Concurrent chemotherapy and "concomitant boost" radiotherapy for unresectable head and neck cancer

PURPOSE: For patients with advanced head and neck cancer, various combined chemoradiotherapy regimens have been used to improve local control. This study was carried out to assess the outcome of concomitant chemotherapy with a "concomitant boost" radiotherapy in the treatment of advanced unresectable head and neck cancer patients. MATERIALS AND METHODS: Forty-eight patients were treated with combined chemoradiotherapy between the years of 1990 and 1995. Cisplatinum (100 mg/m2) was given intravenously during week 1 and week 5. A "concomitant boost" external beam radiotherapy approach was used with twice-daily treatment delivered during the last 2 weeks. A total of 70 Gy was delivered over 6 weeks. Median follow-up was 23.5 months (2-79 months). RESULTS: Thirty-one (65%) and 17 (35%) patients achieved complete and partial response, respectively. Median survival in complete responders has not been reached. Overall survival at 2 years, 3 years, and 5 years were 58.7%, 52.8%, and 42.4%, respectively. Median overall survival was 38.8 months. Acute confluent mucositis (Radiation Therapy Oncology [RTOG] grade 3) developed in 50% of patients, but there was no severe long-term treatment-related toxicity. CONCLUSION: This combined chemoradiotherapy approach is safe and efficacious for advanced unresectable head and neck cancer. Treatment-related toxicity was acceptable with 50% of patients developing acute confluent mucositis. There was no severe long-term treatment-related toxicity.     

Planned post-chemoradiation neck dissection: significance of radiation dose

OBJECTIVE: The increasing prominence of multimodality therapy for patients with advanced head and neck cancer reflects its high survival and functional preservation rates. We report the pathologic data on patients undergoing neck dissection (ND) after induction chemotherapy followed by concomitant chemoradiotherapy (IC-CRT) in three similar protocols utilizing decreasing doses of radiation therapy. MATERIALS AND METHODS: The databases of 221 patients who underwent IC-CRT between 1999 and 2002 were reviewed. Based on posttreatment residual or pretreatment N2a or greater neck disease, 73 patients without pretreatment neck surgery were eligible for analysis (1 N1, 3 N2a, 26 N2b, 20 N2c, 23 N3). Three additional subgroups were also analyzed with respect to outcome: Undissected patients with less than N2 disease, patients who had neck surgery prior to IC-CRT, and patients with N2a or greater neck disease who did not have post-IC-CRT ND. STUDY DESIGN: Retrospective analysis. RESULTS: Sixty-seven patients underwent unilateral or bilateral selective neck dissection. Six patients had modified or radical ND. There were no wound healing complications. Pathologic analysis revealed viable cancer in 15 of 73 patients (20.5%): 1 had N1, 3 had N2b, 4 had N2c, and 7 had N3 neck disease. The incidence of viable cancer in the neck dissection specimen increased as radiation dose decreased. Complete response induction chemotherapy predicted negative pathology (P = .003). In the subgroup analysis, patients who had pretreatment surgery had a lower risk of dying from the primary cancer CONCLUSIONS: 1) The incidence of positive pathology after IC-CRT increases as radiation dose decreases. 2) Selective neck dissection after CRT has been demonstrated to be feasible and safe; the complication rate of ND after IC-CRT is acceptably low. 3) There is viable posttreatment cancer in 20.5% of patients, indicating necessity of ND in these patients.     

