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Biomedical subjects

R D Errington

Publications and source records attributed to R D Errington.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of outcomes for patients with oral squamous cell carcinoma at intermediate risk of recurrence treated by surgery alone or with post-operative radiotherapy.

Controversy remains about which patients at intermediate risk of recurrence of oral squamous cell carcinoma would benefit from radiotherapy. A retrospective review of computerised database and medical records for 462 consecutive patients at the Regional Maxillofacial Unit in Liverpool who were treated with primary surgery with or without post-operative radiotherapy was carried out. We classified 29% (134) of patients as being at 'low' risk of disease recurrence (pT1-2, N0 with clear margins), 29% (135) at 'high' risk (involved margins or lymph node extracapsular spread) and the remaining 42% (193) at 'intermediate' risk. Of those at intermediate risk, 41% (80/193) received adjuvant radiotherapy and their 5 year survival (SE) was 54% (6%) compared to 71% (5%) for those with primary surgery alone (P=0.002). A higher proportion of patients having radiotherapy had loco-regional recurrence (19/80 24%) compared to those treated by surgery alone (17/113 15%). The improved salvage rate for recurrent disease in the surgery alone group (8/17 53%), compared to those receiving radiotherapy (2/19 13%, P=0.05), indicates an advantage in withholding radiotherapy for patients at intermediate risk of recurrence. This study indicates a potential disadvantage associated with the use of postoperative radiotherapy for patients at intermediate risk of recurrence. A randomised trial comparing a watch and wait policy to postoperative radiotherapy in patients with an intermediate risk of recurrence is required to confirm the trend indicated in this retrospective data.

Aged↗
PubMed2005

Proton beam therapy and iris neovascularisation in uveal melanoma.

PURPOSE: Local treatment of uveal melanoma by radiotherapy involves the use of brachytherapy with radioactive plaques attached to the sclera, or proton irradiation. Both treatments induce growth arrest within the tumour and its slow involution over several years. Although ocular retention rates are excellent, regrowth of tumours due to resistance and neovascular glaucoma leads to enucleation of up to 10% of affected eyes. Proton irradiation involves part of the iris in most cases and we noticed that neovascularisation only occurred in the part of the iris that was not irradiated. We therefore conducted this study to determine the relationship between the development of iris neovascularisation and iris irradiation. METHODS: A total of 21 enucleation specimens from patients who had previously had proton irradiation were collected from the files of the Department of Pathology, Moorfields Eye Hospital during the 5-year period from 1994 to 1999. Sections of these eyes were assessed for VEGF-A, bFGF, and von Willebrand Factor (vWF) by immunohistochemistry. Ophthalmic notes and radiotherapy records were reviewed to assess the extent of iris irradiation. RESULTS: In all, 11 cases showed clinical evidence of iris neovascularisation and were selected for further study. Three of these eyes also showed clinical evidence of regrowth of the tumour. Histological evidence of iris neovascularization was noted in all 11 of the eyes examined, and was only present in the nonirradiated side of the iris in 8/11 eyes. NVI was present on both sides of the iris in three cases, but was less severe in the irradiated part. Expression of VEGF-A was at most weak within the tumour, but was present in the detached retina and in the epithelium of both ciliary body and iris. Some bFGF staining was noted around vessels in the iris stroma. CONCLUSIONS: Our results suggest that irradiation leads to iris atrophy, and that atrophic, irradiated iris is resistant to the development of neovascularisation.

Adult↗
PubMed1999

Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection.

The outcome of 200 patients with squamous cell carcinoma of the oral/oropharyngeal mucosa managed by primary radical surgery and simultaneous neck dissection and followed for 2.2-8.5 years is reported and related to the pathological features. Ninety-nine patients (50%) had cervical lymph node metastases including 16 (8%) with bilateral metastases. Actuarial (life tables) survival analysis showed the overall 2-year survival probability was 72%, falling to 64% at 5 years. The 5-year survival probability was 81% for patients without metastasis, 64% for patients with intranodal metastases and 21% for patients with metastases showing extracapsular spread. A total of 60 patients (30%) died of/with their cancer: 36 (18%) of local recurrence; 4 (2%) of a metachronous primary tumour; 14 (7%) of regional disease, and 6 (3%) with systemic metastases. A further 15 patients (8%) had relapsed but were clinically disease-free after additional surgery. In all, 7% of the series developed metachronous primary tumours. In addition to nodal metastasis, survival was related to the site and stage of the primary tumour, the histological grade and pattern of invasion, status of the resection margins and pathological TNM stage. For patients with lymph node metastasis, extracapsular spread was an important indicator of tumour behaviour and we recommend its use as a criterion for pathological N staging.

