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.     

Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundh?hlenkarzinome

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.     

Long-term results of a phase III randomized trial of postoperative radiotherapy with or without carboplatin in patients with high-risk head and neck cancer

BACKGROUND: The role of postoperative radiotherapy and carboplatin in squamous cell carcinoma of the head and neck (SCCHN) has not been established. METHODS: Patients with macroscopically resected stage III/IV SCCHN with high-risk pathologic features (> or =3 lymph nodes, extracapsular extension, perineural or angiolymphatic invasion, or involved margins) were randomized to receive postoperative radiotherapy alone (arm A) or the same radiotherapy plus carboplatin 100 mg/m intravenously once weekly during radiation (arm B). The primary endpoint was 2-year disease-free survival. RESULTS: Seventy-six patients were randomized, of whom 72 were eligible and analyzable (36 in each arm). The study was prematurely closed because of slow accrual. With a median follow-up of 5.3 years, the disease-free survival at 2 and 5 years was 71% and 53% in arm B versus 58% (P = .27) and 49% (P = .72) in arm A. The overall survival at 2 and 5 years was 74% and 47% in arm B versus 51% (P = .04) and 41% (P = .61) in arm A. Serious toxicities were infrequent in both arms. CONCLUSIONS: We could not demonstrate a benefit with the addition of carboplatin to postoperative radiotherapy, possibly because of insufficient sample size.     

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.     

Concomitant chemoradiotherapy in pyriform sinus carcinoma

OBJECTIVES: To test the effectiveness of concurrent chemoradiotherapy in patients with pyriform sinus carcinoma and to demonstrate the feasibility of an organ preservation approach. DESIGN: Clinical trial phase 2. SETTING: University Hospital Center, St-Etienne, France. PATIENTS: The study population comprised 46 male patients with resectable stage III and IV pyriform sinus carcinoma. METHODS: Two successive chemoradiation regimens were investigated. In protocol 1 (24 patients), carboplatin was given on days 1 through 5 and 28 through 33, with an area under the curve dose of 5 mg/mL for 1 minute per day and bifractionated radiotherapy (160 rad [1.6 Gy]/fraction) delivered on days 1 through 16 and 28 through 38. A treatment break was planned on days 16 through 27. In protocol 2 (22 patients), chemotherapy was given with the same dose of carboplatin on days 1 and 21, and fluorouracil (750 mg/m(2) per day) on days 1 through 7 and 21 through 28. Radiotherapy with a single fraction of 180 rad (1.8 Gy)/d was delivered during the first 2 weeks and then 150 rad (1.5 Gy) twice a day during the next 3 weeks. MAIN OUTCOME MEASURES: Patients were evaluated for tumor response, toxic reactions, and organ preservation and survival rates. Statistical analysis of disease-free survival and overall survival was performed using the Kaplan-Meier method. RESULTS: A complete response was noted in 21 (88%) of the 24 patients following protocol 1 and 16 (73%) of the 22 patients following protocol 2. After 2 years of follow up, 16 patients (67%) (protocol 1) and 12 patients (55%) (protocol 2) retained their larynx without evidence of disease. During therapy, 15 patients (63%) (protocol 1) and 19 patients (86%) (protocol 2) required unplanned hospitalization for toxic effects. The overall survival and disease-free survival rates at 2 years were 58% (protocol 1) vs 53% (protocol 2) and 39% (protocol 1) vs 41% (protocol 2) (P =.80), respectively. CONCLUSION: Concomitant chemotherapy and bifractionated radiotherapy, although toxic, leads to good locoregional control and therefore to a significant level of laryngeal preservation.     

Concurrent chemoradiotherapy with carboplatin and uracil-ftegafur in patients with stage two (T2 N0 M0) squamous cell carcinoma of the glottic larynx

This study aimed to evaluate the efficacy and toxicity of concurrent chemoradiotherapy as a primary treatment modality for larynx preservation in patients with stage two squamous cell carcinoma (SCC) of the glottic larynx. Between February 2000 and August 2003, a total of 20 patients received concurrent chemoradiotherapy. Carboplatin was given intravenously once a week during the period of radiotherapy. The weekly carboplatin dose was based on the area under the curve 1 to 1.25. Uracil-ftegafur (UFT) was given in a daily oral dose of 300 mg as tegafur. Radiotherapy was delivered five days a week using a once-daily fractionation of 2.0 Gray (Gy), to a total dose of 66-72 Gy. The three-year overall survival rate with larynx preservation was 100 per cent. Concurrent chemoradiotherapy with carboplatin and UFT for stage two SCC of the glottic larynx was safe and effective in improving local control with larynx preservation.     

