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.

Comparison of adaptive radiotherapy techniques for the treatment of bladder cancer.

OBJECTIVE: Day-to-day anatomical variations complicate bladder cancer radiotherapy treatment. This work quantifies the impact on target coverage and irradiated normal tissue volume for different adaptive strategies. METHODS: 20 patients were retrospectively planned using different three-dimensional conformal radiotherapy treatment strategies for whole-bladder carcinoma: (i) "conventional" treatment used isotropic expansion of the clinical target volume (CTV) by 15 mm to the planning target volume (PTV) for daily treatment; (ii) "plan of the day" used daily volumetric on-treatment imaging [cone beam CT (CBCT)] to select from four available plans with varying superior PTV margins; (iii) "composite" strategies used on-treatment CBCTs from Fractions 1-3 to inform a composite CTV and adapted PTV (5- and 10-mm margins for composite 1 and composite 2, respectively) for subsequent treatment. Target coverage was evaluated from available CBCTs (the first three fractions then the minimum weekly thereafter), and the reduction in the irradiated volume (i.e. within the 95% isodose) was quantified. RESULTS: Plan of the day improved target coverage (i.e. all of the bladder within the 95% isodose throughout the treatment) relative to conventional treatment (p=0.10), while no such benefit was observed with composite 2. Target coverage was reduced with composite 1 relative to conventional treatment. The mean irradiated volume was reduced by 17.2%, 35.0% and 14.6% relative to conventional treatment, for plan of the day, composite 1 and composite 2, respectively (p<0.01 in all cases). No parameters predictive of large changes in bladder volume later in the treatment were identified. CONCLUSIONS: Adaptive techniques can maintain or improve target coverage while allowing for reduced irradiated volume and possibly reduced toxicity. The plan-of-the-day technique appeared to provide the optimal balance between target coverage and normal tissue sparing. ADVANCES IN KNOWLEDGE: This study suggests that plan-of-the-day techniques will provide optimal outcomes for adaptive bladder radiotherapy.

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.

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.

External-beam radiotherapy in T1-2 N0 penile carcinoma.

AIMS: To review the outcome of 41 patients with invasive carcinoma of the penis treated with external-beam radiotherapy using a consistent technique and dose. MATERIALS AND METHODS: Forty-one patients with carcinoma of the penis treated at Christie Hospital, Manchester, UK, between 1995 and 2000 were reviewed retrospectively. Radiotherapy was delivered using 4 MV linear accelerators with a dose of 50 Gy or 52.5 Gy in 16 fractions over 22 days. RESULTS: The distribution of patients according to stage was T1=37, T2=4, N0=40, N3=1. Median follow-up was 4.5 years. The local control rate was 62%, nodal relapse-free rate of 88%, relapse-free rate of 51% and overall survival of 88% at 5 years. All recurrences were salvaged by surgery. Penile ulceration occurred in 8% and urethral stenosis requiring dilatation in 29%. There were no penectomies for penile necrosis. CONCLUSION: EBXRT may be offered for T1-2 cancer of the penis with close surveillance to detect local recurrences early for salvage surgery without jeopardising overall survival. It remains an alternative option to penis-preserving surgery and should be discussed in a multidisciplinary setting and with the patient.

Development of a simultaneous boost IMRT class solution for a hypofractionated prostate cancer protocol.

The purpose of this work was to develop a robust technique for planning intensity-modulated radiation therapy (IMRT) for prostate cancer patients who are to be entered into a proposed hypofractionated dose escalation study. In this study the dose escalation will be restricted to the prostate alone, which may be regarded as a concurrent boost volume within the overall planning target volume (PTV). The dose to the prostate itself is to be delivered in 3 Gy fractions, and for this phase of the study the total prostate dose will be 57 Gy in 19 fractions, with 50 Gy prescribed to the rest of the PTV. If acute toxicity results are acceptable, the next phase will escalate doses to 60 Gy in 20 x 3 Gy fractions. There will be 30 patients in each arm. This work describes the class solution which was developed to create IMRT plans for this study, and which enabled the same set of inverse planning parameters to be used during optimization for every patient with minimal planner intervention. The resulting dose distributions were compared with those that would be achieved from a 3D conformal radiotherapy (3DCRT) technique that used a multileaf collimator (MLC) but no intensity modulation to treat the PTV, followed by a sequential boost to raise the prostate to 57 Gy. The two methods were tested on anatomical data sets for a series of 10 patients who would have been eligible for this study, and the techniques were compared in terms of doses to the target volumes and the organs at risk. The IMRT method resulted in much greater sparing of the rectum and bladder than the 3DCRT technique, whilst still delivering acceptable doses to the target volumes. In particular, the volume of rectum receiving the minimum PTV dose of 47.5 Gy was reduced from a mean value of 36.9% (range 23.4% to 61.0%) to 18.6% (10.3% to 29.0%). In conclusion, it was found possible to use a class solution approach to produce IMRT dose escalated plans. This IMRT technique has since been implemented clinically for patients enrolled in the hypofractionated dose escalation study.

