2. Topics to be covered:
• Pre-treatment evaluation
• Staging
• Treatment overview
• Evidence based treatment
• NCCN guidelines
Surgery
Radiotherapy
Chemotherapy
Biological therapy
3. Evaluation of patients with suspected
hypopharyngeal cancer
Clinical Exanimation of head & neck
Fiber optic laryngopharyngoscopy & biopsy of primary tumor
Contrast enhanced CT scan face and neck
Contrast enhanced MRI face & neck
Chest X Ray
Blood investigations
Optional investigations
CECT chest
PET Scan
Barium swallow
4. Fiber-optic direct laryngoscopy
• used routinely to complement the laryngeal mirror examination.
• assessment of extent of primary tumor & mobility of vocal cords.
• critical in assessing the superficial spread of neoplasm
• superior to any imaging modality in detecting mucosal spread
• can be attached to a photographic device
• biopsy of the tumor is done for histopathological confirmation.
5. Typical findings of hypopharyngeal cancer on endoscopy:
Ulceroproliferative/infiltrative growth.
mucosal ulceration.
pooling of the saliva in the pyriform fossa.
oedema of the arytenoids.
fixation of the cricoarytenoid joint,
or true vocal cords or both.
6. CECT Scan Face & Neck
• Timing: should be done before biopsy of to avoid post biopsy oedema.
• Advantages: aids in staging by detection of:
Limitations
invasion into larynx.
extra laryngeal/extra pharyngeal spread.
paraglottic space spread.
spread to retropharyngeal space.
clinically occult metastatic lymphadenopathy.
Failure to detect small superficial tumours & early laryngeal cartilage involvement.
Underestimating ulcerative and infiltrative lesions
overestimating tumor extent due to inflammation/ oedema & distortion of adjacent normal
structures
7. MRI Face & Neck
• Compared to CECT shows better soft tissue contrast & less artifact from
dental fillings.
• An important adjunct study in three situations:
• Disadvantages :
Determining cartilage invasion :shown by increase T2 signal & post contrast
enhancement.
Determining extent of extralaryngeal/paraglottic space involvement
Determining oesophageal involvement shown by increased T2 signal, wall thickening
and effaced fat planes
motion artefacts.
overestimating tumour extent :inflammation/ oedema /distortion
8. In detection of unknown /small primary tumor
In evaluating clinically occult nodal involvement
In follow up to differentiate between treatment sequelae & tumor
recurrence/residual
Role Of 18FDG PET-CT
9. Impact Of FDG-PET On Staging &Management of H&N
SCC*
A multicenter study of 233 H&N SCC patients (including
46 hypopharyngeal cancer)
TNM staging and therapeutic decisions were first
determined based on conventional workup & then FDG-
PET data was used to restage the patients & reanalyse their
management.
PET and conventional workup revealed discordant
TNM staging in 100 patients (43%).
PET was deemed significantly more accurate than
conventional staging & improved the staging in 20%
of patients.
Incorporation of PET data ultimately impacted
management in 32 patients (13.7%).
*Lonneux M, Hamoir M, Reychler H, et al. Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient
management in patients with head and neck squamous cell carcinoma: a multicenter prospective study. J Clin Oncol 2010;28:1190–1195.
10. CONCLUSIONS:
FDG-PET is a reliable imaging procedure in the detection of clinically
occult primary tumor/node and recurrent/residual carcinomas localized in
the head and neck.
it cannot as yet replace other diagnostic procedures in pretreatment planning
but does contribute valuable complementary diagnostic information.
11. TNM STAGING- AJCC 7TH edition (2010)*
T1: Tumour limited to one subsite of hypopharynx and ≤ 2 cm in greatest
dimension.
T2: Tumour invades more than one subsite or adjacent site or measures >2cm
but ≤ 4 cm without fixation of hemilarynx.
T3: Tumours > 4 cm or with fixation of hemilarynx or extension into esophagus
T4a: Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland,
central compartment of soft tissue.
