Does the Use of Volumetric Modulated Arc Therapy Reduce Gastrointestinal Symptoms after Pelvic Radiotherapy?

AIMS: Growing numbers of patients with cancer are surviving after treatment with pelvic radiotherapy. We evaluated the technique of volumetric modulated arc therapy (VMAT), which delivers a decreased dose to the organs at risk. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects and correlate the frequency of gastrointestinal symptoms with the volume of bowel receiving radiation dose. MATERIALS AND METHODS: Patients who were to receive VMAT for gynaecological malignancy completed patient-reported outcomes at baseline, the end of treatment, 8 weeks and 1 year. The rates of patient-reported toxicity were correlated with the volume of bowel irradiated. RESULTS: The frequencies of patient-reported gastrointestinal symptoms increased in the acute toxicity phase and tended to improve at 1 year, with the exception of faecal incontinence and rectal bleeding (P < 0.05). There was not a strong association between the volume of small bowel that was irradiated (P > 0.05 at all dose levels) and reported toxicity, suggesting that other factors are involved in the development of toxicity. CONCLUSION: Although VMAT decreases the dose delivered to the small bowel, this does not translate into a reduction in patient-reported toxicity.

Insufficiency fractures in patients treated with pelvic radiotherapy and chemotherapy for uterine and cervical cancer.

Insufficiency fractures are recognised consequences of radiotherapy in gynaecological malignancy with reported incidences between 2.7% and 89%. We aimed to determine the incidence and risk factors for insufficiency fractures in patients receiving radical pelvic radiotherapy for uterine and cervical cancer. A case-note review was undertaken of patients treated between January 2007 and December 2008. Insufficiency fractures were identified from radiographs, computed tomography and magnetic resonance images. Chi-squared and Mann-Whitney tests were performed to determine associations between insufficiency fractures and chemotherapy, steroids and age. A total of 285 patients received pelvic radiotherapy, 137 with uterine and 148 with cervical cancer. Mean age was 59 years. A total of 144 patients received chemotherapy, 101 concurrently and 35 adjuvantly. Bone abnormalities affected 67 patients, 33 had pelvic insufficiency fractures, 12 had multiple fractures and 3 patients developed femoral head avascular necrosis. Use of chemotherapy was not associated with development of fractures (P = 0.949). However, cervical cancer patients had a significantly higher incidence of insufficiency fractures (P = 0.018) and bone pain (P = 0.03) compared with uterine cancer patients. This suggests concurrent chemotherapy may be a significant factor in increasing insufficiency fractures and bone morbidity in these patients and highlights a need for further research to identify, prevent and reduce these long-term complications.

The effects of pelvic radiotherapy on cancer survivors: symptom profile, psychological morbidity and quality of life.

AIMS: As cancer survival rates continue to increase, it is important to maximise the quality of life of cancer survivors. Pelvic radiotherapy is a common cancer treatment. Bladder, bowel and sexual dysfunction are recognised side-effects of treatment, and yet relatively little is known of the extent to which they remain problems in the longer term when patients are often managed by primary care, nor of the psychological impact of symptoms and effects on quality of life. Therefore, the aims of this study were to estimate the prevalence of bladder, bowel and sexual dysfunction late effects in a sample of cancer survivors; assess the impact of time since treatment on symptom prevalence; and explore the relationship between symptoms, psychological morbidity and quality of life. MATERIALS AND METHODS: A questionnaire was given to a sample of cancer survivors treated in Oxford who had pelvic radiotherapy 1-11 years previously. The questionnaire measured patient-reported toxicity (Common Toxicity Criteria of Adverse Events/Late Effects of Normal Tissues--Subjective, Objective, Management and Analytic Measure), psychological morbidity (Hospital Anxiety and Depression Scale) and quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30). RESULTS: In total, 418 (57.1%) completed questionnaires were received. Moderate/severe problems with bowel, urinary and sexual functioning were relatively common: bowel urgency (59% women, 45% men); urine urgency (49% women, 46% men); ability to have a sexual relationship affected (24% women, 53% men). Symptoms were just as frequent in those 6-11 years after treatment as in those 1-5 years after treatment. Symptom severity was significantly associated with poorer overall quality of life and higher levels of depression. CONCLUSIONS: Late effects are common among long-term cancer survivors who have had pelvic radiotherapy, and are associated with reduced quality of life and psychological morbidity. It is imperative due attention is paid to this issue during the follow-up phase--both in secondary and primary care. Health care professionals providing follow-up care need to be aware of the importance of assessing and monitoring symptoms, and need to be adequately informed on the most appropriate management strategies.

Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma.

OBJECTIVE: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. METHODS: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength. RESULTS: When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/ß ratios as a consequence of the described concept of extended equivalence. CONCLUSION: The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed. ADVANCES IN KNOWLEDGE: Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/ß ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma.

Value of the Hospital Anxiety and Depression Scale in the follow up of head and neck cancer patients.

BACKGROUND: Few studies have prospectively investigated psychological morbidity in UK head and neck cancer patients. This study aimed to explore changes in psychological symptoms over time, and associations with patients' tumour and treatment characteristics, including toxicity. METHODS: Two hundred and twenty patients were recruited to complete the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) ('LENT-SOMA') questionnaires, both pre- and post-treatment. RESULTS: Anxiety was highest pre-treatment (38 per cent) and depressive symptoms peaked at the end of treatment (44 per cent). Anxiety significantly decreased and depression significantly increased, comparing pre- versus post-treatment responses (p < 0.001). Hospital Anxiety and Depression Scale scores were significantly correlated with toxicity, age and chemotherapy (p < 0.01 for all). CONCLUSION: This is the first study to analyse the relationship between Hospital Anxiety and Depression Scale scores and toxicity scores in head and neck cancer patients. It lends support for the use of the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) questionnaire in routine clinical practice; furthermore, continued surveillance is required at multiple measurement points.

Gastrointestinal symptoms after pelvic radiotherapy: a national survey of gastroenterologists.

PURPOSE: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. Up to 50% develop significant gastrointestinal symptoms. The National Cancer Survivorship Initiative has identified access to specialist medical care for those with complications after cancer as one of their four key needs. We aimed to determine the current practice of British gastroenterologists with regards to chronic gastrointestinal symptoms after pelvic radiotherapy. METHODS: A questionnaire was developed and sent up to a maximum of five times to all UK consultant gastroenterologists. RESULTS: Eight hundred sixty-six gastroenterologists were approached and 165 (20%) responded. Sixty-one percent saw one to four patients annually with bowel symptoms after radiotherapy. Eighteen percent rate the current treatments as effective "often" or "most of the time". Forty-seven percent of gastroenterologists consider themselves "confident with basic cases", with 11% "confident in all cases". Fifty-nine percent thinks a gastroenterologist with a specialist interest should manage these patients. Although only 29% thinks a specific service is required for these patients, 34% rates the current service as inadequate. The ideal service was considered to be gastroenterology-led, multidisciplinary and regional. Low referral rates, poor evidence-base and poor funding are cited as reasons for the current patchy services. CONCLUSIONS: The low response rate contrasts with that from a parallel survey of clinical oncologists. This may reflect the opinion that radiation-induced bowel toxicity is not a significant issue, which may be because only a small proportion of patients are referred to gastroenterologists. The development of new, evidence-based gastroenterology-led services is considered the optimal way to meet the needs of these patients.

SCOTCERV: a phase II trial of docetaxel and gemcitabine as second line chemotherapy in cervical cancer.

OBJECTIVE: The aim of the study was to determine the response rate and response duration of cervical cancer previously treated by cisplatin (with or without radiation) to a combination of docetaxel and gemcitabine. Secondary endpoints were assessment of toxicity and quality of life (QoL) of patients receiving the treatment. METHODS: This was a multicentre phase II trial of 3 weekly docetaxel 75 mg/m(2) day 1 (reduced to 60 mg/m(2) after 32 cycles had been administered) and gemcitabine 1000 mg/m(2) (days 1 and 8). A two stage Gehan design was used initially. Twenty-nine patients recruited had disease outside the irradiated pelvis (Group 1), and 21 had disease confined to the irradiated pelvis (Group 2). The target response for the Gehan 2 design was 25% (Group 1) and 10% (Group 2). RESULTS: The overall response rate for Group 1 was 21.4% (95% CI 8.3-41.0%). Amongst those who had at least 3 cycles of chemotherapy the response rate was 27.3% (95% CI 10.7-50.2%). The median survival was 7.3 months (95% CI 5.4 to 9.2 months) with 39.3% (95% CI 21.7-56.5%) alive at 1 year. In Group 2 the overall response rate was 9.5% (95% CI 1.2%-30.4%). The response rate for those who had at least 3 cycles of chemotherapy was 12.5% (95% CI 1.6-38.4%). The median survival was 7.9 months (95% CI 2.2-13.6 months). Toxicity was mainly haematological with 51% developing grade 3 or 4 neutropenia after at least 1 cycle of chemotherapy. QoL showed a significant deterioration from baseline for physical and role function but there was an improvement in emotional function during treatment. CONCLUSION: Response rates and survival duration were similar to those reported following treatment with platinum based doublets. In view of the relatively poor response rates (no more than 36%) to conventional chemotherapy future developments should be a combination of chemotherapy and biological agents such as VEGFR inhibitors.

