Benefits and drawbacks of short-course preoperative radiotherapy in rectal cancer patients aged 75 years and older.

PURPOSE: To study incidence of local recurrences, postoperative complications and survival, in patients with rectal carcinoma aged 75 years and older, treated with either surgery and pre-operative 5 × 5 Gy radiotherapy or surgery alone. PATIENTS AND METHODS: A random sample of patients aged over 75 years with pT2-T3, N0-2, M0 rectal carcinoma diagnosed between 2002 and 2004 in the Netherlands was included, treated with surgery alone (N = 296) or surgery in combination with pre-operative radiotherapy (N = 346). Information on local recurrent disease, postoperative complications, ECOG-performance score and comorbidity was gathered from the medical files. RESULTS: Local recurrences developed less frequently in patients treated with pre-operative radiotherapy compared to surgery alone (2% vs 6%, p = 0.002). Postoperative complications developed more frequently in irradiated patients (58% vs 42%, p < 0.0001). Especially deep infections (anastomotic leakage, pelvic abscess) were significantly increased in this group (16% vs 10%, p = 0.02). 30-day mortality was equal in both groups (8%). A significant increase in postoperative complication rate and 30-day mortality was only seen in those with "severe comorbidity" compared to patients without comorbidity (respectively 58% and 10% vs 43% and 3%), COPD (59% and 12%), diabetes (60% and 11%) and cerebrovascular disease (62% and 14%). In multivariable analysis, postoperative complications predicted 5-year survival. CONCLUSION: Elderly patients receiving pre-operative radiotherapy show a lower local recurrence rate. However, as incidence rates of local recurrent disease are low and incidence of postoperative complications is increased in irradiated patients, omitting preoperative RT may be suitable in elderly patients with additional risks for complications or early death.

Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.

Mapping use of radiotherapy for patients with non-small cell lung cancer in the Netherlands between 1997 and 2008.

AIM: After the publication of several reports that the utilisation rate of radiotherapy for patients with non-small cell lung cancer (NSCLC) varies for both medical and non-medical reasons, the utilisation of radiotherapy was studied in four regions in the Netherlands. MATERIALS AND METHODS: Data from 1997-2008 were collected from the population-based cancer registries of four comprehensive cancer centres ('regions'), which represent about half of the Dutch population, resulting in 24 185 non-metastatic patients with NSCLC. Treatment had to be started or planned within 6 months of diagnosis. We evaluated the utilisation of radiotherapy according to age, gender and period for each region. RESULTS: The utilisation of radiotherapy alone decreased over time (from 35 to 19%), whereas the utilisation of radiotherapy in combination with chemotherapy increased (from 5 to 19%). The total utilisation rate remained rather stable at about 40%. The differences between the four regions remained in general no more than 15%. Elderly patients with stage I and II disease had increased odds of receiving radiotherapy (≥75 versus <50 years: odds ratio 2.6, 95% confidence interval 2.0-3.3, whereas this was the opposite for patients with stage III disease: odds ratio 0.5, 95% confidence interval 0.4-0.6). For 17-24% of all patients, especially the elderly, best supportive care was applied. CONCLUSIONS: In the Netherlands, with good accessibility to medical care and well-implemented national guidelines, variation between the four regions is limited for the treatment of non-metastatic NSCLC with radiotherapy.

Use of primary radiotherapy for rectal cancer in the Netherlands between 1997 and 2008: a population-based study.

AIMS: To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects. MATERIALS AND METHODS: Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055). RESULTS: An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]. CONCLUSIONS: The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients.

Assessing cancer patients' trust in their oncologist: development and validation of the Trust in Oncologist Scale (TiOS).

PURPOSE: The aim of this study was to develop and validate the Trust in Oncologist Scale (TiOS), which aims to measure cancer patients' trust in their oncologist. Structure, reliability and validity were examined. METHODS: Construction of the TiOS was based on a multidimensional theoretical framework. Cancer patients were surveyed within a week after their consultation. Trust, satisfaction, trust in health care, self-reported health and background variables were assessed. Dimensionality, internal consistency, test-retest reliability and construct validity were investigated. RESULTS: Data of 423 patients were included (response rate = 65%). After item reduction, the TiOS included 18 items. Trust scores were high. Exploratory factor analysis suggested one-dimensionality. Confirmatory factor analysis nevertheless indicated a reasonable fit of our four-dimensional theoretical model, distinguishing competence, fidelity, honesty and caring. Internal consistency and test-retest reliabilities were high. Good construct validity was indicated by moderate correlations of trust (TiOS) with satisfaction, trust in health care, willingness to recommend and number of consultations with the oncologist. Exploratory analyses suggested significant correlations of trust with ethnicity and age. CONCLUSIONS: The TiOS reliably and validly assesses cancer patients' trust in their oncologist. The questionnaire can be employed in both clinical practice and future research of cancer patients' trust.