T4b: Tumor invades prevertebral fascia, encases the carotid artery or involves
mediastinal structures.
*Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging handbook, 7th ed. New York: Springer, 2010.*
12. TNM STAGING- AJCC 7TH edition (2010)*
• N0: No regional LN
• N1: Single ipsilateral LN ≤ 3cm
• N2a: Single ipsilateral LN 3-6cm
b: Multiple ipsilateral LNs ≤ 6cm
c: Bilateral or contralateral LNs ≤ 6cm
• N3: Any LN more than 6cm
• M stage:
• Mx- cannot be assessed,
• M0- no distant metastasis,
• M1- distant metastasis
13. Stage grouping
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T1, T2
T3
T3
N1
N0
N1
M0
M0
M0
Stage IV A T1,T2,T3
T4a
N2
N0,N1,N2
M0
M0
Stage IV B Any T
T4b
N3
Any N
M0
M0
Stage IV C Any T Any N M1
16. Single Modality:
• – Surgery or RT
Choice depends on
• – Tumor: site, extension
• – Patient: preference, comorbidities
• – Expertise of the multidisciplinary team, available resources
Equally effective: however no randomised trials for surgery vs. RT.
Each modality can salvage the other if local recurrence.
EARLY STAGE (I-II)(T1-T2, N0)
17. ADVANCED STAGE:(III/IV)
T1-2, N1-3 / T3-4, N0-N+
Multi Modality:
• Radiotherapy with altered fractionation schedules
• Radiotherapy with chemotherapy
• Radiotherapy with biological therapy
• Neoadjuvant chemotherapy f/b surgery
• Surgery f/b RT/CT-RT
Choice depends on
• Tumor: site, extension
• Patient: preference, comorbidities
• Expertise of the multidisciplinary team, available resources
20. Benefits of RT over surgery
• Probability of functional morbidity or cosmetic defects is reduced.
• Risk of a major postoperative complication is avoided
• Elective neck RT can be included with little added morbidity.
• Surgical salvage of RT failure is supposed to have better outcome than the RT salvage
of a surgical failure.
Indications for primary radiotherapy
• small sized tumor
• larynx/voice preservation
• those who refuse surgery
21. CAUSE-SPECIFIC AND OVERALL SURVIVAL FOR
CARCINOMA OF THE PYRIFORM SINUS TREATED WITH
RADIATION ALONE
2001
As stage increases 5 years
survival with RT alone
decreases
22. Radiation treatment intensification
2. Addition of chemotherapy
to RT
1. Altered fractionation RT
3.Chemotherapy +Altered
fractionation RT
4. Addition of biological
therapy to RT
23.
24.
25. *2Horiot JC. Controlled clinical trials of hyperfractionated and accelerated radiotherapy in otorhinolaryngologic cancers [in
French].Bull Acad Natl Med 1998;182(6)
*#Cummings B, O’Sullivan B, Keane T. 5-year results of a 4 week/twice daily radiation schedule: the Toronto Trial. Radiother Oncol2000
*2
*3
TRIALS OF HYPERFRACTIONATION
27. TRIALS OF PURE ACCELERATED FRACTIONATION
*!Jackson et al. A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer.Radiother Oncol 1997
*2Skladowski Ket al. 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer—. Radiother Oncol 2000;55
*3Overgaard J,. The DAHANCA 6 and 7 trial: a study of 5 versus 6 fractions per week of conventional radiotherapy of (SCC) of the head and neck. Radiother Onco
*4Hliniak AZ.. Radiother Oncol 2000;56:S5.
*1
*2
*3
*4
28. Aim: to find whether shortening of treatment time by use of six instead of five radiotherapy
fractions per week improves the tumour response in squamous-cell carcinoma.
