management of carcinoma nasopharynx

1. MANAGEMENT OF
CARCINOMA
NASOPHARYNX
DR SAILENDRA NARAYAN
PARIDA
SENIOR RESIDENT
DEPARTMENT OF

2. • STAGE I & STAGE IIa – Only RT.
• STAGE IIb to STAGE IVb – CTRT +/-
ADJUVANT CT
• STAGE IVc – CHEMOTHERAPY +/-
PALLIATIVE RT
• PERSITENT OR RECURRENT –
SURGERY/RT/CTRT

3. SURGERY
RADIOTHERAPY
CHEMOTHERAPY

4. ROLE OF SURGERY
• Anatomic location, proximity to critical
structures
• Surgical exposure and tumor resection with
sufficient margins is challenging.
• Surgical interventions employed mainly for
biopsy to gain histologic confirmation and
salvage therapy for persistent or recurrent
cancer.

5. RADIOTHERAPY IS THE
CORNER STONE OF THE
TREATMENT

6. TREATMENT PREPARATION
• Localization of gross tumor and target
volumes
• Optimization of dose fractionation
• Determination of treatment techniques
• Patient positioning
• Immobilization
• Precision in RT delivery

7. • Planning CT covering from skull vertex to
2 cm below clavicles, with 3-mm slice
thickness at gross tumor regions, is
performed.
• IMRT technique is recomended if
resources are available.

8. • supine position with
Neck hyperextended
• thermoplastic mask
covering the head-to-
shoulder region
• mouth bite is useful to
minimize the dose to
the oral cavity

9. TIME,DOSE,FRACTIONATION
• Marks et al. and Vikram et al. showed that
local control was significantly improved in
patients who received >67 Gy to the tumor
target.
• Perez et al. observed that patients with T1-2
tumors had a local tumor control rate of 100%
for those given >70 Gy, compared with 80%
for those treated with 66 to 70 Gy.
• However, local control for patients with T3-4
tumors remained <55%,even with total dose
>70 Gy.

10. Lee et al.
• Dose fraction did not affect local
control; however, it was a significant
risk factor for temporal lobe necrosis.
• Fractional dose of >2 Gy should be
avoided

11. PRESCRIPTION
RECOMMENDED
• Total dose of about 70 Gy over 7 weeks to
the gross tumor @ 2Gy per # and 5 # per
week.
• 50 to 60 Gy for elective treatment of
potential risk sites.

12. TARGET VOLUMES
• GTV - primary nasopharyngeal tumor,
gross retropharyngeal lymphadenopathy,
and gross nodal disease.
• CTV - Includes the GTV, regions of
microscopic disease, and potential
infiltrative spread.

13. • HIGH RISK CTV(CTV70) - GTV plus 5 mm to 1 cm
margin
• LOW RISK CTV (CTV59.4) - GTV including all
potential areas of microscopic spread of disease
• entire nasopharynx and its boundaries
• bilateral upper deep jugular
• submandibular
• jugulodigastric
• midjugular
• posterior cervical
• retropharyngeal lymph nodes.

14. • In patients with clinically N0 neck, it is not
necessary to include level I nodal regions.
• The planning target volume (PTV) - CTV
+ 3 to 5 mm margin to account for setup
errors and potential patient motion.

15. CONVENTIONAL TWO-
DIMENSIONAL TREATMENT
TECHNIQUES• Phase I
large bilateral opposing pair faciocervical fields
that encompass the primary tumor and the upper
neck nodes in one volume, with a matching lower
anterior cervical field for the lower cervical
lymphatics.
• Phase II
After 40-44Gy to limit the dose to the spinal cord.
• Shrinking field arrangement with cone-down after
50 to 60 Gy should be made whenever possible to
maximize protection of critical structures.

16. CONVENTIONAL PORTAL
• Superior - cover sphenoid sinus and base
of skull
• Inferior - above true vocal
• Posterior – tip of spinous processes
• Anterior - 2–3 cm anterior to GTV (and
include pterygoid plates and posterior 1/3
of maxillary sinuses)

18. THREE-DIMENSIONAL
CONFORMAL TREATMENT
TECHNIQUES
• 3D treatment plan is an important
technical advance for improved radiation
delivery.
• Jen et al. who compared 72 patients
treated with 3D conformal technique with
108 patients treated with 2D technique.

19. RESULT
• A significant improvement in 3-year L-
FFR for T4 (86% vs. 47%) and event-free
survival for both stage III (80% vs. 56%)
and stage IV (82% vs. 33%) was
observed.
• Incidence of xerostomia at 3 years was
significantly less with 3D conformal
treatment (69.2% vs. 98.0%).