Treatment and survival of patients with small-cell lung cancer: small steps forward, but not for patients >80.

BACKGROUND: Seventy-five percent of newly diagnosed patients with small-cell lung cancer (SCLC) are aged 60+ and quite a few are treated less aggressively because of fear of toxic effects. We described trends in treatment and survival of unselected SCLC patients. PATIENTS AND METHODS: For the present study, all 13,007 SCLC patients aged 60+ diagnosed in The Netherlands from 1997 to 2007 were included. RESULTS: Among patients with limited disease, the proportion receiving chemoradiation increased from 35% to almost 60% for those aged 60-69, from 28% to 48% in age group 70-74, from 17% to 33% in age group 75-79, but remained <10% for those aged 80+. Among patients with extensive disease, the proportion receiving chemotherapy (CT) decreased from 81% of patients aged 60-64 to 23% of those aged 85+, without substantial changes over time. Survival has only improved for patients <80 years. CONCLUSIONS: CT (+radiotherapy) has improved survival for unselected SCLC patients <80. A better understanding of the impact of frailty on completion of treatment and toxic effects among patients aged 80+ would enable the treating physician to anticipate toxic effects better and to discuss risks and benefits of treatment with the patient.

A population-based study on the utilisation rate of primary radiotherapy for prostate cancer in 4 regions in the Netherlands, 1997-2008.

AIM: The purpose was to study variations in utilisation rates of external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer patients. MATERIALS AND METHODS: We calculated the proportion and number of EBRT and BT given or planned within 6 months of diagnosis in 4 Dutch regions, according to stage and age in a population-based setting including 47,259 prostate cancer patients diagnosed from 1997 until 2008. RESULTS: During this study period, the overall utilisation rate of EBRT remained stable at around 25%, while the rate of BT for non-metastasized patients increased from 1% (95% CI:0-1%) to 12% (11-13%) in 2006 and slightly decreased towards 10% (9-11%) in 2008. From 2001 on, the overall utilisation rate of EBRT decreased significantly in one region (p<0.05). In this region, a sharp rise in the utilisation rate of BT for non-metastatic patients was noted to 17% (14-20%) in 2008 after a peak of 24% (21-27%) in 2006. For localised disease, BT was used more often at the expense of EBRT while for locally advanced disease the utilisation rate of EBRT increased. In the multivariate analysis, regional differences in the utilisation rate of EBRT persisted with odds ratios ranging from 0.7 to 0.9 compared to the reference region. Moreover, low rates of EBRT were associated with high BT rates. The regional differences could not be explained by differences in risk profiles. CONCLUSIONS: The utilisation rate of EBRT remained stable with limited variation between regions while BT was used increasingly with clear regional differences. To cope with this and in view of the increasing incidence of prostate cancer, adequate resources have to be planned for the optimal care of these patients.

Improving bladder cancer treatment with radiotherapy using separate intensity modulated radiotherapy plans for boost and elective fields.

The aim of this study is to investigate to what extent IMRT can decrease the dose to the organs at risk in bladder cancer treatment compared with conformal treatment while making separate treatment plans for the elective field and the boost. Special attention is paid to sparing small intestines. Twenty patients who were treated with the field-in-field technique (FiF) were re-planned with intensity modulated radiotherapy (IMRT) using five and seven beams, respectively. Separate treatment plans were made for the elective field (including the pelvic lymph nodes) and the boost, which enables position correction for bone and tumour separately. The prescribed dose was 40 Gy to the elective field and 55 or 60 Gy to the planning target volume (PTV). For bladder and rectum, V(45Gy) and V(55Gy) were compared, and for small intestines, V(25Gy) and V(40Gy.) The dose distribution with IMRT conformed better to the shape of the target. There was no significant difference between the techniques in dose to the healthy bladder. The median V(40Gy) of the small intestines decreased from 114 to 66 cc (P = 0.001) with five beam IMRT, and to 55 cc (P = 0.001) with seven beam IMRT compared with FiF. V(45Gy) for rectum decreased from 34.2% to 17.5% (P = 0.004) for both five and seven beam plans, while V(55Gy) for rectum remained the same. With IMRT, a statistically significant dose decrease to the small intestines can be achieved while covering both tumour and elective PTV adequately.

