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oropharyngeal cancer
- 1. Management of Recurrent Oral Squamous Cell Carcinoma Mark Zafereo Assistant Professor Head and Neck Surgery MD Anderson Cancer Center
- 2. Management of Recurrent Oral Squamous Cell Carcinoma • Demographics and changing patterns of recurrence • Surgical salvage – Survival – Functional outcomes – Reconstruction • Reirradiation, chemotherapy, supportive care
- 3. 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
- 4. Trends in Head & Neck Ca Incidence in U.S.: Increase in Pharyngeal & Tongue Cancers Sturgis and Cinciripini, Cancer 2007 12,000 10,000 8,000 6,000 4,000 2,000 1987 1990 1993 1996 1999 2002 2005 Year Number of Cancers Larynx Mouth Pharynx Tongue Oral-other SEER
- 5. 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.
- 6. 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.
- 7. 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.
- 8. 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.
- 9. 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.
- 10. 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.
- 11. SCCOP: Locoregional Control • Decrease in locoregional failures – Improvements in multimodality therapy – Changing demographics: Improved prognosis of HPV positive tumors, especially in nonsmokers
- 12. 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.
- 13. Anecdotal report of 4 cases with bone, GI, brain metastases Huang, O’Sullivan, et al. Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal SCC treated with radical radiotherapy. Int J Radiation Oncology. 2012
- 14. 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
- 15. Treatment Locally Recurrent SCCOP • Surgical Salvage • Reirradiation • Palliative Chemotherapy • Supportive Care
- 16. Surgical Salvage Overall 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.
- 17. Surgical Salvage Overall 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.
- 18. Surgical Salvage: MDACC Overall 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
- 19. 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.
- 20. 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.
- 21. Surgical Salvage: MDACC Prognostic Factors: Disease-Free Interval and Recurrent Tumor Stage But we started with 434 patients with recurrent SCCOP. 14/434 = 3% Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2009.
- 22. Surgical Salvage: MDACC Prognostic 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.
- 27. Surgical Salvage Reconstruction • Secondary intention • Skin graft • Local flap (e.g. temporalis) • Regional pedicled flap (pectoralis major) • Microvascular free flap
- 28. Surgical Salvage Reconstruction Zafereo, Weber, Lewin, Roberts, Hanasono. Complications and Functional Outcomes Following Complex Oropharyngeal Reconstruction. Head and Neck. 2010
- 29. MDACC Treatment Algorithm for Oropharyngeal Reconstruction Zafereo, Weber, Lewin, Roberts, Hanasono. Complications and Functional Outcomes Following Complex Oropharyngeal Reconstruction. Head and Neck. In Press
- 30. Radial Forearm Fasciocutaneous Free Flap Pictures courtesy Dr. Matthew Hanasono, MDACC
- 31. Anterolateral Thigh Free Flap Pictures courtesy Dr. Matthew Hanasono, MDACC
- 32. Quality of Life and Recurrent Oropharyngeal SCC • Principle concerns at initial diagnosis 1. Survival 2. Pain 3. Ability to maintain usual activities • Principle concerns with recurrence 1.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.
- 33. Surgical Salvage Functional 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.
- 34. Functional Outcomes for 41 Oropharyngeal Salvage Surgery Patients at MDACC Oral intake Partial oral intake/partial feeding tube Feeding tube dependent Speech Nutrition Oral speech Other 32% Decannulated Permanent tracheostomy Tracheostomy (N =30) 78% 22% 87% 13% 37% 32% Zafereo, Hanasono, Rosenthal, Sturgis, Lewin, Roberts, Weber. The Role of Salvage Surgery in Recurrent Oropharyngeal Squamous Cell Carcinoma. Cancer. 2010.
- 35. 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.
- 36. 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.
- 37. 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.
- 38. 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.
- 39. 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.
- 40. 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.
- 41. 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.
- 42. 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.
