Celine Celine BicquartBicquart

Advanced Advanced Laryngeal Laryngeal CancersCancers

October 19, 2006October 19, 2006

Overview of TalkOverview of Talk

Case PresentationCase Presentation Anatomy and Lymph Node Drainage of the Anatomy and Lymph Node Drainage of the

LarynxLarynx Overview of Laryngeal EpidemiologyOverview of Laryngeal Epidemiology Staging of PatientStaging of Patient Review of LiteratureReview of Literature Patient Treatment PlanPatient Treatment Plan

DSDS ID: 49 y/o maleID: 49 y/o male HPI: Hoarse since January 2006 with HPI: Hoarse since January 2006 with

odynophagia and dysphagia. 10 lb wt loss odynophagia and dysphagia. 10 lb wt loss in August.in August.

Referred to ENT at OHSU.Referred to ENT at OHSU. 8/16/06- CT neck- 17 x 14mm enhancing 8/16/06- CT neck- 17 x 14mm enhancing

soft tissue lesion filling L piriform sinus. soft tissue lesion filling L piriform sinus. Involves L. supraglottis, L glottis, L Involves L. supraglottis, L glottis, L subglottis with midline focal area of subglottis with midline focal area of destruction of thyroid cartilage. +Posterior L destruction of thyroid cartilage. +Posterior L level III adenopathy.level III adenopathy.

HPI cont’dHPI cont’d

FNA of L neck node- Metastatic poorly- differentiated FNA of L neck node- Metastatic poorly- differentiated SqCCa with high N:C ratio.SqCCa with high N:C ratio.

9/15/06- Total larynectomy, L neck dissection II-IV, L 9/15/06- Total larynectomy, L neck dissection II-IV, L hemithyroidectomy, Pec major flap. hemithyroidectomy, Pec major flap.

Path: 4.3cm G3 Invasive Squamous Cell, negative Path: 4.3cm G3 Invasive Squamous Cell, negative margins. Invades through thyroid cartilage, but thyroid margins. Invades through thyroid cartilage, but thyroid gland uninvolved. 4/14 Level II. +ECE. 2/6 Level III. gland uninvolved. 4/14 Level II. +ECE. 2/6 Level III.

– –ECE. 1/8 Level IV. –ECE. +perineural invasion. ECE. 1/8 Level IV. –ECE. +perineural invasion. Indeterminate angiolymphatic space invasion.Indeterminate angiolymphatic space invasion.

PMH: SeizuresPMH: Seizures

Meds: Dilantin 300mg qd, Oxycodone q3-5h, Nicotine Meds: Dilantin 300mg qd, Oxycodone q3-5h, Nicotine patch 21mg qdpatch 21mg qd

Allergies: NKDAAllergies: NKDA

PSH: LaryngectomyPSH: Laryngectomy

SH: Single. Lives in Portland. Receives disability, SH: Single. Lives in Portland. Receives disability, previously did odd jobs. Smoked 1.5ppd x 30y. Cut back previously did odd jobs. Smoked 1.5ppd x 30y. Cut back in 05/06. Now uses nicotine patch. Drinks 1-2 drinks qd.in 05/06. Now uses nicotine patch. Drinks 1-2 drinks qd.

PE: Healing incisions of left neck dissection and pec PE: Healing incisions of left neck dissection and pec major flap. Stoma appears patent. No fistula noted. No major flap. Stoma appears patent. No fistula noted. No discharge from stoma noted. discharge from stoma noted.

Supraglottis- high incidence of LN metastasis: jugulodigastric, jugulocarotid, juguloomohyoid.

Glottis-

Subglottis- 1 ant: mid and lower jugular to prelaryngeal node ????