Prognostic factors and outcome for nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal cancer (NPC) is a distinct form of cancer of the upper respiratory or digestive tract in which the epidemiologic features, origin, histopathologic types, treatment, and prognosis are different from those associated with other malignant neoplasms of this anatomical area. Recent publications have demonstrated the advantage of aggressive multimodality treatment for advanced NPC. OBJECTIVES: To evaluate the results of standardized treatment of NPC during 11 years and to identify pertinent factors for clinical outcome. METHODS: Between January 1, 1989, and December 31, 2000, 173 patients with newly diagnosed NPC were treated at Instituto Nacional de Cancer. Clinical records and radiographic studies of the patients were retrospectively reviewed. Documented data of the initial presenting symptoms, head and neck examination, radiotherapy protocols, chemotherapy regimens, and surgical technique were analyzed. To determine important prognostic factors, we correlated survival rates with age, clinical stage, tumor extent, histopathological type, and therapeutic approach. The major end point used for assessment was relapse-free survival. Survival curves were estimated by the Kaplan-Meier product-limit method. Multivariate analysis was performed using the Wilcoxon signed rank and Cox proportional hazards regression tests. RESULTS: Most patients (88.5%) had locoregional advanced disease, mostly (53.4%) of the nonkeratinizing subtype. Forty-seven percent of patients had clinical cervical nodal metastases at first consultation. Gross extension of the primary tumor involving the facial bones and skull base was observed in 39.3% and 20.8%, respectively. Just under 75% of patients were treated with radiotherapy (median dose, 6600 cGy), and 25.4% underwent concomitant chemoradiotherapy with adjuvant chemotherapy (cisplatin plus 5-fluorouracil) (median dose, 6800 cGy). The 5-year disease-specific survival for the 173 patients was 32.3%. The disease-specific survival for the radiotherapy group was 22.5%, compared with 61.4% for the chemoradiotherapy plus adjuvant chemotherapy group (P =.004). Factors associated with adverse outcomes were age older than 40 years at treatment (P =.001), advanced TNM stage (P =.002), skull base invasion (P =.004), and facial bone invasion (P<.001). CONCLUSIONS: Compared with radiotherapy alone, concomitant chemoradiotherapy with adjuvant chemotherapy improved the treatment outcome of patients with NPC treated in our institution. Advanced age, local extension, and stage of the disease adversely affected the prognosis in our patients. Compared with reirradiation, salvage brachytherapy and radical neck dissection for local and regional residual or recurrent NPC were associated with increased rates of locoregional control and survival.     

Effectiveness of superselective and selective neck dissection for advanced nodal metastases after chemoradiation

OBJECTIVE: To determine the efficacy of selective and superselective neck dissection for patients with bulky or residual nodal metastasis treated with concomitant intra-arterial cisplatin and radiotherapy. DESIGN: Prospective study. SETTING: University of Tennessee, Memphis. PATIENTS: A total of 240 patients with stage III or IV head and neck squamous cell carcinoma. INTERVENTIONS: Treatment with cisplatin, 150 mg/m2 intra-arterially, and sodium thiosulfate, 9 g/m2 intravenously, weekly for 4 weeks; and radiotherapy, 2 Gy per fraction per day, 5 times weekly, for a total of 68 to 74 Gy over 6 to 7 weeks. MAIN OUTCOME MEASURES: Regional control, distant metastases, and overall survival for patients undergoing radical or modified radical neck dissection (n = 12), selective neck dissection (n = 65), and superselective neck dissection (levels II-III only) (n = 7). RESULTS: Among the total group of 240 patients, 106 neck dissections were performed on 84 patients who had bulky nodal disease. With a median follow-up of 58 months (range, 12-96 months), regional failure occurred in 11 (4.6%) of 240 patients: 2 (17%) of the 12 who had modified radical neck dissection, 3 (5%) of the 65 who had selective neck dissection, none of the 7 patients who had superselective neck dissection, and 6 (4%) of the 156 who had no neck dissection. The rates of overall survival and distant metastases were not significantly different among the 3 neck dissection subsets. CONCLUSION: Selective and superselective neck dissection, which spare function and minimize morbidity, are viable therapeutic alternatives for patients with residual disease confined to 1 level after intra-arterial chemoradiation treatment, and possibly for other chemoradiation protocols.     

Clinical review of mucoepidermoid carcinomas

Mucoepidermoid carcinoma is a rare head and neck cancer tumor, composed of both mucous and epidermoid cells. We retrospectively reviewed the case of 36 such patients hospitalized in the last 24 years (between 1978 and 2002) at Kurume University Hospital, focusing on origin, treatment, and treatment outcome. In this study, 33 patients undergoing currative treatment were studied in detail. Tumors originated in major salivary glands in 24 and in the oral cavity, paranasal cavity, and oropharynx in 3 each. Salivary gland carcinomas were graded, clinically and histopathologically based on the criteria of Goode et al. as follows: low (n = 3), intermediate (n = 3), and high (n = 18). All patients underwent radical surgery. Lymphnode metastasis was detected in 9, distant metastasis in 6 (lung: 4; liver: 1; bone: 1), and local recurrence in 5 patients. Lymphnode recurrence was detected in 3. Survival was calculated with Kaplan-Meier's methods. Five-year overall survival was 64%, i.e., 56% in salivary gland malignancy, 67% in oral cavity malignancy, 100% in paranasal cavity malignancy and 100% in oropharynx malignancy. Five-year survival was 76% in T2, 75% in T3, 51% in T4. Five-year survival in NO was 80% and 22% in N+ cases, with a statictically significant difference (p < 0.05). Five-year survival was 71% in stage I, 83% in stage II, and 54% in stage IV. Five-year survival in low and intermediate grade was 100%, whereas that in high grade was 43%. The 21 patients undergoing modified neck dissection has a 5-year survival of 52%. In 20 patients undergoing postoperative radiotherapy, 4 died of local recurrence. In 31 patients not undergoing chemotherapy, 6 died of distant metastasis. These results emphasize the necessity of radiotherapy and chemotherapy after surgical treatment for head and neck mucoepidermoid carcinoma.     