- 43. 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
- 44. 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
- 45. Background • ~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
- 46. Objectives Identify patient, tumor, and treatment related characteristics associated with improved survival in patients with recurrent oral cavity squamous cell carcinoma
- 47. Methods • Retrospective chart review 1996-2010 of patients treated at MDACC for recurrent Oral Cavity Squamous Cell Carcinoma (OCSCC)
- 48. Overall Survival Overall survival of patients who did and did not undergo surgical salvage for recurrent OCSCC n=150 n=250 Expectedly, selected patients that could undergo surgical salvage had improved overall survival.
- 49. 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
- 50. Impact of Disease Free Interval Overall survival of surgical salvage patients stratified by duration of disease free interval 68 Improved survival following a recurrence when the disease free interval was greater than 6 months
- 51. Impact of Age Overall survival stratified by age at the time of recurrence Patient age at recurrence did not correlate with overall survival
- 52. Impact of Recurrent Stage Overall survival of salvage surgery patients stratified by local and regional recurrent disease stage Early vs. late recurrent T stage Node negative vs. positive Improved overall survival following recurrence for •rT1 and rT2 •rN0
- 53. Impact of Previous Treatment Overall survival of salvage surgery patients stratified by treatment for initial disease Surgical vs. non-surgical treatment Radiation vs. no radiation Improved survival following a recurrence when initial disease was treated: •With surgical resection of the primary site •Without radiation
- 54. Impact of Post- Operative Radiation Overall survival of salvage surgery patients stratified by post-operative radiation for recurrence Improved survival observed in patients that did not receive post-operative radiation therapy for recurrence very likely due to selection bias
- 55. Impact of Post- Operative Radiation Overall survival of salvage surgery patients stratified by post-operative radiation for recurrence and recurrent stage Late recurrent Early recurrent overall stage disease overall stage disease Post operative radiation improved survival in patients with advanced stage recurrent disease but not early stage recurrent disease.
- 56. Impact of Re-irradiation Overall survival of salvage surgery patients stratified by post-operative re-irradiation for recurrence No observed benefit for re-irradiation among patients with history of previous head and neck radiaiton
- 57. 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)
- 58. 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
- 59. 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.
- 60. Functional Outcomes Although 60% of patients had tracheostomies, 75% were able to be decannulated.
- 61. 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
- 62. Management of Recurrent Oral Squamous Cell Carcinoma Mark Zafereo Assistant Professor Head and Neck Surgery MD Anderson Cancer Center
Editor's Notes
- Beginning in the 1980s and 90s, management for this disease has shifted from surgery to radiotherapy with or without chemotherapy, though there are some centers that have reported good results in terms of survival and recurrence with primary surgery, especially with renewed interest in surgery with the advent of transoral laser and transoral robotic surgery, for which we will have clinical trials soon, but here, at most major centers, and in the community, the vast majority of these tumors are still being treated with primary radiation therapy.
- So hopefully we’ll have some answers soon with these clinical trials. And it’s a good thing, because In depth look at data from the SEER database reveals that over the last 2 decades, oropharyngeal and tongue cancer absolute numbers (illustrated by the dark lines) have increased, while other oral cavity sites and larynx are declining. And this is thought to be related to the humanpapillomavirus.
- But increase in incidence of primary oropharygneal tumors has not led to an increase in recurrent oropharyngeal tumors, due improvements in treatment and the better prognosis associated with HPV-driven tumors. In fact locoregional control has improved. Drs. Gilbert and Kagan performed a metanalysis in 1974, reporting a range of 20-40% disease-free survival. Recent Stanford study, they had 81 % 3-year DF survival. 2012. MSK. Reported in terms of failure rates; 5% each for local and regional failure at 3 years and 12.5% distant failure rate at 3 years
- Locoregional control high80s-mid90s. Garden 2007 paper updated in 2013, which was just published in the Red Journal in January.