Concurrent chemotherapy and radiotherapy as initial treatment for stage II supraglottic squamous cell carcinoma

Objective: To evaluate the efficacy and safety of concurrent carboplatin (CBDCA) and radiotherapy for laryngeal carcinoma, we investigated survival rates and laryngeal preservation rates in patients with this treatment modality and those with radiation therapy only. Methods: We underwent chemotherapy with CBDCA and conventional radiotherapy concurrently to 17 patients with untreated stage II (T2N0M0) supraglottic squamous cell carcinoma since November 1990. CBDCA (100 mg/m²) was administered intravenously once a week concurrently with radiotherapy (2.5 Gy/fr, 4 times a week). At the dose of 40 Gy, the results were evaluated, and some of the patients underwent planned surgery and others continued the radiotherapy up to 65 Gy. Results: Overall 5-year survival rate by Kaplan–Meier method was 81.1%. Actual laryngeal preservation rate was 76.0%. Toxicity over grade III was noticed in two patients. Compared with 14 cases of historical controls, which were treated by radiation therapy alone between 1988 and 1990, the cases with concurrent radiotherapy and chemotherapy had statistically significant advantage in overall successful laryngeal preservation rate (P<0.05), whereas the two groups were not significantly different in the overall 5-year survival rate.     

Concurrent chemoradiotherapy with carboplatin and uracil-f tegafur (UFT) for patients with poor performance status with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

CONCLUSIONS: Concurrent chemoradiotherapy with carboplatin and uracil-f tegafur (UFT) seems to be a promising and appropriate regimen for patients with poor performance status (PS) with locally advanced squamous cell carcinoma of the head and neck (SCCHN). OBJECTIVE: We designed a regimen based on divided low-dose administration to reduce toxicity for patients with poor PS with locally advanced SCCHN. PATIENTS AND METHODS: Sixty-two patients with previously untreated stage III-IV SCCHN and PS of 2 or 3 were entered into this study. They received radiotherapy: 70 Gy/35 fractions. The chemotherapy consisted of a combination of carboplatin (Calvert's formula: (GFR+25) x AUC (=5)/4 mg/week; where AUC area under the curve and GFR = glomerular filtration rate) and UFT (300 mg/day, per os). RESULTS: The overall clinical response rate and the pathological complete response (CR) were 90% (56/62) and 61% (38/62), respectively. Grade > or =3 mucositis occurred in only 6% of patients (4/62) and grade 2 > or =3 leukocytopenia and neutropenia occurred in only 5% (3/62).     

Therapeutic efficacy of selective intraarterial chemoradiotherapy with docetaxel and nedaplatin for human papilloma virus-negative oropharyngeal cancer

