This document summarizes guidelines for the management of carcinoma of the hypopharynx and larynx. It covers topics like NCCN guidelines, treatment options including surgery, radiotherapy, chemotherapy and biological therapy. It describes TNM staging according to AJCC 7th edition and provides general treatment recommendations based on tumor stage. It discusses the benefits of radiotherapy over surgery and indications for primary radiotherapy. It also summarizes various studies comparing altered fractionation radiotherapy with or without chemotherapy to conventional radiotherapy for improved survival outcomes in advanced stage disease.

1. Management of carcinoma
hypopharynx & Larynx
Dr Dinesh K Singh
Senior Resident, BMCHRC

2. Topics to be covered:
• NCCN guidelines
• Treatment overview
• Evidence based treatment
• RT Technique
 Surgery
 Radiotherapy
 Chemotherapy
 Biological therapy

3. 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.*

4. 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

5. 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

14. Treatment options
Surgery
Types
Indications
Evidence
 Targeted therapy
Types
Indications
Evidence
 Chemotherapy
Types
Indications
Evidence
 Radiotherapy
Types
Indication
Evidence
Multi modality treatment

15. General Treatment Recommendations Based On
Hypopharynx Tumor Stage*
*Perez & Brady's Principles and Practice of RadiationOncology

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

18. 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

19. 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

20. 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. 2010
IAEA-ACC

24. 1997

25. 2010

26. .
• Patients with stage III or IV SCC
(n=1076) were randomized to 4
treatment arms:
2000

27. (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)

28. 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.

29. 2006
GORTEC 9402

30. MARCH META-ANALYSIS
2006
2010
The Lancet, Volume 368, Issue 9538, Pages 843 - 854, 2 September 2006

31. 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

32. 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,

33. 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

34. CHEMOTHERAPY
• NEOADJUVANT
• CONCURRENT
• ADJUVANT

35. 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

37. • 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

38. Choice of chemotherapy regimen:
2 drug vs.3 drug regimen

39. 2007:
TAX323/EORTC 24971

41. 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

42. 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.

43. 2007: TAX 324

44. 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

48. 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

49. 2009 GORTEC 2000-01

53. CONCURRENT CHEMORADIOTHERAPY

54. 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?

55. 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.

57. 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

60. 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

61. Loco regional control Overall survival
Larynx preservation
2012 UPDATE

62. No Published Phase 3 Trial Study Have Tested
Induction Chemotherapy f/b chemoradiotherapy
Vs Upfront Chemoradiotherapy

63. ALTERED FRACTIONATION
± CHEMO-RADIOTHERAPY

64. 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.

65. STAGE III/IV, M0
HNSCC
n=840
R
A
N
D
O
M
I
Z
E
D
Arm A
Conventional
chemo radiotherapy

66. 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

67.  Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional
chemoradiotherapy or very accelerated radiotherapy
 conventional chemoradiotherapy improved PFS compared with very accelerated chemoradiotherapy
 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

69. 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.

70. Role of biological therapy
•Cetuximab with RT
• Bonner et al-
• 424 patients
• Locally advanced SCCHN
• 15% pt : Ca hypopharynx

71. Bonner et al,
2006
Drawback: in control arm
RT alone given (not a
standard treatment for
stage III and IV HNSCC)

73. • LOCOREGIONAL CONTROL • OVERALL SURVIVAL

75. Bonner et al 2010 update: 5 years follow up

76. 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.

77. 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

78. 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

79. 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

80. 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

81. 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

82. ADJUVANT RADIOTHERAPY
IN
OPERATED HNSCC

83. 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

84. 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

85. 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

86. 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

87. POSTOPERATIVE RADIOTHERAPY
Is PO CTRT better than PORT alone?

88. 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

89. • RESULTS OF POSTOP CHEMORADIATION TRIAL

90. EORTC 22931
only
Bernier et al
N=334
EORTC 22931
and RTOG 9501
RTOG 9501
only
Cooper et
al.2004
N=459
stage III/IV disease
margin+ ≥2positive
l.n
ECE+
ECE + ECE +
margin + margin+
PNI+
embolism

92. RT Techniques in Hypopharynx
• CTV for curative radiotherapy T1/T2 N0
• GTV is defined using
• Endoscopy
• EUA reports and diagrams
• Diagnostic imaging
• There is no evidence on which to base GTV-CTV margins at the primary site but
submucosal spread is common and can extend at least 10 mm from the GTV
• GTV is grown by a 10mm axial margin and a 15 mm longitudinal margin to create
a CTV70
• Edited to take account of patterns of spread and natural barriers to tumour progression (e.g.
bone)
• CTV70 is also edited to include adjacent lymph nodes (usually level III but occasionally part of
levels II and IV) on the same axial slices as the CTV70