- N1-2 HPV surrogates did better
- Tonsil, BOT and never smokers (HPV surrogates) did better
- When you look at distant metastases in relative terms, as the rate of locoregional failures have decreased in the HPV era, the rate of distant metastases when compared to locoregional failures has been increasing, but most studies have indicated that there has not been a signficant change in the rate of distant failures. In a study of 280 oral cavity and oropharyngeal cancers in Boston, locoregional failure decreased from 26% during 88’-93’ to 16% during 94’-99’, but distant failures increased significantly from 3% to 8%. So likely that the relative rate of DM to LR recurrence may be changing, but there’s not sufficient evidence to suggest that the overall rate of DM is changing much in either direction.
- This is a study from Princess Margaret in Toronto, similarly showing
- Reviews of the effectiveness of salvage surgery for patients with locoregionally recurrent SCCOP are rare in the literature, and there are no studies in the literature directly comparing salvage surgery with nonsurgical treatment for recurrent SCCOP. Gilbert and Kagan reviewed surgical salvage in the 1970’s and found that less than 10% of tonsillar SCC were successfully surgically salvaged.
- In a more recent metanalysis in 2000, Goodwin reviewed patients with recurrent pharyngeal cancer previously treated definitively with radiation, reporting only 25% recurrence-free survival at two years and 26% overall survival at 5 years. You can see from the table that patients with recurrent pharynx cancer who underwent surgical salvage had lower higher recurrence and lower survival than patients with oral cavity or larynx cancer.
- In looking at the experience at MDACC, 3-year overall survival for surgical salvage of squamous cell carcinoma of the oropharynx was only 42%, while recurrence-free survival was even lower 26% at 3 years. This graph compares overall survival with salvage surgery versus those patients who were reirradiated or had palliative chemotherapy or supportive care only. While these groups are not directly comparable, as there is a selection bias, it places salvage surgery within the context of other treatment options. There was no statistically significant difference in survival among patients who had salvage surgery versus those who were reirradiated, and as expected 3-year survival was less than 10% for patients who had palliative chemotherapy or supportive care only.
- In looking at further at the MDA experience, the graph to the left illustrates overall survival coupled with disease-free interval. The patients with a disease-free interval who underwent salvage surgery illustrated by the red line had 3-year overall survival of almost 60%, while those who did not have a disease-free interval illustrated by the green line had a 3-year overall survival of less than 20%. This difference was highly significant. Even for patients who underwent nonsurgical treatment, illustrated by the purple and blue lines, the presence of a disease-free interval significantly influenced their life expectancy. Whereas, 80% of patients with a disease-free interval were alive at one year in patients who underwent reirradiation and/or chemotherapy, only 30% were alive at one year if they had no disease-free interval. Looking at the figure to the right, at three years, over 60% surgical salvage patients with recurrent stage T1 and T2 disease were alive, as compared to a little over 20% of surgical slavagepatients with recurrent T3 and T4 disease.
- In looking at further at the MDA experience, the graph to the left illustrates overall survival coupled with disease-free interval. The patients with a disease-free interval who underwent salvage surgery illustrated by the red line had 3-year overall survival of almost 60%, while those who did not have a disease-free interval illustrated by the green line had a 3-year overall survival of less than 20%. This difference was highly significant. Even for patients who underwent nonsurgical treatment, illustrated by the purple and blue lines, the presence of a disease-free interval significantly influenced their life expectancy. Whereas, 80% of patients with a disease-free interval were alive at one year in patients who underwent reirradiation and/or chemotherapy, only 30% were alive at one year if they had no disease-free interval. Looking at the figure to the right, at three years, over 60% surgical salvage patients with recurrent stage T1 and T2 disease were alive, as compared to a little over 20% of surgical slavagepatients with recurrent T3 and T4 disease.