Lancet. 2003
randomised trial between January, 1992, and December, 1999,
1485 patients treated with primary radiotherapy 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)
29. TWO SUBPROTOCOLS: DAHANCA 6, which
included all glottic carcinomas, and DAHANCA 7,
included tumours of the supraglottic larynx,pharynx,
and oralcavity
The only difference in the two subprotocols was that
DAHANCA 6 dealt only with the fractionation effect,
whereas the DAHANCA 7 also included treatment with
the hypoxic radiosensitiser nimorazole.
More than 97% of the patients received the planned
total dose.
Median overall treatment times were 39 days (six-
fraction group) and 46 days (five-fraction group).
30. Primary locoregional tumour control as
function of number of fractions per week
Overall 5-year locoregional control rates were
70% and 60% for the six-fraction and five-
fraction groups, respectively (p=0.0005).
primary tumour control (76 vs 64% for six and five
fractions, p=0.0001), but was non-significant for neck-
node control
31. Disease specific survival Overall survival
Disease-specific survival improved (73 vs 66%) for six and five fractions
but not overall survival
32. Early and late radiation-related morbidity
Acute morbidity was significantly more frequent with six than
with five fractions, but was transient.
CONCLUSION
Accelerated radiotherapy applied to squamous-
cell carcinoma of the head and neck yields better
locoregional control than does a conventional
schedule with identical dose and fractionation.
34. *1 Dische, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol 1997;
*2 Poulsen, et al. A randomised trial of accelerated and conventional radiotherapy for stage III and IV SCCHN: aTTROG Radiother Oncol 2001;
*3 Bourhis, et al. Preliminary results of the GORTEC 96–01 randomized trial, comparing very accelerated radiotherapy versus concomitant
radio-chemotherapy for locally inoperable HNSCC. Int J Radiat Oncol Biol Phys 2001;
*1
*2
*3
37. .
• Patients with stage III or IV SCC
(n=1076) were randomized to 4
treatment arms:
2000
38. (1) Standard fractionation
70 Gy/35 daily fractions/7 weeks
(2) Hyper fractionation
81.6 Gy/68 twice-daily fractions/7 weeks
(3) Accelerated fractionation with split
67.2Gy(1.6bid)/42 fractions/6 weeks
with a 2-week rest after 38.4 Gy
(4) Accelerated fractionation with concomitant boost
72 Gy/42 fractions/6 weeks.(1.8Gy/f with 1.5 Gy /f boost on last 12 fractions)
39. RTO 90-03 Results: at 2years
• LRC:
• significant improvement in 2 yr locoregional control
for the hyper fractionation and concomitant boost arms
.
• DFS:
• trend toward improved disease-free survival (p = 0.067
and p = 0.054 respectively for the hyper fractionation
and concomitant boost arms
• OS: difference in overall survival was not significant.
• TOXICITY:
• altered fractionation regimens were associated with
higher incidence of grade 3 or worse acute mucosal
toxicity, but no significant difference in overall toxicity
at 2 years following completion of treatment.
42. 1996
EORTC 24891
EORTC trial 24891 compared PF (cisplatin and 5-FU) induction chemotherapy followed
by radiation therapy (RT) versus total laryngectomy, radical neck dissection, and
postoperative RT in patients with hypopharyngeal cancer
Role of NACT for larynx preservation
NACT-RT Vs Surgery-RT
45. • Treatment failures occurred at approximately
the same frequencies in both arms.
• Fewer failures at distant sites in the induction-
chemotherapy arm
• The median duration of survival was 25
months in the immediate-surgery arm and 44
months in the induction-chemotherapy arm
• The 3- and 5-year estimates of retaining a
functional larynx in patients treated in the
induction chemotherapy arm were 42% and
35% respectively.
CONCLUSION OF EORTC 24891
49. PATIENT CHRACTERISTICS:
29%pts of ca hypopharynx
Aim :
compare TPF with PF as induction
chemotherapy in patients with
locoregionally advanced,
unresectable disease.
