Results of Surgical Treatment of T3 and T4 Tumors of the Oral Cavity and Oropharynx Jacques Pinsolle, Mr), H~l~ne Demeaux, MD, Benbit Coustal, MD, Francois Siberchicot, MD, Michel Caudry, MD, Jean-Philippe Maire, MD, Franq~is-Xavier Michelet, s4D, Bordeaux,France
The combined use of surgery and radiotherapy is e o m m o u l y accepted as the most effective treatment
for locally advanced head and neck cancers. T3 and "1"4tumors of the oral cavity and oropharynx often necessitate extensive local surgery. From 1981 to 1988, 199 patients with T3 and "1"4tumors of the oral cavity and oropharynx were treated. One hundred seventeen patients underwent surgery plus postoperative radiotherapy; 78 had flap reconstructions. This series is extremely homogeneous because surgery was always performed by two surgeons, whereas radiotherapy was the responsibility of the same physician. The results of this study show a 96% loeal control rate at the end of treatment among the patients with combined treatment. The average time by which hospitalization was prolonged due to surgery was 2 9 days. The type and delay of recurrences and survival in relation with node involvement are also diseussed. Extensive surgery in association with radiotherapy remains a reliable treatment in such patients.
he combined use of surgery and radiotherapy is commonly accepted as the most effective treatment for T locally advanced head and neck cancers [1,2]. T3 and T4 tumors of the oral cavity and oropharynx often involve adjacent structures, particularly the mandible, and therefore necessitate extensive local surgery and, in most cases, flap repair. A series of 199 consecutive patients was reviewed to assess the results of this type of surgery in association with radiotherapy.
PATIENTS AND METHODS The medical records of 199 previously untreated patients with T3 and T4 oral cavity and oropharyngeal cancer, seen between January 1981 and December 1988, were reviewed. From 1981, we decided to utilize combined therapy, involving both surgery and postoperative irradiation, whenever possible. However, no surgery was performed in patients with unreseetable tumors, those with a poor general status, or those who had a complete response to induction chemotherapy. All such patients underwent definitive radiotherapy. No patient had distant metastases at the first consultation. All patients had histologically proven squamous cell carcinoma. Tumors were classified (Tables I and H ) according to the 1987 recommendations of the Union Internationale Contre le Cancer; tumors of patients admitted before this year were reclassified. There were 109 (55%) T3 tumors and 90 (45%) T4 tumors. The primary sites of tumors are listed in Table HI. All patients were presented at an interdisciplinary head and neck tumor conference before any treatment was given. All surgical treatment was performed by two surgeons in the same department; chemotherapy and radiotherapy were the responsibility of one physician: The pretreatment evaluation usually included clinical history and physical examination, biopsy, panorex roentgenography, chest roentgenography, endoscopy, and a complete blood cell count. One hundred seventy-four patients were men (87%), and 25 were women (13%); the median age was 60 years (range: 20 to 87 years). Mean follow-up was 6.5 years (range: 3 to 10 years). It was decided that 122 patients would undergo surgery and postoperative radiotherapy and 77 patients would undergo def'mitive radiotherapy. For the complete series, 84 patients (42%) underwent induction chemotherapy, 34 patients in the surgery and From the Departmentsof Maxillofacialand Plastic Surgery (JP, BC, postoperative radiotherapy group and 50 patients in the FS, FXM), and Oncology(HD, MC, JPM), Centre HospitalierUni- radiotherapy group. versitairede Bordeaux,Bordeaux, France. Among the 122 patients included in the first group, Requests for reprintsshouldbe addressedto Jacques Pinsolle,MD, one patient died between the administration of preoperaDepartment of MaxiUofacialand Plastic Surgery, Centre Hospitalier tive chemotherapy and surgery, so 121 patients underUniversitaire,33076 BordeauxC&lex, France. Presentedat the Third InternationalConferenceon Head and Neck went extensive surgery. There were 163 neck dissections Cancer, San Francisco,California,July 26-30, 1992. in 121 patients, with 145 (89%) modified and 18 (11%) THE AMERICAN JOURNAL OF SURGERY VOLUME 164 DECEMBER 1992 587
PINSOLLE El" AL