- So looking at the 14 salvage surgery patients with both a disease-free interval and small tumors for which it is possible to obtain negative surgical margins, over 70% were alive at 3 years and 45% alive at 5 years. However, this is a very select group of 14 patients, only 3% of the initial 434 patients who presented with locally recurrent orophayngeal cancer.
- So the clinical factors that are most important when deciding if patients are reasonable candidates for surgical salvage include disease-free interval and recurrent tumor size, as well as age and recurrent neck disease. In this study, all 10 patients who had recurrent neck disease developed a second recurrence after surgical salvage. So it becomes clear that based on these criteria, few patients will be considered favorable salvage candidates. And in fact, while there were 41 patients who had surgical salvage in this study, only 14 would be considered favorable surgical candidates, which is less than 3% of the initial 434 patients who presented with recurrent oropharyngeal SCC. However, as illustrated on the previous slide, for these few patients, long-term disease is attainable.
- Equally important as the decision whether or not to attempt surgical salvage is the reconstruction and rehabilitation following the ablative procedure. Because of large surgical defects in a bed of often previously irradiated tissue, oropharyngeal reconstruction and rehabilitation following salvage surgery represents one of the greatest challenges in the treatment of head and neck cancer. Reconstruction with a regional pedicled, most commonly the pectoralis major, or microvascular free flap, is preferred over healing by secondary intention, skin grafting, or reconstruction with a local flap such as the temporalis because of concerns of insufficient tissue to close large defects, poor healing in previously irradiated tissues, and the development of scar contracture that limits the chance for any postoperative speech and swallowing rehabilitation.
- In a study of 65 microvascular free flap and/or regional pedicled oropharyngeal reconstruction patients at MDACC between 1997 and 2007, a total of 48 microvascular free flaps and 12 pectoralis major pedicled flaps were performed, with three patients undergoing double free flaps. Although the rectus abdominis was the most commonly utilized flap during the study period, the ALT flap has largely replaced the rectus in recent years at MD Anderson. Only 5 patients underwent bony mandibular reconstruction with a fibula osseocutaneous flap.
- This is an MDACC institutional treatment algorithm for oropharyngeal reconstruction after oncologic resection of advanced cancer. Pectoralis major pedicled flaps are reserved for patients with limited defects, poor-quality recipient vessels, either because of neck dissection or radiation history, significant medical comorbidities, and a poor prognosis. Temporalis muscle flaps are an alternative for patients with limited superior defects, such as of the tonsillar fossa or palate. Patients with more extensive defects, adequate recipient vessels, favorable medical status, and an acceptable prognosis undergo free flap reconstruction. When the mandible is not involved and the surgical defect is primarily mucosal, radial forearm fasciocutaneous free flaps offer good functional outcomes for limited defects, while anterolateral thigh free flaps are used for larger defects because they provide more soft tissue bulk to reconstruct the base of tongue, reducing the risk of long-term aspiration. As mentioned, at MDACC, rectus abdominis free flaps are now less often used in oropharyngeal reconstruction because of increased donor site morbidity including pain limiting deep breathing and clearance of tracheal secretions, risk of abdominal hernia or bulge, and difficult primary closure of large donor site wounds. There is also a greater propensity for the rectus abdominis muscle to undergo atrophy after free tissue transfer, and it is difficult to perform simultaneous resection and flap harvest with two surgical teams because of the closer proximity of the primary and donor sites. But the rectus abdominis free flap remains a reasonable selection for oropharyngeal reconstruction and is used by many centers as a first-line option. Fibula free flaps are considered for tumors involving the mandible with extension to the body or anterior mandibular arch. For patients with defects limited to the posterior mandible, including the condyle, soft tissue reconstruction alone is considered. For patients with complicated soft tissue defects in addition to posterior mandibular defects extending no farther anteriorly than the mid-body, the anterolateral thigh free flap is usually selected, as tongue and pharyngeal reconstruction is simplified, trismus is rare, and dental occlusion is approximately comparable to that with bony reconstruction when the condyle is not preserved. Patients with tumors that involve a significant amount of the mandible (posterior and anterior) and substantial amounts of tongue and pharyngeal mucosa ideally undergo reconstruction with a combination of free flaps, such as a fibula and a radial forearm for smaller tongue defects, or a fibula and an anterolateral thigh for larger defects involving substantial amounts of the oral tongue or base of tongue.
