Local control of T3N0 glottic carcinoma by 60 Gy given over five weeks in 2.4 Gy daily fractions. One more point on the biological effective dose (BED) curve.

Seventy patients with T3N0 glottic cancer who received a total dose of 60 Gy in twenty-five 2.4 Gy daily fractions over 5 weeks had an initial post radiation primary recurrence free rate of 65% at 5 years. This provides one more point for the dose response for T3 glottic cancer Radiother Oncol (1999) 15.

Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors.

AIM: To identify the prognostic significance of different factors in patients with squamous cell carcinoma of the tongue. PATIENTS AND METHODS: Seventy-seven patients with carcinoma of the tongue were treated radically at the King Faisal Specialist Hospital and Research Centre between 1980 and 1989. Twenty patients (26%) were treated by resection alone, 11 (14%) with radiotherapy alone, and 46 (60%) with combined resection and radiotherapy. RESULTS: Forty-seven patients (61%) had T(1-2), 28 (36%) T(3-4), and two T(x) tumours. The regional nodes were clear in 53 (69%) and contained metastases in 24 patients (31%). Thirty patients (39%) developed recurrences, which were local in 9, regional in 14, locoregional in 5, and locoregional with metastatic disease in 2. The five and 10-year overall actuarial survival for all patients were 65% and 53%, respectively, and the corresponding relapse-free survival 56% and 50%. Univariate and multivariate analyses were done of seven variables - age (<40 compared with >/=40 years), sex, chewing tobacco use, smoking, TNM stage, surgical margins (clear or invaded), and treatment (resection, radiotherapy, or the combination). On univariate analysis chewing tobacco (P=0.04), smoking (P=0.01), invaded resection margins (P=0.04), involved regional lymph nodes (P=0.009), T4 tumours, and patients treated with radiotherapy alone (P=0.001) were associated with poor overall survival. Factors associated with shorter relapse-free survival were age >40 (P=0.03), chewing tobacco (P=0.04), invaded resection margins (P=0.01), and smoking (P=0.01). On multivariate analysis, invaded resection margins and smoking (P=0.04)(P=0.02) were associated with shorter overall survival and relapse-free survival (P=0.03 and (P=0.01), while chewing tobacco independently influenced relapse-free survival only (P=0.03). CONCLUSION: Invaded resection margins and smoking were the only independent prognostic factors that affected both overall and relapse-free survival. Those who chewed tobacco were at high risk of locoregional failure.

Cancer of the tonsil: the results of ipsilateral radiation treatment.

BACKGROUND AND PURPOSE: The use of ipsilateral irradiation techniques to treat patients with carcinoma of the tonsil reduces the acute radiation reaction in the contralateral pharynx and late damage to the contralateral salivary tissue. However, this may also spare microscopic disease in apparently uninvolved contralateral lymph nodes. The purpose of this study was to analyse the survival and recurrence rates and sites of recurrance in a group of patients with carcinoma of the tonsil treated with ipsilateral techniques. MATERIALS AND METHODS: Between 1975 and 1993, 271 patients with invasive squamous cell cancer of the tonsil were referred to the Vancouver Cancer Centre (VCC). One hundred and seventy-eight received ipsilateral radiation treatment. Three received surgery only, six post-operative radiation, 12 supportive treatment only and 72 bilateral radiation treatment. In the absence of bilateral neck nodes and extensive lymphodenopathy, field sizes were generally kept small to include the primary tumour and the first echelon of nodes. The most common dose was 60 Gy in 25 daily fractions in 5 weeks (2.4 Gy per day). RESULTS AND DISCUSSION: The disease specific survival for all patients treated by radical radiation treatment was 61% at 5 years. For the 178 patients who received ipsilateral radiation treatment the overall primary tumour control rate by ipsilateral radiation treatment alone was 75% and for T1 and T2 tumours 84%. Eight (7.5%) of 101 of these patients with N0 nodes at presentation and without prior failure at the primary site, developed nodal recurrence (four within the initially radiated high dose volume). Two developed contralateral nodes, and two developed field edge nodal recurrence, one cured by surgery. In 54 patients with N1 disease, five developed nodal recurrence, two within field, two contralateral, one of whom was cured by surgery, and one at field edge. In 23 patients with N2a, N2b or N3 disease node control was achieved from radiation treatment in 11 and two more were cured by surgery. All nodal failures were within the radiated volume. Overall, 10 of the 25 patients with nodal failure were cured by subsequent surgery. CONCLUSIONS: Ipsilateral treatment of patients with carcinoma of the tonsil gives survival results that are at least as good as those reported with bilateral treatment with fewer side effects and a very low risk of failure in the contralateral neck.

