My lecture at H&N oncology meeting

1. Laryngeal cancer: Multidisciplinary
Management Guidelines
By Dr. Ahmed El-Azony, MD
Lecturer of Clinical Oncology
Zagazig University
1

2. So, Why Bother?
• Laryngeal cancer is a complex & potentially
devastating disease.
• The aim of any clinician treating laryngeal carcinoma
should be to cure the disease whilst maintaining
maximum laryngeal function.
• Deciding how best to achieve this aim in any given
patient needs complex discussions within a multi-
disciplinary team (MDT).
• There are multiple treatment modalities and for this
to be successful, it must be appropriately selected by
personalizing the patient’s approach according to
evidence-based guidelines.
2

3. Milestones of Larynx Surgery
Total
Laryngectomy
Billroth 1873
Conservation
Laryngeal
Surgery
1947 Alonso,
1953 Ougra
Supraglottic
laryngectomy
Endolaryngeal
Laser Surgery
1970s
Tracheo-
esophageal
Puncture
method
1978 by
Singer &
Bloom
1990
Suracricoid
Laryngectomy
by
Laccourreye
3

4. Milestones in Radiotherapy &
Combined treatment
Definitive
EBRT
by
Coutard
1932
Co-60
LINACs
2D
planning
1991
VA
Larynx
Trial
3DCRT
IMRT
CCRT
2003
RTOG 91-11
2009
MACH-NC
Induction
CT
Altered
Fractionation
Targeted
therapy
Cetuximab
Immunottt
4

5. A simplified Work-up Plan
Endoscopy and Biopsy
Complete History and Physical Examination
Larynx Cancer Suspected
Imaging
Studies
Lab Studies Interventions
•CT or MRI or PET/CT
of primary and neck
•Chest imaging
•CBC
•Serum Chemistry
•Dental Evaluation
•Speech and Swallowing
Evaluation if needed
5

6. TNM Stage Grouping
• Stage 0 Tis N0M0
• Stage I T1 N0M0
• Stage II T2 N0M0
Early
• Stage III T3 N0M0, T1-3 N1M0
• Stage IVA T4a N0-1 M0, T1-2 N2 M0
Locally
Advanced
Far Advanced
• Stage IVA T3-4a N2 M0
• Stage IVB T4b any N M0, Any T N3 M0
Metstatic
Stage IVC = M1
Staging is a mechanism that permits
assortment of tumors into groups having
similar prognosis and therefore facilitates
comparison of the outcome of therapy. 6

7. 7

8. Triage of laryngeal cancer
Lesions Incapable
of Regional
Metastasis
Early Glottic
T1-2,N0,M0
Small Lesions
Capable of
Regional
Metastasis
Early
Supraglottic
T1N0 – small N1,
most T2N0M0
Advanced
Lesions Suitable
for
Organ
Conservation
T2N1-3M0,
T3N0-3M0
Advanced
Lesions
Beyond
Organ
Conservation
T4N0-3M0-1
Operable Inoperable
For practical purposes, potentially
curable laryngeal cancers can be
grouped into 5 cohorts based on the
nature of the therapy they ideally
should receive.
8

9. Surgery
Microlaryngeal surgery
Hemi-largyngectomy (Vertical)
Supraglottic laryngectomy
ESGL
Near-total laryngectomy
Total laryngectomy
Radiation Therapy
3DCRT
IMRT
Altered Fractionation
(Accelerated Or Hyper-fr.)
Chemothrapy
Concurrent (Cisplatin)
Sequential
Induction (TPF vs. PF)
Targeted therapy
(Cetuximab)
?Immunotherapy
Treatment
Options
9

10. Level of
EvidenceTreatmentClinical Stage
2AEndoscopic ResectionTotal Laryngectomy
Not Required
Stage I/II
(T1-2, Selected T3)
↓
Single Modality
Surgery or RT
2ARadiation Therapy
5Open Partial Laryngectomy
1Chemoradiation (CCRT)Total Laryngectomy
Required
Stage III/IV
(most T3 , T4a)
↓
Combined Modality
2BCCRTInduction CT →
2ATotal Laryngectomy + PORT
Surgical
Non-Surgical
10

11. 1) Localized Lesions Incapable of Regional Metastasis
• Limited-extent SCC of the glottis (i.e., T1 or T2, N0) do
not spread to regional lymph nodes and are effectively
treated by radiation therapy to the primary tumor
alone or by surgery.
• A single modality of treatment should suffice.
• Treatment Goals:
1.Cure of Disease
2. Laryngeal Voice Preservation
3. Optimal Voice Quality ↑QOL
4. Minimizing Risk of Complications
5. Less Cost 11

