Management of Carcinoma oropharynx

1. Management Carcinoma
Oropharynx
Dr. Sagar N. Raut
PGT 2nd year

2. HPV-Mediated (p16+)
Oropharyngeal Cancer
Oropharynx (p16-)

3. HPV-Mediated (p16+)
Oropharyngeal Cancer
Oropharynx (p16-)

4. HPV-Mediated (p16+)
Oropharyngeal Cancer
Oropharynx (p16-)

5. HPV-Mediated (p16+)
Oropharyngeal Cancer
Oropharynx (p16-)
AJCC 8th Edition

6. Management Goals
• Based on the critical function of the oropharynx in speech and
swallowing, the treatment of oropharyngeal carcinomas can
significantly impact patient quality of life.
• Appropriate treatment strategies should focus on maintaining high
cure rates while minimizing long-term, treatment-induced functional
morbidity.
• Functional organ preservation with minimal toxicity is the
management goal for all oropharyngeal cancer patients.

7. • Early stage (locally confined disease) - stage I and stage II tumors
• For all subsites, early-stage tumors are usually well controlled with a single local
modality, either radiotherapy or surgery.
• Selection of local modality should be based on the primary tumor size, extent of
local spread, and subsite involved.
• Small tumors of the tonsil and small exophytic tumors of the base of tongue can be
well managed surgically, whereas the morbidity of surgery on the soft palate favors
radiotherapy.
• Locoregionally advanced disease - stages III and IV (nonmetastatic)
disease.
• For locoregionally advanced disease, two appropriate treatment strategies are
used:
(a) Either surgery followed by radiation therapy with or without chemotherapy based on
pathologic risk factors or
(b) Radiotherapy usually given with chemotherapy
Perez and Brady’s 6E 2013

8. Treatment Modalities
• Surgery
• Radiotherapy
• Chemotherapy

9. Base of Tongue
• Surgery plays a limited role in the management of base of tongue tumors.
• For select, well-lateralized base of tongue tumors with minimal cervical
lymphadenopathy, a partial glossectomy with B/L cervical LN dissection
can be performed.
• Base of tongue tumors in close proximity to the laryngeal apparatus, such
as those arising in the vallecula, often require a supraglottic or total
laryngectomy to achieve adequate margins of resection.

10. Soft Palate Cancers
• Surgical resection is rarely recommended as initial therapy because
• Often associated with significant reflux into the nasopharynx during
swallowing, even with the use of custom prostheses.
• Because of the midline location, primary disease spreads bilaterally to the
neck with frequency high enough to require elective treatment.
• Nasal speech is also often a consequence
• In General, Radiotherapy alone or along with concurrent chemo is
preferred.

11. Tonsil Cancer
• Wide local excision - For small (<1 cm) early-stage tonsil cancers
confined to the anterior pillar.
• Radical tonsillectomy - Larger tumors with extension onto the tongue,
onto the mandible or into surrounding tissue often require a composite
resection, including resection of
• The tonsil,
• Tonsillar fossa, pillars,
• A portion of the soft palate,
• Tongue, and
• Mandible.
• But, In general apart from small tonsillar lesion surgery is generally not
done and chemoradiation is preferred.

12. • Midline mandibulectomy
• Lateral mandibulectomy
• Transoral laser microsurgery (TLM) and/or transoral robotic surgery
(TORS) is an emerging approach for resectable oropharynx cancers.
• Recent meta-analyses report similar DSS and OS with primary
transoral surgery or radiotherapy for early stage tumors ().
• However, postoperative radiotherapy may be indicated in up to 90%
of pts and about one third of patients receive postoperative
chemoradiation.
de Almeida Laryngoscope 2014;
Morisod Head Neck 2016

13. Margins
• Clear margin: the distance from the invasive tumour front is 5 mm or
more from the resected margin.
• Close margin: the distance from the invasive tumour front to the
resected margin is less than 5 mm.
• Positive margin: carcinoma in-situ or invasive carcinoma at the
margin of resection. If carcinoma in-situ is present and additional
margins can be obtained that is the favoured approach. Carcinoma in-
situ should not be considered an indication for concurrent post-
operative chemoradiation.

14. Adjuvant Therapy Following
Definitive Surgical Resection
• High risk for Locoregional recurrence in, pathologic features including
• Advanced primary T-stage (T3 or T4),
• Lymphovascular space invasion, perineural invasion,
• Positive margins,
• Multiple pathologically involved cervical lymph nodes, and
• Extranodal extension.

