Long-term efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell carcinoma

ObjectiveThe present study aimed to retrospectively analyze the long-term efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell carcinoma.MethodsThe study enrolled 53 patients (23 with stage II disease, 13 with stage III disease, and 17 with stage IV disease). S-1 was administered orally twice a day for 14 days, followed by a two-week rest period. Nedaplatin was intravenously administered on day 4. Where possible, two courses of chemotherapy were performed. Radiotherapy was started with the administration of S-1. We analyzed the clinical response, survival rate, acute adverse events, and late swallowing toxicity.ResultsThe complete response rates for the primary tumor and neck lymph node metastases were 94.3% and 79.3%, respectively. The five-year overall survival rate was 79.5%, the five-year disease-specific survival rate was 84.8%, and the five-year relapse-free survival rate was 73.7%. The main acute adverse events were leukopenia, neutropenia, mucositis, and dermatitis. No patient had severe nephrotoxicity. Late swallowing toxicity was observed in 13 patients.ConclusionsThe low toxicity, and low nephrotoxicity of chemoradiotherapy with nedaplatin and S-1 have a positive impact on long-term survival. The combination of nedaplatin and S-1 can be used instead of cisplatin and 5-?uorouracil as a safer regimen, especially in patients with some complications and those requiring treatment in an outpatient setting.     

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.     

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.     

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.     

Real-life assessment of Volumetric Modulated Arc Therapy (VMAT) toxicity in Head and Neck Squamous Cell Carcinoma (HNSCC) treatment

Conclusion: The present study demonstrates the feasibility of VMAT in association with platin or cetuximab in HNSCC and reports VMAT-related acute and late toxicities for the first time. Objectives: New radiotherapy techniques, such as Volumetric Modulated Arc Therapy (VMAT) were developed to lower RT-related toxicity. The aim of the present study was to investigate acute and late toxicities of head and neck squamous cell carcinoma (HNSCC) patients treated using VMAT. Methods: This study investigated retrospectively all patients with HNSCC who received VMAT in curative intent. Results: From 2010–2013, 150 patients were treated. Seventy-five patients (50%) received concurrent chemotherapy with VMAT, 51 patients (34%) received VMAT alone and 24 patients (16%) received concurrent cetuximab with VMAT. Mean delivered dose to planning target volume tumor (PTV T), high risk nodes (PTV HNR), low risk nodes (PTV LNR) and prophylactic nodes (PTV PN) were: 65.2 Gy, 62.9 Gy, 55.4 Gy, and 51.5 Gy, respectively. PTV mean coverages were higher than 96.5%. Most common grade 3/4 acute infield toxicities were mucosis (n?=?28, 19%), dysphagia (n?=?24, 16%), and dermatitis (n?=?24, 16%). With a median follow-up of 16.0 months, most common late toxicities were dysphagia (n?=?30, 20%), xerostomia (n?=?28, 19%), larynx stiff (n?=?17, 11%), and skin fibrosis (n?=?14, 9%).     

Diagnostic work-up and outcome of cervical metastases from an unknown primary

Conclusions. An intensive diagnostic work-up including ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) detects many unknown primary tumours, leads to a low emergence rate of primary tumours, and selects carcinoma of unknown primary with much more favourable results after neck dissection and postoperative radiotherapy. Objective. To investigate the optimal diagnostic approach and best treatment modality for rare head and neck cancer of unknown primary. Patients and methods. In a retrospective study, 69 patients admitted from 1987 to 2002 with cervical lymph node metastases without apparent primary were reviewed. Test characteristics of all diagnostic procedures were calculated. Disease-free and overall survival rates were calculated. Major prognostic factors were analysed univariately. Results. At the primary site FDG-PET showed the best sensitivity with 69% and the highest negative predictive value with 87%. Computed tomography and magnetic resonance imaging had a better specificity with 87% and 95%, respectively. The primary tumour was detected in 23 cases (33%). Frequent primary tumour origin was the palatine tonsil (n=8, 35%), base of the tongue (n=6, 26%) and lung (n=4, 17%). All patients with unknown primary were treated by neck dissection. Adjuvant radiotherapy was performed in 26 patients (57%), concurrent radiochemotherapy was performed in 12 patients (26%). The primary emergence rate was 7%. The 5-year overall survival rate was inferior in patients with detected primary in comparison with patients with unknown primary (22% versus 52%). Significant prognostic factors in case of unknown primary were M stage, smoking, alcohol consumption and tonsillectomy. Radiotherapy but not chemotherapy with carboplatin influenced the overall survival.     

