Hypopharynx Research Articles

Concurrent platinum-based chemotherapy with intensity modulated radiation therapy (IMRT) for locally advanced squamous cell carcinoma of the head and neck (SCCHN): A retrospective single institution analysis

16511 Background: Randomized clinical and meta-analysis data support the use of concurrent chemoradiation for treatment of locally advanced (SCCHN). IMRT is increasingly being used in treating SCCHN. We present outcome data from Emory University Winship Cancer Institute (WCI) with concurrent platinum based chemotherapy and IMRT, and analyze results according to primary site and nodal status. Methods: Between February 2003, and November 2005, 87 patients with locally advanced SCCHN underwent concurrent IMRT and platinum based chemotherapy. A total of 62 patients were treated with Cisplatin 100 mg/m2 d1,21,43, while 19 were treated with paclitaxel and carboplatin weekly for 7 weeks. Five patients were treated with other platinum based regimens. Follow up was documented in all cases with a median of 520 days (range 107 - 1269 days). Results: Patients were distributed among primary sites as follows: Hypopharynx (HP) 7 (8.0%), Larynx (L) 11(12.4%), Nasopharynx (NP) 13 (14.6%), and Oropharynx (OP) 56 (63.0%). T stage distribution was: T1: 16 patients (18.0%); lesions more advanced than T1 (>T1): 68 (76.4%). N stage distribution was, N0 :16 patients (18.0%), N1: 8 (9.0 %),nodal stage N2a or higher: 61 (68.5%). Median age was 57 years (range 32–75), and 63 patients (71.0%) were male. The median overall survival (OS) and disease-free survival (DFS) post-therapy was not reached. The 3 year OS rate for the entire cohort was 86% (L 82%, NP 89 %, OP 86 % HP 80%). The 3 year DFS rate for the entire cohort was 74%, (L 85%, NP 60%, and OP 75%, HP 76%). There was no correlation between OS and T or N stage (p=0.143 and 0.44 respectively), or between DFS and T-stage (p=0.4). A significant correlation was found between DFS and N stage (p=0.008). Conclusion: With moderate follow up, this retrospective analysis reveals an excellent outcome for patients with locally advanced SCCHN treated with chemotherapy and IMRT concurrently, supporting concurrent therapy as the current standard of care. The significant correlation of DFS and nodal status suggests a possible greater impact future approaches such as induction therapy may have on patients with advanced nodal disease. No significant financial relationships to disclose.

Oral mucositis is associated with increased resource use among patients receiving treatment for cancers of the head and neck

6070 Background: Oral mucositis (OM) is the oral manifestation of mucosal injury (MUI), and is a common, bothersome, and treatment-interrupting toxicity of chemoradiation therapy for squamous cell cancers (SCC) of the head and neck. Retrospective studies have reported that OM increases healthcare resource use. We present interim results of an international, multicenter, prospective study undertaken to characterize the clinical and economic burden of OM in patients with cancers of the oral cavity (OC), oropharynx (OP), larynx (L) and hypopharynx (HP). Methods: Patients (pts) with histologically proven SCC of the designated anatomical sites, whose planned treatment included full-cycle conventional or intensity modulated (IM) radiation therapy (RT) with or without chemotherapy, were enrolled at least one week prior to the start of treatment. Pts completed the Oral Mucositis Daily Questionnaire (OMDQ), a validated questionnaire developed to document patient-reported symptoms of OM and MUI including mouth and throat soreness (MTS), at baseline and daily throughout RT. MTS was assessed using a 5-point numeric rating scale, ranging from 0 (“no soreness”) to 4 (“extreme soreness”). Results: Of the first 61 pts to complete RT, 72% had cancers of the OC or OP, 49% received IMRT with concomitant chemotherapy, and 68% were male. 95% of pts reported OM symptoms (MTS>0); 80% had one or more scores =2. Pts with OC or OP cancers reported more symptoms than those with L or HP tumors (mean maximum score: 3.3 vs 2.8; p= 0.12). MTS scores were positively related to levels of resource use. Conclusions: Symptoms of radiation-induced OM are positively correlated with levels of resource utilization in patients with head and neck cancers. No significant financial relationships to disclose. [Table: see text]