Late-onset bowel dysfunction after pelvic radiotherapy: a national survey of current practice and opinions of clinical oncologists.

AIMS: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. It is common for patients to develop gastrointestinal symptoms after treatment. The aim of this study was to determine the current practice of clinical oncologists in the UK with respect to late-onset bowel dysfunction after pelvic radiotherapy, and to discuss the wider issues surrounding current and future service provision for this patient group. MATERIALS AND METHODS: A questionnaire was developed to establish current practice. This was sent to the 314 clinical oncologists in the UK who treat pelvic malignancies up to a maximum of three times. RESULTS: One hundred and ninety (61%) responses were received. Most oncologists (76%) screen for gastrointestinal dysfunction after pelvic radiotherapy, usually through history taking rather than formal tools. Clinical oncologists view toxicity as a significant problem, with most estimating that up to 24% of patients at 1 year have bowel symptoms. Most oncologists refer less than 50% of their symptomatic patients, with most referring less than 10%. These referrals are 31% to a gastroenterologist, 23% to a gastrointestinal surgeon and 33% to both. Most (58%) do not have access to a gastroenterologist or a gastrointestinal surgeon with a specialist interest in their area. Sixty-five per cent of oncologists think a service is required specifically for patients with bowel dysfunction after pelvic radiotherapy, but half (52%) think that the current service in their area is inadequate. CONCLUSIONS: Clinical oncologists recognise late-onset bowel dysfunction after pelvic radiotherapy as a significant problem, but one that is linked to poor recognition of symptoms and an inadequate patchy service.

Substantial improvement in UK cervical cancer survival with chemoradiotherapy: results of a Royal College of Radiologists' audit.

AIMS: To compare survival and late complications between patients treated with chemoradiotherapy and radiotherapy for locally advanced cervix cancer. MATERIALS AND METHODS: A Royal College of Radiologists' audit of patients treated with radiotherapy in UK cancer centres in 2001-2002. Survival, recurrence and late complications were assessed for patients grouped according to radical treatment received (radiotherapy, chemoradiotherapy, postoperative radiotherapy or chemoradiotherapy) and non-radical treatment. Late complication rates were assessed using the Franco-Italian glossary. RESULTS: Data were analysed for 1243 patients from 42 UK centres. Overall 5-year survival was 56% (any radical treatment); 44% (radical radiotherapy); 55% (chemoradiotherapy) and 71% (surgery with postoperative radiotherapy). Overall survival at 5 years was 59% (stage IB), 44% (stage IIB) and 24% (stage IIIB) for women treated with radiotherapy, and 65% (stage IB), 61% (stage IIB) and 44% (stage IIIB) for those receiving chemoradiotherapy. Cox regression showed that survival was significantly better for patients receiving chemoradiotherapy (hazard ratio=0.77, 95% confidence interval 0.60-0.98; P=0.037) compared with those receiving radiotherapy taking age, stage, pelvic node involvement and treatment delay into account. The grade 3/4 late complication rate was 8% (radiotherapy) and 10% (chemoradiotherapy). Although complications continued to develop up to 7 years after treatment for those receiving chemoradiotherapy, there was no apparent increase in overall late complications compared with radiotherapy alone when other factors were taken into account (hazard ratio=0.94, 95% confidence interval 0.71-1.245; P=0.667). DISCUSSION: The addition of chemotherapy to radiotherapy seems to have improved survival compared with radiotherapy alone for women treated in 2001-2002, without an apparent rise in late treatment complications.

Enhancing fraction measured using dynamic contrast-enhanced MRI predicts disease-free survival in patients with carcinoma of the cervix.

BACKGROUND: There is a need for simple imaging parameters capable of predicting therapeutic outcome. METHODS: This retrospective study analysed 50 patients with locally advanced carcinoma of the cervix who underwent dynamic contrast-enhanced MRI before receiving potentially curative radiotherapy. The proportion of enhancing pixels (E(F)) in the whole-tumour volume post-contrast agent injection was calculated and assessed in relation to disease-free survival (DFS). RESULTS: Tumours with high E(F) had a significantly poorer probability of DFS than those with low E(F) (P=0.011). INTERPRETATION: E(F) is a simple imaging biomarker that should be studied further in a multi-centre setting.