surgery. Systematic histologic examination was performed on tumor and neck dissection specimens, with Tumor and Node Staging for Complete Series special attention to margins and lymph node invasion. Margin involvement was divided into three groups acT3 T4 Total % cording to the histologic fmdings: margins free of tumor, NO 43 27 70 35 margins with tumor in situ, and margins with tumor N1 23 11 34 17 invasion. Similarly, node involvement was divided into N2a 18 6 24 12 N2b 10 13 23 12 three groups according to the histologic f'mdings: lymph N2c 3 14 17 9 nodes free of invasion, lymph node invasion without exN3 12 19 31 16 tracapsular spread, and lymph node invasion with extraTotal 109(55) 90 ~5) 199 capsular spread. Among the 121 patients who underwent extensive surgery, 3 patients died postoperatively, and 1 patient with protracted postoperative issue failed to respond to T A B L E II postoperative radiotherapy. Therefore, 117 patients comTumor and Node Staging for Combined Treatment Group pleted a regimen of surgery and postoperative irradiation, with or without previous chemotherapy. Among the 77 T3 T4 Total (%) patients in the second group, 2 patients refused to underNO 33 17 50 41 go radiotherapy after primary chemotherapy. A total of N1 17 9 26 21 75 patients completed definitive radiotherapy, with or N2a 13 3 16 13 without previous chemotherapy. Finally, seven patients N2b 6 9 15 12 N2c 3 4 7 6 were ineligible for the study, and they were classified as N3 4 4 8 7 "failures." Total 76(62) 46(38) 122 Postoperative radiotherapy was begun as soon as possible, even in the case of incomplete healing. Patients received 5,500 to 6,500 rads. Every patient completed a course of postoperative radiotherapy. Patients were treatT A B L E III ed with a telecobalt unit. We used lateral opposing recPrimary Sites of Tumors tangular portals, which encompassed the primary site and upper neck. Bilateral fields were treated in each session. Complete Sites Series S+XRT XRT The lower neck and supraelavicular areas were irradiated to a depth of 3 era with a single anterior field, using a Oral cavity midline block. The lateral portals received 4,000 rads in Oral tongue 34 26 8 Floor of the mouth 65 32 33 22 fractions of 180 rads, and the anterior portal received Buccal mucosa 17 13 4 5,000 rads in 25 fractions, over 5 weeks. A boost was Lower gum 4 4 0 given on the primary site (2,000 rads in 10 fractions over Oropharynx 2 weeks). The posterior cervical area received a boost of Faucial arch (anterior pillar, retromo27 19 8 1,000 rads (four times 250 rads over 1 week) by electron lar triangle, soft palate, uvula) beam. Neck areas with extracapsular spread received a Tonsillar fossa 12 7 5 boost with electrons, up to 6,500 rads. Posterior pillar and lateral wall 17 8 9 Patients were reviewed during follow-up every 3 Pharyngeal tongue and vallecula 23 13 10 months up to 18 months, then every 6 months up to 5 S+ XRT = surgery and postoperative radiotherapy; XRT = definitive radiotheryears, and every year afterward, l_xx~oregionalcontrol apy. was assessed 1 month after completion of primary therapy. Recurrence was defined as a lesion at the primary site, lymph node metastasis, or distant metastasis compatible radical neck dissections. Reconstruction after extensive with the previously treated tumor but without any new surgery required 78 flaps, including 49 pectoralis major oral or oropharyngeal primary lesion. Confirmation of flaps (63%), 17 lateral trapezius flaps (22%), 5 latissimns each recurrence was assessed histologically whenever dorsi flaps (6%), 4 nasolabial flaps (5%), 2 scapular flaps possible. We used a computer f'ile to record aH patient (3%), and 1 forearm flap (1%). As for mandibular recon- data. The Kaplan-Meier method was used to calculate struction, all anterior defects (eight patients) were recon- survival probabilities regarding the period between the structed. For these eight patients, reconstruction was a f'LrStand last consultations or death; the log-rank test was scapular flap in two patients, a lateral osteocutaneous used to assess significance. Data from aH patients in each trapezius flap in four patients, and, in two patients, plates group were included in the calculation of survival curves, combined with one forearm flap and with one latissimus including patients who had died postoperatively or padorsi flap. Five of 37 patients (14%) with lateral mandib- tients who had undergone incomplete treatment. Eightyular defects underwent reconstruction with a myocutan- one patients in the surgery and postoperative radiotheraeous flap and a plate. py group participated in the study of treatment sequelae. Frozen sections were not routinely obtained during Each patient was evaluated 1 year after surgery and TABLE
588
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THE AMERICAN JOURNAL OF SURGERY
VOLUME 164 DECEMBER 1992
T3 AND T4 TUMORS OF THE ORAL CAVITY AND OROPHARYNX
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I ~ "i. Curves of survival probabllity for complete series end combined therapy group. Thln llne = combined treatment group; lhlck line = complete series.
