The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Systematic Review
A Systematic Review of Transoral Robotic Surgery and Radiotherapy for Early Oropharynx Cancer: A Systematic Review John R. de Almeida, MD, MSc; James K. Byrd, MD; Rebecca Wu, BSc; Chaz L. Stucken, MD; Uma Duvvuri, MD, PhD; David P. Goldstein, MD, MSc; Brett A. Miles, MD, DDS; Marita S. Teng, MD; Vishal Gupta, MD; Eric M. Genden, MD Objectives/Hypothesis: To demonstrate the comparative effectiveness of transoral robotic surgery (TORS) to intensity modulated radiotherapy (IMRT) for early T-stage oropharyngeal cancer. Data Sources: The search included MEDLINE, EMBASE, CENTRAL, PsychInfo, CINAHL, and bibliographies of relevant studies through September 2012. Methods: Studies included patients treated for early T-stage oropharynx cancer with TORS or IMRT. Study retrieval and data extraction were conducted in duplicate and resolved by consensus. Treatment- specific details, as well as recurrence, survival, and adverse events, were collected. Methodologic quality for each study was appraised. Results: Twenty case series, including eight IMRT studies (1,287 patients) and 12 TORS studies (772 patients), were included. Patients receiving definitive IMRT also received chemotherapy (43%) or neck dissections for persistent disease (30%), whereas patients receiving TORS required adjuvant radiotherapy (26%) or chemoradiotherapy (41%). Two-year overall survival estimates ranged from 84% to 96% for IMRT and from 82% to 94% for TORS. Adverse events for IMRT included esophageal stenosis (4.8%), osteoradionecrosis (2.6%), and gastrostomy tubes (43%)—and adverse events for TORS included hemorrhage (2.4%), fistula (2.5%), and gastrostomy tubes at the time of surgery (1.4%) or during adjuvant treatment (30%). Tracheostomy tubes were needed in 12% of patients at the time of surgery, but most were decannulated prior to discharge. Conclusion: This review suggests that survival estimates are similar between the two modalities and that the differences lie in adverse events. Key Words: TORS; IMRT; oropharynx cancer; survival; adverse events; outcomes. Laryngoscope, 124:2096–2102, 2014
INTRODUCTION Since the introduction of transoral robotic surgery (TORS) as a treatment paradigm for early T-stage oropharyngeal carcinoma, concerns have surrounded this technology and its comparative effectiveness to existing treatment. Although its feasibility has been established,1–3 ongoing studies are aimed at examining the perioperative outcomes, complications, and functional and oncologic outcomes.4,5
Additional Supporting Information may be found in the online version of this article. Department of Otolaryngology–Head Neck Surgery, University of Toronto (J.R.DA., D.P.G.), Toronto, Ontario, Canadathe Department of Otolaryngology, University of Pittsburgh (J.K.B., U.D.), Pittsburgh, Pennsylvania the Department of Otolaryngology (R.W., C.L.S., B.A.M., M.S.T., E.M.G.); and the Department of Radiation Oncology (V.G.), Icahn School of Medicine at Mount Sinai, New York, New York, U.S.A. Editor’s Note: This Manuscript was accepted for publication April 4, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to John R. de Almeida, MD, MSc, Princess Margaret Hospital–University Health Network, 610 University Avenue, 3-955, Toronto, ON, Canada, M5G 2C4. E-mail: [email protected] DOI: 10.1002/lary.24712
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Newer techniques in nonsurgical treatment of oropharyngeal carcinoma such as intensity modulated radiotherapy (IMRT) have improved on traditional threedimensional conformal radiotherapy by limiting the toxicity burden while also affording similar disease control.6,7 Among other advantages, the reduction in dosage to the critical swallowing structures and salivary glands may result in improved swallowing and quality of life.6,7 The addition of chemotherapy to IMRT techniques has been shown to improve overall survival but likely has an increased toxicity burden associated with it.8 To date, there have been no comparative trials to evaluate the outcomes of these modalities, although randomized trials such as the ORATOR trial are now open, and future studies spearheaded by the Radiation Therapy Oncology Group (RTOG) and the Eastern Cooperative Oncology Group (ECOG) comparing TORS to chemoradiotherapy are on the horizon.9,10 One nonrandomized prospective study suggested that TORS may offer some shortterm benefit with eating ability and diet—and a higher likelihood of returning to baseline diet when compared to chemoradiotherapy.11 However, one challenge in the interpretation of the literature is the heterogeneity of patients reported. Herein, we summarize the available knowledge
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survival. Adverse outcomes for IMRT included osteoradionecrosis, esophageal stenosis, febrile neutropenia, tracheostomy, and gastrostomy tube rates. Adverse outcomes for TORS included primary site hemorrhage, neck hematoma, pharyngocutaneous fistulae, tracheostomy or gastrostomy tube rates, and readmission for dehydration. Methodologic quality was assessed using an 18-item validated quality appraisal tool for case series.12 Quality appraisal judgments for each item were binary determinations of various facets of the study, including study objectives, population, interventions and cointerventions, outcome measures, statistical analysis, results and conclusions, and competing interests.
RESULTS Studies
Fig. 1. Study inclusion flow diagram.
base for the treatment of early T-stage oropharyngeal cancer with TORS and IMRT. We have chosen to limit the surgical side of this discussion to TORS only—and not to other transoral techniques such as transoral laser microsurgery.