The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: the feasibility of selective neck dissection

OBJECTIVES: To evaluate the necessity, technical feasibility, and complication rate of neck dissection performed on patients with head and neck cancer after 5 cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck dissection (SND) approach and define the optimal timing of post-CRT neck dissection. DESIGN AND SETTING: Retrospective analysis in an academic university medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients ranged in age from 36 to 75 years, and surgical procedures were performed over a 4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck dissection (most commonly unilateral SND) performed within 5 to 17 weeks after CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of positive pathology (viable cancer) in pathologic neck dissection specimens. RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%) of whom required surgical intervention for ultimate closure. There were no wound infections. Other complications occurred in 11 (16%) of 69 patients and included need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia. Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%) of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of 39 patients with N2 disease had viable carcinoma in the dissection specimen (P =.09 by chi(2) analysis). There was no significant relation between radiologic complete response or partial response and residual microscopic cancer. In 1 patient, disease recurred in the neck after dissection. Mean follow-up time was 30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater neck disease after CRT is necessary to eradicate residual disease. (2) The complication rate of SND after CRT with hyperfractionated radiotherapy is low. (3) SNDs are technically feasible when performed within the "window" between the acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical procedures, appear to be therapeutically appropriate in this group of patients because of the low incidence of disease recurrence in the neck.     

The impact of early percutaneous endoscopic gastrostomy placement on treatment completeness and nutritional status in locally advanced head and neck cancer patients receiving chemoradiotherapy

To investigate the impact of early insertion of percutaneous endoscopic gastrostomy-tube on nutritional status and completeness of concurrent chemotherapy in locally advanced head and neck cancer patients treated with chemoradiotherapy. Twenty-three patients were enrolled into this prospective study. Gastrostomy-tube was inserted in patients before the initiation of chemoradiotherapy. There was not any significant change in nutritional parameters of patients that used their tube during treatment. Despite the grade 3 mucositis, the planned concurrent chemotherapy could be given in 70% of the patients. However, nine patients had weak compliance and their body weight (P = 0.01) and body mass index (P = 0.01) deteriorated in the first 4 weeks of chemoradiotherapy. The completeness of concurrent chemo-rate was 44% in these patients. Toxicity, requiring aggressive supportive care, may limit the chemotherapy part of curative concomitant chemoradiotherapy. By providing adequate enteral nutrition the insertion of gastrostomy-tube can increase the completeness rate of concurrent chemotherapy.     

Presence of malignant tumor cells in persistent neck disease after radiotherapy for advanced squamous cell carcinoma of the oropharynx is associated with poor survival

Non-surgical therapy consisting of external beam radiation with or without chemotherapy is an effective treatment for patients with squamous cell carcinoma (SCC) of the oropharynx with advanced neck disease (N2a or greater). However, many of these patients have to undergo a neck dissection for clinically persistent regional disease. It is reported that nearly 50% of the neck dissection specimens contain residual viable tumor cells that may indicate partial radiation failure and as a consequence poor survival. In order to address the significance of this finding, we conducted a nonrandomized retrospective study, including 35 patients who underwent definitive radiation therapy followed by either a radical or modified radical (RND/MRND) or a selective neck dissection (SND) for clinically persistent neck disease 6 weeks after completing therapy for stage III/IV SCC of the oropharynx (base of the tongue =15, tonsil =12, soft palate =7 and pharyngeal wall =1). All neck dissection specimens were reviewed according to histological criteria indicating viable residual tumor. We observed an increased relative risk (RR) for local and regional failures in the patient population with viable cancer cells in the post-irradiation neck specimens (RR=6.7 and 4.1, respectively). The presence of malignant tumor cells in residual disease in the neck correlated with poor disease-specific and overall survival ( P =0.03 and P =0.01, respectively). Of note, the extent of neck dissection did not improve the disease-free or overall survival in this patient population ( P =0.5 and P =0.6, respectively). In conclusion, the presence of viable cancer cells in radiated neck nodes is a novel prognostic marker for disease-specific survival in patients treated for SCCs of the oropharynx with advanced neck disease and may serve as an identifier for patients who will benefit from post-treatment chemoprevention.     