2 post: paratracheal

12000 new cases yearly- 2% of all cancers12000 new cases yearly- 2% of all cancers60-65% glottic60-65% glottic

30-35% supraglottic30-35% supraglottic5% subglottic5% subglottic

M:FM:Fp53-mutated in 47% smokersp53-mutated in 47% smokers

Signs and SymptomsSigns and Symptoms Hoarseness- MC presenting sx of glottic caHoarseness- MC presenting sx of glottic ca Sore throat- MC presenting sx of supra caSore throat- MC presenting sx of supra ca Odynophagia- MC presenting sx of supra caOdynophagia- MC presenting sx of supra ca Foreign Body SensationForeign Body Sensation DysphagiaDysphagia StridorStridor PainPain HemoptysisHemoptysis Otalgia- via vagus and nerve of Arnold.Otalgia- via vagus and nerve of Arnold. Weight lossWeight loss Airway obstructionAirway obstruction Risk Factors:

-Tobacco

-Alcohol

Evaluation and Work-upEvaluation and Work-up

Complete H&PComplete H&P

Assess for adenopathy in neck.Assess for adenopathy in neck.

Loss of Thyroid click: sign of post-cricoid extension.Loss of Thyroid click: sign of post-cricoid extension.

Mass over thyroid signifies thyroid cartilage invasion.Mass over thyroid signifies thyroid cartilage invasion.

Indirect mirror exam for visualization. “EEEeeeeee.”Indirect mirror exam for visualization. “EEEeeeeee.” Fiberoptic flexible laryngoscopy.Fiberoptic flexible laryngoscopy.

CXR for metastatic evaluationCXR for metastatic evaluation CBC, LFTs. If abnormal, may get CT abd, bone scan.CBC, LFTs. If abnormal, may get CT abd, bone scan.

CT, MRICT, MRI

Performed before bx.Performed before bx. MRI is better to delineate soft-tissue extent of primary tumor.MRI is better to delineate soft-tissue extent of primary tumor. CT is better for evaluating bone invasion.CT is better for evaluating bone invasion. CT also very useful for detecting subclinical LN metastasis. CT also very useful for detecting subclinical LN metastasis. Want to look for pre-epiglottic, periglottic space invasion, Want to look for pre-epiglottic, periglottic space invasion,

subglottic and extralaryngeal extension, and cartilage invasion.subglottic and extralaryngeal extension, and cartilage invasion.

Direct laryngoscopy Direct laryngoscopy with bx for tissue dx, with bx for tissue dx, disease extent.disease extent.

Usually performed as Usually performed as part of panendoscopy part of panendoscopy to r/u multiple tumors.to r/u multiple tumors.

Squamous Cell Carcinoma of the LarynxSquamous Cell Carcinoma of the Larynx

95% SqCCa.

TVC- well to mod-diff

Supra and subglottis- more poorly diff

Following surgery, DS has had a slow Following surgery, DS has had a slow recovery. FT still in place secondary to recovery. FT still in place secondary to residual swelling. Patient reports residual swelling. Patient reports dysphagia.dysphagia.

Patient also reports dyspnea on exertion.Patient also reports dyspnea on exertion.

Clinical QuestionClinical Question

My patient’s cancer was a T4, for which the standard of My patient’s cancer was a T4, for which the standard of care had been a total laryngectomy followed by adjuvant care had been a total laryngectomy followed by adjuvant radiation.radiation.

TL results in disease control rates of 70-80%; and with TL results in disease control rates of 70-80%; and with TE punctures for voice restoration, patients can TE punctures for voice restoration, patients can eventually regain their verbal communication skills.eventually regain their verbal communication skills.

In light of this good disease control rate, is there a way to In light of this good disease control rate, is there a way to obtain equivalent survival while sacrificing less quality of obtain equivalent survival while sacrificing less quality of life?life?

Looked at induction chemo + definitive RT vs. conventional TL + PORTLooked at induction chemo + definitive RT vs. conventional TL + PORT Stratified according to KPS, Stage III vs. IV, Nodes, tumor siteStratified according to KPS, Stage III vs. IV, Nodes, tumor site

322 T3 or T4 SqCC

2 cycles cisplatin + 5-FU Larynectomy + RT: 50, 60, 65-73.8cGy

+ Response (CR of PR)No response

1 more cycle + RT 66- 76 cGySalvage laryngectomy

Patients with no response or locally recurrent disease underwent salvage laryngectomy.