MATERIALS AND METHODS We searched MEDLINE (from 1946), EMBASE (from 1947), CENTRAL (start date not specified), CINAHL (start date not specified), and PsychInfo (from 1806) through September 2012 for relevant studies. Our search included screening bibliographies of relevant studies and querying experts for unpublished literature. Medical subject headings and key words for treatment modality (TORS and IMRT), histopathology (squamous cell carcinoma), tumor location (oropharynx, tonsil, tongue base, soft palate, pharyngeal wall), and outcomes (survival, recurrence) were used to identify studies. Two reviewers (J.R.D., J.K.B.) screened all studies for eligibility. Studies initially were screened using subject title or abstract for further full-text retrieval. Study eligibility was reviewed in duplicate, and disagreements were resolved by consensus (Fig. 1). Studies were included if they contained patients diagnosed with predominantly early T-stage (T1 and T2) oropharyngeal squamous cell carcinoma treated with either TORS or IMRT. Due to the scarcity of studies restricted to T1 and T2 tumors, studies were included if they contained at least 75% of patients with these stage tumors or if they contained subgroup data pertaining to patients with T1 and T2 tumors. Studies were excluded if they involved nonoropharyngeal head and neck cancers. Data was extracted in duplicate (J.R.D., J.K.B.) and inconsistencies were resolved by consensus. For each included study, we recorded the number of patients and the treatment strategy, including additional neoadjuvant, concurrent, or adjuvant therapies. The primary outcome of interest was 2-year actuarial overall survival. Additional outcomes included 2-year actuarial local recurrence, regional recurrence, locoregional recurrence, distant recurrence, disease-free survival, and disease-specific
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The initial search yielded 569 studies (Fig. 1), of which 20 studies were included. Eight studies13–20 with 1,337 patients (1,010 patients with T1 or T2 tumors) investigated the role of IMRT. Twelve studies including 772 patients (502 patients with T1 or T2 tumors; 185 patients did not have stage indicated) investigated TORS.21–32 Of the IMRT studies, seven were single-institution studies13,15–20 and one study was a multi-institution study.14 One institution (MD Anderson Cancer Center) contributed to three studies,14,16,17 and another institution (University of Wisconsin) contributed to two studies.14,18 Five studies reported the use of either standard fractionation or concomitant boost schemes.13,16–19 One study used standard fractionation only20; one study reported the use of accelerated hypofractionation14; and one study did not report fractionation schemes.15 Five studies contained information relating to chemotherapy for early T-stage tumors.14–18 For early T-stage tumors, 350 of 794 patients (44%) received chemotherapy in addition to IMRT, likely due to advanced nodal disease. Three studies reported that 57 patients of 152 patients (38%) received neck dissections for possible residual disease following treatment.15,16,18 Nodal classification was generally not advanced in most of the studies. Among the TORS studies, the incidence of N2c or N3 metastases was always less than 16%25—and among the IMRT studies, it was less than 17%.17 The details of treatment can be found in Appendices 1 and 2 (Appendices can be viewed in the online issue, which is available at wileyonlinelibrary.com.). Twelve studies reported outcomes for early T-stage oropharyngeal cancers treated primarily with TORS.21–32 Eleven studies were single-institution studies,21,23–32 and one was a multi-institution study.22 One institution (Pennsylvania) contributed to six of the studies21,27,29–32; two institutions (University of Alabama–Birmingham; Mayo Clinic) contributed to three studies each22,23,25,26,28; and one institution (Mount Sinai) contributed to two studies.22,24 All patients were treated with transoral robotic resection of an oropharyngeal primary cancer. Of 687 patients whose neck dissection status was reported, 654 patients (95%) received a neck dissection, of which 396 (61%) were concurrent and 258 (39%) were staged neck dissections. Four studies reported that unilateral neck dissections were performed in 88% (246/279) of patients and bilateral neck dissections were performed in 12% of patients.22,24,25,30 Adjuvant radiotherapy was given to
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26% (154/590) of patients, and adjuvant chemoradiotherapy was given to 41% of patients (244/590).21,22,24,25,27–32
Quality Appraisal Appraisal of all IMRT studies can be found in Appendix 3 (Appendix can be viewed in the online issue, which is available at wileyonlinelibrary.com.) and of all TORS studies in Appendix 4 (Appendix can be viewed in the online issue, which is available at wileyonlinelibrary. com.). All studies met at least 15 of the 18 criteria deemed important for the quality of case series.
Recurrence and Survival Outcomes Six studies included either recurrence or survival outcomes for early T-stage oropharynx cancer treated with IMRT (Table I).14–16,18–20 Only one study reported 2-year local control (96%), regional control (97%), and distant control (87%).16 Three studies reported 2-year locoregional control (91%–96%).14,15,18 One study reported a 2-year disease-specific survival of 97.7%.18 Three studies reported 2-year disease-free survival ranging from 82% to 90%.14–16 Four studies reported a 2-year overall survival ranging from 84% to 95.5%.14–16,18 Six studies included either recurrence or survival outcomes for early T-stage oropharynx cancer treated with TORS (Table I).21,22,25,27,31,32 Four studies reported local, regional, and distant control.22,25,31,32 Only one study reported 2-year actuarial local control (95%), regional control (95%), locoregional control (94%), and distant control (97%).22 Four studies reported 2 year disease specific survival which ranged from 90– 98%.21,22,25,31 One study reported 2-year disease-free survival (79%).31 Two studies reported 2-year overall survival ranging from 82% to 94%.22,31
DISCUSSION