1106: Randomized Trial of Conventional Fractionated RT (CFRT) vs. Concomitant Chemo Radiotherapy (CTRT) and Accelerated Radiotherapy (ACRT) in Patients With Advanced, Non Nasopharyngeal, Squamous Cell Cancers of the Head and Neck Region

Randomized trial comparing efficacy and sequelae of conventional fractionated RT (CFRT) vs. concomitant chemo radiotherapy (CTRT) vs. accelerated fractionated radiotherapy (ACRT) in patients with advanced HNSCC. Between April 2000 and Dec 2004, 150 untreated patients with Stage III and IV non nasopharyngeal, squamous cancers of the head and neck region were included in this 3 arm trial. Arms A: CFRT (66-70Gy in 6-7wks @ 5 fractions per week), Arm B: CTRT (66-70Gy in 6-7wks @ 5 fractions per week + concomitant weekly Inj. Cisplatin 30mg/m2), Arm C: ACRT (66-70Gy in 6.5wks @ 6 fractions per week). The sixth fraction was delivered using the reduced fields. For randomization patients were stratified by site and stage. The analysis was on an intention to treat basis. Response and toxicity were documented according to the WHO response assessment and RTOG criteria, respectively. Results were analysed after a median follow-up of 17 months (Range: 0-68months). Median age of patients was 53.6 years (range 20-70). Majority were males (95%) with a male: female ratio of 17:1. Oropharynx was the most commonly involved sub site (56%), followed by larynx (23.3%) and hypo pharynx (18%). Treatment was completed as per protocol in 94%, 90 % and 86% of patients in arms A, B and C respectively. The median duration of treatment was 49(31-68), 51(32-63), and 40(1-55) days for arms A, B, and C respectively. The median RT dose was 70Gy in each arm. In the CTRT arm the median weekly dose of Cisplatin was 45mg (range: 30-50mg). Seventy four percent received more than 5 cycles of Cisplatin. The overall CR rates were 43%, 53% and 31% in the three arms respectively. The 2yr DFS were 38%, 55% and 31% (p=0.07) for arms A, B, and C respectively and the 2yr OS were 44%, 58% and 44% (p=0.35). For each arm univariate analysis of all known prognostic factors was done to assess their impact on DFS and OS. There was a significant improvement in DFS for pts in the CTRT arm with oropharyngeal tumours (p=0.01). CTRT also resulted in improved DFS compared to CFRT and ACRT in pts with stage III disease (p=0.04) although it did not translate into a significant difference in OS, although the CTRT arm did better (p =0.09). When the DFS was analysed according to the T-stage, the benefit with chemotherapy was seen in patients with low primary tumor volume (T1-T2) which was statistically significant (p= 0.02). On further analysing patients in T1-2 subgroup, the results were in favour of the CTRT arm in the presence of nodal disease (p= 0.03), especially in patients with higher nodal involvement i.e. N2c (p = 0.03). These results did not translate into a benefit in OS. For larger tumours (T3-T4) with N0 status the DFS in the three arms was 71%, 58.9% and 39%, respectively (p= 0.12).The incidence of grade II skin reactions was higher in the accelerated arm (p = 0.482). Seventeen percent, 28%, 28.6% of patients on arm A, B and C respectively experienced grade III mucosal toxicity. CTRT resulted in superior DFS in pts. with advanced disease compared to CFRT & ACRT, especially for oropharyngeal tumors. This improvement did not translate into an improved OS and was associated with acceptable toxicity and compliance. The toxicity of CTRT is acceptable with a marginal increase in hospital support.

