Cancers of the pharynx

Definitive radiotherapy alone or combined with a planned neck dissection for squamous cell carcinoma of the pharyngeal wall
William M. Mendenhall, Department of Radiation Oncology, University of Florida Health Science Center, see outcome graphs
Between 1964 and 2000, 148 patients were treated with definitive radiotherapy. All patients had a 2-year minimum follow-up. The following 5-year rates of local and ultimate local control were obtained: T1 disease, 93% and 93%; T2 disease, 82% and 87%; T3 disease, 59% and 61%; and T4 disease, 50% and 50%, respectively. Multivariate analysis revealed that twice-daily fractionation (P = 0.0009), American Joint Committee on Cancer Stage I-II disease (P = 0.0051), and oropharyngeal primary site (P = 0.0193) were associated with improved locoregional control. The following 5-year absolute and cause-specific survival rates were obtained: Stage I, 56% and 89%; Stage II, 52% and 88%; Stage III, 24% and 44%; Stage IV, 22% and 34%; and overall, 30% and 49%, respectively. Eight patients (5%) died of complications. Our current approach is to employ altered fractionation using hyperfractionation for patients undergoing three-dimensional conformal radiotherapy. Patients receive 74.4-76.8 Gy at 1.2 Gy per fraction twice daily with a minimum 6-hour interfraction interval. Patients who undergo intensity-modulated radiotherapy receive 72 Gy in 42 fractions over 6 weeks using the M. D. Anderson Cancer Center concomitant-boost technique. Patients with T3-T4 and/or bulky N2/N3 disease receive concomitant weekly cisplatin or weekly carboplatin and paclitaxel. Patients with clinically positive neck lymph nodes undergo a CT scan 4 weeks after chemoradiation and a neck dissection is performed if the likelihood of residual neck disease is believed to be greater than 5%. Patients receive aggressive swallowing therapy during and after chemoradiation to reduce the risk of long-term gastrostomy tube dependence. Cancer 2003;98:2224.

Int J Radiat Oncol Biol Phys 1996 Jun 1;35(3):477-83

Squamous cell carcinoma of the pharyngeal walls treated with radiotherapy.

Chang L, Stevens KR, Moss WT, Marquez Cm, Pearse HD, Cohen JI

Department of Radiation Oncology, Oregon Health Sciences University, Portland, OR, USA.

Between May 1971 and December 1991, 74 patients with previously untreated squamous cell carcinoma of the pharyngeal walls (excluding nasopharynx, tonsil, and pyriform sinus) were treated with radical megavoltage irradiation with or without chemotherapy at Oregon Health Sciences University. RESULTS: Two-year local control rates by stage were: T1: 100%, T2: 55%, T3: 31%, and T4: 29% . Twice-a-day irradiation improved local control rates as compared with once-a-day irradiation for patients with Stage T3 lesions, with 5 out of 7 (71.4%) vs. 4 out of 19 (21%) patients controlled at 2 years (p = 0.015). No improvement was seen in 2-year local control of all stages when chemotherapy was used in conjunction with once-a-day fractionation; however, six of eight patients (75%) treated with twice-a-day irradiation combined with either induction or concurrent chemotherapy had local control. The 2-year local control rate of 100% (6 out of 6) for the group of patients treated with concurrent chemotherapy and b.i.d. irradiation (all with Stage T3 and T4 tumors) is a dramatic improvement over the 2-year local control rate of 30% (10 out of 33) for our entire group of patients with Stage T3 and T4 tumors. Local control rates did not differ by tumor location on the pharyngeal walls. Adjusted disease-specific survival rates by stage were: 1: 100%, II: 85%, III: 58%, IV: 40%. Overall survival rates by stage were: I: 75%, II: 67%, III: 33%, IV: 30%. CONCLUSION: We advocate radical irradiation as the primary therapy for pharyngeal wall carcinomas with the use of twice-a-day fractionation for Stages T2-T4. Our preliminary results with concurrent chemotherapy and b.i.d. irradiation for advanced T3 and T4 tumors appear to be comparable to reported results with hyperfractionated radiation alone. The relative contribution of chemotherapy to b.i.d. irradiation cannot be determined from this small retrospective series; however, in view of the relatively poor results for patients with advanced stage disease, we feel this treatment combination deserves further investigation.