Adverse Events Five IMRT studies reported adverse event outcomes (Table II).13–16,18 Three studies described a cumulative proportion of 2.6% (4/151) for osteoradionecrosis of the mandible.13,14,16 Esophageal stenosis was reported in two studies with a rate of 4.8% (4/84). Gastrostomy tubes were inserted into 43% of the patients in three studies reporting this outcome.15,16,18 All of the studies reported gastrostomy tube placement during treatment only when needed versus prophylactically. No studies reported the need for tracheostomies in their cohorts. One study reported a hospital readmission rate of 17% (9/52).18 Nine studies reported adverse events or complications related to TORS (Table III).23–26,28–32 Seven studies reported postoperative bleeding in 2.4% (6/247) of patients and neck hematomas in 0.4% (1/247) of patients.23–25,29–32 Eight studies reported a cumulative pharyngocutaneous fistula rate of 2.5% (10/395).23–26, 29–32 Reporting of gastrostomy tube insertions was variable among seven studies.23–25,28–30,32 One study reported prophylactic insertion for all patients with gastrostomy tubes (a practice that subsequently has changed at that particular institution).29 Two subsequent studies from the same institution reported 2% and 0% patients being gastrostomy tube dependent at 1 year.30,32 Three studies from three other institutions reported a cumulative gastrostomy tube rate of 1.4% (2/139) at the time of surgery, and 30% (32/107) placed expectantly at the time of adjuvant therapy.24,25,28 Tracheostomies were inserted at the time or around the time of surgery in 12% (31/258) of patients treated with TORS.23–25,28–30,32 One study reported hospital readmission due to dehydration in one patient (3%).32 Laryngoscope 124: September 2014
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The implementation of new surgical technology requires rigorous study of the comparative effectiveness with the existing treatment modalities. Although several randomized trials are commencing patient accrual, to date9,10 there have been no prospective studies measuring the comparative effectiveness of TORS with IMRT (or other therapies) for the treatment of early T-stage oropharyngeal cancer. In the present study, we systematically reviewed the literature for case series that reported outcomes pertaining to survival and adverse events. Because of the heterogeneity of existing studies and the lack of comparator arms, meta-analysis could not be performed. However, pooled analysis was performed for certain outcomes where possible. Several interesting findings can be gleaned from the included studies: Treatment trends in patients with early T-stage oropharynx cancer demonstrate a need for multimodal therapy in both IMRT and TORS studies. Several authors have suggested the possibility of single-modality treatment—particularly for early T-stage tumors without other poor prognostic features such as advanced nodal disease.8,33 In IMRT studies, however, as many as 43% require the addition of chemotherapy. Although advanced nodal disease (N2c–N3) was rare in either group, 38% of patients required neck dissections for residual neck disease following treatment. In TORS studies, as many as 67% of patients are receiving adjuvant therapy, most of who received adjuvant chemoradiotherapy. This administration of three modalities of treatment for early tumor stage may suggest a need for improved patient selection to minimize toxicities and costs of treatment without compromising oncologic control. Nevertheless, preferences of the general public may depend on the perceived benefits of treatment—and in some instances individuals may prefer multimodal treatment to fewer modalities.34 The present study suggests that there is no survival advantage of surgery over radiation. Both modalities confer excellent survival and locoregional control. The lack of individual patient level data, however, precludes a summary estimate comparing the two treatment modalities. The excellent survival likely represents an improvement in treatment techniques over time in the case of radiotherapy, improved imaging techniques that help to more accurately stage patients, as well as a rising incidence of prognostically favorable HPV-positive tumors.35 What also is not readily apparent from the present study is how the early T-stage HPV-positive and HPV-negative subgroups perform and whether there are subgroup differences between IMRT-treated and TORS-treated populations. Only one of the included studies had relevant subgroup
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24 (3–53)
MD Anderson Cancer Center Hodge et al.18
12.7 years
2010 Weinstein et al.32
18 months (97); crude numbers not actuarial
3 years (97) Exact numbers not given (survival curves only) 18 months (98); crude numbers not actuarial
95
NS
NS
T1: 5 years (93) T2: 5 years (1)
NS
96
NS
NS
2-Year Local Control (%)
18 months (90); crude numbers not actuarial
18 months (96); crude numbers not actuarial)
3 years (94)
95
NS
NS
NS
NS
97
NS
NS
2-Year Regional Control (%)
NS
NS
NS
94
NS
T2: 3 years (79)
T1: 3 years (97)
NS
96.1
NS
92
91
2-Year Locoregional Control (%)
18 months (100); crude numbers not actuarial)
18 months (91); crude numbers not actuarial
3 years (98.4)
97
NS
T2: 3 years (85)
T1: 3 years (97)
NS
NS
87
NS
NS
2-Year Distant Control (%)
CI 5 confidence interval; F/U 5 follow-up; IMRT 5 intensity modulated radiotherapy; NS 5 not stated; TORS 5 transoral robotic surgery.
University of Pennsylvania, 2012
Mean F/U 26 (18–44)
University of Pennsylvania,
(2.5–63.3)
University of Pennsylvania
Weinstein et al.31
36 (24–45) 38.8
24
23
36
Moore et al.25 Mayo Clinic Quon et al.27
Mount Sinai School of Medicine, University of Alabama Birmingham, Mayo Clinic, University of Pittsburgh Medical Center, Albert Einstein University, MD Anderson Cancer Center
de Almeida et al.22
University of Pennsylvania
Cohen et al.21
Dana Farber Cancer Institute Transoral Robotic Surgery (TORS) Studies
Scher et al.20
Mendenhall et al.19 University of Florida 42 (2–92)
45 (15–63)
Garden et al.16
University of Wisconsin
27 (1–77)
34 (17–58)
Galloway et al.15 Fox Chase Cancer Center
University of Michigan, MD Anderson Cancer Center, University of Wisconsin, University of Texas Medical Branch at Galveston
Eisbruch et al.14
Intensity Modulated Radiotherapy (IMRT) Studies
Author/ Institution
Median Follow-up in Months (range)
TABLE I. Control Rates and Survival Outcomes for IMRT and TORS Studies.
NS
90
3 years (95.1)
98
92.6; crude numbers not actuarial
NS
NS
97.7
NS
NS
NS
2-Year Disease Specific Survival (%)
NS
79
3 years (92.4)
NS
NS
T2: 3 years (74)
T1: 3 years (85)
NS
NS
88
90
82
2-Year Disease-Free Survival (%)
NS
82
NS
94
80.6; crude numbers not actuarial
T2: 3 years (86)
T1: 3 years (89)
NS
94.5
93
84
95.5
2-Year Overall Survival (95% CI)
TABLE II. Adverse Events for IMRT Studies. Author/ Institution
N
Osteoradione crosis (%)
Esophageal Stenosis (%)
Febrile Neutropenia (%)
De Arruda et al.13
33
0 (0)
1 (3)
NS
Memorial Sloan Kettering Cancer Center 67
3 (4)
NS
NS
Galloway et al.15
48
NS
NS
NS
Hospital Readmission (%)
NS
NS
NS
NS
NS
NS
20 (42)
NS
NS
NS
NS
NS
9 (17)
4% at 1 year 51
1 (2)
3(6)
NS
MD Anderson Cancer Center Hodge et al.18 University of Wisconsin
TracheostomyTube (%)
84% for all T class
Eisbruch et al.14 University of Michigan, MD Anderson Cancer Center, University of Wisconsin, University of Texas Medical Branch at Galveston Fox Chase Cancer Center Garden et al.16
Gastrostomy Tube (%)
21 (41) 0 % at 1 year
52
NS
NS
NS
24 (46)
IMRT 5 intensity modulated radiotherapy; NS 5 not stated.
