James T. Parsons

Squamous Cell Carcinoma of the Oropharynx Surgery, Radiation Therapy, or Both

The treatment of patients with squamous cell carcinoma (SCC) of the oropharynx remains controversial. No randomized trial has addressed adequately the question of whether surgery (S), radiation therapy (RT), or combined treatment is most effective.

Radiation optic neuropathy after megavoltage external-beam irradiation : analysis of time-dose factors

PURPOSE To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. RESULTS Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of < 59 Gy. Among nerves that received doses of > or = 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic neuropathy after doses of > or = 60 Gy was 11% when treatment was administered in fraction sizes of < 1.9 Gy, compared with 47% when given in fraction sizes of > or = 1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. CONCLUSION As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced-field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation.

A re-evaluation of split-course technique for squamous cell carcinoma of the head and neck

Abstract Therapeutic results of split-course vs. continuous-course external beam irradiation were analyzed retrospectively in 468 consecutive patients with squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, and supraglottic larynx who were treated with curative intent at the University of Florida between September 1964 and August 1976. 214 patients received split-course treatment and 254 were treated by the continuous-course method. Except for the planned 14–16 day interruption after 2820–3000 rad in the split-course group, the techniques and total doses of irradiation did not differ. Local control was poorer for all T-stages in patients who were treated by the split-course technique. Control of neck disease by irradiation alone was also poorer among split-course irradiation patients. For each stage of disease, patients who received continuous-course irradiation had approximately 10% higher 5-year survival rates than patients who were treated by the split-course technique. The rate of development of late radiation complications was similar for the 2 treatment techniques. Routine use of the split-course technique has been discontinued since the dose required to compensate for the rest interval is unknown.

Postoperative irradiation for squamous cell carcinoma of the head and neck: an analysis of treatment results and complications☆

One hundred thirty-four patients with advanced head and neck cancer were treated with radical surgery and postoperative radiation therapy between October 1964 and October 1984. All patients had greater than or equal to 2 years and 84% had greater than or equal to 5 years of follow-up. All patients included in the study were scheduled to receive continuous-course irradiation following a major cancer operation for previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx and began radiation treatment less than or equal to 3 months after the surgical procedure. Ninety-six percent had AJCC pathologic Stage III or IV cancer, and all were without evidence of gross disease at the start of irradiation. The majority of recurrences above the clavicles occurred in the primary field (84%) as opposed to the posterior strip (8%) or low neck (8%). Based on multivariate analysis and tabular comparisons, 4 factors were found to be significantly important for predicting disease control above the clavicles: (a) Surgical margin (5-year actuarial control with invasive cancer at the margin, 53%, versus 81% with negative margins, p = .009). Patients with close margins or in situ cancer at the margins had the same rate of control as those with negative margins. (b) Primary site (oral cavity, 64%, versus other sites, 83%; p = .029). (c) Neck Stage (N0-1 versus N2-3). (d) Number of indications for irradiation--for example, bone invasion, multiple positive nodes, perineural invasion (1-3 indications, 85%, versus greater than or equal to 4, 62%; p = .06). The rate of disease control above the clavicles did not correlate well with AJCC pathologic stage: Stage I-II, 67%; Stage III, 81%; Stage IVA (T1-3, N2-3A), 68%; Stage IVB (T4 and/or N3B), 80%. The interval between surgery and the start of irradiation (range 1-10 weeks) also was not prognostically important, even with stratification by tumor dose, surgical margin, and number of indications for irradiation. At 5 years, the actuarial survival rate was 33% for the entire group; for patients with invasive cancer at the margin, the survival rate was approximately half that of those whose margins were free of invasive cancer (17% versus 37%). Based on multivariate analysis, 2 factors were found to significantly increase the probability of death due to cancer: (a) neck Stage (N0-1 versus N2-3); (b) extension of tumor from the primary site into the skin or soft tissues of the neck.(ABSTRACT TRUNCATED AT 400 WORDS)

RADIATION RETINOPATHY AFTER EXTERNAL-BEAM IRRADIATION: ANALYSIS OF TIME-DOSE FACTORS

PURPOSE To investigate the risk of radiation-induced retinopathy according to total radiation dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS Between October 1964 and May 1989, 68 retinae in 64 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 26 years; mean, 9 years; median, 8 years). RESULTS Twenty-seven eyes in 26 patients developed radiation retinopathy resulting in visual acuity of 20/200 or worse. The mean and median times to the onset of symptoms attributable to retinal ischemia were 2.8 and 2.5 years, respectively. Fourteen of the injured eyes developed rubeosis iridis and/or neovascular glaucoma. Radiation retinopathy was not observed at doses below 45 Gy, but increased steadily in incidence at doses > or = 45 Gy. In the range of doses between 45 and 55 Gy, there was an increased risk of injury among patients who received doses per fraction of > or = 1.9 Gy (p = .09). There was also a trend toward increased risk of injury among patients who received chemotherapy (two of two vs. four of ten in the 45-51 Gy range; p = .23). The lowest dose associated with retinopathy was 45 Gy delivered to a diabetic patient by twice-a-day fractionation. The data did not suggest an increased risk of radiation retinopathy with increasing age. CONCLUSION The current study suggests the importance of total dose as well as dose per fraction, and adds support to a small body of literature suggesting that patients with diabetes mellitus or who receive chemotherapy are at increased risk of injury. A sigmoid dose-response curve is constructed from our current data and data from the literature.