Primary end point :PFS
358 patients underwent
randomization, with 177 assigned to
the TPF group and 181 to the PF
group
ARM A (N=177) ARM B(N=181) TOTAL P value
50. CONCLUSION OF TAX 323
At a median follow-up of 32.5 months, the median PFS was 11.0 months in the TPF group and 8.2
months in the PF group .
There were more grade 3 or 4
events of leukopenia and
neutropenia in the TPF group and
more grade 3 or 4 events of
thrombocytopenia, nausea,
vomiting, stomatitis, and hearing
loss in the PF group.
52. 15% patients of ca
hypopharynx
Aim:
compare induction
chemotherapy with docetaxel
plus cisplatin and fluorouracil
(TPF) with cisplatin and
fluorouracil (PF), followed by
chemoradiotherapy for
treatment of SCCH& N
53.
54.
55.
56. Results of TAX 324
more patients survived in the TPF group than in the PF group
estimates of overall survival at 3 years were 62% in theTPF group and 48% in the PF
group,
median overall survival was 71 months and 30 months, respectively (P = 0.006).
better locoregional control in the TPF group than in the PF group (P = 0.04)
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
62. An Intergroup Phase III Comparison of Standard Radiation Therapy and Two
Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable
Squamous Cell Head and Neck Cancer.
J Clin David J. Adelstein Oncol 21:92-98. 20032003
CTRT VS RT ALONE
which one is better in unresectable HNSCC?
63. ARM C
CTRT of 2 Gy/d, was split between the first CT
course (30 Gy) & third CT course (30 to 40 Gy).
A total dose of 60 to 70 Gy was given
The radiation therapy break was planned to
allow for the possibility of surgical resection in
those patients rendered resectable after the first
two courses of chemotherapy and the first
30 Gy of radiation.
Patients who had achieved a complete response
after this induction or who remained
unresectable proceeded, without surgery, to
complete chemoradiotherapy.
64.
65. 2003, 2006,2012
Forastiere et al
•RT Vs. CTRT Vs. NACT-RT
which one is better?
J Clin Oncol. 2013 Mar 1;31(7):845-52. doi: 10.1200/JCO.2012.43.6097. Epub 2012 Nov 2
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Vol 24, No 18S (June
20 Supplement), 2006: 5517
66.
67.
68. 2012
Radiotherapy Alone Vs. Concurrent
CTRT Vs. Sequential NACT-RT
J Clin Oncol. 2013 Mar 1;31(7):845-52. doi:
10.1200/JCO.2012.43.6097. Epub 2012 Nov 2
72. Lancet Oncol. 2012 Feb;13(2):145-53. doi: 10.1016/S1470-2045(11)70346-1. Epub 2012 Jan 18
2012
aimed to assess the efficacy and safety of a combination of approaches.
74. RT – 70Gy/6w
1st 40Gy 2Gy/#/d, 5#/w
Next 30Gy (off the spinal cord)
1.5Gy/#/BD
CT – 2 cycles of 5days each, 4w
apart.
Carboplatin 70mg/sqm/d
+ 5FU 600mg/sqm/d
RT – 70Gy/35#/7w at 2Gy/#,
5#/w
CT – 3 cycles of 4days each, 3w
apart.
Carboplatin 70mg/sqm/d
+ 5FU 600mg/sqm/d
RT – 64.8Gy/3.5w
at 1.8Gy/#/BD,
5#/w
Arm A
Conventional
chemoradiotherapy
Arm B
Accelerated RT with
concomitant CT
Arm C
Very
Accelerated RT
. Median follow-up was 5·2 years
75. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional
chemoradiotherapy or very accelerated radiotherapy
conventional chemoradiotherapy improved PFS compared with very accelerated chemoradiotherapy,
34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very
accelerated radiotherapy.
More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal
toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205
[76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001).
(60%) of patients in the conventional chemoradiotherapy group, (64%) of patients in the
accelerated radiotherapy-chemotherapy group, and (70%) of patients in the very accelerated
radiotherapy group were intubated with feeding tubes during treatment (p=0·045).
