A randomized study of the effect of patient positioning on setup reproducibility and dose distribution to organs at risk in radiotherapy of rectal cancer patients.

BACKGROUND: The patient positioning in pelvic radiotherapy (RT) should be decided based on both reproducibility and on which position that yields the lowest radiation dose to the organs at risk (OAR), and thereby less side effects to patients. The present randomized study aimed to evaluate the influence of patient positioning on setup reproducibility and dose distribution to OAR in rectal cancer patients. METHODS: Ninety-one patients were randomized into receiving RT in either supine or prone position. The recruitment period was from 2005 to 2008. Position deviations were derived from electronic portal image registrations, and setup errors were defined as deviations between the expected and the actual position of bony landmarks. Setup deviations were expressed into three table shift values (∆x, ∆y, ∆z) from which the deviation vector [Formula: see text] were calculated. The estimated lengths of [Formula: see text] defined the main outcome and were compared between prone and supine positions using linear mixed model statistics. The mean volume of each 5 Gy increments between 5 and 45 Gy was calculated for the small bowel and the total bowel, and the dose volumes were compared between prone and supine position. RESULTS AND CONCLUSION: Data from 83 patients was evaluable. The mean [Formula: see text] was 5.8 mm in supine position and 7.1 mm in prone position (p = 0.024), hence the reproducibility was significantly superior in supine position. However, the difference was marginal and may have borderline clinical importance. The irradiated volumes of the small bowel and the total bowel were largest in the supine position for all dose levels, but none of those were significantly different. The patient positioning in RT of rectal cancer patients may therefore be decided based on other factors such as the most comfortable position for the patients.

Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines.

OBJECTIVE: To evaluate treatment outcome in a large population-based cohort of patients with anal cancer treated according to Nordic guidelines. MATERIAL: Clinical data were collected on 1266 patients with anal squamous cell carcinoma diagnosed from 2000 to 2007 in Sweden, Norway and Denmark. 886 of the patients received radiotherapy 54-64Gy with or without chemotherapy (5-fluorouracil plus cisplatin or mitomycin) according to different protocols, stratified by tumor stage. RESULTS: High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor performance status, and non-inclusion into a protocol were all independent factors associated with worse outcome. Among patients treated according to any of the protocols, the 3-year recurrence-free survival ranged from 63% to 76%, with locoregional recurrences in 17% and distant metastases in 11% of patients. The highest rate of inguinal recurrence (11%) was seen in patients with small primary tumors, treated without inguinal irradiation. CONCLUSIONS: Good treatment efficacy was obtained with Nordic, widely implemented, guidelines for treatment of anal cancer. Inguinal prophylactic irradiation should be recommended also for small primary tumors.

Quality assurance in radiotherapy on a national level; experience from Norway: the KVIST initiative.

BACKGROUND AND PURPOSE: In radiotherapy (RT), there are high requirements for quality assurance (QA) in all the steps of the process. Development of QA systems are demanding in terms of financial and human resources. A national QA programme (KVIST) has been established in Norway to facilitate implementation of QA activity on hospital level. METHOD: The KVIST organisation comprises the KVIST team, the reference group (RG) and the working groups (WGs). The KVIST team is multidisciplinary and are employed in permanent positions. The RG acts as an advisory body for the KVIST team in defining and ranking the priority of projects. Relevant national QA projects are identified in collaboration with the RG, and WGs are established to carry out the various projects. RESULT: Several national consensus documents have been prepared by the various WGs. Systems for incident handling and activity reporting have been established and clinical audits have been implemented in Norwegian RT. Guidelines for RT of various diagnoses have also been prepared in collaboration with National Cancer groups. CONCLUSION: The KVIST programme has been very well acknowledged in the Norwegian RT community. It has succeeded in creating a positive attitude towards QA and improved the communication between centres and the various professions.

Faecal incontinence after chemoradiotherapy in anal cancer survivors: long-term results of a national cohort.