ObjectiveHuman papilloma virus-negative oropharyngeal cancer has not achieved satisfactory outcomes compared with those of human papilloma virus-positive oropharyngeal cancer. This study evaluated the therapeutic efficacy of selective intraarterial chemoradiotherapy with the docetaxel and nedaplatin regimen for human papilloma virus-negative oropharyngeal cancer.MethodsTwenty-two consecutive patients with human papilloma virus-negative oropharyngeal cancer who had undergone selective intraarterial chemoradiotherapy were retrospectively analyzed. The primary tumor and whole neck were irradiated (50 Gy). Subsequently, the primary site and metastatic lymph nodes were boosted by 20 Gy. The intraarterial chemotherapy regimen comprised a combination of nedaplatin (80 mg/m²) and docetaxel (60 mg/m²), which was initially administered at the start of radiotherapy and was given every 4 weeks for three sessions. Each intraarterial dose of an anticancer agent was determined according to the percentage of the tumor volume supplied by the target artery to the total tumor volume, which was intraoperatively measured via cone-beam computed tomography. The outcome measures were locoregional control, disease-free survival, and overall survival rates and adverse events. Statistical analyses were performed using the Kaplan–Meier method.ResultsThe median follow-up period was 59 (range, 15–103) months. The T stage was T1/T2 in 5 patients (23%), T3 in 5 patients (23%), and T4 in 12 patients (54%). Cervical lymph node metastasis was staged as ≥N2c in 7 (32%) patients. Complete response was achieved in all patients at the first imaging examination after intraarterial chemoradiotherapy. The 5-year locoregional control, disease-free survival, and overall survival rates were 96% (95% confidence interval, 0.72–0.99), 91% (95% confidence interval, 0.68–0.98), and 100% (95% confidence interval, not available), respectively. Regarding serious acute adverse events, grade 4 laryngeal edema and leukopenia were observed in 1 (5%) and 11 patients (50%), respectively. No other serious acute adverse events were observed.ConclusionSelective intraarterial chemoradiotherapy with docetaxel and nedaplatin has the potential to achieve favorable locoregional control, disease-free survival, and overall survival rates in human papilloma virus-negative oropharyngeal cancer.     

T-status and an oral fluoropyrimidine,S-1, adjuvant chemotherapy are prognostic factors in reduced-RADPLAT for resectable hypopharyngeal cancer

Conclusion: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit. Objectives: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC). Methods: Between 1999–2012, 50 patients with stage II–IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2–5 courses of IA cisplatin infusion (100?mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66–70?Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients. Results: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively.     

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer

Objective

In this study we evaluate the clinical response and safety profile of a regimen of docetaxel + carboplatin concurrent with radiotherapy (RT) in locally advanced squamous cell carcinoma of head and neck (HNSCC).

Methods

Between January 2006 and December 2008, we enrolled 38 patients (stage IVA: 29 patients; stage III: 9 patients). Fourteen had oral cavity cancer (tongue 10, buccal mucosa 2, alveolar ridge 1, floor of mouth 1), 10 had oropharyngeal cancer (base of tongue 5, tonsil 5), 13 had laryngeal cancer, and 1 had maxillary sinus cancer. Patients received concurrent docetaxel 15 mg/m² 1-h infusion plus carboplatin AUC of 2, 30-min infusion on days 1, 8, 15, 22, 29, and 36. RT began on day 1 of concurrent chemotherapy with 2 cGy/fraction, 5 fractions/week (total dose: 66-70 cGy). Tumor was assessed by CT scan 3 months post-completion of concurrent chemoradiotherapy.

Results

Thirty-five patients were evaluated (2 refused to receive all treatments, 1 had serious adverse event [rash, wheezing] from docetaxel first dose). The primary study endpoint of clinical response was achieved in 26 (74.3%) patients, 6 (17.1%) had stable disease, and 3 (8.6%) had disease progression. The 2-year disease-free survival was 62.9% (CI: 45.85-79.95%). The 2-year overall survival was 64.1% (CI: 43.52-84.68%). The most common Grade 3 toxicities were mucositis, xerostomia and dysphagia (13.9% each) and dermatitis (11%). No Grade 4 toxicities were observed.

Conclusion

In conclusion, this study with a limited number of patients, docetaxel + carboplatin concurrent with RT appears to show acceptable activity and is generally well tolerated in patients with locally advanced HNSCC.     

Prognostic impact of perineural invasion in hypopharyngeal squamous cell carcinoma

Objectives: The aim of this study was to evaluate the role of PNI in HPSCC.

Methods: The medical records of 105 patients who underwent surgery-based treatment for HPSCC were reviewed. Clinicopathologic parameters including disease-specific survival were correlated with PNI.

Results: PNI was identified in 27 of the 105 (25.7%) cases of HPSCC. Correlation analysis demonstrated that PNI in HPSCC was significantly correlated with pN classification (10.3% in N0/N1 vs 34.8% in N2/N3, p?=?0.006). Patients with PNI had decreased 5-year disease-specific survival with borderline significance (p?=?0.065). In a sub-set of 31 patients who did not receive post-operative radiotherapy, PNI was determined to be a significant prognostic predictor (p?=?0.033). In multivariate analysis, extracapsular invasion was the only independent prognostic factor for disease-specific survival (p?=?0.001).