Therapeutic selective neck dissection: a 25-year review

OBJECTIVES/HYPOTHESIS: The aim of the study was to show the efficacy of selective neck dissection in combination with postoperative radiation therapy in controlling squamous cell carcinoma metastatic to the cervical lymph nodes. The study compared the incidence of recurrences and overall disease-free survival between comparable cohorts undergoing a selective neck dissection and classic radical or modified neck dissection. STUDY DESIGN: Retrospective, 25-year review was made of data from a tertiary care academic facility comprising both private patients and veterans. METHODS: Inclusion criteria studied patients with untreated head and neck cancer who had squamous carcinoma metastatic to cervical lymph nodes on histological examination and were treated with a selective (n = 61), modified (n = 54), or radical neck dissection (n = 61). The three groups were compared with respect to regional control and overall cancer-free survival. All patients remained cancer free at the primary site, received postoperative radiation therapy, and had a minimum follow-up of 2 years. The median follow-up was 4.3 years. RESULTS: Control of recurrent carcinoma in the neck, as well as the incidence of overall cancer-free survival, was comparable in the three cohorts with no significant statistical difference. Eight of 176 sides of the necks (4.5%) showed evidence of recurrence (2 of 61 [3.3%] in the selective neck dissection group and 6 of 115 [5.2%] in the radical and modified neck dissection group. Disease-free 2-year survival was 80% in the selective neck dissection group and 64% in the radical and modified neck dissection group. CONCLUSION: Selective neck dissection, when used in combination with postoperative radiation therapy, is an efficacious way to manage metastatic squamous cell carcinoma to the neck.     

Functional organ preservation after chemoradiotherapy in elderly patients with loco-regionally advanced head and neck squamous cell carcinoma

The aim of the present investigation is to evaluate the outcome after induction chemotherapy and concurrent multi-drug chemoradiotherapy (IC/CCRT) with or without post-chemoradiation neck dissection in medically fit elderly patients with loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective study including 44 elderly patients (median age 71 years; range 66–77 years) with previously untreated, inoperable, histologically proven non-metastatic stage III or IV HNSCC. Following one cycle of IC, two cycles of cis-platinum and 5-fluorouracil CCRT with conventional fractionated radiotherapy up to a dose of 66–70 Gy were administrated. A neck dissection was recommended for patients with node metastasis larger than 3 cm regardless of the response to therapy and for patients who had suspected persistent neck disease 8–12 weeks after completing treatment. Salvage surgery was considered for histologically proven persistent or recurrent tumor in the primary site. Time-to-event data were described using Kaplan–Meier actuarial curves. Overall, 37 patients (84.1%) completed the planned treatment. There were no cases of treatment-related deaths. Twenty-nine patients (65.9%) developed severe toxicities with grade 4 toxicity accounting for 22.7%. The median follow-up time in survivors was 41 months. Three-year overall survival, progression-free survival, and functional progression-free survival estimates were 70.9, 67.0, and 57.3%, respectively. In selected medically fit elderly patients with loco-regionally advanced HNSCC, cis-platinum-based chemoradiotherapy can be successfully applied, with moderate adverse events, in attempt to preserve a functional upper aerodigestive tract.     