Results of GORTEC 9902
76.
77. CONCLUSION OF GORTEC 9902
1. Chemotherapy has a substantial treatment effect given concomitantly with
radiotherapy.
• 2. Acceleration of radiotherapy cannot compensate for the absence of
chemotherapy.
• 3. Acceleration of radiotherapy is probably not beneficial in concomitant chemo-
radiotherapy schedules.
78. 2000Lancet. 2000 Mar 18;355(9208):949-55
2007Radiother Oncol. 2007 Oct;85(1):156-70. Epub 2007 May 4.
2009Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 14
2011Radiother Oncol. 2011 Jul;100(1):33-40. doi: 10.1016/j.radonc.2011.05.036. Epub 2011 Jun 16
84. 15 Randomized Trials of Varied Fractionation (1970-1998)
PATIENT CHARACTERISTICS
7073 patients
Tumours sites: mostly oropharynx and larynx
74% patients had stage III—IV disease
hyper fractionated
accelerated
accelerated with
total dose reduction
Overall survival was
the main endpoint
median follow up:6 yr
85. benefit Conventional vs Altered Hyper fractionation vs
Accelerated fractionation
Locoregional
control
Loco regional control
6.4 %times higher
benefit was higher with hyper
fractionated radiotherapy
( OS 8% at 5 years) than with
accelerated radiotherapy
(2% with accelerated
fractionation without total dose
reduction and 1·7% with total
dose reduction at 5 years, p=0·02)
Survival benefit absolute benefit of 3·4% at
5 years with altered
fractionated radiotherapy,
86. RESULTS OF MARCH META-ANALYSIS:
There was a significant survival benefit in altered
fractionation.(3.4%at 5 years)
There was a benefit on locoregional control in favour of altered
fractionation versus conventional radiotherapy (6·4% at 5 years;
p<0·0001
The benefit was significantly higher in the youngest patients
Interpretation
Altered fractionated radiotherapy improves survival in patients with
head and neck squamous cell carcinoma. Comparison of the different
types of altered radiotherapy suggests that hyperfractionation has the
greatest benefit
87. Role of biological therapy
•Cetuximab with RT
• Bonner et al-
• 424 patients
• Locally advanced SCCHN
• 15% pt : Ca hypopharynx
88. Bonner et al,
2006
Drawback: in control arm
RT alone given (not a
standard treatment for
stage III and IV HNSCC)
93. subgroups analysis
demonstrated effect of
cetuximab was pronounced in
patients with
oropharyngeal carcinoma,
T1-T3 disease,
concomitant boost radiation,
N1-N3,
KPS 90-100 ,
male patients,
EGFR expression ≤ 50%,
≤65 years.
94. Surgical options in operable Ca hypopharynx
Voice preservation surgery
in early hypopharynx cancer
Supraglottic laryngectemy
Hemilaryngectomy
Partial laryngopharyngectomy
Radical Laryngectomy in
advanced stages
Total laryngectomy
Total laryngopharyngectomy
95. Primary Surgery
• T1 and T2 Tumors: voice
conservation surgery
• INDICATIONS
• CONTRAINDICATIONS
voice conservation approaches possible
refuse radiation
vocal fold fixation,
cartilage invasion,
postcricoid invasion,
deep pyriform sinus invasion,
extension beyond the larynx
• T3 / T4 Tumors
• INDICATIONS
dysfunctional larynx
pt. with bulky destructive tumor that
severely compromise airway or destroy
cartilage, bone, soft tissue undergo
immediate laryngopharyngectomy and post
op radiation
96. operation indication parts removed contraindication
hemilaryngectomy
horizontal partial
supraglottic
laryngectomy(SGL)
T1/T2 pyriform
sinus tumor
voice
preservation for
early
supraglottic
extension
epiglottis
aryepiglottic fold
false cords
upper 1/3-1/2 of
thyroid cartilage
±hyoid bone
preserves one or
both arytenoids &
true vc
thyroid,cricoid cartilage
invasion
arytenoid involvement
vocal fold fixation
postcricoid invasion
deep pyriform sinus invasion
extension beyond the larynx
fixed neck nodes
inadequate pulmonary
function
extended
supraglottic
laryngectomy
supraglottic
lesion with<1cm
base of tongue
invasion
same as SGL with
removal of i/l bot
upto circumvallete
papillae
97. operation indications removes contraindication
partial
laryngophary
ngectomy
used for small
medial and
anterior pyriform
sinus lesion
false vocal cord
epiglottis
aryepiglottic fold
pyriform sinus,
tvc are preserved
transglottic extension,
cartilage invasion
vocal cord paralysis,
pyriform apex invasion,
postcricoid invasion
extralaryngeal spread
poor pulmonary reserve
total
laryngectomy
Advanced
pyriform sinus
lesion
cartilage invasion
removes hyoid, thyroid,
cricoid cartilage,
epiglottis strap muscle.