Adult↗
PubMed1998

Early closure of a randomized trial: surgery and postoperative radiotherapy versus radiotherapy in the management of intra-oral tumours.

Tumours of the oral cavity/oropharynx occur relatively infrequently in the UK. The management of such lesions, especially the squamous cell carcinomas, is still a little controversial. Some centres advocate radiotherapy while others adopt surgery and radiotherapy. In an attempt to resolve the question of which approach gives the better results, a multicentre randomized trial was established to compare surgery plus postoperative radiotherapy with radical radiotherapy alone. It was anticipated that 350 patients would be required to give a statistically significant result, but, after 35 patients had been entered, the trial was closed prematurely with a marked difference in overall survival in favour of the combination arm (P = 0.0006). At this analysis, carried out 23 months after trial closure, the survival difference between the two arms remains statistically significant for all causes of mortality (P = 0.001; relative death rate = 0.24; 95% CI 0.10-0.59).

Adult↗
PubMed1997

Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma.

AIMS/BACKGROUND: Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS: The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS: Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS: Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.

Adult↗
PubMed1996

The treatment of recurrence following fast neutron therapy for head and neck malignancy.

Twenty-eight patients received fast neutron therapy for head and neck malignancy. Of these, seven had no recurrence, 13 had a recurrence at the primary site, five had a recurrence in the neck and three had a recurrence in the neck and at the primary site. Treatment of a primary site recurrence was difficult with seven of the eight patients submitted for major surgical resection developing serious complications. Of the six patients developing a fistula four required flap repair. The tumour specific 5-year survival for the whole group of 28 patients was 29%. The surgical treatment of locoregional recurrence following fast neutron therapy is fraught with problems and some type of flap repair is usually necessary.

Adult↗
PubMed1995

Fast-neutron therapy in advanced head and neck cancer: a collaborative international randomized trial.

PURPOSE: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. RESULTS: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). CONCLUSION: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity.

Adult↗
PubMed1992

Accelerated fast neutron therapy: a pilot study.

The clinical role of fast neutron therapy has been limited by excessive late normal tissue damage. A pilot study of accelerated fractionation of fast neutron therapy was performed, based on the rationale that this should result in an increase in the response in acute reacting tissues (normal and malignant), with no change in late damage and a consequent increase in the therapeutic ratio. Further accelerated fractionation should improve the local control of rapidly proliferating tumour, without the potential problem of inadequate reoxygenation inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be) neutrons were given over 12 days to 27 sites in 23 patients with locally advanced tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa early reactions were obtained. A larger dose reduction (15%) was required at pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The overall response rate was 76% with a complete response rate of 16%. For locally advanced breast cancer, the complete response rate was 9%, which compares unfavourably with previous results with conventional neutron fractionation schedules. The combination of a low overall complete response rate and excessive late normal tissue toxicity suggests that accelerated fractionation of fast neutrons does not lead to an improvement in the therapeutic ratio, and that late normal tissue damage will continue to be dose limiting.

Adult↗
PubMed1991

High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.

OBJECTIVE: To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN: Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING: Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS: 151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION: Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES: Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS: In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS: The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.

Fast Neutrons↗
PubMed1989

Alternating six-drug combination chemotherapy induction for intermediate and high-grade non-Hodgkin's lymphoma.

31 patients with intermediate and high-grade non-Hodgkin lymphomas were treated by a six-drug alternating regime comprising four cycles of 200 mg/m2 i.v. methotrexate on days 8, 15, 28 and 35, 50 mg/m2 i.v. Adriamycin on day 1, 40 mg/m2 oral prednisolone on days 1-7 and 21-27, 120 mg/m2 i.v. etoposide on days 21-23, 600 mg/m2 i.v. cyclophosphamide on day 21 and 1.4 mg/m2 i.v. vincristine on day 1 (MAPECO). In all, 3 patients had stage I disease, 12 stage II, 6 stage III and 10 stage IV. Of 28 evaluable patients, 19 were complete responders (68%) and 9 were partial responders (32%); at 2 years, the actuarial relapse-free survival of the 19 patients achieving complete remission is 80%, and 5 patients remain in complete remission at 3 years. This is a preliminary report of an effective intensive regime with acceptable toxicity.

