oropharyngeal cancer

Mark ZafereoAssistant Professor

Head and Neck SurgeryMD Anderson Cancer Center

Management of Recurrent Oral Squamous Cell Carcinoma

Management of Recurrent Oral Squamous Cell

Carcinoma• Demographics and changing patterns of

recurrence

• Surgical salvage– Survival– Functional outcomes– Reconstruction

• Reirradiation, chemotherapy, supportive care

Squamous Cell Carcinoma of the Oropharynx

• Management has transitioned from primary surgery to primary radiotherapy with or without chemotherapy

• Renewed interest in transoral laser and robotic surgery over the last 5 years as a primary treatment modality

Trends in Head & Neck Ca Incidence in U.S.:Increase in Pharyngeal & Tongue Cancers

Sturgis and Cinciripini, Cancer 2007

2,000

4,000

6,000

8,000

10,000

12,000

1987 1990 1993 1996 1999 2002 2005

Year

Nu

mb

er

of

Ca

nc

ers

Larynx

Mouth

Pharynx

Tongue

Oral-other

SEER

SCCOP: Locoregional control

• Improved locoregional control– 1960s: ~20-40% disease-free survival– 2010 Stanford: 81% 3-year disease-free

survival– 2012 MSK

• 3-year local failure = 5.4%• 3-year regional failure = 5.6%• 3-year distant failure = 12.5%

Gilbert H, Kagan AR. Recurrence patterns in squamous cell carcinoma of the oral cavity, pharynx, and larynx. J Surg Oncol. 1974;6:357-380.Daly, et al. IMRT in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure . Int J. Radiation Oncology. 2010.Setton J, et al. IMRT in the treatment of oropharynx cancer: an updated of the Memorial Sloan-Kettering Cancer Center Experience. Int J Radiation Oncology. 2012.

Setton J, et al. IMRT in the treatment of oropharynx cancer: an updated of the Memorial Sloan-Kettering Cancer Center Experience. Int J Radiation Oncology. 2012.

SCCOP: Locoregional control

Garden, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int. Journal Radiation Oncology. 2013.

SCCOP: Locoregional control• MDACC: Retrospective review of 776

patients between 2000-2007 treated with IMRT with/without chemotherapy

• 5-year overall survival: 84%• 5-year recurrence-free survival: 82%

– 7% recurred primary site– 4% recurred neck– 10% developed distant metastases– 8% had second primary cancers

Garden, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int. J. Radiation Oncology. 2013.

SCCOP: Locoregional control

Garden, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int. J. Radiation Oncology. 2013.

SCCOP: Locoregional control

Garden, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int. J. Radiation Oncology. 2013.

SCCOP: Locoregional Control

• Decrease in locoregional failures– Improvements in multimodality therapy– Changing demographics: Improved

prognosis of HPV positive tumors, especially in nonsmokers

SCCOP: Change in Distant Failures?

• Teneja, et al.: Distant failures increased while locoregional failures decreased – 1988-1993: 26% LR failure; 3% distant failure– 1994-1999: 16% LR failure; 8% distant failure

• Ang, et al: Distant failure rate lower among HPV positive patients– HPV positive: 14% LR failure; 9% distant failure– HPV negative: 35% LR failure; 15% distant failure

Taneja et al. Changing patterns of failure of head and neck cancer. Archives of Otolaryngology Head Neck Surgery. 2002.Ang, et al. HPV and survival of patients with oropharynx cancer. NEJM. 2010.

Huang, O’Sullivan, et al. Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal SCC treated with radical radiotherapy. Int J Radiation Oncology. 2012

Anecdotal report of 4 cases with bone, GI, brain metastases

SCCOP: Change in Distant Failures?

• Relative increase in distant metastases compared to locoregional metastases

• No signficant difference in rate of distant metastases among HPV positive and HPV negative patients

• Multiple and unusual sites of distant metastases in HPV positive patients

Treatment Locally Recurrent SCCOP

• Surgical Salvage

• Reirradiation

• Palliative Chemotherapy

• Supportive Care

Surgical SalvageOverall survival

• Gilbert and Kagan, J Surg Onc, 1974: <10% of recurrent tonsil SCC successfully surgically salvaged

Gilbert H, Kagan AR. Recurrence patterns in squamous cell carcinoma of the oral cavity, pharynx, and larynx. J Surg Oncol. 1974;6:357-380.

Surgical SalvageOverall Survival

Goodwin WJ. Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means? Laryngoscope. 2000;110(Suppl. 93):1-18.

Surgical Salvage: MDACCOverall Survival

• 3-year Overall Survival (following diagnosis of recurrence):– 42% for surgical salvage

– 32% for reirradiation

– 4% for palliative chemotherapy

– 5% for supportive care

• 3-year Recurrence-Free Survival: – 26% for surgical salvage

Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2009

Surgical Salvage: MDACC Prognostic Factors: Disease-Free Interval

Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2009.

Surgical Salvage: MDACC Prognostic Factors: Recurrent Tumor Stage

Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2009.