Patient left with a
permanent
tracheostoma and
pharynx reconstruction
total
laryngophary
ngectomy
for more advanced
hypopharyngeal
lesion
total laryngectomy
plus removal of varying
amount of pharyngeal
wall
98. Advances in surgery
• In recent years, advancements in organ preservation surgery have
included the use of
• Transoral laser microsurgery
• Transoral robotic surgery.
• Advantage
Less morbidity
avoiding tracheostomy and the use of feeding tubes
99. Transoral Laser Surgery: Inclusion Criteria *
Complete endoscopic visualization of the growth
Tumor extension to the contralateral VC < 3mm
Absence of arytenoid involvement (except vocal process)
Subglottic extension < 5mm
Supraglottic extension no further than lateral extension of ventricle
Mobile vocal folds
No cartilage involvement
*Motamed M, et. al. Salvage conservation laryngeal surgery after irradiation failure
for early laryngeal cancer. Laryngoscope 2006; 116:451-455
101. Preoperative RT Vs postoperative RT:
RTOG 73-03
Phase III study of preoperative radiation therapy (50.0 Gy) versus
postoperative radiation therapy (60.0 Gy) for supraglottic larynx and
hypopharynx primaries
duration of follow-up was 9-15 years,
Loco-regional control& absolute survival was estimated & compared
1987
102. N=277 patients.
Operable stage T2-T4 /N±
oral cavity(14%)
Oropharynx(17%)
Supraglottic larynx(26%)
Hypopharynx(43%)
Postoperative stage III or
IV SCCHN
R
A
N
D
O
M
I
Z
E
Arm 2:Post-op RT 60 Gy.
n= 141
Arm 1: Pre-op RT 50 Gy
n=136
103. Long-term Follow-up Of RTOG Study 73-03
*(Tupchong L et al. Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):21-8.)
outcome preopRT postopRT
LRC 58% 70%
LRF within 2 years 59% 58%
LRF after 2years 27% 8%
Overall survival similar
toxicity similar
• Post op RT is better than preop RT for LRC
1991
104. Indications for post operative radiotherapy
Primary:
Large primary - T4 or T3 with soft tissue
infiltration
Close or positive margins of excision
Deep infiltrative tumour
High grade tumour
Lympho-vascular and perineural invasion
Lymph nodes:
Bulky nodal disease N2 / N3
Extra nodal extension
Multiple level involvement
106. R
A
N
D
O
M
IZ
E Cisplatin
100 mg/m2 d 1, 22, 43
XRT
XRT
Cooper et al, 2004; Bernier et al, 2004.
S
U
R
G
E
R
Y
RTOG 95-01
459 patients
EORTC 22931
334 patients
EORTC (66 Gy over 6 ½ wks)
RTOG (60–66 Gy over 6-6 ½ wks)
Postoperative Chemoradiotherapy