Treatment outcomes of concurrent chemoradiotherapy for locally advanced sinonasal squamous cell carcinoma: A single-institution study

Conclusions: CCRT is a potential treatment option for locally advanced sinonasal SCC in terms of organ preservation. Objectives: Concurrent chemoradiotherapy (CCRT) is increasingly used for patients with advanced head and neck cancer to preserve organ function and improve survival. In the present study, treatment outcomes were compared between surgery and post-operative radiotherapy (PORT) and CCRT in patients with locally advanced sinonasal squamous cell carcinoma (SCC). Methods: The records of 30 patients with non-metastatic stage III and IV sinonasal SCC were retrospectively reviewed. Fifteen patients were treated with CCRT and 15 patients underwent PORT. Results: The locoregional recurrence-free, distant metastasis-free, disease-free, disease-specific, and overall survival rates did not differ between PORT and CCRT groups. In addition, there were no significant differences in incidence rates of acute and chronic toxicities between the two groups.     

Recurrence patterns after postoperative radiotherapy for squamous cell carcinoma of the pharynx and larynx

Conclusions: Distant metastasis was a major pattern of recurrence after postoperative radiotherapy (PORT) for squamous cell carcinoma (SCC) of the oropharynx, hypopharynx, and larynx. PORT provided good loco-regional control, with tolerable toxicities. Advanced pT and pN were unfavorable prognostic factors. Objective: To determine the clinical outcomes, and the patterns and risk factors for recurrence of SCCs of the oropharynx, hypopharynx, and larynx treated with surgery and PORT. Methods: We retrospectively reviewed 84 patients who received PORT after definitive surgery for SCC of the oropharynx, hypopharynx, or larynx between 2000 and 2010. The primary sites were the oropharynx in 25 patients, hypopharynx in 47 patients, and larynx in 12 patients. Results: The 3-year overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) rates were 64.9%, 56.7%, and 92.1%, respectively. Recurrences were observed in 27 patients: 6 patients had loco-regional recurrence and 23 patients developed distant metastasis. On multivariate analysis, pT4 and pN2c-N3 displayed significantly worse effects on OS (p = 0.02 and p < 0.01, respectively) and PFS (p = 0.02 and p < 0.001, respectively). In the acute phase, 12 patients experienced grade 3 or 4 toxicities. There were no grade 5 toxicities. Late grade 3 toxicity developed in six patients and no grade 4 or 5 toxicities were observed.     

High-dose cisplatin concurrent to conventionally delivered radiotherapy is associated with unacceptable toxicity in unresectable,non-metastatic stage IV head and neck squamous cell carcinoma

Unresectable head and neck squamous cell carcinoma (HNSCC), non-metastatic, comprises a heterogeneous group of patients (pts), formed of stage III and IV pts. Since the available literature had not distinguished among these two groups, we prospectively addressed whether the recommended regimen involving cisplatin 100 mg/m² concurrent to conventionally delivered radiotherapy (RT) is feasible in stage IV pts, based on the efficacy and safety of this regimen. A total of 30 pts were enrolled onto this study. Chemoradiation (CRT) consisted of RT 70 Gy, delivered in 35 daily fractions of 2 Gy, in 7 weeks, concurrent to cisplatin 100 mg/m² on days 1, 22 and 43. Supportive treatment was provided as needed. Twenty-eight pts had tumors staged as T4 and 20 had N2 or N3 cervical involvement. The most common primary sites were the oral cavity and the oropharynx (23 pts). We observed six complete responses and 12 partial responses, with an overall response rate of 60%. A high rate of treatment-related toxicities was observed, with three deaths during CRT, and 26 pts suffering from one or more grade 3/4 toxicities, mainly dysphagia, mucositis, dermatitis, vomiting, infection or anemia. A prolonged treatment time was observed (63 days), as a result of unplanned treatment breaks. The lack of requirement of red blood cell transfusion was favorably related to the response to the treatment (93% vs. 50%, P = 0.033). For the whole population, with a median follow-up of 20.8 months, the median progression-free survival (PFS) was 8.0 months, and the median overall survival (OS) was 17.3 months. Longer median PFS and OS were seen in responding pts (12.8 vs. 4.1 months, P = 0.0001; and not reached (NR) vs. 10.4 months, P = 0.0037, respectively), as well as in those pts not requiring red blood cell transfusion (12.8 vs. 3.9 months, P = 0.0162; and NR vs. 10.4 months, P = 0.0176, respectively). In conclusion, this concurrent CRT regimen is hardly delivered in stage IV, unresectable, locally advanced HNSCC pts, due to treatment-related toxicities and longer RT duration. As a subset of pts may benefit from this regimen, adequate patient selection and aggressive supportive measures are essential.     