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postoperative radiotherapy. Four levels of shoulder disability were listed; A, B, C, and D represented normal function, slight discomfort, considerable disability, and complete disability, respectively. Moreover, the nutritional status of patients was assessed as follows: permanent nasogastric tube, liquid diet, soft diet, or solid diet. RESULTS Among the 121 patients who were surgically treated, 3 patients died postoperatively (1 myocardial infarction, I hyperglycemic nonketotic coma, and I delirium trcmens associatedwith pneumonia). Ninety-three patients (77%) experienced no complications. Severe complications occurred in seven patients:one patient had serious hemorrhage, two patients had complete flap necrosis, three patientshad delirium tremens, and one patienthad acute renalfailure.There were 18 minor complications:7 cases of delayed healing, 5 local infections, 5 cases of moderate pneumonia, and I transientstroke.The average time by which hospitalizationwas prolonged due to surgery was 29 days, and the length of hospitalizationwas lessthan 20 days in 92% of patients.Postoperativeradiotherapy was performed an average of 18 days after surgery (range: I0 to 29 days). The resultsof histologicexamination of tumor specimens from 121 patientswere margins free of tumor in 109 patients (91%), margins with tumor in situ in 7 patients (5%), and margins with tumor invasion in 5 patients (4%). Histologic f'mdings on neck dissection specimens showed no lymph node invasion in 52 patients (43%), lymph node invasion without extracapsular spread in 36 patients (30%), and lymph node invasion with extracapsular spread in 33 patients (27%). Locoregional controlof diseasefor the complete series was achieved in 133 patients (67%). Of the 122 patients in w h o m surgery and postoperative radiotherapy were planned, 117 patients were available to assess locore~ gional controldue to 4 perioperativedeaths and I postoperativeradiotherapyfailure.In thisgroup, diseasecontrol was achieved for 112 patients(96%); on the other hand,
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locoregional control was 28% (21 of 75 patients) for the defmitive radiotherapy group. The overall 1- and 5-year survival rates for the complete series were 70% and 34%, respectively (F'~m'e 1). As for survival according to primary site, 1- and 5-year survival rates for patients with neoplasms of the oral cavity and oropharynx were 68% and 39%, and 71% and 27%, respectively. We found no significant difference (p = 0.1928). Similarly, 1- and 5-year survival rates were 72% and 35%, respectively, for patients with neoplasms of the tongue and 60% and 30%, respectively, for patients with neoplasms of the floor of the mouth. No significant difference could be found (p = 0.2799). For the 122 patients in the surgery and postoperative radiotherapy group, 1- and 5-year survival rates were 86% and 48%, respectively (Figure 1), and, for the 77 patients in the definitive radiotherapy group, survival rates were 45% and 10%, respectively. For the 109 patients with tumorfree margins, 1- and 5-year survival rates were 85% and 48%, respectively. For the 12 patients with tumor invasion on margins, these rates were 85% and 53%, respectively. However, there were only a few margins with tumor invasion. Of the 121 patients in whom histologic results of neck dissection specimens were available, 1and 5-year survival rates were 96% and 71%, respectively, for 52 patients free of node invasion, 80% and 30%, respectively, for 36 patients with lymph node invasion and no extracapsular spread, and 77% and 33%, respectively, for 33 patients with lymph node invasion and extracapsular spread. The results were better for patients free of node invasion than for those with lymph node invasion, and the difference was statistically significant (p = 0.0001). For patients with lymph node invasion, we found no significant difference according to extracapsular spread (p = 0.9503). In the surgery and postoperative radiotherapy group, recurrences occurred in 45 patients (40%) among the 112 patients with loeoregional control. The mean time for recurrence was 15 months (range: 4 to 50 months). There were 23 local recurrences (51%), 2 local and neck recur-
THE AMERICAN JOURNAL OF SURGERY
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DECEMBERI992
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PINSOLLE ET AL
renccs (4%), 4 local and distant recurrences (10%), 5 neck recurrences (11%), and 11 distant recurrences (24%). Of the 23 patients with local recurrences, 19 had tumor-free specimen margins, and 4 had a tumor on the margins. Among the seven patients with neck recurrcnces, four had no lymph node invasion on the neck dissection specimens, one had lymph node invasion without extracapsular spread, and two had lymph node invasion with extracapsular spread. The results of the assessment for shoulder disability showed 14 level A patients, 32 level B patients, 25 level C patients, and 10 level D patients. Shoulder discomfort was slight or nonexistent (levels A and B) in 58% of the patients with modified neck dissection and 50% of patients with radical neck dissection. The large difference in the numbers of patients between the two groups did not allow statistical investigation of the results of both techniques. Among the 81 patients in the study, only 12% had complete shoulder disability, regardless of the form of neck dissection. As for the nutritional status of the 81 patients, 1 patient had a permanent nasogastric tube, 27 patients were able to ingest a liquid diet, 37 patients were able to ingest a soft diet, and 16 patients were able to ingest a solid diet. COMMENTS This series includes only patients with T3 and T4 tumors, rather than patients with stage III and IV tumors, as most reports do. This choice was made deliberately so that the result of extensive local surgery could be assessed, since, in stages III and IV, there are patients with T1 and T2 tumors who arc not likely to undergo wide excision and complicated repairs on the primary site. Similarly, only 57% of our patients had node involvement, unlike many series reporting on patients with stage III and IV tumors [2-4], yet all T1 and T2 patients listed in these series had node involvement, which artificially increases the percentage. Considering only patients with T3 and T4 tumors in these reports, we found a percentage around 60%, which is comparable with our results. Our group of patients is particularlyhomogeneous, both in terms of theirmanagement and primary tumor site.Unlike a recent report, we did not fred any statistically significantdifference in survival rates between patients with tumors of the oropharynx and those with tumors of the oral cavity and between patientswith tumors of the tongue and those with tumors of the floor of the mouth [5]. The decision to perform primary surgical treatment and postoperativeradiotherapy was made as a principle, since it appears to be the most effectivetreatment for such patients [I-3,6]. However, as in another report [7], patients who had a complete response to induction che` motherapy underwent no surgery but def'mitiveradiotherapy. N o attempt at randomization was made, since, like many physicians, we were reluctant to enter such patients in a portion of a trialin which definitiveradiotherapy was one of the options. All patientsin the combined therapy group underwent wide localresections,with flap repairsin most. The margins of surgicalspecimens wcrc safe in a high proportion (91%), even if we did not systematicallyuse frozen sec590