20. IMRT TECHNIQUES
• 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 tissues.

21. IMRT
• Two different IMRT approaches are being
utilized by different centers:
• Extended-whole field (EWF) IMRT
technique, in which the total target volume is
encompassed in the IMRT plan
• Split-field (SF) IMRT technique, in which the
target volumes superior to the vocal cords
are treated with an IMRT plan and the lower
neck nodes are treated with a conventional
low anterior neck field.

24. DOSE ESCALATION
• Excellent local tumor control has been
reported by delivering an additional boost
to patients with early disease treated by
conventional 2D technique.
• A. Brachytherapy
• B. Stereotactic Radiosurgery
• Altered Fractionation

25. BRACHYTHERAPY
• Used in T1 to T3 nasopharyngeal
carcinomas as a boost treatment following
external beam irradiation (EBRT) or in the
treatment of recurrent disease, either alone
or in combination with EBRT.
• Brachytherapy is not suitable for treatment
of tumors with intracranial extension
because of the rapid reduction of dose as
distance from the radioactive source
increases.

26. A: The Rotterdam nasopharyngeal applicator.
B: The simulator check-film showing the position of
the radioactive sources and the dose distribution.

27. • In the past, intracavitary brachytherapy was
delivered using low–dose rate (LDR)
techniques. However, at present, remote
afterloading, fractionated high–dose rate
(HDR) techniques are more commonly used.
• Most studies demonstrated that local control
of up to 90% to 95% could be achieved
forT1-2 tumors without excessive late
damages.

29. LIMITATION OF
BRACHYTHERAPY
• One major limitation of brachytherapy is
that the dose delivered is adequate only
for superficial nonbulky tumors.
• Optimal positioning of the applicators
depends both on the individual clinician’s
skill and the patient’s anatomic features.

30. • Stereotactic radiosurgery (SRT) or
fractionated radiotherapy allows for
precise delivery of highly conformal RT
with a rapid dose falloff and provides an
alternative for dose escalation(Hara et al.)

31. ACCELERATED
FRACTIONATION
• The first randomized trial on accelerated
fractionation (AF) for NPC by Teo et al.
• The trial was terminated early because of
excessive neurologic toxicities in the AF
arm (49% vs. 23%).

32. CHEMOTHERAPY
NEOADJUVANT
CONCURRENT
ADJUVANT

33. CONCURRENT
CHEMORADIOTHERAPY
• The landmark Intergroup 0099 trial was the first to
document a significant survival benefit for CRT versus
RT alone
• This trial randomized 147 patients with locally
advanced NPC to either RT alone or CRT followed
by adjuvant chemotherapy.
• Chemotherapy consisted of concurrent cisplatin
(CDDP;100 mg/m2 on days 1, 22, and 43), followed by
three cycles of adjuvant CDDP (80 mg/m2 on day 1)
and 5-FU (1000 mg/m2/d on days 1 to 4) every 4
weeks.
• Radiotherapy was delivered in 1.8- to 2-Gy fractions to
a total dose of 70 Gy.

34. • The trial was closed early due to a
significant overall survival benefit in
favor of CRT (78% vs. 47% at 3 years).
• A 5-year update confirmed progression-
free survival (58% vs. 29%) and overall
survival (67% vs. 37%) in favor of CRT.

35. • Wee et al.reported the results of 221
stage III-IVB patients from Singapore
randomized to receive either RT alone or
CRT.
• Three-year overall survival for the CRT
and RT arms was 85% and 65%,
respectively (p = .006).
• CRT reduced the incidence of distant
metastasis by 17% at 2 years (p = .003).

36. • Langendijk et al.performed a meta-
analysis of 10 trials that randomized NPC
patients to conventional RT or CRT.
• The authors found an absolute survival
benefit of 4% at 5 years.
• Overall survival benefit of 20% at 5 yr
with CRT.

37. • Analysis of the neoadjuvant
chemotherapy trials found a significant
reduction in locoregional recurrence and
distant metastasis but no overall survival
benefit.

38. ADJUVANT CHEMOTHERAPY
• the greatest body of evidence for
chemotherapy has been with the CDDP-
based U.S.Intergroup regimen of
concurrent plus adjuvant chemotherapy.

39. • Chen et al. compared concurrent CRT to
concurrent CRT plus adjuvant
• Compliance was an issue in this study
• 18% of patients in the adjuvant arm did
not complete adjuvant chemotherapy.
• Failure rates at any site is same in both
the arms.