Sudden periodic paralysis: rare manifestation of thyrotoxicosis.

Nonfamilial hypokalemic thyrotoxic periodic paralysis is rarely diagnosed among Caucasians and blacks in the western world but it is relatively common among Asiatics. Sudden paralysis occurring while at rest after a large carbohydrate meal or strenuous exercise in an undiagnosed mild thyrotoxic patient is a common presentation. A case illustrating such presentation is reported. Intracellular shifts of potassium triggered or facilitated by hyperthyroidism and hyperinsulinemia are the biochemical features. Correction of the thyrotoxic state is the definitive treatment for this disorder. Judicious administration of potassium is indicated during the hypokalemic episode to prevent life-threatening arrhythmias.

Sudden periodic paralysis: rare manifestation of thyrotoxicosis

Nonfamilial hypokalemic thyrotoxic periodic paralysis is rarely diagnosed among Caucasians and blacks in the western world but it is relatively common among Asiatics. Sudden paralysis occurring while at rest after a large carbohydrate meal or strenuous exercise in an undiagnosed mild thyrotoxic patient is a common presentation. A case illustrating such presentation is reported. Intracellular shifts of potassium triggered or facilitated by hyperthyroidism and hyperinsulinemia are the biochemical features. Correction of the thyrotoxic state is the definitive treatment for this disorder. Judicious administration of potassium is indicated during the hypokalemic episode to prevent life-threatening arrhythmias

Seven fractions of twice daily high dose-rate brachytherapy for node-negative carcinoma of the mobile tongue results in loss of therapeutic ratio.

From June 1989 to December 1993, a Phase I/II protocol using high dose-rate (HDR) interstitial brachytherapy for early stage node-negative squamous cell carcinoma of the mobile tongue was undertaken to assess the toxicity and efficacy of this modality. A total of 27 patients were treated: T1-10 patients, T2-15 patients, and T3-two patients. Seven fractions x 6.5 Gy of HDR brachytherapy were given on a twice daily schedule, with a minimum interval time of 6 h, over a period of 3.5 days. The actuarial tumor control probability after HDR brachytherapy was 53% at 5 years. Local control rates for the T1 and T2 tumors were lower than comparable historical controls treated at our institution using low dose-rate (LDR) radium or cesium needle implants and iridium wire implants. This is despite the fact that the HDR schedule was calculated by the linear quadratic formula to have equal tumor killing effects as 60 Gy in 6 days of LDR radiation. In addition, there was a trend towards higher incidence of severe complications for the HDR patients compared to historical controls treated with LDR. We would caution against the use of this schedule of HDR brachytherapy until further studies are done.

The Saudi experience with neutron therapy in locally advanced head and neck cancers.

The neutron therapy program at King Faisal Specialist Hospital and Research Center conducted a phase II study to evaluate the toxicity and efficacy of neutrons against conventional external megavoltage irradiation in patients with locally advanced head and neck malignancy. One hundred and nineteen patients were allocated to receive either photons (46/119) or neutrons (73/119). Radiation effects were scored according to the EORTC/RTOG criteria; data was collected weekly during treatment, once a month for the first year and at 6-month intervals subsequently. While acute effects were scored in all patients, only 59 were evaluable for late effects and locoregional control. A composite of the average reaction results were obtained using this information, to compare them in time, for acute and late effects in both arms of the study. The maximum acute reactions in the two groups were similar. In the majority of the patients (80%) acute skin and mucosal reactions occurred during the last week of treatment. The changes in the subcutaneous tissues and salivary glands became clinically apparent at 3 months or later. Salivary gland toxicity was more severe in the photon arm and the difference was statistically significant at 3 months (P = 0.04) but this was lost at 12 months. Late effects for skin and subcutaneous tissues were significantly more severe in the neutron arm with P values of 0.04 and 0.01 respectively. Three patients in the neutron arm died of grade 4 radiation complications. The local control and survival were similar in both groups.