Radiother Oncol 1988 Mar;11(3):205-12

Squamous cell carcinoma of the pharyngeal wall treated with irradiation.

Mendenhall WM, Parsons JT, Mancuso AA, Cassisi NJ, Million RR

Department of Radiation Oncology, University of Florida College of Medicine, Gainesville 32610.

This is an analysis of 74 patients with 75 squamous cell carcinomas of the pharyngeal wall treated with radical irradiation at the University of Florida between October 1964 and December 1984. All patients have a 2-year follow-up and 69% have a minimum 5-year follow-up. All patients were treated with continuous-course irradiation: 56 with once-a-day fractionation and 18 with twice-a-day fractionation. Patients treated with the split-course technique are not included in this series. Sixty-three patients were treated with external beam irradiation alone; 11 patients underwent an interstitial implant to the primary lesion following external beam irradiation. The local control rates with irradiation are as follows: T1, 3/4; T2, 12/21; T3, 12/27; and T4, 2/10. Only two patients were salvaged by operation for a local recurrence following irradiation. There was an improvement in the rate of local control with the use of twice-a-day fractionation and a decrease in the rate of local control with the combination of external beam irradiation and interstitial implant, compared with external beam irradiation alone. The 5-year determinate survival rates by AJCC stage are as follows: I, no data; II, 4/9; III, 3/16; and IV, 1/18.

Int J Oncol 2000 Mar;16(3):611-5

Radiotherapy for carcinoma of the posterior pharyngeal wall.

Cooper RA, Slevin NJ, Carrington BM, Sykes AJ, Birzgalis A, Mott D

Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester, M20 4BX, UK.

Posterior pharyngeal carcinoma has an extremely poor prognosis regardless of the method of treatment. Between January 1991 and December 1995, 22 patients with a mean age of 60 years (range 44-82) received definitive radiotherapy, using a homogeneous technique, for carcinoma of the posterior pharyngeal wall. The median follow-up was 42 months (range 25-66). The overall 3-year survival and local control for the whole group was 50% and 73% respectively. Patients with early stage (T1 and T2) disease had a significantly better overall 3-year survival rate of 77% compared to 11% for patients with advanced stage (T3 and T4) disease (p=0.0010). Similarly, patients with early stage disease had a significantly improved 3-year local control rate compared to patients with more advanced stage disease (92% and 44% respectively, p=0.0080). Patients with node positive disease had an inferior survival rate of 29% compared to 60% for those with node negative disease though the difference did not reach statistical significance. In addition only one patient with initial node negative disease had isolated nodal relapse. There was no significant late morbidity. For patients with early stage disease we have obtained local control and survival rates comparable to other groups with a once daily, short fractionation radiotherapy scheme but with reduced morbidity. In late stage disease altered fractionation schemes should be considered in order to achieve better local control and survival. Isolated nodal relapse was not a significant problem in this cohort of patients. Outcome correlates with primary tumour size and this is reflected in the current UICC staging classification. \

Ann Otolaryngol Chir Cervicofac 1986;103(8):559-63

Carcinomas of the posterior pharyngeal wall. Experience of the Institut Curie. Analysis of the results of radiotherapy.

Jaulerry C, Brunin F, Rodriguez J, Bataini JP, Brugere J

Between 1960 to 1982, 98 patients with squamous cell carcinomas of the posterior pharyngeal wall were treated at the Curie Institute by radiotherapy alone. The absolute survival is 30% and 18% at three and five years. The major cause of death is loco-regional failure. 95% of the local failures arrived within the 18 first months. The 2 years control rate ranged from 80% for T1, 64% for T2, to 36% for T3 and 22% for T4. The local control is so depending on the radiation induced regression of the primary. The 2 years control rate is 71% for the patients with complete regression and 12% for the patients with not complete regression at the end of the treatment.

Laryngoscope 1990 Sep;100(9):985-90

Squamous cell carcinoma of the oropharynx: an analysis of 213 consecutive patients scheduled for primary radiotherapy.

Johansen LV, Overgaard J, Overgaard M, Birkler N, Fisker A

Department of Oncology, Danish Cancer Society, Aarhus, Denmark.