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.     

A comparison of radiotherapy or radiochemotherapy with symptomatic treatment alone in patients with advanced head and neck carcinomas

The choice of palliative treatment and the prognostic factors in unresectable head and neck cancer cases continue to be controversial. In the present study we compared the survival rates of untreated stage IV head and neck cancer patients with cases managed prospectively at A.C. Camargo Hospital for Cancer with neoadjuvant chemotherapy, concomitant chemotherapy or radiotherapy alone. Previous results had shown that while the type of treatment did not influence survival rates (P = 0.706), tumor response to treatment (whether complete, partial or none) significantly influenced survival (P = 0.00002). In the present study we compared the survival rates in the groups with untreated patients (who remained untreated until death) with the same demographic and clinical characteristics of patients receiving treatment. We found that there was a significant difference between the survival rates of the untreated group and those of the treated groups that was independent of the type of treatment performed (P < 0.00001) or the tumor response to treatment (P < 0.0001). Received: 19 October 1998 / Accepted: 15 April 1999     

Chemoradiotherapy for advanced head and neck cancer — Analysis of a prospective, randomized trial

Objective: To study the efficacy of neo-adjuvant chemotherapy followed by radiotherapy in advanced head and neck cancer.Study design: Randomised, prospective study.Setting: Tertiary academic referral center.Patients: One hundred and eighty patients of advanced head and neck squamous cell carcinoma.Intervention: Patients were randomized into two arms. The study arm (CT-RT arm) received 3 cycles of anterior chemotherapy with Inj. Cisplatin 100 mg/m² on D₁ and Inj 5F.U. 700 mg/m² on D₁-D₄ at an interval of 21 days, followed by external radiation. The control arm (RT arm) received external radiotherapy only. The dose of Radiotherapy was 64 to 68 Gy in conventional fractionation.Results: Patients of CT-RT showed better tumour control locally than patients who received only RT. Toxicities were commoner in CT-RT arm but they were manageable. 5 year survival is higher in the CT-RT arm (21% vs 16%; p value> 0.05).Conclusion: Anterior chemotherapy with Cisplatin and 5F.U. is associated with good clinical response which is translated into increased survival along with acceptable toxicities.     

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.     

Evaluation of survival of patients with locally advanced head and neck cancer treated in a single center

