maxm <54Gy 1% PTV < 60 Gy.
Spinal cord Maxm <45Gy 1cc < 50Gy.
Mandible & TMP joint Maxm <70 Gy 1cc < 65Gy.
Brachial plexus Maxm <66 Gy
Temporal lobes Maxm <60 Gy 1% PTV < 65 Gy.
OTHER NORMAL
STRUCTURES
Oral cavity Mean <40 Gy
Parotid Gland Mean < 26 Gy
(atleast in one gland)
20 cc of combined volume of
both parotids < 20Gy.
Cochlea V55 < 5%
Eyes Mean < 35 Gy Maxm < 50 Gy
Lens Maxm < 25 Gy
Glottic larynx
Oesophagus
Post cricoid pharynx
Mean < 45 Gy
25. Our institute:
24 yr old male with c/o neck swelling for 2 months
On evaluation was diagnosed as carcinoma nasopharynx with:
PET CT:
2.0x2.6x2.1cm lesion involving nasopharynx in the midline with
obliteration of right fossa of rossenmuller (suv-20) .
Multiple lymph nodes with B/L level II + Rt RP + Rt III,IV,V with largest
being 2.5x1.9 cm.(suv-15.11).
Dose:
ctv1- 70/2 Gy
ctv2- 61.25/1.75 Gy
ctv3- 56/1.6 Gy
26.
27.
28.
29.
30.
31. Dose Escalation: excellent tumor control was reported
by delivering additional boost to patients with early disease
treated by conventional 2D technique.
• ALTERED FRACTIONATION
• STEREOTACTIC RADIOSURGERY
• BRACHYTHERAPY
33. Brachytherapy
• The following requirements should be fulfilled prior to taking up a
patient for brachytherapy:
• Tumor thickness less than 10 mm.
• Absence of intracranial, paranasal sinus and oropharyngeal
involvement.
• Absence of involvement of underlying bone or infratemporal
fossa.
• Absence of metastatic disease.
• Expertise in nasopharyngeal intracavitary brachytherapy.
“In effect, nasopharyngeal brachytherapy is ineffective in tumors
extending beyond the nasopharynx” -Xiao-Kang Zheng
34. PRESENT STATUS OF BRACHYTHERAPY
Since the advent of IMRT as primary radiotherapy for nasopharyngeal
carcinoma and with its excellent local control, the use of brachytherapy
as a boost treatment following definitive EBRT has declined.
35.
36. Dose prescribed :
• In case EBRT given in dose of 60 Gy:
• 3 Gy x 6 fractions by HDR
• Total dose ~ 78 Gy
• In case of EBRT given in dose of 70 Gy:
• 3 Gy x 4 fractions by HDR
• Total dose ~ 82 Gy
40. The first trial that achieved a significant survival benefit was Intergroup-0099
Lin et al also reported significant benefit of concurrent
Kwong et al showed non significant benefits
clinical trials on CTRT
41. CCRT Versus RT in Patients With Advanced
Nasopharyngeal Cancer: Phase III Randomized Intergroup
Study 0099 Al-Sarraf, et al
Journal of Clinical Oncology, Vol 16, No 4 (April), 1998: pp 1310-1317
• Pts. were stratified by tumor stage, nodal
stage, performance status & histology
• Radiotherapy 1.8- to 2.0-Gy/d fractions for 35
to 39 fractions for a total dose of 70 Gy.
• investigational arm received chemotherapy
with cisplatin 100 mg/m 2 on days 1, 22, and
43 during radiotherapy;
• adjuvant chemotherapy with cisplatin 80
mg/m 2 on day 1 and fluorouracil 1,000mg/m
2/d on days 1 to 4 was administered every 4
weeks for three courses.
42. • 3Y PFS 69% (CRT) vs. 24% (RTalone),
p<0.001
• 3Y OS 78% (CRT) vs. 47% (RTalone),
p=0.005
• The trial was closed early due to a significant
overall survival benefit in favour of CRT
45. NEOADJUVANT CHEMOTHERAPY
One strategy to improve the efficacy of chemotherapy is to use an
neoadjuvant-concurrent sequence.
Advantages of neoadj chemotherapy better tolerated than
adjuvant chemotherapy:
1.Early use of a potent combination of cytotoxic drugs at full dose
may eradicate micrometastases.
2.Can shrink primary tumor to give a wider margin for irradiation,
can save adjacent critical neural structures during RT
No significant adv in OS but HIGHER TOXICITIES.
46. ADVERSE EFFECTS
Hypothalamo-Pituitary dysfunction
Most common- hyperprolactinemia ----hypothyroidism-----hypoadrenalism.
Hearing defects:
SNHL
Temporal lobe injury:
Hallucinations, absence attacks, déjà vu.
Cranial nerve injury:
CN IX thro XII (m/c XII.)
Oral Complications:
Xerostomia
Carotid artery injury:
In high risk pts with >60 yrs, smoking, hypertension, hypercholesterolemia, cerebrovascular
symptoms.
Second malignancies
47. Conclusion :
• Nasopharyngeal malignancies make up a different
population of head and neck malignancies.
• These are eminently radio sensitive and curable.
• Treatment planning is by necessity complicated and time
consuming.
• Brachytherapy can be used for boosting the local activities.
• Chemoradiation is standard treatment in locally advanced
tumors