Surgical Salvage: MDACC Prognostic Factors: Disease-Free Interval and

Recurrent Tumor Stage

Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2009.

But we started with 434 patients with recurrent SCCOP. 14/434 = 3%

Surgical Salvage: MDACCPrognostic Factors

• Favorable salvage surgery candidates:

– Disease-free interval after definitive therapy

– Small recurrent tumors

– Younger

– No recurrent neck disease

• Only 14 of 434 (3%) patients with recurrent oropharyngeal SCC met these criteria

• Salvage surgery can provide a very select group of patients with long-term disease control and quality of life.

Surgical SalvageReconstruction

• Secondary intention

• Skin graft

• Local flap (e.g. temporalis)

• Regional pedicled flap (pectoralis major)

• Microvascular free flap

Surgical SalvageReconstruction

Zafereo, Weber, Lewin, Roberts, Hanasono. Complications and Functional Outcomes Following Complex Oropharyngeal Reconstruction. Head and Neck. 2010

MDACC Treatment Algorithm for Oropharyngeal Reconstruction

Zafereo, Weber, Lewin, Roberts, Hanasono. Complications and Functional Outcomes Following Complex Oropharyngeal Reconstruction. Head and Neck. In Press

Radial Forearm Fasciocutaneous Free Flap

Pictures courtesy Dr. Matthew Hanasono, MDACC

Anterolateral Thigh Free Flap

Pictures courtesy Dr. Matthew Hanasono, MDACC

Quality of Life and Recurrent Oropharyngeal SCC

• Principle concerns at initial diagnosis1. Survival

2. Pain

3. Ability to maintain usual activities

• Principle concerns with recurrence1.Pain

2.Ability to maintain usual activities

3.Survival

List MA, Butler P, Vokes EE, et al. Head neck cancer patients: How do patients prioritize potential treatment outcomes. American Society for Clinical Oncology, Los Angeles, CA, May 16-19, 1998 (abstr 1472).Arnold DJ, Goodwin J, Weed DT, Civantos FJ. Treatment of recurrent and advanced stage squamous cell carcinoma of the head and neck. Semin Radiat Oncol. 2004;14:190-195.

Surgical SalvageFunctional Outcomes and Survival

• Netscher, Stewart et al, Plast Reconstr Surg, 2000– 6 months: Return to baseline functional status– 1 year: Surpass pretreatment functional status

• Rerecurrence and survival following surgical salvage– MDACC: 67% rerecurrence, median 8 months– Kim et al: 74% rerecurrence, median 9 months– Goodwin et al: Median disease-free survival 8 months

Netscher DT, Meade RA, Goodman CM, Alford EL, Stewart MG. Quality of life and disease-specific functional status following microvascular reconstruction for advanced (T3 and T4) oropharyngeal cancers. Plast Reconstr Surg. 2000;105:1628-1634.

Functional Outcomes for 41 Oropharyngeal Salvage Surgery Patients at MDACC

Oral intake

Partial oralintake/partialfeeding tube

Feeding tubedependent

Oralspeech

Other

Nutrition Speech

Decannulated

Permanenttracheostomy

Tracheostomy (N =30)

78%

22%

87%

13%

37%

32%

32%

Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2010.

Surgical Salvage

• Average hospital and physician charges for surgical salvage:– Pharynx: $86,000– Oral cavity: $82,000– Larynx: $70,000– Neck: $48,000

Goodwin WJ. Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means? Laryngoscope. 2000;110(Suppl. 93):1-18.

Reirradiation

• 13-22% 5-year overall survival

• 9-32% experience severe or fatal complications

Garofalo MC, Haraf DJ. Reirradiation: a potentially curative approach to locally or regionally recurrent head and neck cancer. Curr Opin Oncol. 2002;14:330-333.

Reirradiation

• Radiation Therapy Oncology Group 9610 – 2-year survival: 15%– 5-year survival: 4%– Median survival 8 months– Grade 4 or higher acute toxicity: 25%– Treatment-related death: 8%

Spencer SA, Harris J, Wheeler RH, et al. Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Head Neck. 2008;30:281-288.

Reirradiation

• Radiation Therapy Oncology Group 9910– 25% 2-year overall survival– Median survival 12 months– Grade 4 or worse acute toxicity: 28%– Treatment-related death: 11%

Langer CJ, Harris J, Horwitz EM, et al. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: Results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol. 2007;25:4800-4805.

Palliative Chemotherapy

• 33% of patients have partial response to platinum-based regimens

• Median survival 4-6 months

• 2-year overall survival 5-10%

Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous cell carcinoma of the head and neck: A Southwest Oncology Group study. J Clin Oncol. 1992;10:1245-1251.

Supportive Care

• Natural history of untreated head and neck cancer– Median 3-4 month survival– Performance status best indicator of

survival

Kowalski LP, Carvalho AL. Natural history of untreated head and neck cancer. Eur J Cancer. 2000;36:1032-1037.Stell PM. Survival times in end-stage head and neck cancer. Eur J Surg Oncol. 1989;15:407-410.