VA TrialVA Trial

After two cycles of chemotherapy: CR After two cycles of chemotherapy: CR 31% and PR 54%. (Overall response 31% and PR 54%. (Overall response 85%)85%)

At median f/u of 33 months, the estimated At median f/u of 33 months, the estimated 2-year survival was 68 percent (95% CI, 2-year survival was 68 percent (95% CI, 60 to 76%) for both tx groups (P = 0.9846) 60 to 76%) for both tx groups (P = 0.9846)

VA TrialVA Trial

VA TrialVA Trial

Toxicity due to RT was similar in both Toxicity due to RT was similar in both arms.arms.

Grade 2 mucositis slightly higher in chemo Grade 2 mucositis slightly higher in chemo group 38% vs. 24% in TL group.group 38% vs. 24% in TL group.

Higher incidence of surgical complications Higher incidence of surgical complications in salvage cases after RT vs. just after in salvage cases after RT vs. just after chemo.chemo.

VA TrialVA Trial

Patterns of recurrence differed significantly between Patterns of recurrence differed significantly between the two groups, with more local recurrences (P = the two groups, with more local recurrences (P = 0.0005) and fewer distant metastases (P = 0.016) in 0.0005) and fewer distant metastases (P = 0.016) in the chemotherapy group than in the surgery group. the chemotherapy group than in the surgery group.

A total of 59 patients in the chemotherapy group A total of 59 patients in the chemotherapy group (36 percent) required total laryngectomy. (36 percent) required total laryngectomy.

So….64% preserved their larynx without So….64% preserved their larynx without compromising OS.compromising OS.

Induction chemo does enhance the Induction chemo does enhance the effectiveness of RT, but since no direct effectiveness of RT, but since no direct comparison was made between chemoRT vs. comparison was made between chemoRT vs. RT alone, the role of chemo remains uncertain.RT alone, the role of chemo remains uncertain.

Determine if chemo followed by XRT was comparable with standard surgery Determine if chemo followed by XRT was comparable with standard surgery +PORT in pts with T2-4, N0-2b SCCA of the pyriform sinus or AE fold+PORT in pts with T2-4, N0-2b SCCA of the pyriform sinus or AE fold

Multi-centered, prospective, randomized trialMulti-centered, prospective, randomized trial

T2-4 SqCCa of pyriform sinus of AE fold

100 induction chemo x 3 cycles 94 TL, PP + PORT

CR: XRT

PR or CR assessed after each cycle. If after any cycle, no response, went directly to surgery. Only CR went on to XRT

EORTC TrialEORTC Trial

97/100 pts. started chemo as randomized. 97/100 pts. started chemo as randomized. 60/97 proceeded to complete chemo + RT. 60/97 proceeded to complete chemo + RT.

(70Gy, 65Gy)(70Gy, 65Gy) 8/97 required surgical salvage. (55Gy, 60Gy) 8/97 required surgical salvage. (55Gy, 60Gy) 92/94 pts. had surgery as randomized.92/94 pts. had surgery as randomized. 89/92 had post-op RT. (60Gy)89/92 had post-op RT. (60Gy)

Chemotherapy complete responders were more Chemotherapy complete responders were more frequent among those with T2 disease (82%) frequent among those with T2 disease (82%) than those with T3 (48%) or T4 (0%) disease. than those with T3 (48%) or T4 (0%) disease.

Disease Free Disease Free SurvivalSurvival

CI: 0.52-1.43CI: 0.52-1.43

Overall survival chemo Overall survival chemo (57%)>surgery (43%) at 3 (57%)>surgery (43%) at 3 years but equal at 5 years. years but equal at 5 years. NB- small number of pts. at NB- small number of pts. at 5y.5y.CI: 0.50- 1.48CI: 0.50- 1.48

3y3y 5y5y

Chemo Chemo + RT+ RT

43%43% 25%25%

S + S + PORTPORT

31%31% 27%27%

3y3y 5y5y

Chemo Chemo + RT+ RT

57%57% 30%30%

S + S + PORTPORT

43%43% 35%35%

No difference in locoregional failure.No difference in locoregional failure.