Patterns of relapse following radiotherapy for stage I seminoma of the testis: implications for follow-up.

A retrospective review was undertaken of 409 consecutive patients treated with adjuvant radiotherapy for Stage I seminoma between 1988 and 1997. A total of 339 men were treated to a volume encompassing the para-aortic nodes and 70 were treated with extended field radiotherapy. The patients were followed up within oncology clinics adhering to a standard protocol of clinical examination, chest radiography and measurement of serum marker levels. No routine computed tomographic (CT) scans were carried out. At a median follow-up of 57 months, 13 patients have relapsed, giving a recurrence-free rate of 97.2% at 3 years and 96.8% at 5 years. Of these, eight (62%) were detected at routine appointments and five (38%) requested early appointments. Chest radiography (2/5) and serum marker levels (3/5) identified disease in asymptomatic patients. Eight patients (62%) had raised markers at relapse, including two with normal serum markers at original presentation. The median size of pelvic node recurrences in the para-aortic-treated group was 7.3 cm (2.8-13 cm). Four patients have developed second testicular primaries: three were detected at routine appointments and one patient had requested an early appointment. We conclude that regular follow-up with serum marker estimations and chest radiography is sufficient to detect recurrence at an early stage and that our policy of no routine CT scanning has been shown to give acceptable results.

The effect of radiotherapy treatment changes on sites of relapse in stage I testicular seminoma.

AIM: To evaluate relapse patterns in stage I testicular seminoma related to changes in radiotherapy practice. METHOD: Four hundred and six patients with stage I testicular seminoma were treated with adjuvant radiotherapy following orchidectomy: 338 patients received para-aortic radiotherapy only and 68 patients with added risk factors had radiotherapy extended to include the pelvis. Computed tomograms of relapsed patients were reviewed and sites of relapse were documented with correlation to the radiotherapy field. RESULTS: Thirteen relapses were identified; 10 occurring in the para-aortic radiotherapy group (3.0% relapse rate) and three in the extended radiotherapy field group (4.4% relapse rate). Sites of relapse were; five pelvis, three mediastinum, one lung, one scapula, one scrotum, while one patient had multiple relapse sites including the pelvis and one had a tumour marker relapse with no site identified. All the pelvic relapses occurred in the para-aortic radiotherapy group. CONCLUSION: Pelvic relapse only occurred when radiotherapy had been confined to the para-aortic region. Since para-aortic radiotherapy achieves equivalent outcome to wider field radiotherapy with reduced toxicity, it is likely to become standard practice in stage I seminoma and pelvic relapses will therefore increase in frequency. It is therefore important to include pelvic imaging when relapse is suspected.

Axillary recurrence following conservative surgery and radiotherapy in early breast cancer.

At the institute, since the late 1980s, there has been a uniform treatment protocol for the management of the regional lymph nodes in patients referred for radiotherapy following breast-conserving surgery. An analysis of 2,277 consecutive patients referred for radiotherapy between 1989 and 1992, with particular reference to regional lymph node management, has been undertaken. Axillary surgery alone was used in 517 patients (23%); 1,191 (52%) patients had no axillary surgery but had radiotherapy to the axilla, and infraclavicular and supraclavicular fossae by a single anterior field, delivering 40 Gy in 15 daily fractions over 3 weeks; and 474 patients (21%) had axillary surgery followed by radiotherapy. Ninety-five patients (4%) underwent no axillary treatment. There was a total of 155 axillary recurrences with a median follow-up of 5.9 years, giving an actuarial nodal control rate of 94% at 5 years (95% confidence interval (CI) 93.1-95.1). The overall survival at 5 years was 86% (95% CI 84.6-87.5). There was a trend towards improved axillary control with surgery alone compared with radiotherapy alone (4.5% versus 5.9% actuarial axillary failure rate at 5 years). An extremely low incidence of brachial plexus neuropathy secondary to radiotherapy was reported. The multidisciplinary treatment protocol used gave a high rate of regional node control, with minimal recorded morbidity.