15. • Total Evaluable patients – 325
• Oropharynx – 23% patients
• Preoperative – Primary + Neck Nodes - 50.0 Gy (Sx 4 to 6 weeks later)
• Postoperative – Primary - 60.0 Gy, neck nodes -50.0 Gy (within 4 weeks of Sx)
• Post op RT improved LRC
• Trend towards improvement in OS
• Complications not different
• Established post op RT better than preop RT
Pre-op RT Post-op RT p Value
LRC 58% 70% 0.04
OS 33% 38% 0.10

16. • 334 patients
• Oropharynx – 101(34%)
• Median follow-up of 60 months
• 2 arms
• Radiotherapy alone (60 to 66Gy over a period of 6 to 6 1/2 weeks)
• RT(same) plus concurrent cisplatin (100mg/m2 IV on days 1, 22, and 43 days)
• Primary endpoint – PFS

17. CTRT RT alone p-Value
PFS 47% 36% 0.04
OS 54% 40% 0.02
LRF 31% 18% 0.007
Acute Effects 41% 21% 0.001

18. • 459 Patients
• Oropharynx – 78 (37%) in RT arm vs 99 (48%) in CRT arm
• Median followup of 45.9 months
• Radiotherapy alone (60 to 66Gy in 30 to 33# over period of 6 to 6.6 weeks)
• CRT (Cisplatin 100mg/m2 IV on days 1, 22, 43)
• Primary end point – Local and regional tumour control

19. CT-RT RT Alone p Value
2-yr LRC 82% 72% 0.01
Acute Effects 77% 34% <0.001
Disease-free survival was significantly
longer in the combined-therapy group
than in the radiotherapy, but overall
survival was not.

22. Adjuvant Radiotherapy Dose
• The optimal radiation therapy dose for PORT is also not well defined.
• Most of the randomized studies demonstrating the benefit of concurrent
chemotherapy with PORT used radiotherapy doses of 60 to 66 Gy in 2-Gy
daily fractions to highrisk areas (primary tumor bed with positive margin or
nodal regions with extracapsular spread).
• Doses of 50 to 54 Gy in 2-Gy fractions were usually given to areas at risk for
microscopic involvement.

24. PRINCIPLES OF RADIATION
THERAPY
POSTOPERATIVE:
RT
• Preferred interval between resection and postoperative RT is ≤6 weeks.
PTV
• High risk: Adverse features such as positive margins
• 60–66 Gy (2.0 Gy/fraction); daily Monday–Friday in 6–6.5 weeks
• Low to intermediate risk: Sites of suspected subclinical spread
• 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)3
POSTOPERATIVE CHEMORADIATION:
• Concurrent systemic therapy
• Either IMRT or 3D conformal RT is recommended.
NCCN 2.2018

25. Definitive RT

26. Early-stage oropharyngeal cancers
• Single modality: with good outcomes and functional preservation.
• Although there is not consensus on the optimal dose fractionation
schedule for oropharyngeal cancer patients receiving radiotherapy alone,
randomized data and meta-analyses support an overall survival benefit
with the use of accelerated fractionation or hyperfractionated
radiotherapy.
• Therefore, for oropharyngeal cancer treated with radiotherapy alone,
strong consideration should be given to altered fractionation of some sort.

27. EORTC 22791
Hyperfractionation: Clinical testing
Oropharynx Ca T2-3, N0-1, n=356 (excluding BOT Ca)
70Gy/35#, 2Gy/#, 7weeks vs 80.5Gy/70#, 1.15Gy/#, 4-6hr, 7weeks

28. • Aim: To find out whether shortening of treatment time by use of six instead of five
radiotherapy fractions per week improves the tumour response in SCC
• Multicentre, controlled, randomized trial
• Study Period: Jan 1992 to Dec 1999, 1485 patients treated with RT alone
• 1476 eligible patients were randomly assigned five (n=726) or six (n=750) fractions
per week at the same total dose and fraction number (66–68 Gy in 33–34 fractions
to all tumour sites except well-differentiated T1 glottic tumours, which were
treated with 62 Gy)
• All patients, except those with glottic cancers, also received the hypoxic
radiosensitiser nimorazole.
• Primary end point was LRC