THE AMERICAN JOURNAL OF SURGERY
tions. All patients in this group underwent neck dissection, even those with NO necks, since the probability of neck involvement is high in T3 and T4 tumors [8,9]. The overall survival results were satisfactory in patients without lymph node involvement, and, surprisingly, in the group with cervical node invasion, there was no statistically significant difference in survival according to the extent of capsular spread. The boost with electrous given to the neck area with extracapsular spread could he an explanation; moreover, all patients were irradiated within 4 weeks after surgery, which improves results [4,10]. Despite this, the number of involved nodes should bca more predictive factor for survival [4]. The superiority of combined treatment--surgery and postoperative radiotherapy--over def'mitivc radiotherapy and salvage surgery seems to be probable in locally advanced tumors, at least in terms of local control [1-3,6]. But this would necessitate a randomized study, which is difficult to perform on a large scale for the reasons mentioned earlier [3,6]. The patients in our group with definitive radiotherapy cannot be evaluated, whether they were patients who experienced a complete response to induction chemotherapy, patients who were inoperable due to unresectable tumors or poor general status, or patients who refused surgery. The average time by which hospitalization was prolonged due to surgery was 29 days, with 92% of patients being discharged at 20 days or less, which is an acceptable percentage. Most mandibular ddects were not primarily reconstructed, and only selected patients were opcratccl on later with microsurgical transfer [8], except for the anterior portion of the mandibular arch, which was always reconstructed in the interim, and some lateral de. fects that were reconstructed by plates. As for shoulder disability, no attempt was made to statistically differentiate the results of radical neck dissection from the results of modified neck dissection because of the large difference in the number of patients in the two groups. More` over, other studies [11-I4] have shown that the difference in results between these groups was not as large as we thought. Among the 81 patients in our study, 57% had a slight or nonexistent shoulder discomfort, regardless of the form of neck dissection. The variations in functional disability associated with any kind of neck dissection are probably related to the preoperative status of the patient and to the dissection of the spinal accessory nerve, which can disturb the vascularization of nerve and muscles. Moreover, radiotherapy could be a contributing factor to postoperative disability [11]. We did not investigate nutritional status according to whether the mandible had been reconstructed. Another report [15] has found an insignificantdifferencebetween patientswho have undergone reconstruction and those who have not. A recent study [16] showed an improvement as a resultof reconstruction, but only 20 patients were included. Therefore, extensive surgery in association with radiotherapy remains a reliable treatment, providing indications arc good. The alternative could be concomitant radiotherapy and chemotherapy [17]; these arc encouraging results, but there is still insufficient followup for a proper view and final judgment.
VOLUME 164 DECEMBER 1992
T3 AND I"4 TUMORS OF THE ORAL CAVITY AND OROPHARYNX
REFERENCES 1. Fletcher GH, Jessee RH. The place of irradiation in the management of the primary lesion in head and neck cancers. Cancer 1977; 39: 862-7. 2. Vikram B, Strong EW, Shah J, Spiro RH. Elective postoperative radiation therapy in stages III and IV epidermoid carcinoma of the head and neck. Am J Surg 1980; 140: 580-4. 3. Kumur PP, Good RR, Epstein BE, Yonkers AJ, Ogrcn FP, Moore GF. Outcome of locallyadvanced stage III and IV head and neck cancer treated by surgery and postoperative external beam radiotherapy. Laryngoscope 1987; 97: 615-20. 4,. O'Brien C J, Smith JW, Soong SJ, Urist MM, Maddox WA. Neck dissection with and without radiotherapy: prognostic factors, patterns of recurrence, and survival. Am J Surg 1986; 152: 456-63. 5. Zelefsky MJ, Harrison LB, Fass DE, et al. Postoperative radictherapy for oral cavity cancers: impact of anatomic subsite on treatment outcome. Head Neck 1990; 12: 470-5. 6. Perez CA, Carmichael T, Devineni VR, et al. Carcinoma of the tonsillar fossa: a nonrandomized comparison of irradiation alone or combined with surgery: long-term results. Head Neck 1991; 13: 282-90. 7. Schuller DE, Laramore G, AI-Sarraf M, Jacobs J, Pajak TF. Combined therapy for resectable head and neck cancer. Arch Otolaryngol Head Neck Sure 1989; 115: 364-8. 8. Shaha AR, Spire RH, Shah JP, Strong EW. Squamous carcinoma of the floor of the mouth. Am J Sure 1984; 148: 455-9.
9. Guillamondegui OM, Oliver B, Hayden R. Cancer of the antedor floor of the mouth. Am J Sure 1980; 140: 560-2. 10. Vikram B, Strong EW, Shah JP, Spire R. Failure in the neck following multimodality treatment for advanced head and neck cancer. Head Neck Sure 1984; 6: 724-9. 11. Leipzig B, Suen JY, English JL, Barnes J, Hooper M. Functional evaluation of the spinal accessory nerve after neck dissection. Am J Sure 1983; 146: 526-30. 12. Saunders JR, Hiram RM, Jaques DA. Considering the spinal accessory nerve in head and neck surgery. Am J Sure 1985; 150: 491-4. 13. Schuller DE, Reiches NA, Hamaker RC, et al. Analysis of disabilityresulting from treatment including radical neck disse~--tion or modified neck dissection. Head Neck Surg 1983; 6: 551-8. 14. Short SO, Kaplan ,IN, Laramore GE, Cummings CW. Shoulder pain and function after neck dissection with or without preservation of the spinal accessory nerve. Am J Surg 1984; 148: 478-82. 15. Komisar A. The functional result of mandibular reconstruction. Laryngoscope 1990; 100: 364-74. 16. Urken ML, Buchbinder D, Weinbcrg H, et aL Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and nonreconstructed patients. Laryngoscope 1991; 101: 935-50. 17. Maxcial VA, Pajak TF, Mohinddin M, et al. Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Cancer 1990; 66: 1861-8.
