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Biomedical subjects

T J Keane

Publications and source records attributed to T J Keane.

At least 37 records · Page 2Linked to original sources

Radiation-induced lung damage: dose-time-fractionation considerations.

The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/- 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data.

Animals↗

T3N0M0 glottic carcinoma--a failure analysis.

There is at present considerable controversy regarding the appropriate management of a patient who presents with a T3N0M0 glottic carcinoma. This paper presents the results for 141 patients presenting clinically with T3N0M0 glottic carcinoma between 1964 and 1981 and treated with primary radiotherapy reserving surgery for residual or recurrent disease. The actuarial survival for the entire group of patients was 50.5% at 5 yr; 28% of the patients died of glottic cancer. The local relapse-free rate achieved with radiotherapy was higher in female patients (68%) than male patients (41%) (P = 0.04); the local relapse-free rate was higher in males 60 yr of age or older (46%) than in males 59 yr of age or younger (31%) (P = 0.02). Involvement of all three laryngeal regions and initial tracheotomy were associated with a high primary failure rate. Fifty-nine per cent of patients alive at 5 yr retained and intact and functioning larynx. The time up until diagnosis of recurrence and the number of endoscopies required to establish recurrent or residual disease were all assessed with respect to their effects on survival and were shown to have no significant impact. Methods of improving the results of treatment for those patients with a high primary failure rate following radiotherapy are discussed.

Adult↗

T3N0M0 glottic carcinoma--a pathologic analysis of 41 patients treated surgically following radiotherapy.

Forty-one patients undergoing surgery for recurrent or residual tumour following radical radiotherapy for T3N0M0 glottic carcinoma had their larynges evaluated pathologically by whole organ laryngeal sectioning. All patients had been staged initially as T3N0M0 glottic carcinoma and treated according to a protocol of radical radiotherapy (50-55 Gy in 4-5 weeks) with surgery reserved for radiation failure. Seventeen of the 41 patients died as a result of locoregional or distant recurrence or complications following surgery. Twenty-four patients were either alive or dead with intercurrent disease. Pathologic staging demonstrated 58% of these tumours to be rpT4, 29% rpT3 and the remainder rpT0-2. The incidence of major cartilage invasion, vascular or perineural invasion, and subglottic extension greater than 15 mm was more frequent in patients with locoregional recurrence than in patients without recurrence. The presence of these pathologic features had a positive predictive value of 0.78 in relation to probability of locoregional failure. In addition, there was a significant difference in the frequency of these pathologic features between patients with and without locoregional recurrence (P less than 0.001). The frequency of positive margins (19%) and pattern of involvement are described. The incidence of occult nodes (0%) in patients undergoing neck dissection is presented. The frequency (23%) and pattern of osteo-chondroradionecrosis are also described. The patterns of growth and spread observed were similar to those described previously. The importance of performing wide surgical resections in patients with recurrence following radiotherapy is emphasized.

Carcinoma, Squamous Cell↗

Metastatic inguinal nodes from an unknown primary neoplasm. A review of 56 cases.

Fifty-six cases of this uncommon neoplastic manifestation are presented. These cases represent 0.065% of 86,589 new cases of malignant disease seen at The Princess Margaret Hospital from 1968 to 1982. There were 29 men and 27 women. The median age at presentation was 58 years. Three major groups were identified: inguinal disease, 24 cases; unilateral inguinal plus iliac disease, 16 cases; local plus systemic disease, 16 cases. Pathologic subtypes were anaplastic, 24; squamous, 11; adenocarcinoma, nine; melanoma, nine; and others, three. Survival at 5 years for all patients was 27%. Among 40 patients who presented with inguinal and inguinal plus iliac disease, survival was 37.5% at 5 years. Initial treatment following biopsy was radiation in 35, lymph node dissection in eight, and chemotherapy in four. Excisional biopsy only was performed in nine cases. There were no treatment-related deaths. The findings observed in this study, in which radiation therapy was employed as initial management in the majority of cases, suggests that radiation therapy is a valid alternative to surgery in the management of this disease.

Adult↗

A pilot study of mitomycin-C/5-fluorouracil infusion combined with split course radiation therapy for carcinomas of the larynx and hypopharynx.

Fifty-seven patients with advanced squamous carcinoma of the larynx and hypopharynx were entered on a pilot study of initial therapy using split course radiation therapy combined with simultaneous chemotherapy using mitomycin-C and 5-fluorouracil. The treatment was well tolerated with 90% of patients completing their planned radiation treatment. Seventy percent of this group completed their planned chemotherapy. Significant hematological toxicity was not observed. Survival and loco regional control at one and two years of follow-up were considered at least comparable to that achieved with conventional single-course radical radiation therapy as primary treatment. Based on these results a randomized trial of this radiation-chemotherapy regimen compared to radiation therapy alone as initial therapy is in progress.