29. • Benefit of Shortening of treatment time was
seen for primary tumour control (76 vs 64
% for 6 vs 5 fractions, p=0.0001) but was
non-significant for neck-node control
• No Improvement in overall survival
6# 5# p Value
LRC 70% 60% 0.0005
DFS 73% 66% 0.01
Acute Reactions 53% 33% 0.0001

30. 1) Standard fractionation at 2 Gy/#/day, 5 days/week, to 70 Gy/35 fractions/7 weeks;
2) Hyperfractionation at 1.2 Gy/#, twice daily, 6 hours apart, 5 days/week to 81.6 Gy/68 fractions/7
weeks;
3) Accelerated fractionation with split at 1.6 Gy/#, twice daily, 6 hours apart, 5 days/week, to 67.2 Gy/42
#/6 weeks including a 2-week rest after 38.4 Gy; or
4) Accelerated fractionation with concomitant boost at 1.8 Gy/#/day, 5 days/week to large field + 1.5
Gy/#/day to boost field given 6 hours after treatment of the large field for the last 12 treatment days to
a total dose of 72 Gy/42 fractions/6 weeks.

35. Conclusion
• HFX and AFX-C decreased 5-year local-regional failure by 19% when
compared with SFX
• HFX, unlike AFX-C or accelerated therapy did so without increasing
late toxities.

36. RTOG 0022
• The RTOG completed a study (00-22) in early-stage (T1-2, N0-2) oropharyngeal cancer patients treated
with bilateral neck radiotherapy using doses of 2.2 Gy, 2 Gy, and 1.8 Gy to gross tumor, intermediate risk,
and low-risk planning target volumes (PTVs), respectively.
• The 2-year risk of local progression was 9% and was higher in patients who had significant underdosing
of known tumor.
• Additionally, no local recurrences, distant metastases, or second cancers were seen in never smokers,
possibly representing a surrogate for HPV-related disease, compared to 7 locoregional recurrences, 5
second cancers, and 1 case of distant metastases in smokers.
• Two-year overall survival was 95%, and disease-free survival was 82%.
• Therefore, it appears that for patients with early-stage oropharyngeal cancer treated with radiotherapy
alone, simultaneous integrated boost radiotherapy is a viable treatment option

38. DEFINITIVE:
RT Alone
• PTV
• High risk: Primary tumor and involved lymph nodes (this
includes possible local subclinical infiltration at the primary site
and at the high-risk level lymph node(s)
• Fractionation:
 –66 Gy (2.2 Gy/fraction) to 70 Gy (2.0 Gy/fraction); daily
Monday–Friday in 6–7 weeks
 –Concomitant boost accelerated RT:
-72 Gy/6 weeks (1.8 Gy/fraction, large field; 1.5 Gy boost as
second daily fraction during last 12 treatment days)
-66–70 Gy (2.0 Gy/fraction; 6 fractions/wk accelerated)
 –Hyperfractionation: 81.6 Gy/7 weeks (1.2 Gy/fraction, twice
daily)
-69.96 Gy (2.12 Gy/fraction) daily Monday–Friday in 6–7 weeks3
• Low to intermediate risk: Sites of suspected subclinical spread
44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)4
CONCURRENT CHEMORADIATION:
• PTV:
-High risk: Typically 70 Gy (2.0 Gy/fraction)
-Low to intermediate risk: 44–50 Gy (2.0
Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)
Either IMRT (preferred) or 3D conformal RT is recommended for cancers of the oropharynx in order to minimize dose to critical
structures.
NCCN

39. Locoregionally advanced
• For patients with locoregionally advanced oropharyngeal cancer, concurrent
chemoradiotherapy is the standard treatment.
• Resection is generally not recommended given the associated surgical
morbidity.
• Additionally, adjuvant chemoradiotherapy is frequently necessary and has
similar morbidity to definitive intent chemoradiotherapy.
• Comparisons of outcomes with radiotherapy with or without neck
dissection or surgery with or without adjuvant radiotherapy resulted in
similar outcomes with higher complication rates with surgery.

41. Combined Modality Radiation Alone p Value
5 yrs OS 22% 16% 0.05
5 yrs DFS 27% 15% 0.01
LRC 48% 25% 0.002

42. • Conclusion: Concomitant radiochemotherapy improved overall survival and
locoregional control rates and doesnot statistically increase severe late
morbidity.