The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988.

From 1971 to 1988 72 cases of carcinoma of the anal canal were treated by external beam radiotherapy, most commonly by 5000 cGy in 20 fractions given over 4 weeks. The actuarial survival at 5 years was 66% and the disease specific survival 78%. Nine patients had inguinal node metastases at diagnosis; their 5-year disease specific survival was 75%. 63 patients were inguinal node negative at presentation; their 5-year disease specific survival was 78%, by UICC 1987 staging: T1 71%, T2 88%, T3 41%, T4 42%. 17 patients developed local recurrence; 10 were suitable for abdominoperineal (AP) resection which was successful in 7. The probability of local control was related to T stage. 13 patients were left with a colostomy because of recurrence, 2 had a colostomy for radiation damage and 4 had their local recurrence managed palliatively, without a colostomy. As a result, 53 of the 72 patients (74%) were left with a functional anus. Severe late complications occurred in 6 (8%).

Treatment of paranasal sinus malignancy: the BCCA experience.

A retrospective analysis was undertaken of 119 patients treated at the British Columbia Cancer Agency (BCCA) with a diagnosis of paranasal sinus malignancy. All patients from 1970 to 1987 were included in the review. A comparison is drawn between main treatment modalities, namely primary radiotherapy, primary surgical resection and combined therapy. Clinical characteristics of this relatively rare lesion are elucidated. Recommendations regarding optimal therapy are made on the basis of this data.

Design and evaluation of a subclassification system for supraglottic laryngeal cancer.

The management of supraglottic laryngeal cancer is predicted upon tumor staging as determined by the American Joint Committee Classification (AJCC). Because of changes in both radiotherapy and surgical treatment, the current AJCC may lack the detail and specificity required for accurate selection of treatment. An expanded classification system should provide predictive information that would aid in clinical decision making. Using the AJCC as a foundation, a subclassification system based upon existing knowledge of laryngeal anatomy, embryology and pattern of tumor spread was developed. This system identifies those cancers that involve subsites deemed to represent regions of increased risk for spread. The validity of this subclassification system and its clinical application was assessed by reviewing 139 cases of supraglottic laryngeal cancer and performing a statistical analysis with respect to treatment outcome. The results of this study support the conclusion that two subpopulations of laryngeal tumors, those with a subsite designation of infrahyoid epiglottis, and those demonstrating fixation of the vocal cord, may benefit from a more aggressive treatment protocol.

Phase I study of concurrent carboplatin and radiotherapy in previously untreated patients with stage III and IV head and neck cancer.

This study evaluated the toxicity resulting from combined therapy using carboplatin and radiotherapy in 22 patients with locally advanced (stage III and IV) head and neck cancer. Carboplatin was given after radiotherapy during the first 5 consecutive days of a 16-fraction course of radiotherapy delivered in a total of 22 days. To find the acceptable toxic dose of carboplatin, the patients were treated in groups of 3 patients each. The first group received 50 mg/m2 carboplatin and the dose was increased by 10 mg/m2 in each subsequent group. Unacceptable toxicity (severe mucositis, nausea and vomiting, and/or myelosuppression) was encountered at a carboplatin dose of 80 mg/m2. A further 10 patients were then treated at a dose of 70 mg/m2. At this dose toxicity was acceptable. Although the group of 22 patients is too small for response and survival data to be meaningful, 10 complete responses were seen and median survival is in excess of 67 weeks.

Impact of new radiotherapy modalities on the surgical management of cancer of the esophagus and cardia.