- A few pictoral respresentations of free flaps. To the left is a reconstruction of the tonsillar fossa and lateral pharyngeal wall with a radial forearm fasciocutaneous free flap in a 67-year-old male with recurrent tonsillar cancer, and to the right is a postoperative result 9 months after reconstruction. This is a limited defect, so the radial forearm flap worked well in this example.
- Another example, to the left is a surgical defect in a 60-year-old woman with recurrent tonsillar fossa cancer involving the tonsillar fossa, base of tongue, and posterior mandible. The center is reconstruction of the same defect with an anterolateral thigh free flap. Bony reconstruction was not performed due to the posterior location of the defect and lower extremity peripheral vascular disease precluding harvest of the fibular flap. And finally, to the right is the postoperative result 1 month after reconstruction. So with a more extensive defect, an ALT flap is the better choice, and again bony reconstruction with a double free flap including a fibula would have been a consideration in this case if this lady had not had extensive peripheral vascular disease.
- Quality of life and functional outcomes are closely tied to the ability to perform an adequate reconstruction, and there is evidence that while rerecurrence and survival are important when evaluating the effectiveness of salvage surgery, quality of life may be an even more important concern. Dr. List and others presented a study of principle concerns of head and neck cancer patients at the time of initial diagnosis, finding that survival far outweighed other considerations, including functional concerns such as speech and swallowing. However, it has been suggested that this balance of patient concerns shifts with recurrent disease such that pain and overall quality of life become the most important considerations, with patients perhaps becoming more realistic about chances of long-term survival, especially with recurrent oropharyngeal SCC, which has a poorer prognosis for cure than recurrence at other head and neck cancer sites, such as the oral cavity or larynx.
- It’s important to evaluate functional outcomes in the context of survival as well. Drs. Netscher, Stewart and others here at Baylor studied quality of life and disease-specific functional status following microvascular reconstruction in 34 patients with advanced pharyngeal cancer and found that most patients returned to baseline functional status by 6 months after extensive surgery and surpass pretreatment thresholds by one year. Comparing this data to the median times to recurrence and disease free survivals of 8 and 9 months in studies of surgical salvage for recurrent oropharyngeal SCC, it raises the question whether surgical intervention was beneficial in terms of functional outcomes.
- In the MDACC study, patients were evaluated at last follow-up and prior to any diagnosis of recurrence. Functionally, approximately 80% of patients were able to continue oral speech following surgical salvage, while 20% used either an electrolarynx, TEP, or writing. About one-third of patients were able to tolerate oral feeding without a feeding tube, another one-third remained partially feeding tube dependent, and one-third were completely feeding tube dependent. And of patients who had a tracheostomy, almost 90% were able to be decannulated. But, while these are very reasonable functional outcomes following large surgical resection and reconstruction, they still have to be considered in light of a 67% rerecurrence rate a median of 8 months following surgical salvage, such that most of these patients who rerecurred following surgical salvage were not able to achieve a return to their baseline functional status.
- A final factor to consider in oropharyngeal salvage surgery is cost. While economic factors are not important when considering the individual patient, societal expenditures for expensive interventions with unproven benefit will likely become increasingly scrutinized with rising costs of healthcare and limited private and government healthcare dollars. In Dr. Goodwin’s study, surgical salvage of recurrent pharyngeal cancer was more costly than surgical salvage of the other head and neck sites, with average hospital and physician charges of $86,000 per patient. Similarly, in the MD Anderson study of recurrent oropharyngeal cancer, average hospital and physician charges during the first 30 days averaged $82,500 per patient.