43. MACH NC (Meta-Analysis of
Chemotherapy on Head and Neck
Cancer
• 70 randomized trials between 1965 and 1993
• Patients with carcinoma of the oropharynx, oral cavity, larynx, or
hypopharynx
• Three comparisons
• The effect of chemotherapy – Locoregional treatment was compared with
Locoregional treatment plus chemotherapy
• The timing of chemotherapy – NACT plus radiotherapy was compared with
concomitant or alternating Radio-chemotherapy with same drugs
• Larynx preservation with neoadjuvant chemotherapy – radical surgery plus
radiotherapy was compared with neoadjuvant chemotherapy plus radiotherapy in
responders or radical surgery and radiotherapy in non-responders
Pignon, Lancet 2000; 355:949-55

45. Effect of Chemotherapy on Survival
• Trials were divided according to timing of chemotherapy: Adjuvant,
neoadjuvant, and concomitant or alternating with radiotherapy

46. Conclusion
• The addition of chemotherapy to locoregional treatment – the most
important result was a small, but statistically significant, overall
benefit in survival with chemotherapy (the absolute benefit at 2 and 5
years was 4%)
• No significant benefit of adjuvant or neoadjuvant chemotherapy but a
significant benefit of concomitant chemotherapy (absolute benefit at
2 and 5 years at 2 and 5 years of 8%)

47. MACH-NC Update?
• Update to the meta-analysis by adding the data from the randomized
trials performed between 1994 and 2000
• Added 24 new trials, most of them on concomittant chemotherapy
• 87 trials, 16665 pts
• Median follow up 5.5 yrs
• An absolute benefit for chemotherapy of 4.4% at 5 yrs
• For concomitant CTRT group, the absolute survival benefit at 5 yrs is 8%

48. • The meta-analysis included 87 randomised trials (16,485 patients)
comparing loco-regional treatment versus the same loco-regional treatment
+ chemotherapy

49. • 87 randomised control trials from period 1965 to 2000
• 16,192 patients were analysed in a median follow up of 5.6 yrs
• Evidence of improvement in overall survival
• Absolute benefit 4.5% at 5 yrs
• Benefit more in concurrent CTRT (p<0.0001) and absolute benefit of 6.5%
• Benefit decreases with increasing age
• Absolute benefits
• Oral cavity – 8.9%
• Oropharynx – 8.1%
• Larynx – 5.4%
• Hypopharynx – 4%

50. MACH-NC Conclusions
• Addition of CT – Absolute benefit in survival 5% in 5yrs
• Induction/adjuvant – 2% survival benefit
• Concurrent CTRT 8% - 5yr survival benefit
• Platinum based regimen more effective
• No significant difference in efficacy between mono and multiple drug
platinum regimens
• Small reduction in distant metastasis found in population of patients with
CTRT
• Inverse relation between age and impact of CT.
• Disappears by around age 70.

51. • Locally advanced head and neck squamous-cell carcinoma
• 840 patients (66% oropharynx pts)
• 3 arms
• Conventional CTRT (70Gy/35# + three cycles of 4 days of carboplatin 70 mg/m² per day plus
fluorouracil 600 mg/m² per day from day 1 to 4, day 22 to 25, and day 43 to 46)
• Accelerated CTRT (70Gy in 6 weeks five fractions of 2 Gy per week until 40 Gy and then 1·5 Gy
per fraction twice daily for 5 days per week for the remaining 30 Gy + two cycles of 5 days of
carboplatin 70 mg/m² per day and fluorouracil 600 mg/m² per day from day 1 to 5 and day 29
to 33)
• Very accelerated radiotherapy alone (64·8 Gy in 3·5 weeks without chemotherapy (1·8 Gy
twice daily for five days per week), with spinal cord exclusion at 34·2 Gy)
• Median follow-up was 5.2 yrs
• Primary endpoint - PFS

52. • Conventional CTRT improved PFS compared with very accelerated
radiotherapy
• Grade 3-4 acute mucosal toxicity
• Very accelerated radiotherapy (84%) compared with
• Accelerated CTRT (76%) or
• Conventional CTRT (69%, p+0.001)
• Acceleration of radiotherapy cannot compensate for the absence of
chemotherapy

53. Induction Chemotherapy
• Whether or not induction chemotherapy (ICT) prior to concurrent
chemoradiotherapy improves survival when compared with
chemoradiotherapy is currently unknown.
• Clear guidelines for the optimal use of ICT outside of cases where organ
preservation is a primary goal have yet to be defined.
• Induction chemotherapy has been advocated by some given that distant
metastases is frequently a site of first failure for patients with locoregionally
advanced head and neck cancer in general.
• This is particularly true for patients with oropharyngeal cancer because local
regional therapy has become so much effective.
Perez and Brady’s 6E 2013