Actuarial Analysis↗
PubMed1989

Treatment of small cell lung cancer with induction chemotherapy followed by late intensification.

Seventy-seven patients with small cell lung cancer were entered on a protocol comprising induction chemotherapy with cyclophosphamide 1 g m-2, adriamycin 40 mg m-2 and vincristine 1.4 mg m-2 (CAV) every 21 days for four to six cycles. The overall response rate was 72.8%. Twenty-six patients achieving complete remission received intensification with two further cycles of ifosfamide 5 g m-2, mesna 8 g m-2, methotrexate 30 mg m-2 and etoposide 100 mg m-2 per day for 3 days (IME). Six of the 15 patients in partial remission following CAV achieved a further remission on IME (response rate 40%). Median survival in the limited disease group was 11 months compared with 7 months in the extensive disease patients and four patients are alive at more than 2 yr follow up. There was no significant prolongation of the median survival (11 months) seen in those patients in complete remission who had negative second bronchoscopy examination. This sequential six drug regime produces high response rates in small cell lung cancer, and there is evidence of lack of cross-resistance between CAV and IME.

Adult↗
PubMed1989

Sequential combination chemotherapy and radiotherapy in locally advanced non-small cell carcinoma of the bronchus.

The feasibility, effectiveness and toxicity of a new four drug intensive combination chemotherapy regime has been assessed in 36 patients with inoperable non-small cell lung cancer. Three cycles of adriamycin, vindesine, ifosfamide and cisplatin were given to 36 patients followed by sequential radiotherapy to 25 patients. The overall response rate to chemotherapy was 33%, and median progression free interval was 6 months. Median survival was 8.5 months. Grade 4 WHO neutropenia was seen in 12 patients, there were three episodes of neutropenic fever and one death in which toxicity may have been contributory. Radiotherapy was not associated with serious toxicity. This study demonstrates that a significant response rate can be achieved with short intensive chemotherapy in unresectable non-small cell lung cancer and that it is feasible to combine this with radiotherapy.

Adult↗
PubMed1989

High energy neutron therapy programme at the Douglas Cyclotron Centre, Clatterbridge Hospital.

Preliminary results are reviewed on the outcome of patients treated within two randomized studies with either p(60) + Be-neutrons or photons. Since April 1987 67 patients have been treated of which twelve have been included in a randomized study on head and neck cancer and 40 on pelvic cancer. The clinical treatment planning is presented in detail and discussed. The results presented are considered to be very preliminary, so that no attempt has been made to analyse and discuss them in detail.

England↗
PubMed1988

Sequential chemotherapy, surgery and radiotherapy in locally advanced breast cancer.

Thirty-seven patients with locally advanced breast cancer, 86% of whom had skin involvement, were treated with three to six cycles of vincristine 1.4 mg m-2, doxorubicin 40 mg m-2 and cyclophosphamide 600 mg m-2. A complete response rate of 19%, and overall response rate of 61% were achieved. Fourteen patients had received a trial of hormone therapy, but no patient had been given prior cytotoxic chemotherapy or radiation therapy. In no case was chemotherapy discontinued on account of toxicity. In patients with partial remission where gross disease more than 3 cm remained, mastectomy (10 patients) or local excision (five patients), was carried out increasing the complete remission rate to 49%. Thirty-two patients then received 45 Gy in 24 days to the breast and regional lymphatics with a further 12 Gy boost to the tumour site. The overall response rate achieved was 86% of the 37 patients, with a total, complete response rate of 76%. The median time to relapse in the 28 complete responders was 17 months. Local palliation, defined as absence of pain, ulceration or an enlarging mass was achieved in 92% of the total number of patients, and the projected local palliation rate at 2 years by life table analysis was 60%. Only 50% of the 10 N3 patients were alive at 1 year, compared to 93% of the 27 N0-N2 patients (P less than 0.05). The overall survival in the entire group at 2 years was 50%. This is an effective and tolerable combined modality approach for the control of local disease in a subgroup of breast cancer patients with complex management problems.

Adult↗