data comparing the survival of HPV-positive and HPVnegative populations, and these subgroups were too small to make meaningful conclusions.21 It has been suggested that the surgical management of oropharyngeal neoplasms has different poor prognostic factors compared to nonsurgical treatment.36 Future case series must better elucidate these subgroup differences. Where TORS may be most beneficial, is in the obviation of adjuvant treatment and, thus, the avoidance of its toxicities. Our present study suggests a lower rate of gastrostomy tubes in patients who have adjuvant treatment compared to those treated definitively and a markedly lower rate of gastrostomy tubes in patients having surgery alone. These findings may translate to an improvement in quality of life11 and perhaps a cost savings. However, with surgery comes an added burden of complications that remain difficult to weigh against the burden of toxicity created by radiotherapy. Only comparative studies weighing cost, quality of life, and comparative effectiveness can address these concerns. Perhaps the biggest challenge in interpreting the present findings is due to the retrospective, heterogeneous, and noncomparative nature of the included studies. These limited the analysis in two ways. First, as mentioned previously, we could not perform a meta-analysis because these were single-arm studies and thus were far too heterogeneous in terms of outcomes and treatments to consider. For survival outcomes, only a meta-analysis that is resource-intensive, individual patient level, and pools all of the included institutional data would have yielded a composite survival estimate. Secondly, the heterogeneity of studies precluded the inclusion of patientLaryngoscope 124: September 2014
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reported subjective outcomes. The majority of these outcomes are based on different questionnaires, making the pooling of results challenging. Consequently, we decided to choose mainly binary outcomes for analysis. Despite the inherent low level of evidence of included studies, all included studies met the majority of criteria deemed to be important for case series studies, suggesting that the included studies were of a good quality. Clearly, higher levels of evidence are needed moving forward. With relatively small numbers and early experiences in many of these studies, the absence of the stratification of oncologic outcomes by HPV status makes interpretation difficult. Future comparative studies between IMRT and TORS would require stratification by HPV status in order to be meaningful. Another limitation of the present study is that the majority of the published data is from a select few institutions with expertise. It is uncertain whether some institutions contribute the same patients to multiple studies, which would inevitably bias the results. In this situation, we elected to present all of the data, regardless of how many studies were submitted from a given institution to be more inclusive and to generate more robust estimates. Only an individual patient level analysis would be able to avoid the problem of including the same patients more than once. However, this was beyond the scope of this particular study. Also, the institutions with larger volumes of experience may have more favorable results than the smaller centers and skew the results. In traditional meta-analysis techniques, this can be accounted for using random effects modeling. Lastly, whereas our study attempts to focus on early T-stage tumors, we expanded the definition to include at least 75%
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47
Weinstein et al.30
30
3.6
NS
NS
NS
1 (median)
NS
NS
1.5
2 (7)
0 (0)
0 (0)
1 (4)
NS
NS
1 (1.5)
0 (0)
2 (13)
Hemorrhage from Primary (%)
0 (0)
0 (0)
0 (0)
0 (0)
NS
NS
0 (0)
1 (3)
0 (0)
Neck Hematoma (%)
0 (0)
0 (0)
0 (0)
0 (0)
NS
6 (4)
4 (6)
0 (0)
0 (0)
Pharyngo cutaneous Fistula (%)
*Gastrostomy tube rates and nasogastric tube rates were combined between robotic primary resection and salvage resection rook. NS 5 not stated; PEG 5 percutaneous endoscopic gastrostomy; TORS 5 transoral robotic surgery.
Weinstein et al.32 University of Pennsylvania, 2012
University of Pennsylvania, 2010
2010 Weinstein et al.31 31
27
Weinstein et al.29 University of Pennsylvania, 2007
University of Pennsylvania,
42
148
66
Sinclair et al.28 University Alabama Birmingham
Mayo Clinic, 2011
Moore et al.26
Mayo Clinic, 2012
Moore et al.25
Mount Sinai School of Medicine
Genden et al.24 31
15
Dean et al.23
University of Alabama Birmingham
N
Author/ Institution
Length of Stay (days)
TABLE III. Adverse Events for TORS Studies.
0 (0) at last follow-up
NS
27 (100); all had prophylactic PEG placement; 1 remained PEG dependant at last follow-up 1 (2) at 1 year follow-up
9/32 (28); all during adjuvant therapy; 0 at 1 year
7/20 (35) during adjuvant; 0 were dependent at 6 months 2 (3) after surgery prior to adjuvant; 16/55 (29) during adjuvant NS
Unclear*
Gastrostomy Tube (%)
1 (3)
NS
3 (6) planned tracheostomy
2 (27)
0 (0)
NS
17 (26); all except 1 decannulated before adjuvant
7 (23)
1 (7); decannulated prior to discharge; 0 at 6 months
Tracheostomy Tube (%)
1 (3)
NS
NS
NS
NS
NS
NS
NS
NS
Hospital Readmission (%)
of T1 or T2 tumors to yield a more sensitive search. Differences in tumor stage between the TORS and IMRT groups can account for differences in the results.
CONCLUSION This is the first systematic attempt to compare the effectiveness between the emerging surgical technology—TORS—with IMRT for early T-stage oropharynx cancer. The results suggest that, in many cases, multimodal treatment is employed for both primary treatment modalities. Survival seems comparable, and differences between the two treatments are likely based on the specifics of their toxicity and complication profiles. Further comparative studies are needed to better elucidate these differences.
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15. Galloway TJ, Turaka A, Ruth K, et al. Low rates of gastrostomy tube dependence in patients with T1–T2 Oropharynx Cancer treated without pharyngeal constrictor sparing. Int J Radiat Oncol Biol Physics 2011;81: (suppl):2614. 16. Garden AS, Morrison WH, Wong PF, et al. Disease-control rates following intensity-modulated radiation therapy for small primary oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2007;67:438–444. 17. Garden AS, Dong L, Morrison WH, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys 2013;85:941–947. 18. Hodge CW, Bentzen SM, Wong G, et al. Are we influencing outcome in oropharynx cancer with intensity modulated radiotherapy? An inter-era comparison. Int J Radiation Oncol Biol Physc 2007;69:1032–1041. 19. Mendenhall WM, Amdur RJ, Morris CG, Kirwan JM, Li JG. Intensitymodulated radiotherapy for oropharyngeal squamous cell carcinoma. Laryngoscope 2010;120:2218–2222. 20. Sher DJ, Thotakura V, Balboni TA, et al. Treatment of oropharyngeal squamous cell carcinoma with IMRT: patterns of failure after concurrent chemoradiotherapy and sequential therapy. Ann Oncol 2012;23:2391– 2398. doi: 10.1093/annonc/mdr609. Epub 2012. 21. Cohen MA, Weinstein GS, O’Malley BW, et al. Transoral robotic surgery and human papillomavirus status: oncologic results. Head Neck 2011;33: 573–580. 22. de Almeida JR, Holsinger FC, Duvvuri U, et al. Oncologic outcomes following transoral robotic surgery (TORS) for Oropharyngeal cancer: a multiinstitutional study. Presented at 8th International Conference for Head and Neck Cancer Meeting; Toronto, Canada, July 22, 2012. 23. Dean NR, Rosenthal EL, Carroll WR, et al. Robotic-assisted surgery for primary or recurrent oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 2010;136:380–384. 