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 DECEMBER 1992 591
The combined use of surgery and radiotherapy is e o m m o u l y accepted as the most effective treatment
for locally advanced head and neck cancers. T3 and "1"4tumors of the oral cavity and oropharynx often necessitate extensive local surgery. From 1981 to 1988, 199 patients with T3 and "1"4tumors of the oral cavity and oropharynx were treated. One hundred seventeen patients underwent surgery plus postoperative radiotherapy; 78 had flap reconstructions. This series is extremely homogeneous because surgery was always performed by two surgeons, whereas radiotherapy was the responsibility of the same physician. The results of this study show a 96% loeal control rate at the end of treatment among the patients with combined treatment. The average time by which hospitalization was prolonged due to surgery was 2 9 days. The type and delay of recurrences and survival in relation with node involvement are also diseussed. Extensive surgery in association with radiotherapy remains a reliable treatment in such patients.
he combined use of surgery and radiotherapy is commonly accepted as the most effective treatment for T locally advanced head and neck cancers [1,2]. T3 and T4 tumors of the oral cavity and oropharynx often involve adjacent structures, particularly the mandible, and therefore necessitate extensive local surgery and, in most cases, flap repair. A series of 199 consecutive patients was reviewed to assess the results of this type of surgery in association with radiotherapy.
PATIENTS AND METHODS The medical records of 199 previously untreated patients with T3 and T4 oral cavity and oropharyngeal cancer, seen between January 1981 and December 1988, were reviewed. From 1981, we decided to utilize combined therapy, involving both surgery and postoperative irradiation, whenever possible. However, no surgery was performed in patients with unreseetable tumors, those with a poor general status, or those who had a complete response to induction chemotherapy. All such patients underwent definitive radiotherapy. No patient had distant metastases at the first consultation. All patients had histologically proven squamous cell carcinoma. Tumors were classified (Tables I and H ) according to the 1987 recommendations of the Union Internationale Contre le Cancer; tumors of patients admitted before this year were reclassified. There were 109 (55%) T3 tumors and 90 (45%) T4 tumors. The primary sites of tumors are listed in Table HI. All patients were presented at an interdisciplinary head and neck tumor conference before any treatment was given. All surgical treatment was performed by two surgeons in the same department; chemotherapy and radiotherapy were the responsibility of one physician: The pretreatment evaluation usually included clinical history and physical examination, biopsy, panorex roentgenography, chest roentgenography, endoscopy, and a complete blood cell count. One hundred seventy-four patients were men (87%), and 25 were women (13%); the median age was 60 years (range: 20 to 87 years). Mean follow-up was 6.5 years (range: 3 to 10 years). It was decided that 122 patients would undergo surgery and postoperative radiotherapy and 77 patients would undergo def'mitive radiotherapy. For the complete series, 84 patients (42%) underwent induction chemotherapy, 34 patients in the surgery and From the Departmentsof Maxillofacialand Plastic Surgery (JP, BC, postoperative radiotherapy group and 50 patients in the FS, FXM), and Oncology(HD, MC, JPM), Centre HospitalierUni- radiotherapy group. versitairede Bordeaux,Bordeaux, France. Among the 122 patients included in the first group, Requests for reprintsshouldbe addressedto Jacques Pinsolle,MD, one patient died between the administration of preoperaDepartment of MaxiUofacialand Plastic Surgery, Centre Hospitalier tive chemotherapy and surgery, so 121 patients underUniversitaire,33076 BordeauxC&lex, France. Presentedat the Third InternationalConferenceon Head and Neck went extensive surgery. There were 163 neck dissections Cancer, San Francisco,California,July 26-30, 1992. in 121 patients, with 145 (89%) modified and 18 (11%) THE AMERICAN JOURNAL OF SURGERY VOLUME 164 DECEMBER 1992 587
PINSOLLE El" AL
surgery. Systematic histologic examination was performed on tumor and neck dissection specimens, with Tumor and Node Staging for Complete Series special attention to margins and lymph node invasion. Margin involvement was divided into three groups acT3 T4 Total % cording to the histologic fmdings: margins free of tumor, NO 43 27 70 35 margins with tumor in situ, and margins with tumor N1 23 11 34 17 invasion. Similarly, node involvement was divided into N2a 18 6 24 12 N2b 10 13 23 12 three groups according to the histologic f'mdings: lymph N2c 3 14 17 9 nodes free of invasion, lymph node invasion without exN3 12 19 31 16 tracapsular spread, and lymph node invasion with extraTotal 109(55) 90 ~5) 199 capsular spread. Among the 121 patients who underwent extensive surgery, 3 patients died postoperatively, and 1 patient with protracted postoperative issue failed to respond to T A B L E II postoperative radiotherapy. Therefore, 117 patients comTumor and Node Staging for Combined Treatment Group pleted a regimen of surgery and postoperative irradiation, with or without previous chemotherapy. Among the 77 T3 T4 Total (%) patients in the second group, 2 patients refused to underNO 33 17 50 41 go radiotherapy after primary chemotherapy. A total of N1 17 9 26 21 75 patients completed definitive radiotherapy, with or N2a 13 3 16 13 without previous chemotherapy. Finally, seven patients N2b 6 9 15 12 N2c 3 4 7 6 were ineligible for the study, and they were classified as N3 4 4 8 7 "failures." Total 76(62) 46(38) 122 Postoperative