55. • Available data have been primarily inconclusive regarding whether ICT
confers overall superior benefits versus the standard of care
(concurrent chemoradiotherapy), except in the larynx preservation
setting, because a definitive phase III trial has yet to be completed in
other settings.
• Moreover, it has taken >2 decades to arrive at a consensus, evidence-
based ICT regimen of choice: TPF [docetaxel, cisplatin, and
fluorouracil (5-FU)].
• TPF is now accepted to be superior to PF (cisplatin plus 5-FU) in
multiple phase III trials and a meta-analysis

58. • Locally advanced SCCHN
• Induction TPF CRT vs CRT alone
• Three cycles of 3 weekly TPF (docetaxel 75 mg/m² day 1; cisplatin 100 mg/m² day
1, and fluorouracil 1000 mg/m² on days 1–4 as continuous infusion ) followed by
concurrent chemo-radiotherapy with either docetaxel or carboplatin or
concurrent chemoradiotherapy alone with two cycles of bolus cisplatin
• 145 pts (plan was to accrue a total of 330 patients)
• The study was halted because of slow accrual
• Stage III-IV (55% Oropharynx)
• Median Followup : 49 months
• Primary end point - OS

59. • No significant difference noted between those patients treated with induction chemotherapy
followed by chemo-radiotherapy and those who received chemo-radiotherapy alone.
• They couldnot rule out the possibility of a difference in survival going undetected due to early
termination of the trial.
• Clinicians should still use their best judgment, based on the available data, in the decision of how to
best treat patients.
• The addition of induction chemotherapy remains an appropriate approach for advanced disease with
high risk for local or distant failure

60. • 358 patients (46% oropharynx)
• Unresectable stage III-IV head and neck cancers
• TPF (docetaxel 75 mg/m2, day 1, followed by cisplatin 75 mg/m2, day 1, and
fluorouracil 750 mg/m2 per day, administered by continuous infusion on days 1 to
5) vs
• PF (cisplatin 100 mg/m2, day 1, followed by fluorouracil 1000 mg/m2 per day,
administered by continuous infusion on days 1 to 5) induction chemotherapy
followed by RT alone.
• Primary end point - PFS

61. TPF PF p - Value
PFS 11months 8.2months 0.007
OS 18.8months 14.5months 0.02

62. • 501 patients (52% oropharynx)
• Unresectable stage III-IV head and neck cancer
• TPF (docetaxel 75 mg/m2, followed by cisplatin 100 mg/m2, fluorouracil 1000 mg/m2
per day administered as a continuous 24-hour infusion for 4 days)
• PF(cisplatin (100 mg/m2), followed by fluorouracil (1000 mg/m2 per day) as a
continuous 24-hour infusion for 5 days) induction chemotherapy
• Followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for
5 days per week
• Primary end point - OS

63. TPF PF p-Value
3-yrs OS 62% 48% 0.006
Median Survival 71months 30months 0.004
LRC 70% 62% 0.04
Incidence of
distant metastasis
same (p-0.4)

64. • With a minimum of 2 years of follow-up
(≥3 years for 69% of patients), significantly
more patients survived in the TPF group
than in the PF group (hazard ratio for
death, 0.70; P = 0.006).
• Estimates of overall survival at 3 years
were 62% in the TPF group and 48% in the
PF group; the median overall survival was
71 months and 30 months, respectively (P
= 0.006).
• There was better locoregional control in
the TPF group than in the PF group (P =
0.04), but the incidence of distant
metastases in the two groups did not differ
significantly (P = 0.14).
• Rates of neutropenia and febrile
neutropenia were higher in the TPF group;
chemotherapy was more frequently
delayed because of hematologic adverse
events in the PF group.