Postoperative adjuvant chemoradiotherapy in older patients with head and neck cancer

BACKGROUND: In head and neck cancer, the locoregional failure of patients with positive margins, vascular or perineural invasion, and extracapsular spread is high and results in poor survival. OBJECTIVE: To assess the effect of adjuvant chemoradiotherapy in improving treatment outcomes among older patients with head and neck cancer. METHODS: Forty patients undergoing radical surgery (median age, 73.5 years [range, 70-78 years]) were enrolled (35 men and 5 women; Eastern Cooperative Oncology Group performance status, grade 0-2). Disease sites included the oral cavity (10 patients), oropharynx (12 patients), hypopharynx (8 patients), and larynx (10 patients); pathological TNM classifications included T1 N2 (8 patients), T2 N1-2 (12 patients), T3 N0-2 (8 patients), and T4 N0-2 (12 patients), with the following poor prognostic factors: positive margins (6 patients), vascular invasion (14 patients), neural invasion (16 patients), and extracapsular spread (26 patients). All patients were treated with carboplatin (30 mg/m2 on days 1-5 of weeks 1, 3, and 5) concomitant with radiotherapy (54.0 Gy to all risk volumes plus 10.0 Gy to high-risk volumes; 5 daily fractions of 1.8 Gy each per week). RESULTS: No grade 4 toxicity was observed. Grade 3 toxicity included mucositis (10 patients), neutropenia (6 patients), dermatitis (2 patients), and thrombocytopenia (1 patient). The radiotherapy dose administered was 52.0 Gy to all risk volumes plus 10.0 Gy to high-risk volumes. Thirty-two patients (80%) received 3 cycles, 6 (15%) received 2 cycles, and 2 (5%) received 1 cycle. Three-year survival was as follows: disease-free survival, 58%; overall survival, 64%; and local control, 79%. CONCLUSIONS: Adjuvant chemoradiotherapy may be successful in fit older patients. The results of adjuvant chemoradiotherapy were better than those observed in a comparable group treated with radiotherapy alone and were similar to those observed in a younger group with the same poor prognostic factors treated with adjuvant carboplatin plus radiotherapy.     

Upper neck (level II) dissection for N0 neck supraglottic carcinoma

OBJECTIVES: Elective neck dissection for the N0 neck in head and neck surgery is still controversial. This prospective nonrandomized study of N0 supraglottic carcinoma was designed to find an appropriate method of neck management. STUDY DESIGN: Anatomical studies show that the first echelon of lymphatic drainage from the supraglottic larynx is toward the upper jugular nodes (level II). An upper neck dissection (UND) was applied and all the lymph nodes were sent for frozen section. If the subclinical metastasis was found, a modified neck dissection was performed. If the nodes harbored no foci of cancer, the patients were observed after surgery on the supraglottic lesions. METHODS: Patient records of 142 patients with supraglottic laryngeal cancer (T1-4N0M0) were reviewed, with special attention paid to neck recurrences and survival rates. The cases were treated between 1976 and 1990 and all were observed for at least 5 years after the operation or until the time of death. RESULTS: The UND specimens of 142 patients were negative for metastasis. The 5-year survival rate for this group after surgery was 80.8%, according to the life table analysis. Fifteen of the 142 patients (10.6%) had neck recurrences during the period of observation within 5 years. The recurrence rate of this series with limited dissection on the neck was comparable with those reported in the literature after neck dissection, either radical or modified. CONCLUSIONS: There is no need for a comprehensive neck dissection for N0 supraglottic laryngeal cancer. A selective neck dissection such as UND (level II) or a supraomohyoid neck dissection (sparing the submandibular region) of level II and III will serve the purpose of radical neck treatment for the supraglottic cancer.     

择区性颈清扫术在临床N0舌鳞状细胞癌治疗中的应用

目的比较择区性颈清扫术(selective neck dissection，SND)与经典性或改良性颈清扫术(radical neck dissection，RND)在治疗舌鳞状细胞癌颈淋巴结临床阴性(cN0)患者中的效果。方法将1998年1月-2002年12月之间采用肩胛舌骨肌上颈清扫术(Ⅰ～Ⅲ区)14例及Ⅰ～Ⅳ区清扫19例(SND组)共33例与1980年1月-1997年12月之间112例采用经典性或改良性颈清扫术(RND组)的病例，根据T分期、综合治疗方式和淋巴结病理情况进行随机配对分析。Kaplan—Meier方法计算复发率和颈部淋巴结复发或生存趋势。结果RND组5年颈部复发率为9．1％(3例)，SND组5年同侧颈部复发率12．1％(4例)；两组的5年生存率分别是78．8％和82．9％(分别为26例和28例)。Ⅰ-Ⅲ区清扫组5年颈部复发率为21．2％(3例)，清扫野外复发率为14．3％(2例)；Ⅰ-Ⅳ区清扫组5年同侧颈部复发率5．3％(1例)，清扫野外复发率为0。结论与经典性或改良性颈清扫术相比，择区性颈清扫术并不影响cN0舌癌患者的肿瘤治疗效果，术式以Ⅰ～Ⅳ区清扫为适宜。     