12. 1) Treatment modalities
used for early glottic cancer
Endolaryngeal Surgery
(Endoscopic CO2 Laser
(resection
Indications
Lesions of the free edge of the
vocal cord
Radiation
therapy
Techniques
Small opposed portals (e.g., 5 × 5
or 6 × 6 cm) treating the
primary tumor but not regional
nodes 12

13. Supporting clinical evidence= None
• No high-level evidence exists to select between
treatment options
• There are no prospective, randomized, large-
scale phase III trials upon which to make an
evidence-based choice
• Numerous retrospective trials appear to
demonstrate similar local control rates between
radiation therapy and laser surgery
• Patient-specific (rather than tumor-specific)
factors may favor one form of treatment over
another
13

14. Decision of Treatment Modality
• Oncologic Results
• Impact on UADT Tx:
-Airway
-Voice
-Swallow
• QOL
• Patient Factors
• Surgeon Factors:
-Training
-Experience
• Institutional Philosophy
-MDT
• Resource Availability
• Cost 14

15. 2) Localized Lesions Capable of Regional
Metastasis
• Limited-extent SCC of the Supraglottic larynx
(T1N0-small N1 and most T2N0) have such a
sufficiently high rate of spread to regional LNs that
the nodes need to be addressed as to whether the
tumor is treated by radiation therapy or surgery.
• As a single modality of treatment should suffice,
radiation often is the less morbid option.
15

16. 2)Treatment modalities used for
Early Supraglottic cancer
Radiation therapy
Suitable for
most lesions;
choice of
therapy may be
more influenced
by patient
factors than
lesion itself
RT is preferred
therapy if
size/extent/location
of the tumor would
require a total
laryngectomy to
repair the surgical
defect
Surgical
resection
Supraglottic
Laryngectomy
plus at least
ipsilateral neck
dissection
Akin to RT,
suitable for most
lesions; choice of
therapy may be
more influenced
by patient factors
than lesion itself
16

17. Supraglottic
Laryngectomy
RT/CCRTKey Structure their
invasion
contraindicate →
yesNOPosterior Commissure
? YesNoCricothyroid Membrane (below AC)
NO
NO
NO
NO
Posterior Paraglottic space
Inferior Paraglottic space
NOYesThyroid Cartilage invasion
NoNO
NO
Crico-Arytenoid Unit (single)
Crico-Arytenoid Unit (Both)
Yes
YESYESCricoid Cartilage
YESNOPre-epiglottic Space (Massive)
17

18. 18

19. 3) Advanced Lesions Suitable for Organ
Preservation
• Moderately advanced lesions (T3 and early T4) are potentially
suitable for larynx-sparing therapies.
• With close post-treatment observation and salvage surgery when
needed, survival is not compromised.
• However, not all lesions suitable for organ preservation arise in
patients who are equally suitable for such therapy. Patients who are
unreliable, patients who intend to continuing smoking during
treatment, and hypersensitive patients who cannot tolerate the
likely discomfort of CCRT may be better served by surgery that
removes all gross disease and PORT delivered as attendance and
tolerance permit.
19

20. Treatment modalities used for organ
preservation = CCRT
Source: Forastiere AA, Goepfert H, Maor M et al (2003) Concurrent chemotherapy
and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med
349:2091–2098
20

21. Supporting clinical evidence
• Randomized the care of 332 patients who had stage III or IV laryngeal cancer; median
follow-up of 33 months
• Compared 3 cycles of induction cisplatin plus fluorouracil chemotherapy and then
radiotherapy, versus laryngectomy and postoperative radiotherapy
• 2-Year survival rate was 68% in both treatment groups (p = 0.98)
• There were more local recurrences (p = 0.0005) and fewer distant metastases (p =
0.016) in the induction chemotherapy group than in the other group
• In the induction chemotherapy plus radiation therapy group, at 2 years 64% of all
patients retained their larynxes, and 64% were free of disease.
Department
of Veterans
Affairs
larynx trial
• Randomized the care of 520 patients who would otherwise have required
laryngectomy for cure; median followup of 3.8 years
• Compared induction cisplatin plus fl uorouracil and then radiotherapy, to
radiotherapy with concurrent administration of cisplatin to radiotherapy alone
• Primary endpoint of preservation of the larynx signifi cantly favored concurrent
therapy: at 2 years 88% had intact larynxes after radiotherapy with concurrent
cisplatin versus 75% with induction chemotherapy then radiotherapy (p = 0.005),
versus 70% with radiotherapy alone (p < 0.001)
• Secondary endpoint of locoregional control signifi cantly favored concurrent therapy:
78% after radiotherapy with concurrent cisplatin versus 61% with induction
chemotherapy and then radiotherapy versus 56% with radiotherapy alone
• Overall survival was similar in all 3 groups.
RTOG
91-11
21