PURPOSE: To examine the prevalence and severity of faecal incontinence amongst anal cancer survivors after chemoradiotherapy. MATERIAL AND METHODS: Anal cancer survivors from a complete, unselected, national cohort, minimum 2-years follow-up, were invited to a cross-sectional study. The St. Mark's incontinence score was used to evaluate occurrence and degree of faecal incontinence the last four weeks. The results were compared to age- and sex-matched volunteers from the general population. RESULTS: Of 199 invited survivors and 1211 volunteers, 66% and 21%, respectively, signed informed consent. The survivors had significantly higher St. Mark's score than the volunteers (mean 9.7 vs. 1.1, p<0.001). Incontinence of stool of any degree was reported by 43% vs. 5% (OR 4.0, CI 2.73-6.01), and urgency was reported by 64% vs. 6% (OR 6.6, CI 4.38-9.90) of the survivors and volunteers, respectively. Only 29% of those with leakage of liquid stool used constipating drugs. Survivors of locally advanced tumours had a higher incontinence score (p<0.01). CONCLUSIONS: Moderate to severe faecal incontinence is common amongst anal cancer survivors. Post-treatment follow-up should include the evaluation of continence, and incontinent survivors should be offered better symptom management and multidisciplinary approach if simple measures are insufficient.

Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study.

BACKGROUND: The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study. METHODS: MR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra- and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data. RESULTS: The intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 - 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 - 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength. CONCLUSION: The overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.

Impaired health-related quality of life after chemoradiotherapy for anal cancer: late effects in a national cohort of 128 survivors.

BACKGROUND: Chemoradiotherapy is an effective treatment for anal cancer, yet from follow-up many survivors seem to suffer from late effects. Data of long-term health-related quality of life (HRQOL) in anal cancer survivors are limited, and there is a growing interest in cancer survivorship. MATERIAL AND METHODS: A national cohort of all anal cancer survivors treated with curative chemoradiotherapy in 2000-2007 was invited to a cross-sectional study. Of 199 eligible survivors, 128 (64%) returned the questionnaires, the median time since diagnosis was 66 months. The median age was 61 years and 79% were women. HRQOL was evaluated with EORTC questionnaires QLQ-C30 and QLQ-CR29, and neurotoxicity with the Scale of Chemotherapy-Induced Neurotoxicity. An age- and sex-matched reference group of volunteers (n = 269) not treated for pelvic cancer answered the same questionnaires. Results from QLQ-C30 of the reference group were compared to Norwegian and Dutch normative data. RESULTS: The mean scores of anal cancer survivors were poorer compared to volunteers and normative data. Anal cancer survivors reported significant impairment of function, especially social and role function, compared to the volunteers (difference ≥ 20 points, p < 0.001). Survivors had markedly increased scores for fatigue, dyspnoea, insomnia and diarrhoea (difference ≥ 15 points, p < 0.001). The global quality of life was significantly reduced (difference 15 points, p < 0.001). Anal cancer survivors had increased stool frequency, more buttock pain, flatulence, faecal incontinence, impotence (males), dyspareunia and reduced sexual interest (females) (difference ≥ 15 points, p < 0.001). There was increased frequency of tinnitus in survivors treated with cisplatin-based chemotherapy (p = 0.004). CONCLUSIONS: Survivors after chemoradiotherapy for anal cancer have significant long-term impairment of HRQOL. Reduced social, role and sexual function, and increased diarrhoea, incontinence for gas and stools, and buttock pain were commonly reported. Increased awareness of this may lead to better management of late effects and better care for cancer survivors.

Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results.