40. • Until further data emerge, adjuvant
chemotherapy is considered by many to
be optional in the setting of concurrent
CRT, although it may have a role in
patients with residual EBV DNA after
CRT.

41. NEOADJUVANT
CHEMOTHERAPY
• Role of neoadjuvant chemotherapy to
concurrent CRT is a topic of much current
interest and the subject of two ongoing
phase III randomized trials.

42. OTHER AGENTS
• Weekly oxaliplatin (70 mg/m2)
• Carboplatin
• Cetuximab
• Bevacizumab

43. PERSISTENT/RECURRENT
DISEASE
• What is persistent disease?
• What is recurrent disease?
• When to start the salvage treatment?

44. Kwong et al
• serial biopsies of the nasopharynx were
performed on 803 patients after RT
treatment to observe the time course of
histologic remission for NPC and
determine its prognostic significance.

45. AUTHORS CONCLUSION
• Patients with early remission post RT has a
better prognosis.
• positive biopsies beyond 12 weeks indicate
poor prognosis.
• observation period of 10 weeks before
starting additional treatment.

46. WHAT ARE THE POSSIBLE
OPTIONS?
• Brachytherapy
• Stereotactic radiosurgery or fractionated
stereotactic radiotherapy
• EBRT
• Combined EBRT and Brachytherapy
• Surgery

47. RESULTS OF SURGERY FOR
RECURRENT TUMOURS
• Satisfactory long-term results can be
achieved when persistent/recurrent tumor
are completely resected.
• Several recent surgical series reported
locoregional control and OS rates of 40%
to 72% and 30% to 54% respectively.

48. RESULTS OF TREATMENT AFTER
CONVENTIONAL RADIOTHERAPY
FIVE YEAR LOCAL CONTROL
• T1 - 64% to 97%
• T2 - 54% to 94%
• T3 - 34% to 100%
• T4 - 40% to 71%
5-YEAR NODAL CONTROL
• N0 - 82% to 100%
• N1 - 86% to 92%
• N2 to N3 - 78% to 89%

49. FIVE YEAR SURVIVAL RATES
• T1 - 60% to 76%
• T2 - 48% to 68%
• T3 - 27% to 55%
• T4 - 0% to 29%

50. SEQUELAE OF TREATMENT
The overall complication rate from conventional
treatment ranged from 31% to 66%
• Temporal lobe necrosis
• Hearing loss
• Xerostomia
• Neck fibrosis
• Cranial nerve dysfunction
• Endocrine dysfunction
• Soft tissue necrosis
• Osteonecrosis
• Transverse radiation myelitis

51. TEMPORAL LOBE NECROSIS
• Most troublesome complication
• 65% of all irradiation-induced deaths
• Lee et al. showed that the incidence of
symptomatic TLN ranged from 0% (with 2
Gy/fraction, five fractions/week,for 33
fractions) to 24% (3.5 Gy/fraction, three
fractions/week, for 17 fractions), and 33%
for an altered fractionation schedule
(71.2 Gy in 5 weeks)

52. • Overacceleration and
fractional dose >2 Gy should
be avoided.

53. PRESENTING SYMPTOMS
• classic symptoms are hallucinations,
absence attacks, déjà vu.
• Headaches
• Confusion
• Convulsions
• Hemiparesis
• vague symptoms(dizziness, poor memory,
or sudden changes in behavior)

54. • CRANIAL NERVE PALSY
Cranial nerves IX through XII, particularly XII, are
the most frequently impaired.
• ORAL COMPLICATIONS
Xerostomia, osteoradionecrosis, dental decay
• AURAL COMPLICATIONS
Hearing loss(more with CDDP based CRT),
dysfunction of eustachian tube
• CAROTID ARTERY INJURY
Carotid stenosis,pseudoaneurysms

55. • ENDOCRINE DYSFUNCTION
Amenorrhea and/or Galactorrhea
Hypothyroidism
Hypoadrenalism
• SECOND MALIGNANCY
Incidence of-0.04%
latency period of >10 years
most common-maxillary osteosarcoma

56. FOLLOW UP
• 1–3 month - first year
• every 2–4 months - second year,
• every 4–6 months - 3–5 Years
• then every 1year.

58. TAKE HOME MESSAGE
• IMRT and 3DCRT is preferred over
conventional treatment.
• Dose >2Gy/# and over acceleration should
be avoided.
• Role of surgery is limited to biopsy and in
recurrent disease.
• Adjuvant chemotherapy after CRT is
optional.
• TLN is the most fearful complication.