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Jonas T. Johnson, M.D.

Sisson Symposium - 2013 Management of Laryngeal Cancer

Nothing to disclose

Early Laryngeal Cancer

T1 and T2

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Historical Bias

Radiation gives better voice

Similar cure rates

Radiation is less morbid

T1–T2 Glottic Radiation

Local Control Ultimate Control Voice

T1 95% 98% 95%

T2a 82% 96% 82%

T2b 70% 96% 76%

Mendenhall et al. 2001

Small Glottic Cancers

>30% were gone after the initial biopsy

No further therapy was needed

Personal communication

W Steiner

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Stage I & II

Most patients treated with 1 modality

Chemotherapy experimental

Combined therapy not indicated for primary treatment

Early Laryngeal Cancer

Radiation Therapy or Surgery?

No RCT

Factors

Tumor size and location

Patient-related considerations

Patient preference

Treatment team

Which is Better? Endoscopic Resection vs Radiation Therapy

for T1-T2 Glottic Cancer

No RCT

“limited level 3 evidence suggests comparable survival”

“no significant differences in voice or QOL outcomes”

Shin et al. 2008

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Meta analysis1135 patients 539 laser 596 radiation

local control no diffvoice handicap index no diffcosts lower with laser

Feng et al. 2010

Systematic review7600 patients

survival favors TLM or 0.81Higgins et al. 2009

T1-T2 Glottic Cancer: Laser Surgery (TLM) vs Radiation Endoscopic Resection vs Radiation for

T1-T2 Glottic Cancer

Meta analysis favors surgery

Disease-specific outcome

Laryngectomy-free survival

Treatment time

Cost

Har El et al. 2010

Local control

Overall survival

Disease specific survival

Voice

NO DIFFERENCE

Larynx preservation

Significantly improved with TLM or 8.23 (p=0.0001)

Abdurehim et al. 2012

TLM vs Radiotherapy: A Systematic Review T1-T2 Supraglottic Cancer

Ideally treated with 1 modality

Elective neck dissection gives essential information

Indications for CRT: More than 3 nodes involved

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Supraglottic Cancer

Endoscopic resection

Supraglottic laryngectomy

Supracricoid laryngectomy

All techniques result in temporary dysphagia and aspiration

Comparison of Two-Year Disease-Free Survival

Neck Recurrence

UND BND

20% 7.8%

p=0.009

Disease-Free Survival

72% 83%

p=0.04

Chiu et al. 2004

Stage I & II treated by a single modality

Occult nodes NOT identified with imaging

Pathologic staging best prognostic marker available 2013

Why is Neck Dissection Indicated?

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CT Sensitivity and Specificity

0.92 0.9 0.870.83 0.81

0.7 0.66

0.51

0.2 0.23

0.41 0.410.48

0.65 0.72

0.86

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

5 7 8 9 10 11 12 15

sensitivity

specificity

Size of Node (mm)

Ris

k o

f In

vo

lvem

en

t

by C

an

cer

Curtin et al. 1999

PET/CT detects 50%

Kyzas et al. 2008

Cannot replace accuracy of neck dissection

Agarwal et al. 2008

Pretreatment Detection of Occult Neck Nodes

Early Glottic Cancer Treated by Radiation

Tis,T1,T2 N = 522

105 failed radiation - larynx preserved in 34%

66% required laryngectomy

Smee et al. 2013

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• Cancer control with surgery equals or exceeds radiation Rx

• Concurrent chemotherapy not indicated for Stage I/II (single modality preferred)

• Neck dissection gives the most sensitive prognostic (and therapeutic) information

• Patients treated with primary radiation need improved monitoring [to avoid laryngectomy]

• Cost favors surgery

Early Laryngeal Cancer: Bottom Line

Advanced Laryngeal Cancer

VA Laryngeal Study

Stage

III/IV

Laryngeal

Cancer

Cisplatin/5-FU x 3*

Surgery Radiation

Radiation

RESULTS

• 64% of patients (31% of survivors) preserved a functional larynx in non-surgical arm

• No difference in OS (68% at 2 years)

• Patients undergoing immediate salvage laryngectomy same OS as patients in surgical arm

NEJM 1991

N=332

*evaluation post 2 cycles, only if PR/CR in primary proceeded to further chemo

The Era of Chemo-Radiation Therapy (CRT)

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Larynx Intergroup Study: RTOG 91-11

Radiation (70 gy)

vs

Concurrent chemoradiation (70 gy + Cisplatin)

vs

Induction chemo with CRT (PF x 3 + 70gy)

NEJM. 2003

Larynx Intergroup Study: RTOG 91-11

Radiation (70 gy)

vs

Concurrent chemoradiation (70 gy + Cisplatin)

vs

Induction chemo with CRT (PF x 3 + 70gy)

NEJM. 2003

Association between Treatment and

Long Term Survival [10-year follow up]

Long term results of RTOG 91:11Forastiere et al; 2013

Laryngeal preservation with induction chemo for hypopharyngeal cancer

Lefebvre et al; 2012

Analysis of 3 RTOG trials N = 479

230 assessable patients 99 (43%) severe toxicities

(excluded those with pretreatment obstruction and aspiration)

Toxicity associated with age / T3-T4 / larynx-pharynx / ND

Machtay et al. 2008

Severe Late Toxicity after Chemoradiation

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Best Evidence

Concurrent chemoradiation is superior to induction chemotherapy or radiation alone – LFS

CRT may offer preservation of the larynx to 60% of patients

Update

Long term survival better in induction group

2013

Advanced Fibrosis and Stenosis

Can it be reduced or avoided?