24. Genden EM, Park R, Smith C, Kotz T. The role of reconstruction for transoral robotic pharyngectomy and concomitant neck dissection. Arch Otolaryngol Head Neck Surg 2011;137:151–156. 25. Moore EJ, Olsen SM, Laborde RR, et al. Long-term functional and oncologic results of transoral robotic surgery for oropharyngeal squamous cell carcinoma. Mayo Clinic Proc 2012;87:219–225. 26. Moore EJ, Olsen KD, Martin EJ. Concurrent neck dissection and transoral robotic surgery. Laryngoscope 2011;121:541–544. 27. Quon H, Cohen MA, Montone KT, et al. Transoral robotic surgery and adjuvant therapy for oropharyngeal carcinomas and the influence of p16 INK4a on treatment outcomes. Laryngoscope 2013;123:635–640. 28. Sinclair CF, McColloch NL, Carroll WR, Rosenthal EL, Desmond RA, Magnuson JS. Patient-perceived and objective functional outcomes following transoral robotic surgery for early oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 2011;137:1112–1116. 29. Weinstein GS, O’Malley BW Jr, Snyder W, Sherman E, Quon H. Transoral robotic surgery: radical tonsillectomy. Arch Otolaryngol Head Neck Surg 2007;133:1220–1226. 30. Weinstein GS, Quon H, O’Malley BW Jr, Kim GG, Cohen MA. Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: a subset analysis of the University of Pennsylvania transoral robotic surgery trial. Laryngoscope 2010;120: 1749–1755. 31. Weinstein GS, O’Malley BW Jr, Cohen MA, Quon H. Transoral robotic surgery for advanced oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 2010;136:1079–1085. 32. Weinstein GS, Quon H, Newman HJ, et al. Transoral robotic surgery alone for oropharyngeal cancer: an analysis of local control. Arch Otolaryngol Head Neck Surg 2012;138:628–634. 33. O’Sullivan B, Warde P, Grice B, et al. The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 2001;51:332–343. 34. de Almeida JR, Villanueva NL, Moskowitz AJ, et al. Preferences and utilities for health states following treatment for oropharyngeal cancer: transoral robotic surgery versus definitive (chemo)radiotherapy. Head Neck 2013. doi: 10.1002/hed.23340. Epub ahead of print. 35. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29:4294–4301. 36. Haughey BH, Sinha P. Prognostic factors and survival unique to surgically treated p161 oropharyngeal cancer. Laryngoscope 2012;122(suppl 2): S13–33.
de Almeida et al.: Systematic Review of TORS and Radiotherapy
Rhinological and Otological Society, Inc.
Systematic Review
A Systematic Review of Transoral Robotic Surgery and Radiotherapy for Early Oropharynx Cancer: A Systematic Review John R. de Almeida, MD, MSc; James K. Byrd, MD; Rebecca Wu, BSc; Chaz L. Stucken, MD; Uma Duvvuri, MD, PhD; David P. Goldstein, MD, MSc; Brett A. Miles, MD, DDS; Marita S. Teng, MD; Vishal Gupta, MD; Eric M. Genden, MD Objectives/Hypothesis: To demonstrate the comparative effectiveness of transoral robotic surgery (TORS) to intensity modulated radiotherapy (IMRT) for early T-stage oropharyngeal cancer. Data Sources: The search included MEDLINE, EMBASE, CENTRAL, PsychInfo, CINAHL, and bibliographies of relevant studies through September 2012. Methods: Studies included patients treated for early T-stage oropharynx cancer with TORS or IMRT. Study retrieval and data extraction were conducted in duplicate and resolved by consensus. Treatment- specific details, as well as recurrence, survival, and adverse events, were collected. Methodologic quality for each study was appraised. Results: Twenty case series, including eight IMRT studies (1,287 patients) and 12 TORS studies (772 patients), were included. Patients receiving definitive IMRT also received chemotherapy (43%) or neck dissections for persistent disease (30%), whereas patients receiving TORS required adjuvant radiotherapy (26%) or chemoradiotherapy (41%). Two-year overall survival estimates ranged from 84% to 96% for IMRT and from 82% to 94% for TORS. Adverse events for IMRT included esophageal stenosis (4.8%), osteoradionecrosis (2.6%), and gastrostomy tubes (43%)—and adverse events for TORS included hemorrhage (2.4%), fistula (2.5%), and gastrostomy tubes at the time of surgery (1.4%) or during adjuvant treatment (30%). Tracheostomy tubes were needed in 12% of patients at the time of surgery, but most were decannulated prior to discharge. Conclusion: This review suggests that survival estimates are similar between the two modalities and that the differences lie in adverse events. Key Words: TORS; IMRT; oropharynx cancer; survival; adverse events; outcomes. Laryngoscope, 124:2096–2102, 2014
INTRODUCTION Since the introduction of transoral robotic surgery (TORS) as a treatment paradigm for early T-stage oropharyngeal carcinoma, concerns have surrounded this technology and its comparative effectiveness to existing treatment. Although its feasibility has been established,1–3 ongoing studies are aimed at examining the perioperative outcomes, complications, and functional and oncologic outcomes.4,5
Additional Supporting Information may be found in the online version of this article. Department of Otolaryngology–Head Neck Surgery, University of Toronto (J.R.DA., D.P.G.), Toronto, Ontario, Canadathe Department of Otolaryngology, University of Pittsburgh (J.K.B., U.D.), Pittsburgh, Pennsylvania the Department of Otolaryngology (R.W., C.L.S., B.A.M., M.S.T., E.M.G.); and the Department of Radiation Oncology (V.G.), Icahn School of Medicine at Mount Sinai, New York, New York, U.S.A. Editor’s Note: This Manuscript was accepted for publication April 4, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to John R. de Almeida, MD, MSc, Princess Margaret Hospital–University Health Network, 610 University Avenue, 3-955, Toronto, ON, Canada, M5G 2C4. E-mail: [email protected] DOI: 10.1002/lary.24712
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Newer techniques in nonsurgical treatment of oropharyngeal carcinoma such as intensity modulated radiotherapy (IMRT) have improved on traditional threedimensional conformal radiotherapy by limiting the toxicity burden while also affording similar disease control.6,7 Among other advantages, the reduction in dosage to the critical swallowing structures and salivary glands may result in improved swallowing and quality of life.6,7 The addition of chemotherapy to IMRT techniques has been shown to improve overall survival but likely has an increased toxicity burden associated with it.8 To date, there have been no comparative trials to evaluate the outcomes of these modalities, although randomized trials such as the ORATOR trial are now open, and future studies spearheaded by the Radiation Therapy Oncology Group (RTOG) and the Eastern Cooperative Oncology Group (ECOG) comparing TORS to chemoradiotherapy are on the horizon.9,10 One nonrandomized prospective study suggested that TORS may offer some shortterm benefit with eating ability and diet—and a higher likelihood of returning to baseline diet when compared to chemoradiotherapy.11 However, one challenge in the interpretation of the literature is the heterogeneity of patients reported. Herein, we summarize the available knowledge
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survival. Adverse outcomes for IMRT included osteoradionecrosis, esophageal stenosis, febrile neutropenia, tracheostomy, and gastrostomy tube rates. Adverse outcomes for TORS included primary site hemorrhage, neck hematoma, pharyngocutaneous fistulae, tracheostomy or gastrostomy tube rates, and readmission for dehydration. Methodologic quality was assessed using an 18-item validated quality appraisal tool for case series.12 Quality appraisal judgments for each item were binary determinations of various facets of the study, including study objectives, population, interventions and cointerventions, outcome measures, statistical analysis, results and conclusions, and competing interests.