Effect of a non-adjustable oral appliance on upper airway morphology in obstructive sleep apnoea

To evaluate the effect of oral appliance (OA) on upper airway morphology and its relationship with treatment response in subjects with obstructive sleep apnoea (OSA). Symptomatic OSA subjects were recruited. Non-adjustable OA was custom made. Variables examined at baseline and while wearing the device at 2 months included polysomnographic data, computed tomographic measurements of upper airway cross sectional area at level of velopharynx (VA) and hypopharynx (HA), upper airway volume, and cephalometric parameters. Treatment outcome was based on post-treatment apnoea-hypopnoea index (AHI). Forty patients were recruited and 23 (7 women) completed the study. They were middle-aged (49, 40-58 years) (median, interquartile range) and overweight (BMI 26, 23.3-29.5 kg/m2), with moderate OSA (AHI 26.4, 14.1-36). The overall post treatment AHI was 8.4 (2.4-12.5), with 14 (61%) patients showing good response (AHI<10), and the other 9 patients showing moderate response (>50% reduction in AHI but still 10). OA decreased the cross-sectional area of the HA (P=0.046), showed a trend of decreasing the ratio of cross-sectional area of the HA to cross-sectional area of the VA (P=0.053) and significantly increased the overall upper airway volume (P=0.006, n=11). No significant relationship between upper airway parameters and treatment outcome was identified. OA altered upper airway morphometry towards a profile consistent with decreased propensity to collapse, which may thus have contributed to improvement of OSA.

The Influence of Lymph Node Metastasis in the Treatment of Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, Larynx, and Hypopharynx: N0 Versus N+

Management of the N0 neck is a continuing controversy. The study compares the influence of N0 and N+ disease on the results of treating squamous cell carcinoma (SCCA) of the oral cavity (OC), oropharynx (OP), larynx (LX), and hypopharynx (HP) with five different treatment modalities. The study also compares the results of four different approaches to the treatment of the N0 neck. A retrospective study of 3887 patients. Patients in the Tumor Research Project of the Department of Otolaryngology-Head and Neck Surgery of the Washington University School of Medicine (St. Louis, MO) with biopsy-proven previously untreated SCCA of one of the four above-mentioned regions who were treated with curative intent by one of five modalities and who were eligible for 5-year follow-up were included in the study. The treatment modalities included local resection of primary alone (LR), composite resection (primary with neck dissection) (CR), radiation therapy alone (RT), local resection with radiation therapy (LR/RT), and composite resection with radiation therapy (CR/RT). The N0 neck was treated with one of four approaches: observation with close follow-up reserving treatment only for subsequent neck disease, neck dissection, RT to the neck region, and a combination of neck dissection with RT. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analyses to determine statistical significance. The 5-year disease-specific survival (DSS) for the all-sites group (ASG) was 59%. The DSS for the subsites included the following: OC, 53%; OP, 47%; LX, 70%; and HP, 42%. Patients with N0 disease had significantly better DSS than patients with N+ disease at all sites. Occult neck disease in N0 patients was low with 4% pN1 for ASG, OC, and LX and with 11% pN1 for OP and HP. There was 3% pN2 for LX, 4% pN2 for ASG and OC, and 6% pN2 for OP and HP. The DSS for patients with occult neck disease was statistically similar to that of N+ patients. Prognostic survival indicators included age, decade of treatment, T stage, N stage, TN stage, treatment modality, and recurrence. Patients over 65 years of age had poorer DSS than younger patients. Staging T, N, and TN affected survival at all sites. Local resection produced better DSS for ASG, OC, LX, and HP patients. Local resection with radiation therapy produced increased DSS for ASG and OC patients. There was no survival advantage for HP patients related to treatment modality. Treatment of the N0 neck with observation and later treatment for subsequent neck disease produced a survival advantage for patients in the ASG. This advantage was specific for ASG and LX patients staged T1N0. For patients staged T2N0, T3N0, and T4N0 at all four subsites there was no survival advantage for any of the four neck approaches. Lymph node metastasis significantly and negatively affects DSS in patients with SCCA of the OC, OP, LX and HP. The rate of occult neck disease (pN+) in N0 patients receiving meticulous workup is low. When present, it produces DSS rates similar to those found in N+ patients. In the study series, there was decreased survival in patients older than 65 years of age, in patients with advanced tumor (T, N, TN), and in patients with recurrent disease. None of the four current approaches to treatment of the N0 neck produces a significant survival advantage. Close observation with later treatment reserved for subsequent neck disease produces statistically similar survival (DSS) to the three elective (prophylactic) treatments and is a valid form of treatment. It may preclude unnecessary treatment of the neck with its attendant risks and complications.

Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese

Objectives: To evaluate the relationship between cephalometric parameters, upper airway morphological factors and obstructive sleep apnea (OSA) in Chinese subjects. Design: Polysomnogram (PSG) were performed and scored using standard criteria. Supine lateral cephalometric parameters and pharyngeal cross-sectional areas at the level of velopharynx (VA) and hypopharynx (HA) were measured from computed tomographic scans. The roles of these parameters and other anthropometric/demographic characteristics in OSA (apnea hypopnea index, AHI⩾5) and their relationship with severity of OSA were explored by multiple logistic and multi-nominal regression analysis. Results: Ninety-two subjects, ranging from normal ( n=36), mild/moderate OSA ( n=34) to severe OSA ( n=22), were evaluated. Compared with normal subjects, OSA subjects were heavier (body mass index 27 vs. 24 kg/m 2) and older (47 vs. 42 years of age); had smaller VA size and VA to HA ratio, lower positioned hyoid bone, longer and thicker soft palate, and more retropositioned mandible relative to maxilla. After controlling for body mass index and age, subjects with severe OSA (AHI>30) had more retropositioned mandible relative to maxilla (odds ratio, OR 1.31, P=0.044) and longer soft palate (OR 1.16, P=0.01), while those with mild/moderate OSA had larger VA to HA ratio (OR 0.17, P=0.018). Conclusions: Craniofacial factors and upper airway morphology contributed to severity of OSA in Chinese subjects. Having controlled for obesity, more retropositioned mandible was associated with more severe OSA.

Local tumor control in radiation therapy of cancers in the head and neck.

A retrospective study of 1,493 head and neck cancer patients was designed to test current radiobiological thinking, postulating the detrimental effect of protracted overall treatment times (OTT) and/or split course (SC) regimes in radiation therapy on local tumor control. Primary squamous cell carcinomas of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), nasopharynx (NP), and larynx radiated with a dose of at least 50 Gy were analyzed. Those patients treated by brachytherapy and/or primary surgery were excluded. A detailed analysis of the 997 cancers of the larynx was recently published. This paper focuses on the relationship between local tumor control and treatment characteristics for the 496 tumors originating from the OC, OP, HP, and NP. Total doses of radiation ranged from 50 to 79 Gy, with a mean of 64 Gy. A local failure (LF) was observed for 278 patients. Using Cox regression analysis, T stage and site were strongly related to LF. Corrected for T stage and with reference to OP, tumors in the NP, HP, and OC had a relative LF rate of 0.5, 1.6, and 1.8, respectively. Patients treated with continuous course (CC) and higher doses of radiation therapy fared best. No association was found with OTT and the use of chemotherapy. The results observed for the OC, OP, HP, and NP are in line with the findings for the larynx. Analyzing all 1,493 patients, for SC regimes lower local control rates were observed as opposed to the CC treatment series. Moreover, for the normalized total doses, a dose-effect relationship could be established. This study corroborates that disruption of the treatment per se and/or the use of suboptimal total doses of RT are detrimental; it is argued that these observations could be of relevance when designing combined modality protocols.