N = 37 all to receive CRT

25 had 2 weeks of exercises before Rx

MDADI improved when compared to patients treated after radiation p=0.0002

Kulbersh et al. 2006

Pretreatment Swallowing Exercises Pharyngocise

RCT usual care vs sham vs active intervention

usual - discussion

Sham - buccal extension and diet modification

45 min sessions 2x/day

Active - battery of exercises

45 min sessions 2x/day

Carnaby-Mann et al. 2012

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Functional Swallowing

Significant preservation of “functional” swallowing by exercise (total work performed) at 6 weeks

Intermediate stage primary cancer

T2-T3

Can Primary Surgery Reduce Treatment

Related Toxicity?

Oncologic outcomes

Median follow-up:

33 months

Overall survival

- 2y = 86.2%

- 5y = 72.9%

No CRT Both CRT RT alone

TLM 20 (67%) 7 (23%) 3 (10%)

SCL 22 (81%) 3 (11%) 2 (7%)

________________________________________

Total 42 (74%) 10 (18%) 5 (9%)

Reduced Need for Adjuvant Therapies

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TLM outperformed SCL

Communication (CS)

Swallowing (FOSS)

Functional Scores: TLM vs SCL

N = 46

20 patients – open horizontal supraglottic

26 TLM

function better after TLM

Kollisch et al. 1995

Similar results with TORS Mendelsohn et al. 2012

Ozer et al. 2012

Park et al. 2013

Glottic closure reflex maintained after TLM

Sasaki et al. 2006

Functional Results after Supraglottic Resection

N = 40 patients

oropharynx and larynx

20 had primary surgery

adjuvant CRT or RT based on pathology

mean RT 56 Gy

20 CRT

mean RT 70 Gy

More et al. 2013

Swallowing Function following TORS vs CRTComparative Swallowing Function

TORS

CRT or

RT

More et al. 2013

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Functional results

• Partial laryngectomy offers opportunity for reduced treatment toxicity

• After transoral procedures, patients function better than after open surgery

• The potential to reduce toxicity when adjuvant therapy required after surgery remains unquantitated

Bottom Line

What About T4 Laryngeal Cancer?

T4 Laryngeal Cancer

Cartilage invasion

Aspiration

Dyspnea

Extralaryngeal tumor

Can CRT restore function?

Randomized Trials - Tended to Exclude T4

T4 tumors

RTOG 91-11: 11%

EORTC: 4%

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Induction: If >50% response, proceed with CRT

29/36 received CRT

13 intact and alive

Laryngectomy-free 13/36 = 36%

Worden et al. 2009

Chemoselection in T4 Laryngeal CancerT4 Tumors

N = 120

0 10 20 30 40 50 600

20

40

60

80

100

120Surgery + XRT

Chemoradiation

XRT alone

time (months)

su

rviv

al

(%)

P<0.0001

55%

25%

0%

Gourin et al. 2011

T4 Laryngeal Cancer: Bottom Line

Largely unstudied (RCT)

Disease control less likely

Dysfunction more likely

Many consider surgery/reconstruction/CRT as first line therapy (currently the subject of TALC)

Best adjuvant therapies not yet known

Who will do the surgery as the pendulum swings??

All patients deserve to see a surgeon when planning treatment

The next battle may be over cost

Where Are We Now?

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Immediate Challenges

How best to follow after CRT? (and avoid overuse of PET/CT)

How to avoid complications of CRT? (or reduce long term disability)

How to better “target” patients

Can biologics replace cytotoxic drugs?

Can CRT “save” a destroyed organ?

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Can inoperable tumor be made operable? Characteristics of Recurrent Tumor

Histologic Findings

Concentric growth

primary surgery 77%

Multicentric foci

salvage surgery 86%

Zbaren P et al. 2007

How Does Tumor Respond?

T

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Surgery after CRT

The implications are evident. Resection after CRT is made

difficult because tumor may be multifocal and impossible to

accurately localize

Rapid Evolution of Treatment Alternatives

Cost may be the next hurtle – ACA 2014

CRT > Surg + RT > RT > Surgery

Concern (personal) over a lost generation

Bottom Line

Thank You

Transoral Microsurgery

Trach 0

G-Tube 3% (1/32)

Supracricoid Laryngectomy

7% (2/28)

11% (3/28)

Tracheotomy G-Tube Requirements

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Advanced Laryngeal Cancer

CRT promoted to preserve function

“Organ preservation”

Difficulties in Follow-up

Anatomic deformity

Chronic edema

How to distinguish tumor from scar and edema

Follow-up

PET/CT

False-positive 20-25% after treatment

Recommend biopsy suspicious areas before re-treatment