22. 4) Resectable Advanced Lesions Not
Suitable for Organ Preservation
• Organ conservation is not merely about preserving anatomy. Once
function is irreparably lost, there is little benefit to preserving anatomy.
• The integrity of the cartilages is the best surrogate of non-surgical
curability; once a cartilage is destroyed, surgery followed by adjuvant
radiation therapy generally is considered essential.
• In addition, some patients are better served by definitive surgery followed
by adjuvant irradiation because of:
(1) Co-morbidities or lifestyles that make CCRT particularly toxic (e.g., a
severe collagen-vascular disease or refusal to stop incessant smoking),
(2) patients who emotionally would prefer to have surgery (“I need to have
the cancer taken out as quickly as possible”).
• Furthermore, if the resected specimen reveals + ve microscopic surgical
margin and/or if metastatic disease in a regional lymph node has
transgressed the capsule (+ve ECE), two randomized phase III studies show
that local-regional control can be improved by adding cisplatin
chemotherapy concurrent with PORT.
22

23. Treatment modalities used for advanced operable
laryngeal cancer (beyond laryngeal preservation)
+ Postoperative Radiation therapy
to operative bed and draining LNs
±Chemotherapy
Intravenous cisplatin, 100
mg/m2 on days 1, 22, and
43 of radiotherapy
treatment
1- Microscopically involved
mucosal margins
2- Extracapsular extension
of nodal disease
Total Laryngectomy with Bilateral Neck Dissection
23

24. Supporting clinical evidence
•459 patients who, after defi nitive surgery, had histologic evidence of invasion of 2 or more regional
lymph nodes and/or extracapsular extension of nodal disease and/or microscopically involved
mucosal margins of resection; median follow-up of 45.9 months
•Randomized to radiotherapy alone (60–66 Gy in 30–33 fractions over 6–6.6 weeks) versus identical
treatment plus concurrent cisplatin (100 mg/m2 of body-surface area intravenously on days 1, 22,
and 43)
•Primary endpoint of locoregional control favored concurrent therapy: at 2 years 82% (with
chemotherapy) versus 72% (no chemotherapy), p = 0.01
•Secondary endpoints of disease-free survival also favored concurrent therapy (p = 0.04), but overall
survival was not significantly different (p = 0.19)
RTOG
95-01
•334 patients who, after defi nitive surgery, had histologic evidence of extranodal spread, positive
resection margins, perineural involvement, or vascular tumor embolism; median follow-up of 60
months
•Randomized to radiotherapy alone (66 Gy in 33 fractions over 6.6 weeks) versus identical treatment
plus concurrent cisplatin (100 mg/m2 of body-surface area intravenously on days 1, 22, and 43)
•Primary endpoint of disease-free survival favored concurrent therapy: at 5 years 47% (with
chemotherapy) versus 36% (no chemotherapy), p = 0.04
•Secondary endpoints of overall survival (p = 0.02) and locoregional control (p = 0.007) both
significantly favored concurrent therapy.
EORTC
22931
•Pooled the data sets from RTOG 9501 and EORTC 22931 to analyze the effect of possible
predictors of benefit from chemotherapy
•ECE and/or microscopically involved surgical margins were the only risk factors for which the
influence of CCRT was significant in both trials
•By itself, having 2 or more lymph nodes invaded by tumor did not predict benefit from
chemotherapy
Combined
analysis
24

25. 25

26. 5) Unresectable Advanced Lesions
Not Suitable for Organ Preservation
Unresectable lesions that are detected in patients
with no evidence of hematogenous dissemination
of disease and who are otherwise in good general
condition can still be approached with curative-
intent, i.e. CCRT; however, less effective control of
disease should be expected. .
Altered fractionation regimen can be used.
For very fit patients, the philosophy supporting
induction chemotherapy followed by CCRT is
appealing, but trials that rigorously compare this
approach to the more standard CCRT are ongoing.
26

27. Supporting clinical evidence
TAX 324
27

28. Follow-up schedule
 The majority of laryngeal tumors recur within 3 years if they are
destined to recur (save for a T1 glottic tumor, which can take up to 5
years to recur). This relatively rapid pattern of recurrence justifies
relatively close follow-up in the first few years after treatment.
 Thereafter, the risk of second primary tumors arising in the head
and neck region because of the so-called field effect of carcinogens
justifies long-term follow-up.
28

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31. 31