Developing a CTCAEs patient questionnaire for late toxicity after head and neck radiotherapy.

PURPOSE: Patient-based reporting of symptoms is increasingly important in providing treatment toxicity information. However, observer-based scoring systems such as the CTCAEs which incorporate the LENT-SOMA scales are not adapted for patient-based reporting. We aim to (1) report the late toxicity in patients following head and neck radiotherapy using a LENT-SOMA patient-based questionnaire, (2) describe how the responses help to improve the questionnaire and (3) adapt the questionnaire for patient reporting using CTCAEs. METHODS: A 31-item LENT-SOMA patient questionnaire was administered prospectively to 220 patients pre-treatment and at eight time periods post-radical head and neck radiotherapy over 3 years. Exploratory factor analysis was carried out and questionnaire reliability was evaluated using Cronbach's alpha coefficient. RESULTS: At 3-years follow-up, grade 3/4 toxicity was recorded for xerostomia (44%), hoarseness (14.3%), altered taste (6.1%) and oropharyngeal pain (1.9%). Factor analysis indicated that questionnaire division according to anatomical sub-site was reasonable. Cronbach's alpha was 0.851 (95% CI: 0.820-0.883) indicating high reliability. Good compliance was obtained with all questions except for the 'weight loss' item. A satisfaction survey showed that the questionnaire was clear and concise. Teeth and mandible sections have been removed. Dietary change due to xerostomia has been incorporated in line with CTCAEs. LENT-SOMA scoring of analgesic needs and dysphagia not described in CTCAEs were found useful and have been retained. CONCLUSIONS: The questionnaire has enabled reporting of late toxicity and the responses have enabled refinement of the questionnaire. It is reliable, feasible and has been validated for patient-based collection of CTCAEs late toxicity data.

The impact of radiotherapy late effects on quality of life in gynaecological cancer patients.

The aims of this study were to assess changes in quality of life (QoL) scores in relation to radical radiotherapy for gynaecological cancer (before and after treatment up to 3 years), and to identify the effect that late treatment effects have on QoL. This was a prospective study involving 225 gynaecological cancer patients. A QoL instrument (European Organisation for the Research and Treatment of Cancer QLQ-C30) and late treatment effect questionnaire (Late Effects Normal Tissues - Subjective Objective Management Analysis) were completed before and after treatment (immediately after radiotherapy, 6 weeks, 12, 24 and 36 months after treatment). Most patients had acute physical symptoms and impaired functioning immediately after treatment. Levels of fatigue and diarrhoea only returned to those at pre-treatment assessment after 6 weeks. Patients with high treatment toxicity scores had lower global QoL scores. In conclusion, treatment with radiotherapy for gynaecological cancer has a negative effect on QoL, most apparent immediately after treatment. Certain late treatment effects have a negative effect on QoL for at least 2 years after radiotherapy. These treatment effects are centred on symptoms relating to the rectum and bowel, for example, diarrhoea, tenesmus and urgency. Future research will identify specific symptoms resulting from late treatment toxicity that have the greatest effect on QoL; therefore allowing effective management plans to be developed to reduce these symptoms and improve QoL in gynaecological cancer patients.

Clinical outcome for chemoradiotherapy in carcinoma of the cervix.