65. Study TPF Regimen Detailed Toxicities
TAX 323/EORTC
24971
(four cycles of
TPF)
Docetaxel (75 mg/m2) as a 1-h
infusion on day 1
Cisplatin (75 mg/m2) as a 1-h
infusion on day 1
5-FU (750 mg/m2/day) by
continuous infusion
on days 1–5
• 75.7% completed both TPF and RT per protocol
• 24% had a treatment delay during ICT
• Common (5%) grades 3–4 adverse events included: neutropenia
(76.9%), leukopenia (41.6%), alopecia (11.6%), anemia (9.2%),
infection
(6.9%), febrile neutropenia (5.2%), thrombocytopenia (5.2%)
• 6.2% of patients discontinued treatment due to adverse event
• 2.3% deaths due to toxic effect of study regimen
TAX 324 [5]
(three cycles
TPF)
Docetaxel (75 mg/m2) as a 1-h
intravenous infusion
Intravenous cisplatin (100 mg/m2)
over a period of 0.5–3 h
5-FU (1000mg/m2/day) as a
continuous 24-h infusion for 4 days
• 73% completed TPF followed by carboplatin-RT per protocol
• 29% had a treatment delay during ICT
• Common ( 5%) grades 3–4 adverse events included: neutropenia
(83%), stomatitis/mucositis (21%), nausea (14%), dysphagia (13%),
anemia/
febrile neutropenia/neutropenic infection/anorexia (each 12%),
vomiting (8%), diarrhea (7%), infection (6%), and lethargy (5%)
• 6% of patients discontinued treatment due to adverse event
related
to treatment
• <1% deaths due to toxic effect of study regimen

66. • Both trials concluded that the overall response rate (ORR) with TPF
was significantly (TAX 323/EORTC 24971) or numerically (TAX 324)
higher than with PF.
• Both the TAX 323/EORTC 24971 and TAX 324 TPF regimens
demonstrated clear survival benefits over PF ICT in patients with
unresectable LA SCCHN

67. Targeted Agents in
Combination with
Cytotoxins and
Radiotherapy

68. • 424 patients, multinational study (60% oropharynx)
• Locally advanced SCCHN
• Median follow-up 54 months
• RT v/s RT + Cetuximab
• Cetuximab 400mg/m2 at initial dose followed by 250 mg/m2 weekly for
rest of RT.
• Primary end point – locoregional control

69. Cetuximab + RT RT alone p-value
Median LRC 24.4months 14.9months 0.005
Median OS 49months 29.3months 0.03
With the exception of
acneiform rash and
infusion reactions of
grade 3 or greater
toxic effects, including
mucositis, did not
differ significantly
between two groups

70. • Some preclinical data suggested that HPV-positive squamous-cell
cancers were more sensitive to therapeutic irradiation than HPV-
negative cancers, which supported the potential for
chemoradiotherapy regimens with reduced radiation to be
efficacious.

71. • HPV-associated oropharyngeal cancer de-intensification trials:
RTOG 10–16: Phase III equivalence trial of accelerated RT with concurrent
cisplatin vs. cetuximab
• p16+, stratified by stage, KPS, smoking history.
• Arm 1 (control): 2/70 Gy IMRT (6 fx/week) + 2c cisplatin 100 mg/m2 q3
weeks.
• Arm 2: Same RT + cetuximab 400 mg/m2 loading pre-RT + 250 mg/m2
weekly during RT.
NRG-HN002: Randomized phase II, dose-reduced RT ± cisplatin.
• p16+ with ≤10 pack-years smoking history, T1-3 N1-2b or T3 N0.
• Arm 1: 2/60 Gy IMRT (5 fx/week) + 6c cisplatin 40 mg/m2.
• Arm 2: 2/60 Gy IMRT (6 fx/week) with no chemotherapy.

74. PRINCIPLES OF SYSTEMIC
THERAPY• The choice of systemic therapy should be individualized based on patient characteristics (PS, goals of
therapy).
• The preferred chemoradiotherapy approach for fit patients with locally advanced disease remains
concurrent cisplatin and radiotherapy.
• Cisplatin-based induction chemotherapy can be used, followed by radiation-based locoregional treatment
(ie, sequential chemoRT).
• However, an improvement in overall survival with the incorporation of induction chemotherapy compared
to proceeding directly to state-of the- art concurrent chemoRT (cisplatin preferred, category 1) has not
been established in randomized studies.
• Cisplatin-based induction chemotherapy followed by high-dose, every-3-week cisplatin
chemoradiotherapy is not recommended due to toxicity concerns.
• After induction chemotherapy, multiple options can be used for the radiation-based portion of therapy.