Adult↗

Postoperative local abdominal irradiation for cancer of the colon above the peritoneal reflection.

A retrospective analysis of 82 patients with cancer of the colon above the peritoneal reflection who received postoperative local abdominal irradiation was undertaken to assess the survival, patterns of failure, and toxicity of treatment. Forty-eight patients (adjuvant group) had a complete resection, but were felt to be at high risk for local relapse and received postoperative local abdominal irradiation. Thirty-four patients had gross residual disease following surgery. The 5-year actuarial survival and local relapse free survival were 67 and 67%, respectively, in the adjuvant group. In this group, local relapse was observed in 9 of 28 patients with Stage C disease in contrast to 3 of 20 patients with Stage B2 disease; 1 of 14 patients with lesions in the right colon failed locally compared to 11 of 35 patients with lesions in the left. Only 2 of the 34 patients with gross residual disease remained relapse free from 93% of patients having a component of local failure. The majority of the treatment morbidity was seen in patients with gross residual disease. Prospective randomized studies should be done to determine the efficacy of postoperative irradiation in patients with colon carcinoma who are at high risk for local recurrence following surgical resection.

Abdomen↗

Carcinoma of the tonsil: the effect of dose-time-volume factors on local control.

Between 1970 and 1979, 372 patients with squamous cell carcinoma of the tonsil were treated with primary irradiation therapy, with salvage surgery for failures. The median age was 60 years and the male to female ratio was 2:1. The staging system used was the 1974 UICC TNM system. There were 47 T1 lesions (13%), 161 T2 lesions (43%), and 164 T3 lesions (44%). Regional nodes were not palpable in 173 (46%); 122 had N1 nodes (33%), 6 had N2 nodes (2%) and 71 had N3 nodes (19%). All patients received external beam radiation which was supplemented in 68 patients with a radioactive implant for disease into adjacent tongue. The overall survival for all patients was 38% at 5 years and 54% when corrected for intercurrent disease. Local control was 87% for T1 lesions, 68% for T2 lesions and 50% for T3 lesions. Regional control was 96% for N0, 67% for N1 and 37% for N2-3. A detailed dose-time-volume analysis revealed that increasing volume improved local control in T1 and T2 lesions (77% had local control if the volume was greater than 80 cm2 versus 53% if the volume was less than 80 cm2, p = 0.014), except for T3 lesions. Increasing the dose in the range of 5000 to 6500 rad had no significant effect on primary control in any stage of disease. The addition of a radioactive implant did not increase local control if disease extended into the tongue (57% local control if implant, 52% if no implant). This study demonstrates the significance of adequate treatment volume in local control for carcinoma of the tonsil. No significant dose response was found and subsequent surgery was not compromised when a moderate dose of radiation was used.

Adult↗

Radical radiation therapy with 5-fluorouracil infusion and mitomycin C for oesophageal squamous carcinoma.

Thirty-five patients with clinically staged non-metastatic squamous carcinoma of the oesophagus were treated with radiation combined with mitomycin C, and 5-fluorouracil (5-FUra) infusion. Twenty patients were planned for a split course regimen 2250-2500 cGy in 10 fractions and chemotherapy. This dose of radiation to be repeated with another course of chemotherapy after 4 weeks rest. Fifteen patients were planned for a single course 4500-5000 cGy in 20 fractions and a single course of chemotherapy. Thirty-one patients are available for a minimum follow-up of one year, 26 patients for a minimum follow-up of 2 years. All 35 patients are included in the survival and local relapse-free analysis. Survival at one year is 47% and at 2 years 28%. The local relapse-free rate at both one and 2 years is 48%. There was an improvement in survival and local relapse-free rate for the single course regimen compared to the split course; 2 years survival 48% versus 12% (p = 0.24) local relapse-free rate 79% versus 27% (p = 0.07). All patients receiving radiation and chemotherapy were compared with historical controls treated by radiation alone. This matching procedure was done independent of knowledge of outcome (two controls were matched/case). Patients were matched for age, sex. TNM stage, and total radiation dose. There was a significant difference in survival p = 0.004 and local relapse-free rate p = 0.05 for patients receiving radiation and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The treatment of glomus tumors in the temporal bone by megavoltage radiation.

Forty-five patients with glomus tumors in the temporal bone region were treated by radiation therapy. Only three patients had recurrence or progression of tumor during the follow-up period of 3 to 23 years (median, 10 years). No patient died from uncontrolled glomus tumor. The majority of patients noted symptomatic relief after radiation, but objective neurologic deficits usually remained unchanged or showed only partial improvement. The most commonly used radiation dose was 3500 cGy tumor dose delivered in 15 fractions in 3 weeks by a homolateral wedge technique from megavoltage radiation apparatus. This dose is less than that usually recommended for glomus tumors. From these results and from review of the literature, it is suggested that a moderate radiation dose of 3500 cGy in 3 weeks is effective treatment for glomus tumors, even if complete tumor involution does not occur.