BACKGROUND & AIMS: Different nutrition assessment tools and definitions are proposed for cancer-associated malnutrition and wasting (cachexia). We studied the associations between these assessments and overall survival in stage IV colorectal carcinoma patients. METHODS: Anthropometric measures, energy intake, biochemical variables, nutritional risk screening, assessment of malnutrition, cachexia and body composition from computed tomography images were analysed, in 77 patients from Norway and Canada. Results were dichotomized into presence or absence of nutritional risk, malnutrition, cachexia and sarcopenia (low muscle mass) and associated with survival. RESULTS: Overall, 22% up to 55% of the patients had cachexia according to different cachexia criteria: 34% were malnourished, 42% were at nutritional risk, and 39% were sarcopenic. Forty-four percent of the patients did not meet criteria for any of these conditions. Patients with cachexia defined by Cancer Cachexia Study Group (CCSG) had shorter survival in an unadjusted analysis, [Hazard ratio (HR) = 2.43; 95% confidence interval (CI) 1.32-4.47; P = 0.005]. After adjusting for nation, age and gender, cachexia (HR = 2.26; CI 1.18-4.32; P = 0.014) and malnutrition (HR = 1.83; CI 1.06-3.13; P = 0.029) remained significant predictors of survival. CONCLUSIONS: Nutritional depletion in up to 55% of the patients was found. The lack of concordance between the results obtained by different assessment criteria was obvious. CCSG's cachexia score was the best prognostic factor for overall survival.

Chemoradiotherapy of anal carcinoma: survival and recurrence in an unselected national cohort.

PURPOSE: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. METHODS AND MATERIAL: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. RESULTS: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. CONCLUSIONS: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

Adaptive brachytherapy of cervical cancer, comparison of conventional point A and CT based individual treatment planning.

BACKGROUND: Locally advanced cervical cancer is commonly treated with external radiation therapy combined with local brachytherapy. The brachytherapy is traditionally given based on standard dose planning with prescription of dose to point A. Dosimetric aspects when changing from former standard treatment to individualized treatment plans based on computed tomography (CT) images are here investigated. MATERIAL AND METHODS: Brachytherapy data from 19 patients with a total of 72 individual treatment fractions were retrospectively reviewed. Standard library plans were analyzed with respect to doses to organs at risk (OARs), and the result was compared to corresponding delivered individualized plans. The theoretical potential of further optimization based on prescription to target volumes was investigated. The treatments were performed with a Fletcher applicator. RESULTS: For standard treatment planning, the tolerance dose limits were exceeded in the bladder, rectum and sigmoid in 26%, 4% and 15% of the plans, respectively. This was observed most often for the smallest target volumes. The individualized planning of the delivered treatment gave the possibility of controlling the dose to critical organs to below certain limits. The dose was still prescribed to point A. An increase in target dose coverage was achieved when additional individual optimization was performed, while still keeping the dose to the OARs below predefined limits. Relatively low average target coverage, especially for the largest volumes was however seen. CONCLUSION: The individualized delivered treatment plans ensured that doses to OARs were within acceptable limits. This was not the case in 42% of the corresponding standard plans. Further optimized treatment plans were found to give an overall better dose coverage. In lack of MR capacity, it may be favorable to use CT for planning due to possible protection of OARs. The CT based target volumes were, however, not equivalent to the volumes described in magnetic resonance imaging (MRI) based recommendations. Prescription and assessment of dose, when introducing such target volumes, should be evaluated and preferably compared to well known treatment regimens.

Early effects of contemporary breast radiation on health-related quality of life - predictors of radiotherapy-related fatigue.

BACKGROUND AND PURPOSE: The aim of this study was to report on early effects of contemporary radiotherapy (RT) on health-related quality of life (HRQOL) and explore treatment-related contributors to the development of fatigue during RT in breast cancer (BC) patients. MATERIAL AND METHODS: Consecutive BC patients (n = 248) referred for postoperative RT at St. Olavs University Hospital in Trondheim, Norway were enrolled from February 2007 to October 2008. Clinical- and treatment data were recorded, and HRQOL were assessed before starting (baseline) and immediately after ending RT using the "EORTC QLQ-C30" and the breast module "EORTC QLQ-BR23". Change scores from baseline were calculated. Predictors of increased fatigue during RT were explored with multiple regression analysis adjusted for relevant confounders. RESULTS: The global QOL- and all functional scales remained stable, except for "future perspective" which improved significantly during RT. Breast symptoms and fatigue increased significantly during RT. Groups with elevated baseline fatigue remained more stable during RT than those with lower levels at baseline. The body volume receiving 40 Gy or more (V40) was a significant predictor of increased fatigue during RT adjusted for chemotherapy, comorbidity and age (p = 0.035). CONCLUSION: Contemporary RT has limited early effects on HRQOL. V40 is a significant predictor of RT-related fatigue.