Increase in distant mets in surgery group (36%) compared to Increase in distant mets in surgery group (36%) compared to (25%) in chemo arm. p<.041(25%) in chemo arm. p<.041

Survival with functional larynx with no LR, tracheostomy, FT, Survival with functional larynx with no LR, tracheostomy, FT, gastrostomy at 3 and 5 years = 28% and 17% respectively.gastrostomy at 3 and 5 years = 28% and 17% respectively.

Rate of Rate of functional larynxfunctional larynx in those who died of causes other in those who died of causes other than local disease progression and died with a functional larynx than local disease progression and died with a functional larynx at 3 and 5 years= at 3 and 5 years= 42% and 35% respectively.42% and 35% respectively.

EORTC study: conclusionsEORTC study: conclusions Induction chemo is safe for hypopharyngeal cancer.Induction chemo is safe for hypopharyngeal cancer. Fewer distant mets and increased time until mets appearFewer distant mets and increased time until mets appear CR: T2 (82%) > T3 (48%) > T4 (0%)CR: T2 (82%) > T3 (48%) > T4 (0%)

Conclusions so far…Conclusions so far…

Organ preservation is possibleOrgan preservation is possible Role of induction chemo is still not exactly Role of induction chemo is still not exactly

known.known. Distant metastases decreased, and time to Distant metastases decreased, and time to

DM increased.DM increased. EORTC trial had small number of patients.EORTC trial had small number of patients. Lower larynx preservation rates in the EORTC Lower larynx preservation rates in the EORTC

was a result of more stringent selection was a result of more stringent selection criteria. criteria.

Determine role of induction chemo vs concurrent Determine role of induction chemo vs concurrent chemo vs radiation alone in laryngeal preservation chemo vs radiation alone in laryngeal preservation for pts with stage 3 and 4 SqCCa of the larynxfor pts with stage 3 and 4 SqCCa of the larynx

T1 and high-volume T4 tumors where excluded T1 and high-volume T4 tumors where excluded (>1cm into tongue base or penetrating cartilage (>1cm into tongue base or penetrating cartilage invasion)invasion)

Multi-center, prospective, randomizedMulti-center, prospective, randomized

-cisplatin 100mg/m2; 5-FU 1000mg/m2-cisplatin 100mg/m2; 5-FU 1000mg/m2-For concurrent: cisplatin given on day 1,22,43 of RT-For concurrent: cisplatin given on day 1,22,43 of RT-RT to primary: 70Gy in 35 @2Gy-RT to primary: 70Gy in 35 @2Gy-RT to neck, supraclav, post. neck: 50Gy-RT to neck, supraclav, post. neck: 50Gy-Salvage RT for those who failed induction chemo was 50--Salvage RT for those who failed induction chemo was 50-70Gy70Gy-Questionnaires were filled out at baseline and at each f/u.-Questionnaires were filled out at baseline and at each f/u.

Induction Chemo ArmInduction Chemo Arm

168/174 patients received induction 168/174 patients received induction chemo.chemo.

144 had either a CR (21%) or PR (64%), 144 had either a CR (21%) or PR (64%), allowing them to receive PORT.allowing them to receive PORT.

24/168 patients who could not go onto RT. 24/168 patients who could not go onto RT. Only 7 went directly to RL. Only 7 went directly to RL.

11/24 received chemo/RT, and all had CR, 11/24 received chemo/RT, and all had CR, and of these, only 1 needed TL.and of these, only 1 needed TL.

At end of RT: 150/174 (86%) had CR.At end of RT: 150/174 (86%) had CR.

Concurrent ChemoRT armConcurrent ChemoRT arm

120/172 (70%) received all 3 doses 120/172 (70%) received all 3 doses cisplatin.cisplatin.

40/172 (23%)received 2 doses.40/172 (23%)received 2 doses. At end of RT: 154/172 (90%) had CR.At end of RT: 154/172 (90%) had CR.

RT alone armRT alone arm

At end of RT: 148/172 (86%) had CR.At end of RT: 148/172 (86%) had CR.