radiotherapy was begun as soon as possible, even in the case of incomplete healing. Patients received 5,500 to 6,500 rads. Every patient completed a course of postoperative radiotherapy. Patients were treatT A B L E III ed with a telecobalt unit. We used lateral opposing recPrimary Sites of Tumors tangular portals, which encompassed the primary site and upper neck. Bilateral fields were treated in each session. Complete Sites Series S+XRT XRT The lower neck and supraelavicular areas were irradiated to a depth of 3 era with a single anterior field, using a Oral cavity midline block. The lateral portals received 4,000 rads in Oral tongue 34 26 8 Floor of the mouth 65 32 33 22 fractions of 180 rads, and the anterior portal received Buccal mucosa 17 13 4 5,000 rads in 25 fractions, over 5 weeks. A boost was Lower gum 4 4 0 given on the primary site (2,000 rads in 10 fractions over Oropharynx 2 weeks). The posterior cervical area received a boost of Faucial arch (anterior pillar, retromo27 19 8 1,000 rads (four times 250 rads over 1 week) by electron lar triangle, soft palate, uvula) beam. Neck areas with extracapsular spread received a Tonsillar fossa 12 7 5 boost with electrons, up to 6,500 rads. Posterior pillar and lateral wall 17 8 9 Patients were reviewed during follow-up every 3 Pharyngeal tongue and vallecula 23 13 10 months up to 18 months, then every 6 months up to 5 S+ XRT = surgery and postoperative radiotherapy; XRT = definitive radiotheryears, and every year afterward, l_xx~oregionalcontrol apy. was assessed 1 month after completion of primary therapy. Recurrence was defined as a lesion at the primary site, lymph node metastasis, or distant metastasis compatible radical neck dissections. Reconstruction after extensive with the previously treated tumor but without any new surgery required 78 flaps, including 49 pectoralis major oral or oropharyngeal primary lesion. Confirmation of flaps (63%), 17 lateral trapezius flaps (22%), 5 latissimns each recurrence was assessed histologically whenever dorsi flaps (6%), 4 nasolabial flaps (5%), 2 scapular flaps possible. We used a computer f'ile to record aH patient (3%), and 1 forearm flap (1%). As for mandibular recon- data. The Kaplan-Meier method was used to calculate struction, all anterior defects (eight patients) were recon- survival probabilities regarding the period between the structed. For these eight patients, reconstruction was a f'LrStand last consultations or death; the log-rank test was scapular flap in two patients, a lateral osteocutaneous used to assess significance. Data from aH patients in each trapezius flap in four patients, and, in two patients, plates group were included in the calculation of survival curves, combined with one forearm flap and with one latissimus including patients who had died postoperatively or padorsi flap. Five of 37 patients (14%) with lateral mandib- tients who had undergone incomplete treatment. Eightyular defects underwent reconstruction with a myocutan- one patients in the surgery and postoperative radiotheraeous flap and a plate. py group participated in the study of treatment sequelae. Frozen sections were not routinely obtained during Each patient was evaluated 1 year after surgery and TABLE
588
I
THE AMERICAN JOURNAL OF SURGERY
VOLUME 164 DECEMBER 1992
T3 AND T4 TUMORS OF THE ORAL CAVITY AND OROPHARYNX
l
1
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.9. .8. .7. .6
1 1
I__
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I ~ "i. Curves of survival probabllity for complete series end combined therapy group. Thln llne = combined treatment group; lhlck line = complete series.
I
i 0
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postoperative radiotherapy. Four levels of shoulder disability were listed; A, B, C, and D represented normal function, slight discomfort, considerable disability, and complete disability, respectively. Moreover, the nutritional status of patients was assessed as follows: permanent nasogastric tube, liquid diet, soft diet, or solid diet. RESULTS Among the 121 patients who were surgically treated, 3 patients died postoperatively (1 myocardial infarction, I hyperglycemic nonketotic coma, and I delirium trcmens associatedwith pneumonia). Ninety-three patients (77%) experienced no complications. Severe complications occurred in seven patients:one patient had serious hemorrhage, two patients had complete flap necrosis, three patientshad delirium tremens, and one patienthad acute renalfailure.There were 18 minor complications:7 cases of delayed healing, 5 local infections, 5 cases of moderate pneumonia, and I transientstroke.The average time by which hospitalizationwas prolonged due to surgery was 29 days, and the length of hospitalizationwas lessthan 20 days in 92% of patients.Postoperativeradiotherapy was performed an average of 18 days after surgery (range: I0 to 29 days). The resultsof histologicexamination of tumor specimens from 121 patientswere margins free of tumor in 109 patients (91%), margins with tumor in situ in 7 patients (5%), and margins with tumor invasion in 5 patients (4%). Histologic f'mdings on neck dissection specimens showed no lymph node invasion in 52 patients (43%), lymph node invasion without extracapsular spread in 36 patients (30%), and lymph node invasion with extracapsular spread in 33 patients (27%). Locoregional controlof diseasefor the complete series was achieved in 133 patients (67%). Of the 122 patients in w h o m surgery and postoperative radiotherapy were planned, 117 patients were available to assess locore~ gional controldue to 4 perioperativedeaths and I postoperativeradiotherapyfailure.In thisgroup, diseasecontrol was achieved for 112 patients(96%); on the other hand,