Late side effects and quality of life after radiotherapy for rectal cancer.

PURPOSE: There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort (n = 535). METHODS AND MATERIALS: All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). RESULTS: Median time since surgery was 4.8 years. Radiation-treated (RT+) patients (n = 199) had increased bowel frequency compared with non-radiation-treated (RT-) patients (n = 336); 19% vs. 6% had more than eight daily bowel movements (p < 0.001). In patients without stoma, a higher proportion of RT+ (n = 69) compared with RT- patients (n = 240), were incontinent for liquid stools (49% vs. 15%, p < 0.001), needed a sanitary pad (52% vs. 13%, p < 0.001), and lacked the ability to defer defecation (44% vs. 16%, p < 0.001). Daily urinary incontinence occurred more frequently after radiotherapy (9% vs. 2%, p = 0.001). Radiation-treated patients had worse social function than RT- patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function (p < 0.001). CONCLUSIONS: Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer.

PURPOSE: Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate. PATIENTS AND METHODS: The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109). RESULTS: The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity. CONCLUSION: CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.

[Radiotherapy of rectal cancer]. / Strålebehandling av endetarmskreft.

BACKGROUND: Of the approximately 1,100 new cases of rectal cancer in Norway annually, many can be cured by surgery alone, but a large group of patients need supplemental treatment. We here present the national consensus for radiotherapy of rectal cancer. MATERIAL AND METHODS: This review is based on relevant publications up to April 2007, the authors' own research and clinical experiences, data from The Norwegian Colorectal Cancer Register and guidelines from The Norwegian Gastrointestinal Cancer Group. RESULTS AND INTERPRETATION: It is important to discuss these patients in multidisciplinary teams (surgeon, oncologist, radiologist and preferably pathologist). Indications for preoperative radiotherapy are T4-tumours, tumours independent of the T-stadium that threaten the mesorectal fascie (3 mm or less from the tumour) or a pathologic lymph node in mesorectum. The indication for postoperative radiotherapy is perioperative perforation of a tumour or a R1-resection, i.e. histologically verified circumferential resection margin less than 2 mm. The radiotherapy is given in 2 Gy fractions over 25 days concomitant with chemotherapy.

Proton therapy - a systematic review of clinical effectiveness.

BACKGROUND AND PURPOSE: Proton therapy is an emerging treatment modality for cancer that may have distinct advantages over conventional radiotherapy. This relates to its ability to confine the high-dose treatment area to the tumour volume and thus minimizing radiation dose to surrounding normal tissue. Several proton facilities are currently operating or under planning world-wide - in the United States, Asia and Europe. Until now no systematic review assessing the clinical effectiveness of this treatment modality has been published. MATERIALS AND METHODS: A systematic review of published studies that investigated clinical efficacy of proton therapy of cancer. RESULTS: We included 54 publications: 4 randomized controlled trials (RCTs) reported in 5 publications, 5 comparative studies and 44 case series. Two RCTs addressed proton irradiation as a boost following conventional radiation therapy for prostate cancer, where one demonstrated improved biochemical local control for the highest dose group without increased serious complication rates. Proton therapy has been used to treat a large number of patients with ocular tumours, but except for one low quality RCT, no proper comparison with other treatment alternatives has been undertaken. Proton therapy offers the option to deliver higher radiation doses and/or better confinement of the treatment of intracranial tumours in children and adults, but reported studies are heterogeneous in design and do not allow for strict conclusions. CONCLUSION: The evidence on clinical efficacy of proton therapy relies to a large extent on non-controlled studies, and thus is associated with low level of evidence according to standard heath technology assessment and evidence based medicine criteria.