At the Cancer Control Agency of British Columbia, 483 patients with cancer of the esophagus and cardia were seen from 1970-1980. Four hundred and one out of 483 (83%) had tumors larger than 5 cm (T2) and in 288/483 (60%) the disease had extended beyond the esophageal wall (T3). The overall 5-year survival rate was only 9% for all patients treated by external irradiation. The 5-year survival for a selected group having esophagectomy was 20%. Most patients died of persistent cancer at the primary site (83%); the cause of death was aspiration pneumonia (82%) due to obstruction caused by the persistent cancer. Our most recent experience using intracavitary irradiation either prior to or after external irradiation in 211 patients has been safe and simple and preliminary analysis of treatment results suggests that it has improved the therapeutic ratio. The analysis of quality of life at 6 months following therapy as it relates to performance status, swallowing ability, weight, and pain indicated significant improvement in all of these parameters. Of 171 patients, 33% were still alive at 1 year, 26% at 2 years, and 19% at 3 years following treatment. Of 43 patients suitable for preoperative irradiation, only 26 patients were actually resected and 19 of them are still alive with no evidence of disease, 8 to 30 months. The rationale and technical aspects of the combined treatment are described in detail. Treatment results, complications and an outline for future programs based on this experience are also described.

Pathologic findings in total esophagectomy specimens after intracavitary and external-beam radiotherapy.

Pathologic findings in 21 esophagectomy specimens from patients having preoperative combined intracavitary radiotherapy (ICR) and external-beam radiotherapy (EBR) are described. Eleven patients received 1500 cGY ICR and 4000 cGy EBR (Group 1) and ten patients received 1500 cGy plus 2000 to 3000 cGy EBR (Group 2). Effectiveness of radiotherapy was expressed as the ratio between depth of radiation effect and depth of tumor invasion. Depth was expressed as one of four levels: Level I, not deeper than the muscularis mucosa; Level 2, involving but not deeper than submucosa; Level 3, involving but not deeper than muscularis propria; and Level 4, involving periesophageal soft tissue. The depth of radiation damage to tumor cells was comparable between the two groups. However, residual tumor was present in the periesophageal tissue in only one of 11 patients after high-dose EBR compared to of ten patients with lower dose EBR (P less than 0.01, chi-square test). A ratio of one between radiation effect and depth of tumor invasion was present in six patients receiving high-dose EBR and one patient receiving lower dose EBR (P less than 0.05). The authors conclude that ICR combined with EBR affords good local tumor control in the majority of patients. Higher doses of EBR give a better radiation effect in deeper layers of the esophageal wall. The ratio between depth of radiation effect and tumor invasion provides a simple and objective approach to the pathologic analysis of esophagectomy specimens.

Cancer of the esophagus and cardia: overview of radiotherapy.

Cancers of the esophagus and cardia are aggressive; they behave similarly and are associated with an extremely poor prognosis. Because current treatments (surgical esophagectomy and irradiation) have failed to cure the disease, critical analysis is needed to determine the reasons for this failure. The following problems in disease management have been identified: (a) most patients are old, frail, undernourished and have locally advanced disease at the time of diagnosis, (b) 80% of patients die of locally recurrent disease and aspiration pneumonia caused by the persisting cancer, (c) there is no consensus as to what constitutes the optimum curative treatment for the disease and (d) there is no agreement on the technical aspects and extent of the surgical treatment required or on radiotherapy.

Cancer of the nasopharynx in British Columbia.

The Chinese population in British Columbia has been increasing in recent years due to the migration of the Chinese from Southern China, which has tripled during the last decade. From 1939 to 1980, 296 cases of nasopharyngeal carcinoma (NPC) were seen at the Cancer Control Agency of British Columbia (CCABC). Of these, 167 (56%) were Chinese and 119 (40%) were Caucasians. The incidence of cancer of the nasopharynx in the Chinese born in China was 115 times greater than Caucasians before 1970 and 107 times greater in the 1970s. The incidence of NPC in the Caucasian population remained unchanged as did that of the North American-born Chinese (six times greater than that of the Caucasians) for the last 2 decades. The overall survival for all cases was 39% at 5 years and 28% at 10 years. The survival of cases was better in patients treated after 1970 (48% at 5 years and 36% at 10 years) than in patients treated before 1970 (34% at 5 years and 20% at 10 years). The survival was 50% at 5 years for all N0 cases but it was only 27% in patients with nodal metastasis. The survival of NPC was related essentially to initial staging, type and dose of irradiation, and pre-irradiation biopsy of neck metastasis. The survival was not significantly related to birth place, race, or histological grade.