2 and 5 year overall survival did not differ 2 and 5 year overall survival did not differ • 76% vs 74% vs 75% at 2 years76% vs 74% vs 75% at 2 years• 55% vs 54% vs 56% at 5 years 55% vs 54% vs 56% at 5 years

2y2y 5y5y

InductionInduction 52% 52% p<.02p<.02 38%38%ConcurrentConcurrent 61% 61% p<.006p<.006 36%36%

RT aloneRT alone 44%44% 27%27%

Disease Free Survival

# LF# LF LCRLCR

InductionInduction 6161 64%64%

ConcurrentConcurrent 3535 80%80%

RT aloneRT alone 7272 58%58%

Concurrent resulted in significantly fewer LRs compared to both induction chemo and RT alone.

Concurrent vs Induction p<.02.

Concurrent vs. RT alone p<.001

No statistical difference between induction and RT alone arms.

Effect on Distant MetastasesEffect on Distant Metastases

2y2y 5y5y

InductionInduction 9%9% 15%15%

Concurrent Concurrent p<.03p<.03

8%8% 12%12%

RT aloneRT alone 16%16% 22%22%

Chemo reduced the rate of DMs.

The only statistically significant difference was between the concurrent vs. RT alone arm. p<.03

Laryngeal Laryngeal Preservation Preservation at 3.8yat 3.8y

numbernumber %%

InductionInduction 125/173125/173 72%72%

ConcurrentConcurrent 145/172145/172 84%84%

RT aloneRT alone 116/173116/173 67%67%

IMPORTANT!! Induction chemotherapy followed by RT when compared to RT alone, did not significantly improve the rate of laryngeal preservation.

Conclusion from RTOG 91-11Conclusion from RTOG 91-11 Concurrent chemoRT is superior to both induction Concurrent chemoRT is superior to both induction

chemo and RT alone in regards to locoregional control, chemo and RT alone in regards to locoregional control, laryngeal preservation, and distant metastases.laryngeal preservation, and distant metastases.

Induction chemo showed benefits in only improving DFS, Induction chemo showed benefits in only improving DFS, and decreasing rate of DMs. No effect on LR or OS.and decreasing rate of DMs. No effect on LR or OS.

Overall survival does not differ significantly between Overall survival does not differ significantly between treatment arms. (76% at 2y)treatment arms. (76% at 2y)

Concurrent chemo does cause twice as severe mucosal Concurrent chemo does cause twice as severe mucosal effects, potentially contributing to delayed recovery of effects, potentially contributing to delayed recovery of swallowing in this group.swallowing in this group.

Is laryngeal preservation (LP) with induction chemotherapy (ICT) Is laryngeal preservation (LP) with induction chemotherapy (ICT) safe in the treatment of hypopharyngeal SCC? Final results of the safe in the treatment of hypopharyngeal SCC? Final results of the phase III EORTC 24891 trial.phase III EORTC 24891 trial.

Journal of Clinical OncologyJournal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). , 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 5531Vol 22, No 14S (July 15 Supplement), 2004: 5531

Ultimate disease control, including successful salvage after XRT, was not significantly Ultimate disease control, including successful salvage after XRT, was not significantly different between both arms. different between both arms.

As of 12/2003, 14 % of pts in arm 1 and 17 % of pts in arm 2 were still alive. The As of 12/2003, 14 % of pts in arm 1 and 17 % of pts in arm 2 were still alive. The hypopharynx SCC evolution was the cause of death in 43 pts in arm 1 and in 41 pts hypopharynx SCC evolution was the cause of death in 43 pts in arm 1 and in 41 pts in arm 2. in arm 2.

In arm 2 survival with a functional larynx in place was 22 % at 5y and 9 % at 10y.In arm 2 survival with a functional larynx in place was 22 % at 5y and 9 % at 10y. Conclusions:Conclusions: this final analysis has confirmed the preliminary results with similar this final analysis has confirmed the preliminary results with similar

survival curves as compared with conventional treatment and allowed 2/3 of the survival curves as compared with conventional treatment and allowed 2/3 of the survivors to retain their larynx. survivors to retain their larynx.