Biological Markers and Prognosis

Agra IMG, Carcalho AL, Pinto CAL, et al. Biological markers and prognosis in recurrent oral cancer after salvage surgery. Arch Otolaryngol Head Neck Surg. 2008;134:743-749.

Biological Markers and Prognosis

Agra IMG, Carcalho AL, Pinto CAL, et al. Biological markers and prognosis in recurrent oral cancer after salvage surgery. Arch Otolaryngol Head Neck Surg. 2008;134:743-749.

Conclusions• Increasing incidence oropharyngeal cancer

and younger patient population• Decreasing locoregional failures; Relative

increase distant failures• Careful patient selection for salvage surgery• Good functional outcomes achievable if

patients survive their disease• Biomarkers as prognostic factors

Surgical Salvage for Recurrent Oral Cavity Squamous Cell Carcinoma

David M Neskey1

Ryan M Boerner1

Diana Roberts2

Randal S Weber2

Erich M Sturgis2

Jeffrey N Myers2

Mark E Zafereo2

• ~22,000 new cases of oral cavity cancer per year

• ~7000 deaths per year• 5 year survival:

– Stage I-II: ~70%– Stage III–IV: 35-50%

• Recurrence ~25-35%– Most frequently local and

regional– Correlate with:

• Stage• Pathological features

– Median survival 12-16 months

Background

Objectives

Identify patient, tumor, and treatment related characteristics associated with improved survival in patients with recurrent oral cavity squamous

cell carcinoma

Methods

• Retrospective chart review 1996-2010 of patients treated at MDACC for recurrent Oral Cavity Squamous Cell Carcinoma (OCSCC)

Overall Survival

Overall survival of patients who did and did not undergo surgical salvage for recurrent OCSCC

Expectedly, selected patients that could undergo surgical salvage had improved overall survival.

n=250n=150

Results: 250 Surgical Salvage Patients

• Mean follow-up 40 months (median 23 months) • 123/250 (49%) patients had history of head and

neck radiation• 152/250 (61%) patients had microvascular free

flap reconstruction with surgical salvage• 77/250 (31%) patients had postoperative

radiation therapy following salvage surgery• 123/250 (49%) developed a second recurrence a

median of 17 months following salvage surgery

Impact of Disease Free Interval

Improved survival following a recurrence when the disease free interval was greater than 6 months

68

Overall survival of surgical salvage patients stratified by duration of disease free interval

Impact of Age

Patient age at recurrence did not correlate with overall survival

Overall survival stratified by age at the time of recurrence

Impact of Recurrent Stage

Improved overall survival following recurrence for•rT1 and rT2•rN0

Early vs. late recurrent T stage Node negative vs. positive

Overall survival of salvage surgery patients stratified by local and regional recurrent disease stage

Impact of Previous Treatment

Improved survival following a recurrence when initial disease was treated:•With surgical resection of the primary site•Without radiation

Surgical vs. non-surgical treatment Radiation vs. no radiation

Overall survival of salvage surgery patients stratified by treatment for initial disease

Impact of Post-Operative Radiation

Improved survival observed in patients that did not receive post-operative radiation therapy for recurrence very likely due to selection bias

Overall survival of salvage surgery patients stratified by post-operative radiation for recurrence

Impact of Post-Operative Radiation

Post operative radiation improved survival in patients with advanced stage recurrent disease but not early stage recurrent disease.

Overall survival of salvage surgery patients stratified by post-operative radiation for recurrence and recurrent stage

Late recurrent overall stage diseaseEarly recurrent overall stage disease

Impact of Re-irradiation

No observed benefit for re-irradiation among patients with history of previous head and neck radiaiton

Overall survival of salvage surgery patients stratified by post-operative re-irradiation for recurrence

Results

• Thirty-eight (15%) required an additional surgery for a complication within 3 months of initial surgical salvage

• Surgical and hospital charges – Mean: $99,955 (standard deviation $78,199)– Median: $90,463 (range $6,451-$668,058)

Functional outcomes

Impact of salvage surgery on speech intelligibility as assessed by speech pathologists.

The ability to maintain functional speech was achieved in 95% of patients who underwent salvage surgery

Functional outcomes

Impact of salvage surgery on dietary intake.

~20% of patients who underwent surgical salvage lost their ability to take a full oral diet.

Functional Outcomes

Although 60% of patients had tracheostomies, 75% were able to be decannulated.

Conclusions

• Patients with improved survival outcomes following salvage surgery for oral cavity squamous cell carcinoma:– > 6 month disease free interval– No previous radiation– Small recurrent tumor (rT1-2)– No recurrent neck disease

• Patients that benefit from post operative radiation for recurrent disease:– No previous radiation– Advanced recurrent T stage or concomitant recurrent neck disease

• Functional outcomes following salvage surgery acceptable – >95% able to maintain functional speech– 80% full oral diet– 75% of patients that require tracheostomies decannulated

Mark ZafereoAssistant Professor

Head and Neck SurgeryMD Anderson Cancer Center

Management of Recurrent Oral Squamous Cell Carcinoma