Cancer of the tonsil.

One hundred and twenty-two patients with cancer of the tonsil presented at the University of British Columbia Cancer Control Agency between 1970-80. The results of treatment are reviewed. Eight-six patients (70.5%) were treated with radiotherapy alone. The overall three year corrected survival rate is 54.4% and the five year corrected survival rate is 45.6%. Local control varied from 86% (T1 lesions) to 47.5% (T3 lesions). Nodal disease was present in 65%. Recurrences developed in 55.8% of the patients. Salvage surgery was performed in 15 patients with a success rate of 39%. When compared to a study in 1977, results are improved. We feel that this was due to more standardized treatment, improved salvage surgery, and improved radiation therapy. Findings in this study indicate that primary radiotherapy with salvage surgery is a satisfactory treatment approach for patients with cancer of the tonsil.

Nasopharyngeal carcinoma: an evaluation of 134 patients treated between 1971-1980.

An analysis is made of 134 patients with nasopharyngeal carcinoma treated from 1971-1980 at the Cancer Control Agency of British Columbia. Incidence rate for Chinese born in the Orient was 20.5 per 100,000 per year compared to 1.32 per 100,000 for Canadian born Chinese. The Caucasian rate was .19 per 100,000 per year. These figures confirm a 15 times greater incidence of the disease in Chinese born in the Orient over those born in North America. The 86 Chinese patients were noted to have a 10% poorer survival than the 48 Caucasian patients on long-term follow-up. The main factor affecting survival was initial staging. Overall survival rates were 46.3% three year, no evidence of disease (NED) and 38.3% five year NED survival, but when disease was limited to the nasopharynx (T1, T2, N0) they were 73.9% three year NED and 66.6% five year NED survival. One-third of the patients ultimately developed distant metastases below the clavicle. Although lower T and N stage cases had fewer of these, the overall correlation with staging was poor. Female patients showed statistically significant better survival which was not related to better initial staging. They did, however, have 11% fewer eventual distant metastases.

Preparatory clinical studies of Pi-mesons at TRIUMF.

Eighty patients have been treated with Pi-mesons (pions) at TRIUMF between 1979-1984. The patients had tumors rarely curable by standard methods and had no prior radiotherapy. The distribution by site included skin, metastatic nodules (13), brain, glioblastoma multiforme (32), pelvis, rectosigmoid (15), prostate (12), bladder (7), and ovary (1). The studies involve serial escalations of pion dose until maximum tissue tolerance is reached, monitoring the response at each dose increment. Sites were chosen for study where lack of local control is a significant cause of treatment failure with conventional radiation therapy. The low dose rate and the available beam access at TRIUMF limit the number of patients treated and the volume treatable. A 3-D treatment planning program is in use, and a 3-D display of the dose distribution delivered in brain tumor treatments has been developed using the PET scanner. In practice, new methods introduced for measurement of tissue response include tumor growth delay curves, fine-needle biopsy mapping, and PET scanning of brain tumors. The use of endoscopic assessment of the rectosigmoid region is emphasized. Treatment results of glioblastoma multiforme show that the median survival for patients treated to 125 pion cGy/fx is in the range of 187-198 days; for patients receiving 170 cGy per dose/fraction (fx) the range is 290-315 days, and for those receiving 200-220 cGy/fx the median survival is in excess of 290 days. For pelvic malignancies the local control obtained with doses of 2500 cGy or less was 50% in 12 assessable patients; it was 75% in 20 patients who had 3000 cGy or more.(ABSTRACT TRUNCATED AT 250 WORDS)