5y OS5y OS 10y OS10y OS

Chemo + Chemo + RTRT

38%38% 13%13%

S + S + PORTPORT

33%33% 14%14%

5y PFS5y PFS 10yPFS10yPFS

Chemo + Chemo + RTRT

32%32% 11%11%

S + PORTS + PORT 26%26% 8.5%8.5%

Additional therapiesAdditional therapies Molecular targets have been identified which may hold Molecular targets have been identified which may hold

promise in the treatment of H&N SqCCa. promise in the treatment of H&N SqCCa.

Overexpression of EGFR is recognized in more than Overexpression of EGFR is recognized in more than 95% of SqCCas. The EGFR and its ligands, EGF and 95% of SqCCas. The EGFR and its ligands, EGF and TFG alpha are important in cell proliferation, adhesion, TFG alpha are important in cell proliferation, adhesion, invasion and angiogenesis. invasion and angiogenesis.

Administration of the EGFR monoclonal antibody Administration of the EGFR monoclonal antibody (cetuximab) has been shown to increase (cetuximab) has been shown to increase radiosensitization, decrease tumor cell line growth and radiosensitization, decrease tumor cell line growth and increase apoptosis. increase apoptosis.

Other novel chemotherapeutics include agents to inhibit Other novel chemotherapeutics include agents to inhibit tyrosine kinase, angiogenesis inhibitors, and agents that tyrosine kinase, angiogenesis inhibitors, and agents that have selective toxicity to hypoxic cells.have selective toxicity to hypoxic cells.

Function and Quality of LifeFunction and Quality of Life

Preserving the larynx is great, but not as Preserving the larynx is great, but not as great if the larynx is not effective.great if the larynx is not effective.

How well does it function after concurrent How well does it function after concurrent chemoRT?chemoRT?

How do patients feel about their ability to How do patients feel about their ability to communicate and swallow?communicate and swallow?

Long-term Quality of Life After Treatment of Long-term Quality of Life After Treatment of Laryngeal Cancer Laryngeal Cancer

Jeffrey E. Terrell, MD; Susan G. Fisher, PhD; Gregory T. Wolf, MD; for the Jeffrey E. Terrell, MD; Susan G. Fisher, PhD; Gregory T. Wolf, MD; for the

Veterans Affairs Laryngeal Cancer Study GroupVeterans Affairs Laryngeal Cancer Study Group

Arch Otolaryngol Head Neck Surg.Arch Otolaryngol Head Neck Surg. 1998;124:964-971 1998;124:964-971.. 1998 follow up: 46/65 surviving pts, 71% RR1998 follow up: 46/65 surviving pts, 71% RR

• 25 surgery+PORT, 21 experimental arm25 surgery+PORT, 21 experimental arm

• HNQOL, SF-36 General Health Measure Short HNQOL, SF-36 General Health Measure Short Form, Beck Depression Inventory, alcohol and Form, Beck Depression Inventory, alcohol and smoking surveys. smoking surveys.

Quality of Life f/u of VA StudyQuality of Life f/u of VA Study Those with larynx fared significantly better from the Those with larynx fared significantly better from the

standpoint of speech communication. standpoint of speech communication.

At 2 years post-treatment, patients with successful organ At 2 years post-treatment, patients with successful organ preservation had regained their pretx level of functioning preservation had regained their pretx level of functioning for 2/3 measures tested (intelligibility and reading rate) for 2/3 measures tested (intelligibility and reading rate) and exceeded pretx performance on the 3rd (a and exceeded pretx performance on the 3rd (a communication profile used to assess general communication profile used to assess general communication status). communication status).

TL + PORT pts had a decrease in all 3 speech TL + PORT pts had a decrease in all 3 speech communication-related measures despite availability of communication-related measures despite availability of all modes of speech rehabilitation and therapy. all modes of speech rehabilitation and therapy.

Measures of swallowing dysfunction were similar Measures of swallowing dysfunction were similar between both arms. between both arms.