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locoregional control was 28% (21 of 75 patients) for the defmitive radiotherapy group. The overall 1- and 5-year survival rates for the complete series were 70% and 34%, respectively (F'~m'e 1). As for survival according to primary site, 1- and 5-year survival rates for patients with neoplasms of the oral cavity and oropharynx were 68% and 39%, and 71% and 27%, respectively. We found no significant difference (p = 0.1928). Similarly, 1- and 5-year survival rates were 72% and 35%, respectively, for patients with neoplasms of the tongue and 60% and 30%, respectively, for patients with neoplasms of the floor of the mouth. No significant difference could be found (p = 0.2799). For the 122 patients in the surgery and postoperative radiotherapy group, 1- and 5-year survival rates were 86% and 48%, respectively (Figure 1), and, for the 77 patients in the definitive radiotherapy group, survival rates were 45% and 10%, respectively. For the 109 patients with tumorfree margins, 1- and 5-year survival rates were 85% and 48%, respectively. For the 12 patients with tumor invasion on margins, these rates were 85% and 53%, respectively. However, there were only a few margins with tumor invasion. Of the 121 patients in whom histologic results of neck dissection specimens were available, 1and 5-year survival rates were 96% and 71%, respectively, for 52 patients free of node invasion, 80% and 30%, respectively, for 36 patients with lymph node invasion and no extracapsular spread, and 77% and 33%, respectively, for 33 patients with lymph node invasion and extracapsular spread. The results were better for patients free of node invasion than for those with lymph node invasion, and the difference was statistically significant (p = 0.0001). For patients with lymph node invasion, we found no significant difference according to extracapsular spread (p = 0.9503). In the surgery and postoperative radiotherapy group, recurrences occurred in 45 patients (40%) among the 112 patients with loeoregional control. The mean time for recurrence was 15 months (range: 4 to 50 months). There were 23 local recurrences (51%), 2 local and neck recur-
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renccs (4%), 4 local and distant recurrences (10%), 5 neck recurrences (11%), and 11 distant recurrences (24%). Of the 23 patients with local recurrences, 19 had tumor-free specimen margins, and 4 had a tumor on the margins. Among the seven patients with neck recurrcnces, four had no lymph node invasion on the neck dissection specimens, one had lymph node invasion without extracapsular spread, and two had lymph node invasion with extracapsular spread. The results of the assessment for shoulder disability showed 14 level A patients, 32 level B patients, 25 level C patients, and 10 level D patients. Shoulder discomfort was slight or nonexistent (levels A and B) in 58% of the patients with modified neck dissection and 50% of patients with radical neck dissection. The large difference in the numbers of patients between the two groups did not allow statistical investigation of the results of both techniques. Among the 81 patients in the study, only 12% had complete shoulder disability, regardless of the form of neck dissection. As for the nutritional status of the 81 patients, 1 patient had a permanent nasogastric tube, 27 patients were able to ingest a liquid diet, 37 patients were able to ingest a soft diet, and 16 patients were able to ingest a solid diet. COMMENTS This series includes only patients with T3 and T4 tumors, rather than patients with stage III and IV tumors, as most reports do. This choice was made deliberately so that the result of extensive local surgery could be assessed, since, in stages III and IV, there are patients with T1 and T2 tumors who arc not likely to undergo wide excision and complicated repairs on the primary site. Similarly, only 57% of our patients had node involvement, unlike many series reporting on patients with stage III and IV tumors [2-4], yet all T1 and T2 patients listed in these series had node involvement, which artificially increases the percentage. Considering only patients with T3 and T4 tumors in these reports, we found a percentage around 60%, which is comparable with our results. Our group of patients is particularlyhomogeneous, both in terms of theirmanagement and primary tumor site.Unlike a recent report, we did not fred any statistically significantdifference in survival rates between patients with tumors of the oropharynx and those with tumors of the oral cavity and between patientswith tumors of the tongue and those with tumors of the floor of the mouth [5]. The decision to perform primary surgical treatment and postoperativeradiotherapy was made as a principle, since it appears to be the most effectivetreatment for such patients [I-3,6]. However, as in another report [7], patients who had a complete response to induction che` motherapy underwent no surgery but def'mitiveradiotherapy. N o attempt at randomization was made, since, like many physicians, we were reluctant to enter such patients in a portion of a trialin which definitiveradiotherapy was one of the options. All patientsin the combined therapy group underwent wide localresections,with flap repairsin most. The margins of surgicalspecimens wcrc safe in a high proportion (91%), even if we did not systematicallyuse frozen sec590