A long-term follow-up study after split-course irradiation with concurrent chemotherapy (carboplatin) for locally advanced head and neck cancer and a review of the literature

BACKGROUND: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. The purpose of this study was to evaluate the efficacy and toxicity of split-course radiotherapy combined with concurrent carboplatin chemotherapy after long-term follow-up. PATIENTS AND METHODS: From August 1987 to May 1994, 66 patients (54 males, 12 females, mean age 58 years) with advanced inoperable oropharynx cancer were treated at the University of G?ttingen, G?ttingen, Germany. Tumour localization in the oropharynx was: tonsil (n = 33), base of tongue (n = 28), soft palate (n = 2) and posterior pharyngeal wall (n = 3). Forty-nine patients presented with a T(4) tumour, 15 were T(3) and 2 were T(2). The nodal status was distributed as follows: N0 (n = 7), N1 (n = 5), N2 (n = 28) and N3 (n = 26). A total radiation dose of 5,670 cGy was applied in 6 weeks as a split-course regimen (2 x 2.1 Gy/day, 4 times a week, weeks 1 and 2 and weeks 5 and 6). Concomitant carboplatin chemotherapy was given each radiotherapy day before irradiation (50 mg/m(2)). RESULTS: In December 2003, 12 patients were still alive. Survivors have reached a maximum follow-up of 170.5 months (median 14.3 months). Two- and 5-year overall survival was 32 and 18%, 2-year disease-free survival 27%. Therapy was tolerated moderately (19% grade 3 skin reaction, 26% grade 3 mucositis, 23% grade 3 xerostomia, 20% grade 3 leucopenia, 8% grade 3 thrombopenia and 25% grade 3 anaemia). CONCLUSION: Split-course radiotherapy and concomitant carboplatin chemotherapy can be carried out in inoperable head and neck cancer without severe toxicity. After long-term follow-up, survival rates are unfavourable in this poor prognostic group of patients.     

Planned Early Neck Dissection Before Radiation for Persistent Neck Nodes After Induction Chemotherapy

Optimal management of advanced neck metastases as part of an organ preservation treatment approach for head and neck squamous carcinoma (HNSC) is unclear. Since 1989, our management paradigm for patients on organ preservation was modified to incorporate planned early neck dissection before radiation therapy for patients who did not achieve a complete response (CR) of neck nodes after induction chemotherapy (IC). The purpose of this study was to determine if planned early neck dissection is a safe and effective approach in the management of advanced nodal disease as part of organ preservation. Fifty-eight consecutive patients with advanced HNSC who were entered in organ preservation trials using induction chemotherapy and radiation with surgical salvage were studied. Median follow-up was 26 months. Of the 58 patients, 71% were stage IV. Patients were grouped by nodal response to chemotherapy and N class, and were analyzed with respect to patterns of recurrence, complications, and survival. Overall, the rate of CR of neck nodes was 49%. Fifty-one percent had less than a complete response of neck nodes after IC and required planned early neck dissection. There were no significant differences in patterns of recurrence, complications, interval time to start of radiation, recurrence, or survival rates between the CR and less than CR groups. These data suggest that planned early neck dissection for patients with less than CR in the neck after IC is not detrimental with respect to neck relapse or overall survival. We believe that planned early neck dissection can be safely incorporated into future organ preservation treatment protocols for patients with advanced head and neck carcinoma.     

Selective vs modified radical neck dissection and postoperative radiotherapy vs observation in the treatment of squamous cell carcinoma of the oral tongue