Quality of Life f/u to VA study Quality of Life f/u to VA study

Pts with successful organ preservation:Pts with successful organ preservation:

had better scores on all domains of the SF-36 had better scores on all domains of the SF-36 compared to those who underwent TL.compared to those who underwent TL.

scored significantly better on the bodily pain and scored significantly better on the bodily pain and mental health domain of the SF-36. mental health domain of the SF-36.

scored significantly better on the emotion domain and scored significantly better on the emotion domain and their impression of their response to treatment on the their impression of their response to treatment on the HNQOL survey. HNQOL survey.

At long-term f/u, 10 of 45 patients had BDI scores At long-term f/u, 10 of 45 patients had BDI scores consistent with moderate or severe depression. consistent with moderate or severe depression.

9 of those 10 had undergone TL. 9 of those 10 had undergone TL.

Conclusions from VA StudyConclusions from VA Study

Better QOL in the CT+RT appears to be Better QOL in the CT+RT appears to be related to more freedom from pain, better related to more freedom from pain, better emotional well being, and lower levels of emotional well being, and lower levels of depression than to preservation of speech depression than to preservation of speech functionfunction

RTOG91-11 SpeechRTOG91-11 SpeechPercentages of speech impairment at 1 and 2y.Percentages of speech impairment at 1 and 2y.

No difference among 3 groups in regard to speech at 12 No difference among 3 groups in regard to speech at 12 or 24m.or 24m.

Moderate speech impairment: difficulty in pronouncing some words and being Moderate speech impairment: difficulty in pronouncing some words and being understood on the telephone.understood on the telephone.

1y1y 2y2y

InductionInduction 6%6% 3%3%

ConcurrentConcurrent 11%11% 6%6%

RT aloneRT alone 13%13% 8%8%

RTOG 91-11-Laryngeal Function @1yRTOG 91-11-Laryngeal Function @1y

No difference in groups’ QOLNo difference in groups’ QOL 2-yr all three groups similar with 16%, 15%, 14% reporting difficulty 2-yr all three groups similar with 16%, 15%, 14% reporting difficulty

swallowingswallowing

Soft foodsSoft foods No swallowNo swallow

InductionInduction 9%9% 0%0%

ConcurrentConcurrent 23%23% 3%3%

RT aloneRT alone 15%15% 3%3%

Grade and frequency of toxic acute effects was similar in the induction and RT alone arms: mostly grade 3 in-field effects on skin and mucous membranes.

Concurrent chemoRT had chemo-related toxic acute effects (neutropenia, severe N/V, increased rates of severe radiation-related mucosal, pharyngeal and esophageal effects.

Rates of late toxic effects were similar among groups.

Patients who are treated with larynx-Patients who are treated with larynx-preserving modalities are still at risk of preserving modalities are still at risk of having to undergo salvage laryngectomy having to undergo salvage laryngectomy in the future.in the future.

In these patients, is there any added In these patients, is there any added morbidity associated with salvage morbidity associated with salvage laryngectomy?laryngectomy?

Danish Society for Head and Neck Danish Society for Head and Neck Oncology (2003)Oncology (2003)

Wanted to look at surgical outcome of 472 pts with Wanted to look at surgical outcome of 472 pts with salvage laryngectomy after XRT from 1987-1997salvage laryngectomy after XRT from 1987-1997

Specific outcome looked at was development of Specific outcome looked at was development of pharyngocutaneous fistula. pharyngocutaneous fistula.

89 fistulas lasting > 2 weeks; Overall fistula rate = 19%89 fistulas lasting > 2 weeks; Overall fistula rate = 19% Number of TLs per year decreased linearly (from 58 to Number of TLs per year decreased linearly (from 58 to

37), whereas the annual number of fistulae increased 37), whereas the annual number of fistulae increased slightly (from 7 to 11). slightly (from 7 to 11).