AIMS: Two recent meta-analyses have shown a survival advantage for the addition of concurrent chemotherapy to radiotherapy in the treatment of cervical cancer. However, there is insufficient information available on late toxicity and few data from UK practice. The aims of this study were to examine treatment outcomes (survival and toxicity) in patients with cervical cancer treated with chemoradiation and to compare these with outcomes in patients treated with radiation alone. MATERIALS AND METHODS: Between July 2000 and December 2003, 75 patients with cervical cancer were treated with chemoradiation. Case notes were reviewed retrospectively. Acute and late toxicity were recorded, with late toxicity graded using the Franco-Italian glossary. The median age was 47 years. All patients were staged with examination under anaesthesia and magnetic resonance imaging scans. Forty-two patients were treated with concurrent chemoradiation alone and 33 patients were treated with a combination of neoadjuvant and concurrent chemoradiation. This was due to waiting list problems. The chemotherapy used was cisplatin 40 mg/m(2) weekly with radiotherapy, (the neoadjuvant dose was 60 mg/m(2) 3 weekly). External beam radiotherapy was given to the pelvis (40-45 Gy/20 fractions/4 weeks) followed by low dose rate brachytherapy (22.5-32.5 Gy to point A). Patients who were unable to have brachytherapy were given an external beam boost (15-20 Gy/8-10 fractions). RESULTS: The 3-year overall survival rate was 70%, with an estimated 5-year overall survival rate of 60%. The 3-year disease-free survival was 63.6%, with an estimated 5-year disease-free survival rate of 55%. Compared with the cohort of 183 patients from the Christie Hospital in a 1993 audit, there was a trend towards improved overall survival from 49 to 60% (P=0.06), which may become significant with longer follow-up. There were seven patients (9.3%) with grade 3 toxicity and no cases of grade 4 toxicity. In comparison with patients treated in the 1993 audit, the late toxicity rate has increased from 3.4 to 9.3%, but this was not statistically significant (P=0.14). CONCLUSION: There was a trend towards improved survival with concurrent chemoradiation in this cohort of patients that may become significant with longer follow-up.

Estimation of renal function -- what is appropriate in cancer patients?

AIMS: To compare the accuracy of renal assessment in patients with cancer using radioisotope glomerular filtration rate (GFR), urine collection for creatinine clearance, Cockroft-Gault, Modification of Diet in Renal Disease (MDRD) and Wright formulae. MATERIALS AND METHODS: Measurements of isotope GFR from 367 patients were compared with estimates from the described methods (Cockroft-Gault, MDRD, Wright). An analysis including a further 252 patients with an isotope GFR < or = 50 ml/min was also carried out. RESULTS: The Wright formula was the most accurate form of estimating renal function for the first study group. The formulae were similar in accuracy in the second study group. CONCLUSIONS: The Wright formula is the most accurate form of estimation of renal function in comparison with the isotope GFR for cancer patients. When there is a large proportion of patients with a low isotope GFR (< or = 50 ml/min), the formulae have similar accuracy.

Salvaging locoregional recurrence with radiotherapy after surgery in early cervical cancer.

AIMS: To determine the outcome and morbidity after radiotherapy for locally recurrent cervical cancer. MATERIALS AND METHODS: Women who presented with locally recurrent cervical cancer after surgery alone during 1985 and 1997 were identified from the hospital database. Data were collected and analysed to include the stage at first diagnosis, staging investigations before surgery, the surgical procedure, the indication for radiotherapy, the type of radiotherapy, morbidity and survival. RESULTS: In total, 130 women had radical external beam radiotherapy and/or intracavitary brachytherapy for locoregional recurrence during the defined study period. The 5-year disease-specific survival for the study population was 40.2%. Women who were treated for vault recurrence had a significantly better 5-year disease-free survival compared with women who developed nodal recurrence alone (55.4% vs 12.5%). This group of women also had a significantly slower rate of disease progression after radiotherapy than women with nodal recurrence (48.7% vs 87.5%, P=0.0001). CONCLUSION: Radical radiotherapy alone is able to salvage 55% of vaginal vault recurrences after surgery for cervical cancer with minimal late toxicity. Salvage rates in women with pelvic nodal recurrences are considerably lower. Chemoradiotherapy using intensity-modulated radiotherapy to deliver an escalated radiotherapy dose needs to be pursued to improve locoregional control.

Magnetic resonance imaging of primary vaginal carcinoma.

AIMS: To describe the magnetic resonance imaging (MRI) features of vaginal carcinoma and to suggest a role for MRI in its management. MATERIALS AND METHODS: Twenty-five patients with primary vaginal carcinoma treated at our institution between 1996 and 2005 were included in the study. The MRI examinations were reviewed and tumour dimensions, signal characteristics and involvement of pelvic structures were documented, as were sites of enlarged lymph nodes and metastases. Details of patient treatment and outcome were obtained from the clinical notes. RESULTS: The median patient age was 54 years (range 31-86 years). Tumour maximum diameter ranged from 1.6-11.3 cm (mean 3.7 cm). Most tumours were of iso-intense signal to muscle on T1-weighted images and hyper-intense to muscle on T2-weighted images. Eighty-eight percent of patients had tumour extending beyond the vagina and 56% of patients had Figo stage III or above tumours. Sixteen patients were treated with radiotherapy (two with chemoradiotherapy), five with surgery and four with supportive care. Ten patients (40%) died of their disease during the study period. The MRI stage of the tumour correlated with survival. CONCLUSION: MRI identified over 95% of primary vaginal tumours in the present study, enabled radiological staging, which correlated with outcome, and provided information of use in treatment planning.