Conclusion: Perineural invasion (PNI) should be considered an independent predictor for cervical lymph node involvement. PNI status in primary hypopharyngeal squamous cell carcinoma (HPSCC) specimens should be considered in decisions concerning adjuvant radiotherapy.     

Clinical and pathologic predictors of survival in patients with squamous cell carcinoma of the hypopharynx after surgical treatment

OBJECTIVES: Hypopharyngeal squamous cell carcinoma (HPSCC) usually presents at an advanced stage. Although chemoradiotherapy has become more popular in treating HPSCC in recent years, surgery with postoperative adjuvant therapy still plays an important role. The purpose of this study was to identify the clinicopathologic factors that predict survival in patients with HPSCC who underwent surgical treatment. METHODS: Between 1986 and 1995, 94 previously untreated HPSCC patients who underwent surgery with or without postoperative radiotherapy were enrolled. The surgical specimens were reexamined by a single pathologist. The clinicopathologic parameters and prognostic data were analyzed. RESULTS: With a median follow-up of 50 months, the 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were 47%, 60%, and 58%, respectively. Thirty-seven patients (39%) had tumor recurrence. The level of lymph node metastasis was an independent factor in OS, DSS, and RFS. Neck biopsy before surgery, tumor involvement of more than 1 subsite, and extracapsular spread were independent factors in DSS, as was lymphovascular permeation in RFS. CONCLUSIONS: The level of cervical lymph node metastasis is the only independent prognostic factor in OS, DSS, and RFS. The addition of postoperative chemoradiotherapy may benefit high-risk cases.     

The status of sequential chemo-/radiotherapy in inoperable head and neck cancers. Personal results and review of the literature

Between March 1986 and October 1987 75 patients with advanced cancer of the head and neck were treated with initial chemotherapy before surgery and/or radiotherapy. Chemotherapy consisted of three courses of cisplatin or carboplatin combined with 5-fluorouracil (5-FU). Three weeks after the last course of chemotherapy 34 patients with unresectable tumours received conventional fractionated radiotherapy (60-64 Gy). Of these 34 patients, 32 were evaluated for response and survival with a minimal follow-up of 3 years (22% stage III, 78% stage IV). As the response to cisplatin/5-FU and carboplatin/5-FU was similar (72% versus 64%), survival rates of both chemotherapeutic regimens are presented together. At the end of sequential chemo-radiotherapy 11 patients (34%) were clinically free of disease with an overall response rate of 69%. The survival after 3 years was 12.5% (4 patients) with a median of 15 months. Disease-free survival was 27% (3/11). These poor results confirm the results of other investigators. They indicate that induction chemotherapy does not improve the results of conventional radiotherapy in unresectable carcinomas of the head and neck, even when using highly effective platinum-containing regimens.     

Assessment of Oropharyngeal Cancer

The records of 87 patients with squamous cell carcinoma of the oropharynx, treated between 1971 and 1998 at Kitasato University Hospital, were reviewed with the aim of investigating further directions for oropharyngeal cancer treatment. The patients were divided into four major treatment groups: a radiotherapy group; an operation group; a simultaneous chemoradiotherapy group; and a combination treatment group. The 5-year cumulative survival rates for Stages I-IV were 75%, 78%, 68% and 41%, respectively. None of the T4 cases survived for >5 years. The survival rates of patients with anterior and posterior wall cancers were higher than those with lateral and superior wall cancers. All patients in the operation group survived for 5 years. The survival rates for the combination treatment, radiotherapy and chemoradiotherapy groups were 80%, 57% and 52%, respectively. The 5-year cumulative local control rates for T2-T4 tumors were 61%, 58% and 0%, respectively. The combination therapy (80%) and chemoradiotherapy (66%) groups had significantly higher local control rates than the radiation group (33%). The 5-year cumulative regional control rate according to N classification was 80%, except for N2 lymph nodes, for which only 60% of patients were free of regional recurrences. Approximately 15% of patients with oropharyngeal cancer had either distant metastases or double cancer. We conclude from this review that simultaneous chemoradiotherapy is a good initial therapy for Stages T1-T3 oropharyngeal cancer. However, for T4 tumors, further combinations of both chemoradiotherapy and surgery and the development of new anticancer drugs for use in chemoradiotherapy, immunotherapy or gene therapy may be needed.     