IntroductionEven with improved treatment outcomes with multimodality approaches, the question of what is the best initial treatment for locally advanced head and neck cancer still remains unanswered.ObjectiveTo review the overall survival of a large cohort of head and neck cancer, patients with locally advanced head and neck cancer treated in a single institution.Material and methodsWe studied a cohort of patients with locally advanced head and neck cancer treated in our institution in the last fifteen years. To gather a large sample of patients with adequate follow-up time, a cross-check between ours and Fundação Oncocentro de São Paulo databases were done. We included patients with head and neck cancer, clinical or pathological staging III or IV, treated with surgery followed by radiotherapy or surgery plus chemoradiation or radiotherapy alone or chemoradiation alone.Results796 patients with locally advanced head and neck cancer were included, 88% male, 44% age >60 years and 76% stage IV. The tumor location was the oral cavity (34%), oropharynx (27%), hypopharynx (17%) and larynx (17%). The treatment groups were chemoradiation alone (39.7%), surgery plus chemoradiation (26.3%), surgery followed by radiotherapy (18.5%) and radiotherapy alone (15.5%). Comparing the clinical variables between the treatment groups significant differences in age and clinical stage were observed. With a median follow up of 7.5 years (1–16 years), for the entire cohort, the overall survival at 5 and 10 years was 34.8% and 28%. The overall survival at 5 and 10 years was 16.7% and 12.2% for radiotherapy alone, 38.8% and 26.3% for surgery followed by radiotherapy, 28% and 16.6% for chemoradiation alone, and 37.3% and 23.2% for surgery plus chemoradiation. The staging IV (p = 0.03) and radiotherapy alone (p = 0.05), had a worst survival in multivariate analysis. Surgical groups vs. chemoradiation alone had no significant difference for overall survival.ConclusionThe present study is the largest cohort of locally advanced head and neck cancer of Brazilian patients to evaluate treatment outcomes. Although there were significant clinical differences between surgical and radiotherapy groups, surgery or chemoradiation alone as the initial treatment resulted in no significant difference in survival.     

Planned postradiotherapy bilateral neck dissection for head and neck cancer

Purpose: This is a retrospective analysis of 50 patients with squamous cell carcinoma of the head and neck treated with radiotherapy (RT) to the primary site and bilateral neck followed by a planned bilateral neck dissection approximately 4 to 6 weeks after completion of RT.Patients and Methods: Between November 1964 and March 1997, 50 patients underwent bilateral neck dissections after RT, with minimum 2-year follow-up. Forty-eight patients had bilateral positive neck nodes.Results: At 5 years, the rates of neck disease control, local-regional control, and cause-specific survival were 76%, 70%, and 39%, respectively. Five severe complications developed after surgery, and 1 developed after RT.Conclusions: Radiotherapy followed by a planned bilateral neck dissection resulted in a high rate of local-regional control with acceptable morbidity. The likelihood of severe complications after simultaneous (as opposed to staged) neck dissection was not significantly different (P = .24). (Am J Otolaryngol 2001;22:383-386.     

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.     

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.     

Development of novel radioresistant oral squamous cell carcinoma cell lines.

Objectives. Oral cancer is the most common head and neck cancer with an estimated 2 75 000 new cases in 2002.¹ Currently radiotherapy plays an important role in the management of oral cancer. Rates of radioresistance reported in the literature range from 19–53%.² This wide range of reported rates of radioresistance stems from variation in the definition of a radioresistant tumour. As all tumours in vivo posses a heterogeneous cell population, samples of tumour tissue taken for analysis cannot be guaranteed to have originated from a radioresistant subpopulation. These, and other factors, cause the discrepancy in resistance rates. This study aimed to address these issues by creating novel radioresistant cell lines. Method. Two oral cancer cell lines were studied. They were divided into two samples and cultured in identical conditions. Initial dose response curves and survival fractions were calculated for each at the outset of the study. One sample was then exposed to a course of fractionated radiotherapy at 4 Gy increments on a fortnightly basis whilst the other was cultured without exposure. Dose response curves were then constructed for the two daughter samples. Results. Each daughter cell line was found to survive doses of radiotherapy in excess of their parental counterpart. The LD₅₀ (lethal dose killing 50% of cells) was 5.85 Gy for the daughter cell line and 0.91Gy for the parental cells. Conclusions. We have created two radioresistant oral squamous cell carcinoma cell lines to allow further analysis to be performed on readily available proven radioresistant oral cancer cell lines. References 1 Parkin D.M., Bray F., Ferlay J. et al. (2005) Global Cancer Statistics, 2002. CA Cancer J Clin, 55, 74–108 2 Eckardt A., Barth E.L., Kokemueller H. et al. (2004) Recurrent carcinoma of the head and neck: treatment stratergies and survival analysis in a 20‐year period. Oral Oncology, 40, 427–32     

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.     

The efficacy of superselective intra-arterial infusion with concomitant radiotherapy for adenoid cystic carcinoma of the head and neck

Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery. Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck. Patients and methods: Between 2001–2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100–120 mg/m²/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy). Results: Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9;7) (range = 4;6–12;5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4–9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.