Pattern of failure and long-term morbidity in patients undergoing postoperative radiotherapy for cervical cancer.

The objective of this study was to assess treatment outcomes in a large case series of cervical cancer patients undergoing postoperative radiotherapy in a single center. Case notes of women referred to the Christie Hospital during 1985-1997 for postoperative adjuvant radiotherapy for cervical cancer were reviewed. Of 478 women eligible for analysis, 282 (58.9%) underwent radical hysterectomy and 196 (41.1%) had nonradical hysterectomy. The disease-specific 5-year survival for the study population is 70.1%, with a 5-year risk of developing any recurrence of 30.5% and a 5-year grade 3 morbidity rate of 3.9%. Survival was significantly higher, ie, 80.9% vs 62.7% (P = 0.0001) and recurrence was significantly lower, ie, 18.6% vs 38.8% (P < 0.00005) in the group of women who had adjuvant radiotherapy following a nonradical hysterectomy compared with radical surgery. Thirty percent of women having "radical" surgery had positive resection margins and required postoperative adjuvant pelvic radiotherapy. Women with node-positive disease, who received adjuvant radiotherapy, had a high rate of distant metastases. These women would receive chemoradiotherapy now as primary treatment because of the risk of developing distant metastases. If, despite staging investigations, surgery reveals node-positive disease, then these women should receive adjuvant chemoradiotherapy. Survival was better in women who had nonradical surgery due to smaller volume disease when cancers were unsuspected and hence will have been cured by surgery alone. Multidisciplinary team working, as recommended by national guidelines from 1999, should allow better patient selection for treatment.

No relationship between thymidine phosphorylase (TP, PD-ECGF) expression and hypoxia in carcinoma of the cervix.

The expression of hypoxia-regulated genes promotes an aggressive tumour phenotype and is associated with an adverse cancer treatment outcome. Thymidine phosphorylase (TP) levels increase under hypoxia, but the protein has not been studied in association with hypoxia in human tumours. An investigation was made, therefore, of the relationship of tumour TP with hypoxia, the expression of other hypoxia-associated markers and clinical outcome. This retrospective study was carried out in patients with locally advanced cervical carcinoma who underwent radiotherapy. Protein expression was evaluated with immunohistochemistry. Hypoxia was measured using microelectrodes and the level of pimonidazole binding. There was no relationship of TP expression with tumour pO(2) (r=-0.091, P=0.59, n=87) or pimonidazole binding (r=0.13, P=0.45, n=38). There was no relationship between TP and HIF-1alpha, but there was a weak borderline significant relationship with HIF-2alpha expression. There were weak but significant correlations of TP with the expression of VEGF, CA IX and Glut-1. In 119 patients, the presence of TP expression predicted for disease-specific (P=0.032) and metastasis-free (P=0.050) survival. The results suggest that TP is not a surrogate marker of hypoxia, but is linked to the expression of hypoxia-associated genes and has weak prognostic power.

Expression of the proapoptotic protein Bid is an adverse prognostic factor for radiotherapy outcome in carcinoma of the cervix.

The Bcl-2 family of apoptotic regulators is thought to play an essential role in cancer development and influence the sensitivity of tumour cells to radiotherapy. Bid is an abundantly expressed Bcl-2 family protein playing a central role in various pathways of apoptosis by integrating and converging signals at the mitochondria. The relevance of apoptotic modulation by Bcl-2 and related proteins in tumour development and radiation response for human tumours remains undefined. Therefore, a study was made regarding the expression of Bid in patients with locally advanced cervix carcinoma who received radiotherapy. Bid expression was assessed using immunohistochemistry in pretreatment archival biopsies from 98 patients. The data were correlated with clinicopathologic characteristics and treatment outcome. Pretreatment tumour radiosensitivity data were available for 60 patients. Strong Bid expression was associated with a patient age less than the median of 52 years (P=0.034) and poor metastasis-free survival. In multivariate analysis, after allowing for stage, Bid expression was a significant prognostic factor for both disease-specific and metastasis-free survival (P=0.026). It is concluded that strong tumour Bid expression is associated with poor outcome following radiotherapy regardless of intrinsic tumour cell radiosensitivity, and is adverse prognostic for disease-specific and metastasis-free survival in younger patients.