Radiotherapy was administered to 213 consecutively treated patients with oropharyngeal squamous cell carcinoma. The classification (Union Internationale Contre le Cancer, 1982) showed primary tumors (T1, 13%; T2, 51%; T3, 34%; T4, 2%) and regional lymph nodes (N0, 38%; N1, 38%; N2, 4%; N3, 20%). The 10-year actuarial value for local control was 48%; for regional control, it was 66%. Distant failure occurred in 20 patients. The 10-year actuarially corrected survival rate was 40% (stage I, 57%; stage II, 51%; stage III, 43%; stage VI, 21%). Locoregional tumor control was significantly influenced by irradiation parameters (total dose and treatment time), tumor volume, sex, and hemoglobin value. It is concluded that local control of the tumor while still in the T position is the parameter most crucial to success.

Rev Stomatol Chir Maxillofac 1989;90(1):24-9

Radiotherapy of carcinoma of the oropharynx. Results of 10 years' experience at the University Hospital Center, Tours.

Calais G, Goga D, Garand G, Beutter P, Le Floch O

Clinique d'Oncologie et Radiotherapie, CHRU de Tours.

In our centre, the vast majority of patients with oropharyngeal tumours are treated by irradiation. Over a period of 10 years, between 1976 and 1986 we treated 305 patients with squamous carcinomas of the oropharynx. The mean age was 58.2 years. There were 24 women and 281 men. 59% of the patients had advanced tumours, classified as T3 or T4, 54% of the patients showed the presence of adenopathy at the first examination. All patients received radiation therapy. 69 patients had surgical treatment of the tumour or glands. 21 patients had implant therapy (most often combined with transcutaneous irradiation). 165 patients had induction chemotherapy. Local tumour control was obtained in 124 patients (41%), i.e. 82, 56, 31 and 4% for T1, T2, T3 and T4 respectively. The 5 years survival rate of the overall population was 28%. The principle causes of failure were local progression for T3 and T4 tumours and metastases and second cancers in patients with T1 or T2 tumours. The prognostic factors were gland involvement and general health. The site of the tumour, sex and histological type were not prognostic factors. Induction chemotherapy did not improve the results of treatment.

Bull Cancer Radiother 1996;83(1):54-9

Radiotherapy and curietherapy of squamous cell carcinoma of the posterior pharyngeal wall (excluding the nasopharynx).

Chenal C, Julienne V, Fleury F, Desprez P

Centre regional de lutte contre le cancer, Rennes, France.

From 1986 to 1992, 55 cases of PPWC were treated with a conservative intent at the Regional Cancer Center (Rennes, France) and Saint-Yves Center (Vannes, France): 16 oropharyngeal posterior wall carcinoma (OP) and 39 hypopharyngeal posterior wall (HP); the mean age of the population was 60.3 years (31-81 years). A previous and simultaneous head and neck cancer was noted in 15 and 13% of cases respectively. Half of the cases (55%) were T1 T2 tumors and 82% were N0 N1. Except for three patients treated by curietherapy (5%), all patients were treated by radiotherapy (RT) alone (75%) or associated with curietherapy (7%) or partial pharyngectomy (13%). 15% received neoadjuvant chemotherapy, mainly for T3 tumors. With a followup of 4-88 months (mean: 23 months) 38% of patients are still alive; 8% of loco-regionally controlled patients died of second cancer or intercurrent disease. The tumor control was 67%. The nodes control was 90%. During the course of the disease, 19% of patients had metastases. The complete response at the end of treatment was 78%. Among these patients, 54% remained definitively free of disease. There is no difference between OP and HP. For limited tumors T1 T2 N0 N1, patients managed by radiotherapy associated with complementary local treatment (conservative surgery or curietherapy) do better than patients treated by RT alone (plateau 80% at 18 months+vs plateau 25% at 12 months +). For these limited tumors, our recommendation is to treat patients by external RT (50 Gy) and curietherapy boost (20 Gy) rather than by conservative surgery and external RT (70 Gy). These two treatments have the same efficacity but the first one is expected to diminish late complications of RT. Neo adjuvant chemotherapy does not seen to improve survival even for advanced tumors. Generally speaking these results remain poor for locally advanced desease and for undifferentiated tumors. These patients need a new therapeutic approach (concomittant radio-chemotherapy, hyper or hypofonctionnated RT).