Clinical study of early laryngeal cancer

We retrospectively analyzed 71 consecutive cases of early laryngeal cancer (stage I or II) that had undergone primary treatment in our department between 1999 and 2004. There were 68 males and 3 females, and their ages ranged from 40 to 85 years of age (average; 67.7 years). Eight patients had the supraglottic type, 61 had the glottic type, and 2 had the subglottic type. Chemoradiotherapy was performed as the primary treatment except in the patients with glottic T1a cancer, who received radiotherapy alone. The 5-year survival rates was 91.1% for glottic cancer (T1a: 100%, T1b: 92.3%, T2: 85.8%) and 75.0% for supraglottic cancer. The local control rate of glottic cancer was 79.6% (T1a: 80.0%, T1b: 74.0%, T2: 85.2%), and significantly higher than that of supraglottic cancer (56.2%, p < 0.05). The laryngeal preservation rate was 84.4% in glottic cancer (T1a: 100%, T1b: 76.9%, T2: 77.5%) and 58.3% in supraglottic cancer, and the difference between T1a and T2 glottic cancer was significant (p < 0.05). Local recurrence and cervical lymph node metastasis were seen in 9 patients and 6 patients, respectively. Distant metastasis occurred in 4 patients, all of whom had the glottic type. Four patients died of their disease, and distant metastasis was the major cause of death in 3 of them. These results indicate that additional treatment should be performed in cases in which radiotherapy/chemoradiotherapy is ineffective and that both in the early stages glottic and supraglottic cancers can be successfully treated by radiotherapy/chemoradiotherapy. The results also suggested that the survival of patients with early laryngeal cancer depends on whether they develop distant metastasis. Introduction of adjuvant chemotherapy to improve their prognosis remains to be assessed.     

Hypopharyngeal cancer: results of treatment based on radiation therapy and salvage surgery

OBJECTIVES: The purpose of this study is to present the treatment results and to identify possible prognostic indicators in patients with hypopharyngeal squamous cell carcinoma (HPC). STUDY DESIGN: A consecutively admitted series of 110 patients was analyzed retrospectively. The female male ratio was 29: 81. The sites of the tumors were: pyriform fossa (72%), postcricoid area (18%), and posterior pharyngeal wall (10%). T-status was T1: 15%, T2: 26%, T3: 28%, and T4: 37%. N-status was N0: 27%, N1: 33%, N2: 26%, and N3: 14%. METHODS: One hundred three patients (94%) were treated with curative intent. Two of these received primary surgery; the remaining 101 patients had primary radiotherapy. Seven patients (6%) received no or only palliative treatment. RESULTS: The 5- and 10-year estimates for crude survival (CS) were 16% and 7% and disease-specific survival (DSS) 28% and 23%, respectively. In the group of patients treated with curatively intended radiotherapy, 71 recurrences were observed at the time of analysis. The 5- and 10-year RFS estimates were both 17%. The values for CS were 18% and 8% and the values for DSS were 31% and 26%, respectively. Univariate survival analyses of age, sex, T-status, N-status, and TNM staging did not show any significant influence on survival. CONCLUSIONS: We conclude that the survival of patients with HPC treated with primary radiotherapy and salvage surgery is poor and that other treatment modalities have to be considered.     