Adolescent↗

Linear analogue self-assessment of voice quality in laryngeal cancer.

This study evaluated the reliability and sensitivity of laryngeal cancer patients' linear analogue self-assessments (LASA) of voice quality. Thirty patients completed LASA scales for a number of voice-related symptoms and abilities several times during a standard treatment programme. The study design allowed evaluation of the scales' reliability, both early and late in treatment, and sensitivity to the changes expected during irradiation. Another 29 post-treatment patients completed the same scales in interviews separated by several weeks. Results indicate that LASA scores were generally reliable, sensitive to clinical change, yet stable when clinical status is unaltered. Though further demonstrations of the validity of these scales are required, their possible use as outcome measures in future clinical trials comparing treatments for laryngeal cancer is feasible.

Adult↗

Total abdominal irradiation for cancer of the colon.

A retrospective analysis of 55 patients treated with whole abdominal irradiation following surgical excision for cancer of the colon is presented. Three groups of patients were given whole abdominal irradiation, eight with gross residual tumor following surgery, 17 with peritoneal seeding, and 30 who had complete surgical excision of the tumor but were felt to be at high risk for relapse. Only one of the eight patients with gross residual tumor, and one of the 17 with peritoneal metastases, are currently alive and well, with the majority dying from local or peritoneal metastases. The 5 year actuarial survival for the 30 patients irradiated following complete surgical excision is 55%. The treatment was well tolerated and few complications were observed. It is concluded that whole abdominal irradiation is ineffective for the treatment of colon cancer if peritoneal metastases are present, or if gross residual tumor is left behind following surgery. A randomized controlled clinical trial is being organized to test whether total abdominal irradiation is of benefit in terms of survival in high risk colon cancer patients following complete surgical removal.

Adenocarcinoma↗

Do patients and physicians agree on the assessment of voice quality in laryngeal cancer?

Information is available regarding tumor control rate and survival for patients with cancer of the larynx. Less well known are the effects of treatment upon the patient's quality of voice and way of life because there is at present no suitable method for the routine clinical assessment of these effects. This paper reports some results of the evaluation of one assessment technique using linear analogue scales, and it examines the agreement between patients' and physicians' assessment of severity of voice related function and sound. Each of 20 patients taped a voice recording and subsequently rated his overall functional ability and the sound of his voice. Twenty physicians rated the sound of the 20 patients' voices from the recording and judged functional ability from a written description. Agreement between the scores of patients and physicians indicated that despite being strongly correlated, they were often not the same. Implications of this technique are discussed.

Adult↗

Management of early supraglottic laryngeal carcinoma by irradiation with surgery in reserve.

The results of radical radiotherapy with surgery in reserve for 136 patients with stage T1 and T2 NO supraglottic laryngeal carcinoma seen during a 20-year period are analyzed herein. Approximately one half of all patients were alive and well five years after treatment, while one fifth of patients died of supraglottic cancer. The cancer in two thirds of these patients was locally controlled by irradiation; of particular note was an 11% to 18% recurrence rate in patients whose necks were initially noted to be free of cancer. Analysis of the results of irradiation treatment disclosed a major reduction in nodal recurrence from the use of irradiation fields larger than 7 X 7 cm (3%, as compared with 19% with a smaller irradiation field). During the 20-year period of the study, there was a major reduction observed in tumor-related deaths; this is attributed to the use of larger irradiation fields and more aggressive use of surgery for irradiation failures. The results obtained are compared herein with the results of primary surgery, and conclusions are drawn as to the optimal management of early-stage supraglottic cancer.

Carcinoma, Squamous Cell↗

Radical external beam radiation therapy for adenocarcinoma of the rectum.

External beam megavoltage radiation therapy was used as primary treatment for 123 patients with rectal adenocarcinoma. Surgery was undertaken for some patients who had residual tumor. The overall five-year survival rate was 21 per cent. When patients were separated into those who presented with clinically mobile and those with clinically fixed rectal tumor masses, the survival rates were 38 per cent and 2 per cent, respectively. The primary tumor was controlled by radiation alone in 21 of 56 (38 per cent) patients who had mobile tumors but in only six of 67 (9 per cent) patients who had fixed tumors. Further investigation of high-dose primary radiation, with surgery reserved for patients with residual rectal carcinoma, may allow reduction of the number of patients who require abdominoperineal resection.

Adenocarcinoma↗