75. • Lip, Oral Cavity, Oropharynx, Hypopharynx, Glottic Larynx, Supraglottic
Larynx, Ethmoid Sinus, Maxillary Sinus, Occult Primary:
Primary systemic therapy + concurrent RT
• High-dose cisplatin (preferred) (category 1)
• Cetuximab5 (category 1 for oropharynx, hypopharynx, or larynx; category 2B for
lip, oral cavity, ethmoid sinus, maxillary sinus, occult primary)
• Carboplatin/infusional 5-FU (category 1)
• 5-FU/hydroxyurea
• Cisplatin/paclitaxel
• Cisplatin/infusional 5-FU
• Carboplatin/paclitaxel
• Weekly cisplatin 40 mg/m2
Postoperative chemoradiation
• Cisplatin (category 1 for high-risk non-oropharyngeal cancers)
NCCN

76. • Lip, Oral Cavity, Oropharynx, Hypopharynx, Glottic Larynx,
Supraglottic Larynx, Ethmoid Sinus, Maxillary Sinus, Occult Primary:
Induction/Sequential chemotherapy
• Docetaxel/cisplatin/5-FU (category 1 if induction is chosen)
• Paclitaxel/cisplatin/infusional 5-FU
• Following induction, agents used with concurrent chemoradiation typically
include weekly carboplatin, weekly cisplatin (category 2B), or weekly
cetuximab

77. Role Brachytherapy
• For oropharyngeal tumors, brachytherapy has historically played a role in boosting gross disease
following EBRT, as oropharyngeal tumors have a high propensity for occult nodal spread.
• Developed in the pre-IMRT, preconcurrent chemotherapy era.
• Low dose rate brachytherapy has previously been the most common type of brachytherapy used,
• High dose rate (HDR) and pulsed dose rate (PDR) techniques are becoming much more common and
preferred given the ability to control dwell times and develop more customized dose distributions.
• Interstitial implants selectively used in
• Accessible lesions
• Small (preferably <3cm) tumors
• Lesions away from bone
• N0 nodal status
• Superficial lesions

78. • High rates of locoregional control have been achieved using an integrated
treatment approach of EBRT directed at the primary and bilateral neck, followed
by a brachytherapy boost.
• Complications (30%) of brachytherapy for base of tongue tumors include
osteoradionecrosis of the mandible.
• The CTV used is recommended by the European Society for Radiotherapy and
Oncology (ESTRO) to be 5 mm at minimum and more commonly 1 to 1.5 cm for
base of tongue tumors.
• The PTV is usually equal to the CTV as the implanted catheters move with the
tumor.
• Catheters are typically positioned parallel and equidistant at 1 to 1.5 cm apart.

79. • Recommend – EBRT doses of 45 to 60 Gy f/b an HDR boost of 3-4Gy/# for 6 to 10
doses.
• With Locoregional control of 82% to 94%
• Prophylactic tracheostomy is often required.

80. The European Brachytherapy Group (GEC)
and ESTRO - Guidelines
• Based on consensus recommendations
• For oropharyngeal tumors, these guidelines recommend 45 to 50 Gy EBRT
followed by
• 25 to 30 Gy boost for tonsillar tumors, and
• 30 to 35 Gy boost to base of tongue tumors.
• The total brachytherapy boost dose is fraction-size dependent:
• 21 to 30 Gy in 3-Gy fractions and
• 16 to 24 Gy in 4-Gy fractions.
• Quality of life analyses comparing a combined regimen of brachytherapy
and external-beam radiotherapy to surgery and PORT favored a primary
radiotherapy-only approach, suggesting that in experienced hands, this is
a reasonable treatment method

81. Recurrent Locoregionally
confined squamous cell
carcinoma of oropharynx

82. Reirradiation
• High risk of normal tissue toxicity including upto 20% carotid rupture
rate
• 15% fatal toxicity
• Patients undergoing a second course chemotherapy and radiation
therapy should be managed with experienced centers.
• Failed phase III studies to compare systemic therapy alone or
chemotherapy and reirradiation.

83. Reirradiation
• RTOG 9911
• 105 patients (40% oropharynx) with recurrent SCCHN or SPT in a previous
radiation field.
• RT – 1.5Gy/# twice daily x 5days every other week x 4weeks
• Cisplatin 15mg/m2 and Paclitaxel 20mg/m2 each daily x 5 days every other
week x 4 cycles
• 2-year overall survival – 25%
• Median survival – 12 months
• Grade 4 or worse acute toxicity – 28%
• Treatment related death – 11%

84. Palliative Chemotherapy
• 33% of patients have partial response to platinum-based regimens
• Median-survival 4-6months
• 2-year overall survival 5-10%

87. Thank You