RESULTS Studies
Fig. 1. Study inclusion flow diagram.
base for the treatment of early T-stage oropharyngeal cancer with TORS and IMRT. We have chosen to limit the surgical side of this discussion to TORS only—and not to other transoral techniques such as transoral laser microsurgery.
MATERIALS AND METHODS We searched MEDLINE (from 1946), EMBASE (from 1947), CENTRAL (start date not specified), CINAHL (start date not specified), and PsychInfo (from 1806) through September 2012 for relevant studies. Our search included screening bibliographies of relevant studies and querying experts for unpublished literature. Medical subject headings and key words for treatment modality (TORS and IMRT), histopathology (squamous cell carcinoma), tumor location (oropharynx, tonsil, tongue base, soft palate, pharyngeal wall), and outcomes (survival, recurrence) were used to identify studies. Two reviewers (J.R.D., J.K.B.) screened all studies for eligibility. Studies initially were screened using subject title or abstract for further full-text retrieval. Study eligibility was reviewed in duplicate, and disagreements were resolved by consensus (Fig. 1). Studies were included if they contained patients diagnosed with predominantly early T-stage (T1 and T2) oropharyngeal squamous cell carcinoma treated with either TORS or IMRT. Due to the scarcity of studies restricted to T1 and T2 tumors, studies were included if they contained at least 75% of patients with these stage tumors or if they contained subgroup data pertaining to patients with T1 and T2 tumors. Studies were excluded if they involved nonoropharyngeal head and neck cancers. Data was extracted in duplicate (J.R.D., J.K.B.) and inconsistencies were resolved by consensus. For each included study, we recorded the number of patients and the treatment strategy, including additional neoadjuvant, concurrent, or adjuvant therapies. The primary outcome of interest was 2-year actuarial overall survival. Additional outcomes included 2-year actuarial local recurrence, regional recurrence, locoregional recurrence, distant recurrence, disease-free survival, and disease-specific
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The initial search yielded 569 studies (Fig. 1), of which 20 studies were included. Eight studies13–20 with 1,337 patients (1,010 patients with T1 or T2 tumors) investigated the role of IMRT. Twelve studies including 772 patients (502 patients with T1 or T2 tumors; 185 patients did not have stage indicated) investigated TORS.21–32 Of the IMRT studies, seven were single-institution studies13,15–20 and one study was a multi-institution study.14 One institution (MD Anderson Cancer Center) contributed to three studies,14,16,17 and another institution (University of Wisconsin) contributed to two studies.14,18 Five studies reported the use of either standard fractionation or concomitant boost schemes.13,16–19 One study used standard fractionation only20; one study reported the use of accelerated hypofractionation14; and one study did not report fractionation schemes.15 Five studies contained information relating to chemotherapy for early T-stage tumors.14–18 For early T-stage tumors, 350 of 794 patients (44%) received chemotherapy in addition to IMRT, likely due to advanced nodal disease. Three studies reported that 57 patients of 152 patients (38%) received neck dissections for possible residual disease following treatment.15,16,18 Nodal classification was generally not advanced in most of the studies. Among the TORS studies, the incidence of N2c or N3 metastases was always less than 16%25—and among the IMRT studies, it was less than 17%.17 The details of treatment can be found in Appendices 1 and 2 (Appendices can be viewed in the online issue, which is available at wileyonlinelibrary.com.). Twelve studies reported outcomes for early T-stage oropharyngeal cancers treated primarily with TORS.21–32 Eleven studies were single-institution studies,21,23–32 and one was a multi-institution study.22 One institution (Pennsylvania) contributed to six of the studies21,27,29–32; two institutions (University of Alabama–Birmingham; Mayo Clinic) contributed to three studies each22,23,25,26,28; and one institution (Mount Sinai) contributed to two studies.22,24 All patients were treated with transoral robotic resection of an oropharyngeal primary cancer. Of 687 patients whose neck dissection status was reported, 654 patients (95%) received a neck dissection, of which 396 (61%) were concurrent and 258 (39%) were staged neck dissections. Four studies reported that unilateral neck dissections were performed in 88% (246/279) of patients and bilateral neck dissections were performed in 12% of patients.22,24,25,30 Adjuvant radiotherapy was given to
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26% (154/590) of patients, and adjuvant chemoradiotherapy was given to 41% of patients (244/590).21,22,24,25,27–32
Quality Appraisal Appraisal of all IMRT studies can be found in Appendix 3 (Appendix can be viewed in the online issue, which is available at wileyonlinelibrary.com.) and of all TORS studies in Appendix 4 (Appendix can be viewed in the online issue, which is available at wileyonlinelibrary. com.). All studies met at least 15 of the 18 criteria deemed important for the quality of case series.