• RR in 1987 =12%RR in 1987 =12%• RR in 1997 =30%RR in 1997 =30%

•Grau C, Johansen LV, Hansen HS, Andersen E, Godballe C, Andersen LJ, Hald J, Moller H, Overgaard M, Bastholt L, Greisen O, Harbo G, Hansen O, Overgaard J. Salvage Laryngectomy and Pharyngocutaneous Fistulae after Primary Radiotherapy for Head and Neck Cancer: a National Survey From DAHANCA. Head and Neck. Sep 2003. 25:711-716.

Danish Study Danish Study

Increased rate attributed to:Increased rate attributed to:• Higher stages offered XRT as definitive therapyHigher stages offered XRT as definitive therapy• Decrease in individual surgical experience with TLDecrease in individual surgical experience with TL

Other significant RFs for fistulae included:Other significant RFs for fistulae included:

-younger patient age-younger patient age - primary advanced T and N stage. - primary advanced T and N stage. RR 2x’s higher in initial T3-4 than T1-2RR 2x’s higher in initial T3-4 than T1-2

- nonglottic primary site. Fistula OR 2.08- nonglottic primary site. Fistula OR 2.08

Surgical complication rates were low.Surgical complication rates were low. No differences in systemic complications between No differences in systemic complications between

treatment armstreatment arms Complications independent of the time from the end Complications independent of the time from the end

of treatment to TLof treatment to TL Fistulas occurred in:Fistulas occurred in:

• Arm 1 = 25%Arm 1 = 25%• Arm 2 = 30%Arm 2 = 30%• Arm 3 = 15%Arm 3 = 15%

Conclusions from RTOG SalvageConclusions from RTOG Salvage

Salvage post laryngeal Salvage post laryngeal preservation has preservation has acceptable morbidity.acceptable morbidity.

1/3 will develop fistula1/3 will develop fistula Locoregional control is Locoregional control is

excellent: excellent:

74%, 74%, 90%74%, 74%, 90%

Overall Survival for TL Overall Survival for TL patients at 2y:patients at 2y:

69% 71% 76%69% 71% 76%

Conclusions from RTOG SalvageConclusions from RTOG Salvage

Survival following salvage laryngectomy not influenced by initial organ preservation treatment.

Treatment of DSTreatment of DS

Although had TL, needs post-op RT:Although had TL, needs post-op RT:-cartilage invasion-cartilage invasion-perineural invasion-perineural invasion-multiple positive nodes-multiple positive nodes-nodes with ECE-nodes with ECE

He will be treated on RTOG 0234:He will be treated on RTOG 0234:Surgery + RT + Cetuximab followed by either Surgery + RT + Cetuximab followed by either

docetaxel or cisplatin.docetaxel or cisplatin.

Setup of Radiotherapy of the LarynxSetup of Radiotherapy of the Larynx

Patient supine.Patient supine. Face mask on.Face mask on. Borders: superior- 2cm above mastoid tipBorders: superior- 2cm above mastoid tip

inferior- bottom of cricoid cartilageinferior- bottom of cricoid cartilage posterior- behind spinous processposterior- behind spinous process

Off cord at 40Gy. Off cord at 40Gy. Cord block on laterals.Cord block on laterals.Wedge used.Wedge used.Boost stoma.Boost stoma.

Dose PlanDose Plan

BEV SupraclavBEV Supraclav

BEV- LateralBEV- Lateral

Side Effects of RT to larynxSide Effects of RT to larynx

SorenessSoreness DysphagiaDysphagia OdynophagiaOdynophagia Erythema, Desquamation of NeckErythema, Desquamation of Neck Weight Loss Weight Loss

AcknowledgmentsAcknowledgments

Dr. John HollandDr. John Holland Dr. Carol MarquezDr. Carol Marquez Dr. Charles ThomasDr. Charles Thomas Dr. Arthur HungDr. Arthur Hung Dr. Marsha CrittendenDr. Marsha Crittenden Dr. Parag SanghviDr. Parag Sanghvi Dr. Tarka McDonaldDr. Tarka McDonald Dr. Patrick GagnonDr. Patrick Gagnon Dr. Sam WangDr. Sam Wang Lori IsmachLori Ismach Tony HeTony He