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tions. All patients in this group underwent neck dissection, even those with NO necks, since the probability of neck involvement is high in T3 and T4 tumors [8,9]. The overall survival results were satisfactory in patients without lymph node involvement, and, surprisingly, in the group with cervical node invasion, there was no statistically significant difference in survival according to the extent of capsular spread. The boost with electrous given to the neck area with extracapsular spread could he an explanation; moreover, all patients were irradiated within 4 weeks after surgery, which improves results [4,10]. Despite this, the number of involved nodes should bca more predictive factor for survival [4]. The superiority of combined treatment--surgery and postoperative radiotherapy--over def'mitivc radiotherapy and salvage surgery seems to be probable in locally advanced tumors, at least in terms of local control [1-3,6]. But this would necessitate a randomized study, which is difficult to perform on a large scale for the reasons mentioned earlier [3,6]. The patients in our group with definitive radiotherapy cannot be evaluated, whether they were patients who experienced a complete response to induction chemotherapy, patients who were inoperable due to unresectable tumors or poor general status, or patients who refused surgery. The average time by which hospitalization was prolonged due to surgery was 29 days, with 92% of patients being discharged at 20 days or less, which is an acceptable percentage. Most mandibular ddects were not primarily reconstructed, and only selected patients were opcratccl on later with microsurgical transfer [8], except for the anterior portion of the mandibular arch, which was always reconstructed in the interim, and some lateral de. fects that were reconstructed by plates. As for shoulder disability, no attempt was made to statistically differentiate the results of radical neck dissection from the results of modified neck dissection because of the large difference in the number of patients in the two groups. More` over, other studies [11-I4] have shown that the difference in results between these groups was not as large as we thought. Among the 81 patients in our study, 57% had a slight or nonexistent shoulder discomfort, regardless of the form of neck dissection. The variations in functional disability associated with any kind of neck dissection are probably related to the preoperative status of the patient and to the dissection of the spinal accessory nerve, which can disturb the vascularization of nerve and muscles. Moreover, radiotherapy could be a contributing factor to postoperative disability [11]. We did not investigate nutritional status according to whether the mandible had been reconstructed. Another report [15] has found an insignificantdifferencebetween patientswho have undergone reconstruction and those who have not. A recent study [16] showed an improvement as a resultof reconstruction, but only 20 patients were included. Therefore, extensive surgery in association with radiotherapy remains a reliable treatment, providing indications arc good. The alternative could be concomitant radiotherapy and chemotherapy [17]; these arc encouraging results, but there is still insufficient followup for a proper view and final judgment.
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T3 AND I"4 TUMORS OF THE ORAL CAVITY AND OROPHARYNX
REFERENCES 1. Fletcher GH, Jessee RH. The place of irradiation in the management of the primary lesion in head and neck cancers. Cancer 1977; 39: 862-7. 2. Vikram B, Strong EW, Shah J, Spiro RH. Elective postoperative radiation therapy in stages III and IV epidermoid carcinoma of the head and neck. Am J Surg 1980; 140: 580-4. 3. Kumur PP, Good RR, Epstein BE, Yonkers AJ, Ogrcn FP, Moore GF. Outcome of locallyadvanced stage III and IV head and neck cancer treated by surgery and postoperative external beam radiotherapy. Laryngoscope 1987; 97: 615-20. 4,. O'Brien C J, Smith JW, Soong SJ, Urist MM, Maddox WA. Neck dissection with and without radiotherapy: prognostic factors, patterns of recurrence, and survival. Am J Surg 1986; 152: 456-63. 5. Zelefsky MJ, Harrison LB, Fass DE, et al. Postoperative radictherapy for oral cavity cancers: impact of anatomic subsite on treatment outcome. Head Neck 1990; 12: 470-5. 6. Perez CA, Carmichael T, Devineni VR, et al. Carcinoma of the tonsillar fossa: a nonrandomized comparison of irradiation alone or combined with surgery: long-term results. Head Neck 1991; 13: 282-90. 7. Schuller DE, Laramore G, AI-Sarraf M, Jacobs J, Pajak TF. Combined therapy for resectable head and neck cancer. Arch Otolaryngol Head Neck Sure 1989; 115: 364-8. 8. Shaha AR, Spire RH, Shah JP, Strong EW. Squamous carcinoma of the floor of the mouth. Am J Sure 1984; 148: 455-9.
9. Guillamondegui OM, Oliver B, Hayden R. Cancer of the antedor floor of the mouth. Am J Sure 1980; 140: 560-2. 10. Vikram B, Strong EW, Shah JP, Spire R. Failure in the neck following multimodality treatment for advanced head and neck cancer. Head Neck Sure 1984; 6: 724-9. 11. Leipzig B, Suen JY, English JL, Barnes J, Hooper M. Functional evaluation of the spinal accessory nerve after neck dissection. Am J Sure 1983; 146: 526-30. 12. Saunders JR, Hiram RM, Jaques DA. Considering the spinal accessory nerve in head and neck surgery. Am J Sure 1985; 150: 491-4. 13. Schuller DE, Reiches NA, Hamaker RC, et al. Analysis of disabilityresulting from treatment including radical neck disse~--tion or modified neck dissection. Head Neck Surg 1983; 6: 551-8. 14. Short SO, Kaplan ,IN, Laramore GE, Cummings CW. Shoulder pain and function after neck dissection with or without preservation of the spinal accessory nerve. Am J Surg 1984; 148: 478-82. 15. Komisar A. The functional result of mandibular reconstruction. Laryngoscope 1990; 100: 364-74. 16. Urken ML, Buchbinder D, Weinbcrg H, et aL Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and nonreconstructed patients. Laryngoscope 1991; 101: 935-50. 17. Maxcial VA, Pajak TF, Mohinddin M, et al. Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Cancer 1990; 66: 1861-8.
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