From Cisplatin-Containing Sequential Radiochemotherapy towards Concurrent Treatment for Patients with Inoperable Locoregional Non-Small Cell Lung Cancer: Still Unanswered Questions.

Radiotherapy has been the mainstay of the treatment of stage III non-small cell lung cancer (NSCLC) patients. In the early nineties, combined treatment with chemotherapy was introduced. In 1995, a meta-analysis showed improved treatment outcome of the sequential use of radiochemotherapy (RCT) compared to radiotherapy alone, provided cisplatin was part of the chemotherapy course. Concurrent RCT compared to radiotherapy only yielded the same improvements of 4% in the 2-year and 2% in the 5-year overall survival rates. Just recently, two meta-analyses demonstrated that concurrent RCT is definitely superior to sequential RCT in terms of local control and 2-, 3-, and 5-year survival. However, several unanswered questions remain concerning the optimal chemotherapy regimen and radiotherapy doses and techniques in terms of treatment outcome and toxicity profile. Arguments supporting a daily low-dose cisplatin scheme are presented because of comparable radiosensitizing characteristics and favourable side effects. Increasing radiotherapy doses applied according to up-to-date techniques and combinations with new biologicals might lead to further treatment improvements.

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS).

BACKGROUND: A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial. METHODS/DESIGN: The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm.The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up. DISCUSSION: This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen. TRIAL REGISTRATION: ISRCTN80832026.

[Perspectives in the treatment of non-small cell lung cancer stage III with radiotherapy and concomitant low-dosage chemotherapy]. / Perspectieven in de behandeling van het niet-kleincellige longcarcinoom stadium III met radiotherapie en gelijktijdig gegeven laaggedoseerde chemotherapie.

Patients with a non-small cell lung cancer stage III should preferably be treated with a combination of concomitant radiotherapy and platinum-containing chemotherapy. Concomitant chemoradiation results in improved survival compared to sequential chemoradiation, although this type oftreatment is associated with higher oesophagus toxicity. With concomitant chemoradiation the chemotherapy can be added in several ways to high-dosage radiotherapy, for example in the form of 2 courses of high dose, platinum-containing polychemotherapy once every 3 weeks. Concomitant chemoradiation with just a daily low dose of cisplatin is a good alternative. In view of its low risk of haematological and renal toxicity and ototoxicity and smaller cardiac load this is the therapy of choice and is also highly suitable for elderly patients with comorbidity.

[Guideline 'Melanoma' (3rd revision)]. / Richtlijn 'Melanoom' (3e herziening).

The guidelines 'Melanoma' (3rd revision) are evidence-based in nature. A number of outcomes are summarised in this article. Dermatoscopy deserves a standard role in the clinical diagnosis of pigmented skin abnormalities. Pathological findings from a diagnostic excision should be recorded meticulously to include anatomical localisation, type of intervention used, excision margin, diagnosis, Breslow thickness, and the completeness of the removal. The sentinel node procedure should be reserved for patients who want to be as informed as possible about their prognosis. The procedure is not considered a part of standard diagnosis. Sentinel node assessment should include stains for specific markers and should be conducted in multiple sections. The following margins of non-affected skin are recommended for therapeutic re-excision of melanoma: in situ melanoma, 0.5 cm; Breslow thickness < or = 2 mm, 1 cm; Breslow thickness > 2 mm, 2 cm. Pathological assessment of a re-excised specimen depends on the completeness of the first excision. Systematic adjuvant treatment of patients with melanoma is not recommended outside the context of a clinical study. Patients with metastatic melanoma are preferably treated within a clinical study. Outside of a clinical study, these patients should be treated with dacarbazine. There is no evidence to suggest that survival is improved by frequent follow-up. However, follow-up can be a useful way to meet the information needs of patients and care requirements for physicians.

[Two patients with advanced non-small cell lung cancer (stage IIIB) who still responded very well to combined chemotherapy and radiotherapy]. / Twee patiënten met gevorderd niet-kleincellig longcarcinoom (stadium IIIB) en toch een zeer goede reactie op gecombineerde chemo- en radiotherapie.

In two patients, men aged 58 and 47 years respectively, advanced non-small cell lung cancer (stage IIIB) with mediastinal and supraclavicular lymph-node metastases was diagnosed. Both patients had a good performance score despite the seriousness of their tumours. They were treated with chemotherapy followed by radiotherapy and the treatment was well tolerated. In the patient aged 47 years, lobectomy was performed one year later for a second primary carcinoma. Both patients were still disease-free 5 years after treatment. Although not every patient with stage IIIB lung cancer will respond so well to combined treatment, these cases illustrate that intensive treatment may be recommended for selected patients. The final therapeutic advice has to be made by a multidisciplinary team. If the treatment chosen includes both chemotherapy and radiotherapy then careful scheduling is required.