OBJECTIVES: To assess the role of selective neck dissection in patients with squamous cell carcinoma (SCC) of the oral tongue with advanced nodal disease, and to assess the role of postoperative radiotherapy in patients with SCC of the oral tongue with pathologically N1 necks. DESIGN: Retrospective study of the medical records of all patients who underwent neck dissection for SCC of the oral tongue from January 1, 1980, to December 31, 1995. Median follow-up was 5.7 years. SETTING: The University of Texas M. D. Anderson Cancer Center, Houston, a tertiary care cancer hospital. PATIENTS: A total of 220 patients with SCC of the oral tongue who received surgical treatment of both the primary tumor and the neck and who had an identifiable type of neck dissection, no synchronous or metachronous lesions, and no evidence of local recurrence. INTERVENTIONS: All patients underwent resection of the primary tumor and neck dissection. The extent of neck dissection was determined by surgeon preference. Some patients received radiotherapy to the neck as well. MAIN OUTCOME MEASURES: Clinical and pathological nodal status, type of neck dissection, and use of radiotherapy. The end points evaluated included the regional control rates. RESULTS: For clinically N+ patients, 5 of 45 treated with selective neck dissection and 1 of 19 treated with radical or modified radical neck dissection had recurrences in the ipsilateral neck. If only patients with significant tumor burden on final pathological examination (clinically N+/pathologically N2) are considered, 4 (25.0%) of 16 patients undergoing selective neck dissection had recurrences in the neck, while none of the 14 patients treated with radical or modified radical neck dissection had recurrences in the ipsilateral neck (P = .07). Of the 50 patients who had pathologically N1 disease, 25 received postoperative radiotherapy and 25 did not. Of the latter, 2 had recurrences in the neck, while none of the 25 patients who received radiotherapy had recurrences in the neck (P = .24). CONCLUSIONS: Selective neck dissection may be sufficient for many N+ patients with SCC of the oral tongue, but some patients with extensive nodal disease may benefit from more aggressive treatment of the neck. Radiotherapy may be beneficial for all of the node-positive patients, but further studies are needed. Prospective, randomized clinical trials will be useful in further defining the role of selective neck dissection in the clinically N2 neck and radiotherapy in the N1 neck for patients with SCC of the oral tongue.     

Adjuvant chemotherapy (nedaplatin/UFT) after concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma

To evaluate the efficacy of adjuvant chemotherapy after concurrent chemoradiotherapy, 41 previously untreated patients with locally advanced and resectable head and neck squamous cancer were enrolled in a study to compare adjuvant chemotherapy (Nedaplatin/UFT) after concurrent chemoradiotherapy (CDDP/5-FU) and concurrent chemoradiation alone. Nine of the patients had stage III tumors and 32 had stage IV tumors. The primary tumor site was the hypopharynx in 14 patients, the larynx in 12 patients, the oral cavity in 9 patients, and the oropharynx in 6 patients. Treatment consisted of 6 courses of Nedaplatin (80 mg/m2) repeated at 4-week intervals and one year of the oral administration of UFTE (400 mg/day) after concurrent chemoradiotherapy at an outpatient clinic. Toxicities included leukopenia (grade 3, 15.4%) and thrombocytopenia (grade 3, 7.7%). One death from a gastric ulcer occurred. The median overall survival time was 30.1 months (5.5-50.1 months) for the adjuvant chemotherapy group and 21.7 months (4.0-48.8 months) for the control group. The progression-free survival period was 22.8 months (5.6-33.9 months) for the adjuvant chemotherapy group and 26.5 months (5.6-33.9 months) for the control group. The two-year overall survival rate was 73.3% for the adjuvant chemotherapy group and 55.7% for the control group. A significant difference was observed in the two-year progression-free survival rates: 66.9% for the adjuvant chemotherapy group and 27.8% for the control group (p = 0.03290). Among the patients with a partial response to concurrent chemoradiotherapy, in particular, a significant difference in the two-year progression-free survival rates was seen : 59.3% for the adjuvant chemotherapy group and 15.3% for the control group (p = 0.01102). The rate of loco-regional failure was 29.6% for the adjuvant chemotherapy group and 64.3% for the control group (p = 0.0716). Distant metastasis was not detected in either group. The rate of organ preservation was 66.7% for the adjuvant chemotherapy group and 35.7% for the control group (p = 0.1183). This adjuvant chemotherapy regimen might improve the loco-regional control rates after concurrent chemoradiotherapy.     