The effects of irradiation on the eye and optic nerve

Abstract Late effects of irradiation of the eye and optic nerve in 74 patients are reviewed. Time-dose analyses are performed for lacrimal apparatus, retinal, and optic nerve injuries. Management of radiation complications is discussed. Recommendations are made regarding radiation treatment techniques and methods of reducing the risk of late injury.

Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site

The purpose of this study was to evaluate the efficacy of the modern diagnostic evaluation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site.

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: relationship of dose-fractionation factors to local control and complications

This is an analysis of 304 patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy at the University of Florida between October 1964 and December 1984. All patients had a minimum 2-year follow-up and 82% had at least 5 years of follow-up. Patients were excluded from the analysis of local control if they died within 2 years of treatment with the primary site continuously disease-free; all patients were included in the analysis of treatment complications. Patients were staged according to the 1983 AJCC system. Stage T2 was subdivided into 2 groups as follows: T2a (normal mobility) and T2b (decreased mobility). The rates of local control with radiation therapy were as follows: T1, 159/171 (93%); T2a, 50/65 (77%); and T2b, 31/43 (72%). Patients were further divided into subsets based on T stage and the surgical procedure that would have been required to resect the lesion. Local control was noted to improve with higher doses and dose per fraction in 4 of 7 subsets. In 2 of 3 subsets where a dose-fractionation relationship was not observed, there were no local recurrences in 1 subset and only 2 local recurrences in the other. The overall incidence of serious complications was 5/304 (1.6%) and was associated with T stage and with increasing total dose and dose per fraction.

Hyperfractionation for head and neck cancer

Between March 1978 and April 1984, 144 patients with 148 moderately advanced to advanced primary squamous cell carcinomas of the head and neck received treatment with curative intent with twice-a-day irradiation (120 cGy/fraction, 4-6 hour interfraction interval). Eighty-eight percent of the patients had AJCC Stage III-IV cancers. One hundred and thirty-two patients received irradiation alone to the primary site with or without radical neck dissection, with surgery reserved for salvage. The total doses administered were 7440-7920 cGy in the majority of instances. In 19 patients with oropharyngeal lesions, a 1000-1500 cGy radium needle boost was added after the basic dose. Twelve patients received preoperative irradiation (5040-6000 cGy) followed by primary resection and radical neck dissection. Local control results following irradiation alone to total doses of greater than 7000 cGy with minimum 2-year follow-up were 25/31 (81%), 38/50 (76%), and 5/25 (20%) for T2, T3, and T4 cancers, respectively. Local control rates did not correlate well with total dose. Local control following preoperative irradiation plus primary resection was obtained in 4 of 5 T3 and 2 of 3 T4 primary lesions. The 5-year actuarial rates of neck control were 100% for N0 (45 patients), 90% for N1 (25 patients), 77% for N2 (23 patients), 50% for N3A (9 patients), and 70% for N3B (42 patients). The 5-year actuarial rates of continuous disease control above the clavicles were 73% for Stage III, 64% for Stage IVA, and 32% for Stage IVB. The actuarial 4-year rate of continuous disease control above the clavicles was 78% for Stage II. For patients whose disease was controlled above the clavicles, distant metastases developed in 4% of patients with Stage II-III disease and in 18% of patients with Stage IV disease. Radiation complications following irradiation alone to the primary site correlated with total dose. Complications of planned neck dissection(s) were acceptable. Complications of salvage surgery at the primary site were similar to those seen in patients treated once a day. The actuarial 5-year survival rates, according to modified AJCC stage, were 59% for Stage III, 37% for Stage IVA, and 23% for Stage IVB. The actuarial 4-year survival rate for Stage II was 69%. Compared to historical control groups treated with once-a-day, continuous-course irradiation at our institution, twice-a-day treatment has produced local control results that are higher by 10-15 percentage points.

Preradiotherapy computed tomography as a predictor of local control in supraglottic carcinoma

PURPOSE To determine the utility of pretreatment computed tomography (CT) for predicting primary site control in patients with supraglottic squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT). MATERIALS AND METHODS Pretreatment CT studies in 63 patients were reviewed. Minimum length of follow-up was 2 years. Local recurrence and treatment complications resulting in permanent loss of laryngeal function were documented. Tumor volume was calculated using a computer digitizer, and pre-epiglottic space (PES) spread was estimated. The data were analyzed using a combination of Fishers exact test, logistic regression modeling, and multivariate analyses. Five-year local control rates were calculated using the product-limit method. RESULTS Local control rates were inversely and roughly linearly related to tumor volume, although there seemed to be a threshold volume at which primary site prognosis diminished. Local control was 89% in tumors less than 6 cm3 and 52% when volumes were > or =6 cm3 (P = .0012). The likelihood of maintaining laryngeal function also varied with tumor volume: 89% for tumors less than 6 cm3 and 40% for tumors > or =6 cm3 (P = .00004). Pre-epiglottic space involvement by tumor of > or =25% was associated with a reduced chance of saving the larynx (P = .0076). Multivariate analyses revealed that only tumor volume independently altered these end points. CONCLUSION Pretreatment CT measurements of tumor volume permits stratification of patients with supraglottic SCC treated with RT alone (which allows preservation of laryngeal function) into groups in which local control is more likely and less likely. Pre-epiglottic space spread is not a contraindication to using RT as the primary treatment for supraglottic SCC.