[Guideline on 'non-small cell lung carcinoma; staging and treatment']. / Richtlijn 'Niet-kleincellig longcarcinoom; stadiëring en behandeling'.

A national, evidence-based guideline on the staging and treatment of patients with non-small cell lung carcinoma (NSCLC) has been compiled by the various disciplines involved. The initial diagnostic measures in patients with suspected lung cancer include history taking, physical examination and chest x-ray. Additional examinations include CT scan of the chest and upper abdomen, bronchoscopy, and 18F-fluorodeoxyglucose-positron-emission-tomography(FDG-PET)-scintigraphy, if curative therapy is planned. Cervical mediastinoscopy or endoscopic echography with fine needle aspiration can be performed for mediastinal tissue staging. The preferred treatment in stage I, II or limited III is radical resection. Postoperative radiotherapy is recommended in cases of incomplete resection and can be considered in patients in whom mediastinal lymph-node metastases are unexpectedly encountered. Chemoradiotherapy is recommended in locally advanced NSCLC. In patients with NSCLC stage I-III and poor performance status, palliative radiotherapy may be the only feasible treatment. Some patients with NSCLC stage III and stage IV can be offered palliative chemotherapy and supportive care. In cases of doubt about operability, resectability, significant pulmonary or cardiac comorbidity or combined treatment, a specialist centre should be consulted. Diagnostics should be completed within 3-5 weeks. Ensuing surgery or radiotherapy should be carried out within 2 weeks. Follow-up of patients with NSCLC includes history taking, physical examination and an optional chest x-ray. In the first year after treatment patient visits are planned quarterly, in the second year half-yearly and then yearly for at least five years.

Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study. European Organization for Research and Treatment of Cancer.

The purpose of this work was to study the feasibility of concurrent chemoradiation in patients with inoperable non-small cell lung cancer (NSCLC). 40 patients with inoperable NSCLC were treated with escalating doses of radiotherapy and cisplatin (cDDP). The radiation dose was increased step by step from 60.5 to 66 Gy in daily fractions of 2.75 Gy. Chemotherapy was also increased step by step from 20 to 24 daily doses of cDDP 6 mg/m(2) and given concurrently with radiotherapy. A dose of 40 Gy/2 Gy/20 fractions (fx) was given to the EPTV (elective planning target volume) which included the gross tumour volume with a margin of 2 cm and part of or the entire mediastinum. During each session a boost dose of 0.75 Gy was given simultaneously to the BPTV (boost planning target volume), which encompassed the GTV (gross tumour volume) with a margin of 1 cm, for the first 20 fx, so the total dose to the tumour was 55 Gy. Cisplatin 6 mg/m(2) was given 1 h prior to radiotherapy at each fraction. From then on the dose of radiation to the BPTV and the dose of cDDP were increased step by step. In group I the BPTV was irradiated with two extra fractions of 2.75 Gy to a total dose of 60. 5 Gy without cDDP. In group II the same total dose of 60.5 Gy was given but the last two fractions were combined with cDDP. In group III four extra fractions of 2.75 Gy were given to the BPTV to a total dose of 66 Gy, only two of these fractions combined with cDDP. Finally, in group IV a total dose of 66 Gy was given in 24 fractions, all fractions combined with cDDP. All patients were planned by means of a CT-based conformal treatment planning. The maximal length of the oesophagus receiving >/=60.5 Gy was 11 cm. 40 patients were evaluable for acute and late toxicity and for survival. Acute toxicity grade >/=3 (common toxicity criteria, CTC) was rarely observed; nausea/vomiting in 3 patients (8%), leucopenia in 2 patients (5%), thrombocytopenia in 2 patients (5%), whilst 2 patients (5%) suffered from severe weight loss. Late side-effects (European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group, EORTC/RTOG) were: oesophageal toxicity >/=grade 3 in 2 patients (5%) and radiation pneumonitis grades 1 (3%) and 2 (3%) in 1 patient each. Overall actuarial 1- and 2-year survival was 53% and 40%, respectively. The 1- and 2-year local disease-free interval was 65% and 58% respectively. Radiotherapy at a dose of 66 Gy/2.75 Gy/24 fx combined with daily cDDP 6 mg/m(2) given over 5 weeks is feasible and results in a good local disease-free interval and a good survival rate. This treatment schedule is at present being tested as one of the two treatment arms of EORTC phase III study protocol 08972/22973.

Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement.

BACKGROUND: Uncontrolled studies suggest that high-dose chemotherapy is beneficial in patients with breast cancer and multiple metastases to the axillary lymph nodes. Many physicians accept this treatment as standard care. We aimed to assess adjuvant high-dose chemotherapy in breast cancer in a phase II randomised trial. METHODS: 97 women aged younger than 60 years, who had breast cancer with extensive axillary-node metastases (confirmed by a tumour-positive infraclavicular lymph-node biopsy), received three courses of up-front chemotherapy (FE120C). This regimen consisted of cyclophosphamide 500 mg/m2, epirubicin 120 mg/m2, and 5-fluorouracil 500 mg/m2 once weekly for 3 weeks. After surgery, stable patients or those who responded to chemotherapy were randomly assigned conventional therapy (fourth course of FE120C, followed by radiation therapy and 2 years of tamoxifen [40 patients]) or high-dose therapy (identical treatment but an additional high-dose regimen and peripheral-blood progenitor-cell [PBPC] support after the fourth FE120C course [41 patients]). This high-dose regimen comprised cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, and carboplatin 1600 mg/m2. The primary endpoint was overall and disease-free survival. All analyses were by intention to treat. FINDINGS: No patients died from toxic effects of chemotherapy. With a median follow-up of 49 (range 21-76) months, the 4-year overall and relapse-free survivals for all 97 patients were 75% and 54%, respectively. There was no significant difference in survival between the patients on conventional therapy and those on high-dose therapy. INTERPRETATION: High-dose therapy is associated with substantial cost and acute toxic effects, but also has potentially irreversible long-term effects. Until the benefit of this therapy is substantiated by large-scale phase III trials, high-dose chemotherapy should not be used in the adjuvant treatment of breast cancer, apart from in randomised studies.

High dose rate brachytherapy before external beam irradiation in inoperable oesophageal cancer.

To induce fast relief of dysphagia in patients with oesophageal cancer high dose rate (HDR) brachytherapy was applied before external radiotherapy in a prospective study. Seventy-four patients with inoperable oesophageal cancer (36 squamous cell, 38 adenocarcinoma) were treated with a combination of 10 Gy HDR brachytherapy, followed by 40 Gy in 4 weeks external beam radiotherapy (EBRT), starting 2 weeks later. Tumour response, as measured by endoscopy and/or barium swallow, revealed complete remission in 21 and partial response in 38 patients (overall response rate 80%). Improvement of dysphagia was induced by brachytherapy within a few days in 39%, and achieved at the end of treatment in 70% of patients. Further weight loss was prevented in 39 of the 59 patients who presented with weight loss. Pain at presentation improved in 12 out of 25 patients. Median survival was 9 months. No differences in either response rate or survival were found in squamous cell or adenocarcinoma. Side-effects were either acute with minimal discomfort in 32 (42%) or late with painful ulceration in five patients (7%), occurring after a median of 4 months. A fistula developed in six patients, all with concurrent tumour. In conclusion, brachytherapy before EBRT was a safe and effective procedure to induce rapid relief of dysphagia, especially when combined with EBRT.

Modulation of toxicity following external beam irradiation preceded by high-dose rate brachytherapy in inoperable oesophageal cancer.

To induce fast relief of dysphagia in inoperable oesophageal cancer, we applied high-dose rate (HDR) intraluminal irradiation followed by external irradiation (EBRT) in a phase II study. 15 patients (group A: n = 15; 10 men, 5 women; median age 66 years) were treated with 10 Gy HDR brachytherapy plus 40 Gy EBRT (15 fractions of 2.67 Gy). Severe side-effects were encountered in 60% of patients: 3 late ulceration, 2 pending fistula, 2 fistula and 2 patients with fatal haemorrhage after an interval of 6 months. Overall response was excellent: 9 complete remissions (60%) and 6 partial responses (40%). Because of the high toxicity rate, in a subsequent study (group B: n = 30; 23 men, 7 women; median age 66 years) the EBRT scheme was changed using smaller fractions (2.0 Gy) to reach the same total dose of 40 Gy. The complication rate (17%) was significantly reduced, while the overall response remained excellent (83%): 17 complete and 8 partial responses. The impressive change in complication rate of HDR brachytherapy and EBRT stresses the impact of the fraction per dose and illustrates the small therapeutic margins.