93. RT Techniques in Hypopharynx
• For lateral pyriform fossa tumours these high risk nodes will be ipsilateral
• For other hypopharyngeal tumours they will be bilateral
• The CTV44 is edited to include other lymph node groups at risk of
micrometastases
• For lateral pyriform fossa tumours this will include ipsilateral levels II–IV
• For other tumours with bilateral lymph node drainage, bilateral nodes are
include
• Retropharyngeal nodes are included for tumours involving the posterior
pharyngeal wall

94. RT Techniques in Hypopharynx
• Target volume definition
• CTV for curative radiotherapy T1/T2 N0
• The GTV is defined using endoscopy, EUA reports and diagrams, and diagnostic imaging
• There is no evidence on which to base GTV-CTV margins at the primary site but
submucosal spread is common and can extend at least 10 mm from the GTV
• GTV is grown by a 10mm axial margin and a 15 mm longitudinal margin to create a
CTV70
• This is then edited to take account of patterns of spread and natural barriers to tumour
progression (e.g. bone)
• The CTV70 is also edited to include adjacent lymph nodes (usually level III but
occasionally part of levels II and IV) on the same axial slices as the CTV70
• For lateral pyriform fossa tumours these high risk nodes will be ipsilateral; for other
hypopharyngeal tumours they will be bilateral

95. RT Techniques in Hypopharynx

96. RT Techniques in Hypopharynx
• CTV for curative radiotherapy T 3/4 or N
• Post induction chemotherapy
• CTVs should therefore be based on the initial pattern of disease as well as on
the residual tumour seen on the planning CT
• GTV should be defined on the planning CT from the residual volume but
should include any nodes that were involved at diagnosis even if they are not
now enlarged

97. RT Techniques in Hypopharynx
• To allow for submucosal spread, the GTV is enlarged by 10 mm axially and
15mm longitudinally to form the CTV70
• The CTV70 is edited to take account of natural barriers to tumour
progression and to include all sites of primary disease at presentation.
• For example
• A pyriform fossa cancer invading the tongue base at diagnosis may respond to
induction chemotherapy to leave residual tumour in the pyriform fossa alone
• The tongue base should be included in the CTV70
• CTV is further edited to include sites of high risk nodal disease
• For N disease the CTV70 includes level II–IV nodes adjacent to the primary
GTV, any involved nodes at other levels and any nodes in between

98. RT Techniques in Hypopharynx

99. RT Techniques in Hypopharynx
• CTV for adjuvant radiotherapy
• After careful discussion with the surgeon and pathologist, the CTV60 is
defined as sites of possible residual microscopic disease
• The CTV60 should include the margins of resection and sites of any dissected
nodal levels where there was tumour.
• Sites of positive resection margins or where there was extracapsular nodal
spread should be further defined as CTV66.
• When the patient has had a laryngectomy
• Stoma should be included in the CTV60 if subglottic extension was present or if the
surgeon is concerned about the risk of parastomal recurrence

100. RT Techniques in Hypopharynx
• CTV for adjuvant radiotherapy
• If a clinically node negative tumour has been excised with an elective neck
dissection and there is unexpected tumour in the neck nodes, a CTV44 can
also be defined
• This should ensure that the nodal levels have been treated either surgically or
with radiotherapy
• For example
• If surgery for a T2 pyriform fossa tumour included an ipsilateral level II–IV
neck dissection at which multiple involved nodes were identified (pN2b), the
CTV44 should include ipsilateral levels Ib and V, contralateral levels II–IV and
bilateral retropharyngeal nodes

101. RT Technique of Carcinoma
Larynx

102. RT Technique of Carcinoma Larynx
• Target volume definition
• T1 N0 glottic larynx
• Conventional treatment with small lateral beams is usually successful and well
tolerated
• Records and pictures from nasal endoscopy and EUA should be available as small
primary vocal cord tumours are difficult to see on CT scan
• GTV is defined as the site of primary tumour
• CTV is the glottic larynx with a border at least 10 mm superiorly and inferiorly from
the GTV.
• Axially the bilateral mucosal laryngeal surface is included
• PTV is CTV with a 3–5 mm isotropic margin depending on local assessment of
random and systematic errors assuming tumour movement is minimal
• Motion can be assessed by watching laryngeal movement with fluoroscopy in the
simulator to ensure that the vocal cords remain within the PTV on swallowing

103. RT Technique of Carcinoma Larynx
• In practice, it can be easier to define
• Superior (mid-body of hyoid)
• Inferior (inferior margin of cricoid) beam borders
• On the lateral DRR from the planning CT scan and then check on the
axial slices that the whole glottic larynx is included within the CTV,
assuming a 5 mm penumbra from PTV to beam edge
• Using smaller beams defined solely on the basis of GTV-CTV-PTV
definition has little therapeutic advantage and increases the
possibility of a geographical tumour miss due to intra-fractional
motion from swallowing

106. Thank You