Salvage surgery after locoregional failure in head and neck carcinoma patients treated with chemoradiotherapy

With the increasing use of concomitant chemoradiotherapy (CCRT) in the treatment of advanced head and neck carcinoma, surgery has lost ground as the first therapy and is reserved as a salvage treatment in cases of locoregional failure. The objective of our study was to review our experience in patients who had a local or regional recurrence after treatment with CCRT. Thirty-two patients underwent salvage surgery after CCRT: 24 were treated with a local or locoregional resection and 8 patients with a neck dissection only. In patients who had surgery involving the primary location of the tumor, some kind of reconstruction was required in 83% of cases. One or more postoperative complications occurred in nine patients. The median hospital stay was 18.5 days. There was a significant difference in hospital stay in relation to the appearance of surgical complications. Five-year adjusted survival after salvage surgery was 34.2% (CI 95% 13.2–55.2%). Adjusted survival was related to the status of the resection margins and appearance of neck nodes with extracapsular spread in the neck dissection. In conclusion, salvage surgery after CCRT involves extensive resections, requiring reconstruction techniques with regional or microanastomosed free flaps in most cases, achieving acceptable outcomes.     

Therapeutic outcomes of oral cancers at Kyoto University Hospital

CONCLUSION: The results suggest that early diagnosis and treatment are the most important factors to improve the prognosis in oral cancer patients. OBJECTIVE: In this retrospective study we analyzed the therapeutic outcome of oral cancers at out institute. PATIENTS AND METHODS: Thirty-one patients with oral cancers were treated between January 2000 and December 2004 at the Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital. Transoral resection of tumor with or without neck dissection was performed for early oral cancers (stage I and II), while more extensive resection and radical neck dissection followed by postoperative radiotherapy was performed for advanced cases (stage IIII and IV). In the treatment of early tongue cancer, either partial glossectomy or brachytherapy was selected. The 3-year disease-specific survival rates of all patients, early-staged, and advanced-staged patients were 82.2%, 92.9%, and 63.5%, respectively. The prognosis was significantly related to the clinical stage of the tumor.     

Intensive chemoradiotherapy as a primary treatment for organ preservation in patients with advanced cancer of the head and neck: efficacy, toxic effects, and limitations

OBJECTIVES: To evaluate the efficacy and toxic effects of intensive chemoradiotherapy as a primary modality for organ preservation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and to define the patterns of treatment failure associated with this therapy. DESIGN: Retrospective review. SETTING: Tertiary care referral center. PATIENTS: A total of 127 consecutive patients with advanced SCCHN treated with primary concurrent chemoradiotherapy. MAIN OUTCOME MEASURES: Efficacy data included the rates of tumor response to therapy, organ preservation, disease recurrence, overall and disease-specific survival, and patterns of treatment failure. Toxic effect data included the rate and grade of treatment-related complications and the rate of unscheduled hospital admissions for managing treatment-related toxic effects. RESULTS: Ninety-six patients (76%) were men and 31 (24%) were women. Average age at diagnosis was 62 years (range, 37-85 years). The primary tumor site was the oropharynx in 58 patients (46%), the larynx in 36 (28%), the hypopharynx in 20 (16%), the oral cavity in 10 (8%), and another site in 3 (2%). Most patients (91%) had stage III or IV disease. Average follow-up was 36 months. Primary chemoradiotherapy achieved complete response at the primary tumor site in 109 patients (86%). Patients with partial response, stable or progressive disease, or recurrence at the primary site underwent salvage surgery. Overall, at mean follow-up of 3 years, local disease control was achieved in 113 patients (89%), and organ preservation was possible in 102 patients (80%). Two thirds of all patients (n = 83) had clinical N+ disease. Complete clinical response to chemoradiotherapy in the neck was achieved in 57 of these patients (69%). However, complete response to chemoradiotherapy was 93%, 62%, and 47% for N1, N2, and N3 disease, respectively (P <.001). Patients achieving less than complete clinical response underwent salvage neck dissection. Overall, at an average follow-up of 36 months, regional disease control was achieved in 76 (92%) of the 83 patients with neck metastasis. Despite this high locoregional control rate, distant metastasis occurred in 18 patients (14%), was the most common site of disease recurrence (53%), and accounted for almost 40% of all treatment failures. Severe (grade 3 or 4) mucositis and neutropenia occurred in 33% and 25% of patients, respectively. Two patients (2%) died of treatment-related toxic effects. At 3-year mean follow-up, disease-specific and overall survival were 72% and 57%, respectively. Most deaths were due to distant metastasis, comorbidity, and second primary tumors. CONCLUSIONS: High rates of locoregional disease control and organ preservation are achievable with primary chemoradiotherapy in patients with advanced SCCHN, but they are associated with severe treatment-related toxic effects. Despite this effective local and regional disease control, improved survival is hampered by the relatively high incidence of distant metastasis, second primary tumors, and comorbidity.