Recurrence and Survival Outcomes Six studies included either recurrence or survival outcomes for early T-stage oropharynx cancer treated with IMRT (Table I).14–16,18–20 Only one study reported 2-year local control (96%), regional control (97%), and distant control (87%).16 Three studies reported 2-year locoregional control (91%–96%).14,15,18 One study reported a 2-year disease-specific survival of 97.7%.18 Three studies reported 2-year disease-free survival ranging from 82% to 90%.14–16 Four studies reported a 2-year overall survival ranging from 84% to 95.5%.14–16,18 Six studies included either recurrence or survival outcomes for early T-stage oropharynx cancer treated with TORS (Table I).21,22,25,27,31,32 Four studies reported local, regional, and distant control.22,25,31,32 Only one study reported 2-year actuarial local control (95%), regional control (95%), locoregional control (94%), and distant control (97%).22 Four studies reported 2 year disease specific survival which ranged from 90– 98%.21,22,25,31 One study reported 2-year disease-free survival (79%).31 Two studies reported 2-year overall survival ranging from 82% to 94%.22,31
DISCUSSION
Adverse Events Five IMRT studies reported adverse event outcomes (Table II).13–16,18 Three studies described a cumulative proportion of 2.6% (4/151) for osteoradionecrosis of the mandible.13,14,16 Esophageal stenosis was reported in two studies with a rate of 4.8% (4/84). Gastrostomy tubes were inserted into 43% of the patients in three studies reporting this outcome.15,16,18 All of the studies reported gastrostomy tube placement during treatment only when needed versus prophylactically. No studies reported the need for tracheostomies in their cohorts. One study reported a hospital readmission rate of 17% (9/52).18 Nine studies reported adverse events or complications related to TORS (Table III).23–26,28–32 Seven studies reported postoperative bleeding in 2.4% (6/247) of patients and neck hematomas in 0.4% (1/247) of patients.23–25,29–32 Eight studies reported a cumulative pharyngocutaneous fistula rate of 2.5% (10/395).23–26, 29–32 Reporting of gastrostomy tube insertions was variable among seven studies.23–25,28–30,32 One study reported prophylactic insertion for all patients with gastrostomy tubes (a practice that subsequently has changed at that particular institution).29 Two subsequent studies from the same institution reported 2% and 0% patients being gastrostomy tube dependent at 1 year.30,32 Three studies from three other institutions reported a cumulative gastrostomy tube rate of 1.4% (2/139) at the time of surgery, and 30% (32/107) placed expectantly at the time of adjuvant therapy.24,25,28 Tracheostomies were inserted at the time or around the time of surgery in 12% (31/258) of patients treated with TORS.23–25,28–30,32 One study reported hospital readmission due to dehydration in one patient (3%).32 Laryngoscope 124: September 2014
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The implementation of new surgical technology requires rigorous study of the comparative effectiveness with the existing treatment modalities. Although several randomized trials are commencing patient accrual, to date9,10 there have been no prospective studies measuring the comparative effectiveness of TORS with IMRT (or other therapies) for the treatment of early T-stage oropharyngeal cancer. In the present study, we systematically reviewed the literature for case series that reported outcomes pertaining to survival and adverse events. Because of the heterogeneity of existing studies and the lack of comparator arms, meta-analysis could not be performed. However, pooled analysis was performed for certain outcomes where possible. Several interesting findings can be gleaned from the included studies: Treatment trends in patients with early T-stage oropharynx cancer demonstrate a need for multimodal therapy in both IMRT and TORS studies. Several authors have suggested the possibility of single-modality treatment—particularly for early T-stage tumors without other poor prognostic features such as advanced nodal disease.8,33 In IMRT studies, however, as many as 43% require the addition of chemotherapy. Although advanced nodal disease (N2c–N3) was rare in either group, 38% of patients required neck dissections for residual neck disease following treatment. In TORS studies, as many as 67% of patients are receiving adjuvant therapy, most of who received adjuvant chemoradiotherapy. This administration of three modalities of treatment for early tumor stage may suggest a need for improved patient selection to minimize toxicities and costs of treatment without compromising oncologic control. Nevertheless, preferences of the general public may depend on the perceived benefits of treatment—and in some instances individuals may prefer multimodal treatment to fewer modalities.34 The present study suggests that there is no survival advantage of surgery over radiation. Both modalities confer excellent survival and locoregional control. The lack of individual patient level data, however, precludes a summary estimate comparing the two treatment modalities. The excellent survival likely represents an improvement in treatment techniques over time in the case of radiotherapy, improved imaging techniques that help to more accurately stage patients, as well as a rising incidence of prognostically favorable HPV-positive tumors.35 What also is not readily apparent from the present study is how the early T-stage HPV-positive and HPV-negative subgroups perform and whether there are subgroup differences between IMRT-treated and TORS-treated populations. Only one of the included studies had relevant subgroup
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24 (3–53)
MD Anderson Cancer Center Hodge et al.18
12.7 years
2010 Weinstein et al.32
18 months (97); crude numbers not actuarial
3 years (97) Exact numbers not given (survival curves only) 18 months (98); crude numbers not actuarial
95
NS
NS
T1: 5 years (93) T2: 5 years (1)
NS
96
NS
NS
2-Year Local Control (%)
18 months (90); crude numbers not actuarial
18 months (96); crude numbers not actuarial)
3 years (94)
95
NS
NS
NS
NS
97
NS
NS
2-Year Regional Control (%)
NS
NS
NS
94
NS
T2: 3 years (79)
T1: 3 years (97)
NS
96.1
NS
92
91
2-Year Locoregional Control (%)
18 months (100); crude numbers not actuarial)
18 months (91); crude numbers not actuarial
3 years (98.4)
97
NS
T2: 3 years (85)
T1: 3 years (97)
NS
NS
87
NS
NS
2-Year Distant Control (%)
CI 5 confidence interval; F/U 5 follow-up; IMRT 5 intensity modulated radiotherapy; NS 5 not stated; TORS 5 transoral robotic surgery.
University of Pennsylvania, 2012
Mean F/U 26 (18–44)
University of Pennsylvania,
(2.5–63.3)
University of Pennsylvania
Weinstein et al.31
36 (24–45) 38.8
24
23
36
Moore et al.25 Mayo Clinic Quon et al.27
Mount Sinai School of Medicine, University of Alabama Birmingham, Mayo Clinic, University of Pittsburgh Medical Center, Albert Einstein University, MD Anderson Cancer Center
de Almeida et al.22
University of Pennsylvania
Cohen et al.21
Dana Farber Cancer Institute Transoral Robotic Surgery (TORS) Studies
Scher et al.20
Mendenhall et al.19 University of Florida 42 (2–92)
45 (15–63)
Garden et al.16
University of Wisconsin
27 (1–77)
34 (17–58)
Galloway et al.15 Fox Chase Cancer Center
University of Michigan, MD Anderson Cancer Center, University of Wisconsin, University of Texas Medical Branch at Galveston
Eisbruch et al.14
Intensity Modulated Radiotherapy (IMRT) Studies
Author/ Institution
Median Follow-up in Months (range)
TABLE I. Control Rates and Survival Outcomes for IMRT and TORS Studies.