Concurrent chemoradiotherapy for locally unresectable head and neck cancer

In patients with locally unresectable head and neck cancer with large nodal involvement, the expected five-year survival is as low as 1-2%. To improve the prognosis of these patients, we studied the usefulness of concurrent chemoradiotherapy in a phase II trial. Between September 1996 and May 1999, thirty-five patients with locally unresectable head and neck cancer were administered concurrent chemoradiotherapy consisting of low-dose and long-term treatment with cisplatin (CDDP) plus 5-fluorouracil (5FU), or (L-CF); the L-CF regimen consisted of CDDP, 3 mg/m2 on 5 days of the week and 5FU, 150 mg/m2 as a 24-hour infusion on 5 days of the week. Concurrently, conventional radiotherapy was given up to total dose of around 60 Gy. In the 33 patients evaluable for response, 17 complete and 9 partial responses were noted, with an overall response rate of 79%. Oral mucostis and myelosuppression were the major side effects and mucositis was a dose limiting toxicity. This study demonstrates increase in survival among the responders (complete + partial) in the concurrent chemoradiotherapy setting. However 8 local relapses were eventually noted in the 17 complete responders. We concluded that this treatment strategy was beneficial in patients with locally unresectable head and neck cancer.     

Value of computed tomography-based tumor volume as a predictor of outcomes in hypopharyngeal cancer after treatment with definitive radiotherapy

OBJECTIVES: To investigate the value of pretreatment computed tomography (CT) volumetric analysis for the prediction of treatment outcome in patients with hypopharyngeal cancer (HPC) treated by definitive radiotherapy (RT). METHODS: From January 2000 through February 2004, 63 patients with HPC were enrolled for a retrospective analysis. The pyriform sinus was the principle site of involvement in 62 cases. All patients received with 1.8 Gy daily to a total dose of 68.4 to 73.8 Gy (median, 70.2 Gy). Contrast-enhanced CT images were transferred to a planning system. Tumor volume measurement was derived from summation of the primary and metastatic nodal tumor. RESULTS: With a median follow-up of 38 (range, 24-68) months, the 5 year local relapse-free survival (LRFS) was 83% for patients with T1 to T2 disease, 46% for those with T3 disease, and 40% for those with T4 disease (P = .01). The 5 year LRFS was 75% for those with tumors less than 40 mL and 26% when volumes were 40 mL of larger (P = .0001). For patients with T3 to T4 disease, the 5 year LRFS was 70% for those with tumors less than 40 mL and 24% when volumes were 40 mL or larger (P = .0005). Multivariate analyses of local relapse-free survival revealed two prognostic factors: tumor volume more than 40 mL and the involvement of the larynx. CONCLUSIONS: CT-based tumor volumes are a strong predictor of outcomes for HPC treated using definitive RT. A selected group of patients, mainly those with tumor volumes less than 40 mL, should be considered for laryngeal preservation.     

Sequential external beam radiotherapy and high-dose-rate intracavitary brachytherapy in T1 and T2 nasopharyngeal carcinoma: an evaluation of long-term outcome

OBJECTIVES/HYPOTHESIS: The standard treatment for nonmetastatic nasopharyngeal carcinoma (NPC) is external beam radiotherapy (EBRT), with or without chemotherapy. Because local control in NPC is an independent prognostic factor for distant metastases and survival, various dose-escalation strategies have been used to reduce recurrences at the primary site. The objective of this report was to evaluate the outcome of adjuvant high-dose-rate intracavitary brachytherapy (HDRIB) in patients with T1 and T2 NPC. STUDY DESIGN AND METHODS: Thirty-three consecutive patients with T1 and T2 NPC were treated prospectively according to a standardized institutional protocol between March 1999 and July 2001. Seventeen patients with stage I/II disease were treated with EBRT to 66 Gy followed by HDRIB (10 Gy in 2 weekly 5 Gy fractions). The remaining 16 patients with Stage III to IVb disease received chemotherapy in addition to radiation. All patients were assessed for treatment response, local control, survival, and toxicity. RESULTS: Median follow-up for all surviving patients was 67 (range 52-76) months. Local failure occurred in two patients; both subsequently underwent successful salvage treatments. Three patients died of metastatic disease, whereas two died of unrelated causes. Five year local control, overall survival, and disease-free survival rates were 93.8%, 83.9% and 78.4%, respectively. All patients experienced acute or late radiotherapy-related sequelae. However, no grade 4/5 toxicities were reported. Specifically, toxicities that could be attributed to brachytherapy were not seen, except for in one patient who developed severe choanal stenosis. CONCLUSIONS: EBRT supplemented by HDRIB produced superior local control rates for T1 and T2 NPC at 5 years of follow-up, with acceptable rates of acute and late toxicities.