- So, with such a large percentage of patients developing a second recurrence within 1 year of salvage surgery, it is important for patients and their families to consider all treatment options after primary treatment for recurrent SCCOP has failed. 5-year overall survival rates as high as 20% have been reported for reirradiation in the setting of recurrent head and neck cancer, although up to one-third of patients can experience severe or fatal complications.
- Almost all studies in the literature include multiple head and neck sites, including two recent Radiation Therapy Oncology Group trials that included 40-50% recurrent oropharyngeal cancer patients. The first was RTOG 9610, which was the first prospective multiinstitutional trail testing reirradiation plus chemotherapy consisting of 5FU and hydroxyurea for recurrent squamous cell carcinoma of the head and neck. There were 79 patients in this study with 2-year survival of only 15% and 5-year survival of 4%. In addtion, 25% of patients experienced at least grade 4 acute toxicity, and there was also 8% treatment-related death.
- The second large RTOG study was 9911, which was another phase II prospective, multiinstitutional study which accrued 105 patients who underwent reirradiation combined with cisplatin and paclitaxel. Median survival was one year, only a quarter of patients were alive at 2 years, treatment toxicity occurred in a quarter of patients, and over 10% had fatal treatment-related complications.
- Although chemotherapy alone can provide palliation in patients with recurrent SCCOP, it is not a curative option. Approximately a third of patients with recurrent squamous cell carcinoma of the oropharynx have a partial response to platinum-based chemotherapy regimens, a median survival that ranges from 4 months to 6 months, and a 2-year overall survival rate that ranges from 5% to 10%.
- For patients who forego any treatment for recurrent SCCOP, the median survival can be estimated at 3-4 months. In a study of almost 200 patients with advanced or recurrent oropharyngeal cancer in Brazil who were given supportive care but no oncologic treatment secondary to advanced tumor stage, poor performance status, or patient refusal of treatment, median survival was 4 months, and only 2% of patients were alive at one year. In another study, Dr. Stell examined a case series of over 4,000 untreated head and neck cancer patients in Liverpool over a 25-year time period and found a median survival of a little over 3 months. In both studies, performance status was the best indicator of survival time.
- Looking to the future, perhaps moreso than clinical factors, biological markers will likely help us determine which patients are the best candidates for salvage surgery and which patients would be better suited to reirradiation and/or chemotherapy or supportive care. Dr. Agra and others in Sau Paulo, Brazil studied over 100 patients with oropharyngeal and oral cavity squamous cell carcinoma, examining both clinical factors and biological markers in association with disease-free survival after salvage surgery. What they found is that patients who had a disease-free interval of greater than one year and tumors that were endothelial growth factor receptor negative had an 80% 3-year disease-free survival, while patients who both had a disease-free interval of less than one year and EGFR positive tumors had a 3-year disease-free survival of only 20%.
- They also found that advanced stage recurrent tumors had a poorer prognosis, so they came up with an algorithm using all three of these factors. If patients have a disease-free interval of greater than one year, then they recommend surgery. If they have a disease-free interval of less than one year but small recurrent tumors, surgery is also recommended. If they have a disease-free interval of less than one year, a large recurrent tumor, but had an EGFR negative tumor, they still recommend surgery. But, if they have do not have a significant disease-free interval and have a large recurrent tumor which is also EGFR positive, then they recommend consideration for alternative treatment. So this is an example of a treatment algorithm that could potentially be used in the future, combining both clinical and biological markers to select the best patients for salvage surgery.
- Expectedly, 5-year survival of those patients who were not candidates for surgical salvage and had either radiation, palliative chemotherapy, or supprotive care approached zero.
- For entire cohort of 400 patients
- Selection bias in terms of patient selection and in terms of tumor selection in terms of more aggressive tumor bio
- Many of those with late stage disease did not receive radiation because they had been previously radiated.