NS
90
3 years (95.1)
98
92.6; crude numbers not actuarial
NS
NS
97.7
NS
NS
NS
2-Year Disease Specific Survival (%)
NS
79
3 years (92.4)
NS
NS
T2: 3 years (74)
T1: 3 years (85)
NS
NS
88
90
82
2-Year Disease-Free Survival (%)
NS
82
NS
94
80.6; crude numbers not actuarial
T2: 3 years (86)
T1: 3 years (89)
NS
94.5
93
84
95.5
2-Year Overall Survival (95% CI)
TABLE II. Adverse Events for IMRT Studies. Author/ Institution
N
Osteoradione crosis (%)
Esophageal Stenosis (%)
Febrile Neutropenia (%)
De Arruda et al.13
33
0 (0)
1 (3)
NS
Memorial Sloan Kettering Cancer Center 67
3 (4)
NS
NS
Galloway et al.15
48
NS
NS
NS
Hospital Readmission (%)
NS
NS
NS
NS
NS
NS
20 (42)
NS
NS
NS
NS
NS
9 (17)
4% at 1 year 51
1 (2)
3(6)
NS
MD Anderson Cancer Center Hodge et al.18 University of Wisconsin
TracheostomyTube (%)
84% for all T class
Eisbruch et al.14 University of Michigan, MD Anderson Cancer Center, University of Wisconsin, University of Texas Medical Branch at Galveston Fox Chase Cancer Center Garden et al.16
Gastrostomy Tube (%)
21 (41) 0 % at 1 year
52
NS
NS
NS
24 (46)
IMRT 5 intensity modulated radiotherapy; NS 5 not stated.
data comparing the survival of HPV-positive and HPVnegative populations, and these subgroups were too small to make meaningful conclusions.21 It has been suggested that the surgical management of oropharyngeal neoplasms has different poor prognostic factors compared to nonsurgical treatment.36 Future case series must better elucidate these subgroup differences. Where TORS may be most beneficial, is in the obviation of adjuvant treatment and, thus, the avoidance of its toxicities. Our present study suggests a lower rate of gastrostomy tubes in patients who have adjuvant treatment compared to those treated definitively and a markedly lower rate of gastrostomy tubes in patients having surgery alone. These findings may translate to an improvement in quality of life11 and perhaps a cost savings. However, with surgery comes an added burden of complications that remain difficult to weigh against the burden of toxicity created by radiotherapy. Only comparative studies weighing cost, quality of life, and comparative effectiveness can address these concerns. Perhaps the biggest challenge in interpreting the present findings is due to the retrospective, heterogeneous, and noncomparative nature of the included studies. These limited the analysis in two ways. First, as mentioned previously, we could not perform a meta-analysis because these were single-arm studies and thus were far too heterogeneous in terms of outcomes and treatments to consider. For survival outcomes, only a meta-analysis that is resource-intensive, individual patient level, and pools all of the included institutional data would have yielded a composite survival estimate. Secondly, the heterogeneity of studies precluded the inclusion of patientLaryngoscope 124: September 2014
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reported subjective outcomes. The majority of these outcomes are based on different questionnaires, making the pooling of results challenging. Consequently, we decided to choose mainly binary outcomes for analysis. Despite the inherent low level of evidence of included studies, all included studies met the majority of criteria deemed to be important for case series studies, suggesting that the included studies were of a good quality. Clearly, higher levels of evidence are needed moving forward. With relatively small numbers and early experiences in many of these studies, the absence of the stratification of oncologic outcomes by HPV status makes interpretation difficult. Future comparative studies between IMRT and TORS would require stratification by HPV status in order to be meaningful. Another limitation of the present study is that the majority of the published data is from a select few institutions with expertise. It is uncertain whether some institutions contribute the same patients to multiple studies, which would inevitably bias the results. In this situation, we elected to present all of the data, regardless of how many studies were submitted from a given institution to be more inclusive and to generate more robust estimates. Only an individual patient level analysis would be able to avoid the problem of including the same patients more than once. However, this was beyond the scope of this particular study. Also, the institutions with larger volumes of experience may have more favorable results than the smaller centers and skew the results. In traditional meta-analysis techniques, this can be accounted for using random effects modeling. Lastly, whereas our study attempts to focus on early T-stage tumors, we expanded the definition to include at least 75%
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47
Weinstein et al.30
30
3.6
NS
NS
NS
1 (median)
NS
NS
1.5
2 (7)
0 (0)
0 (0)
1 (4)
NS
NS
1 (1.5)
0 (0)
2 (13)
Hemorrhage from Primary (%)
0 (0)
0 (0)
0 (0)
0 (0)
NS
NS
0 (0)
1 (3)
0 (0)
Neck Hematoma (%)
0 (0)
0 (0)
0 (0)
0 (0)
NS
6 (4)
4 (6)
0 (0)
0 (0)
Pharyngo cutaneous Fistula (%)
*Gastrostomy tube rates and nasogastric tube rates were combined between robotic primary resection and salvage resection rook. NS 5 not stated; PEG 5 percutaneous endoscopic gastrostomy; TORS 5 transoral robotic surgery.
Weinstein et al.32 University of Pennsylvania, 2012
University of Pennsylvania, 2010
2010 Weinstein et al.31 31
27
Weinstein et al.29 University of Pennsylvania, 2007
University of Pennsylvania,
42
148
66
Sinclair et al.28 University Alabama Birmingham
Mayo Clinic, 2011
Moore et al.26
Mayo Clinic, 2012
Moore et al.25
Mount Sinai School of Medicine
Genden et al.24 31
15
Dean et al.23
University of Alabama Birmingham
N
Author/ Institution
Length of Stay (days)
TABLE III. Adverse Events for TORS Studies.
0 (0) at last follow-up
NS
27 (100); all had prophylactic PEG placement; 1 remained PEG dependant at last follow-up 1 (2) at 1 year follow-up
9/32 (28); all during adjuvant therapy; 0 at 1 year
7/20 (35) during adjuvant; 0 were dependent at 6 months 2 (3) after surgery prior to adjuvant; 16/55 (29) during adjuvant NS
Unclear*
Gastrostomy Tube (%)
1 (3)
NS
3 (6) planned tracheostomy
2 (27)
0 (0)
NS
17 (26); all except 1 decannulated before adjuvant
7 (23)
1 (7); decannulated prior to discharge; 0 at 6 months
Tracheostomy Tube (%)
1 (3)
NS
NS
NS
NS
NS
NS
NS
NS
Hospital Readmission (%)
of T1 or T2 tumors to yield a more sensitive search. Differences in tumor stage between the TORS and IMRT groups can account for differences in the results.
CONCLUSION This is the first systematic attempt to compare the effectiveness between the emerging surgical technology—TORS—with IMRT for early T-stage oropharynx cancer. The results suggest that, in many cases, multimodal treatment is employed for both primary treatment modalities. Survival seems comparable, and differences between the two treatments are likely based on the specifics of their toxicity and complication profiles. Further comparative studies are needed to better elucidate these differences.
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