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Abstract Background Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. Methods Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. Results The median accumulated dose was 1.9 Gy (1.5–2.2 Gy) to the hypothalamus and 2.4 Gy (1.8–3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0–9.3 Gy and 33.5–46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. Conclusion In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.

Abstract Background The aim of this treatment planning study was to investigate the potential advantages of intensity-modulated (IM) proton therapy (IMPT) compared with IM photon therapy (IMRT) in nasopharyngeal carcinoma (NPC). Methods Eight NPC patients were chosen. The dose prescriptions in cobalt Gray equivalent (GyE) for gross tumor volumes of the primary tumor (GTV-T), planning target volumes of GTV-T and metastatic (PTV-TN) and elective (PTV-N) lymph node stations were 72.6 GyE, 66 GyE, and 52.8 GyE, respectively. For each patient, nine coplanar fields IMRT with step-and-shoot technique and 3D spot-scanned three coplanar fields IMPT plans were prepared. Both modalities were planned in 33 fractions to be delivered with a simultaneous integrated boost technique. All plans were prepared and optimized by using the research version of the inverse treatment planning system KonRad (DKFZ, Heidelberg). Results Both treatment techniques were equal in terms of averaged mean dose to target volumes. IMPT plans significantly improved the tumor coverage and conformation (P < 0.05) and they reduced the averaged mean dose to several organs at risk (OARs) by a factor of 2–3. The low-to-medium dose volumes (0.33–13.2 GyE) were more than doubled by IMRT plans. Conclusion In radiotherapy of NPC patients, three-field IMPT has greater potential than nine-field IMRT with respect to tumor coverage and reduction of the integral dose to OARs and non-specific normal tissues. The practicality of IMPT in NPC deserves further exploration when this technique becomes available on wider clinical scale.

During fractionated radiotherapy, epithelial cell populations are thought to decrease initially, followed by accelerated repopulation to compensate cell loss. However, previous findings in skin with daily 1.1 Gy dose fractions indicate continued and increasing cell depletion. Here we investigated epidermal keratinocyte response with daily 2 Gy fractions as well as accelerated and hypofractionation. Epidermal interfollicular melanocytes were also assessed. Skin-punch biopsies were collected from breast cancer patients before, during and after mastectomy radiotherapy to the thoracic wall with daily 2 Gy fractions for 5 weeks. In addition, 2.4 Gy radiotherapy four times per week and 4 Gy fractions twice per week for 5 weeks, and two times 2 Gy daily for 2.5 weeks, were used. Basal keratinocyte density of the interfollicular epidermis was determined and immunostainings of keratinocytes for DNA double-strand break (DSB) foci, growth arrest, apoptosis and mitosis were quantified. In addition, interfollicular melanocytes were counted. Initially minimal keratinocyte loss was observed followed by pronounced depletion during the second half of treatment and full recovery at 2 weeks post treatment. DSB foci per cell peaked towards the end of treatment. p21-stained cell counts increased during radiotherapy, especially the second half. Apoptotic frequency was low throughout radiotherapy but increased at treatment end. Mitotic cell count was significantly suppressed throughout radiotherapy and did not recover during weekend treatment gaps, but increased more than threefold compared to unexposed skin 2 weeks post-radiotherapy. The number of melanocytes remained constant over the study period. Germinal keratinocyte loss rate increased gradually during daily 2 Gy fractions for 5 weeks, and similarly for hypofractionation. DSB foci number after 2 Gy irradiation revealed an initial radioresistance followed by increasing radiosensitivity. Growth arrest mediated by p21 strongly suggests that cells within or recruited into the cell cycle during treatment are at high risk of loss and do not contribute significantly to repopulation. It is possible that quiescent (G0) cells at treatment completion accounted for the accelerated post-treatment repopulation. Recent knowledge of epidermal tissue regeneration and cell cycle progression during genotoxic and mitogen stress allows for a credible explanation of the current finding. Melanocytes were radioresistant regarding cell depletion. [ABSTRACT FROM AUTHOR]

Background. When evaluating late toxicity after combined external beam radiation therapy (EBRT) and high-dose rate brachytherapy (HDR BT) prostate cancer treatments, it is important that the composite dose distribution is taken into account. This can be challenging if organ-at-risk (OAR) dose data are incomplete, i.e. due to a limited ultrasound imaging field-of-view in the HDR BT procedure. This work proposes a method that provides estimates of composite OAR doses for such situations. Material and methods. Original EBRT, simulated HDR BT, and composite dose-volume histograms (DVHs) for 10 pelvic OARs in 30 prostate cancer cases were used for method implementation and evaluation (EBRT: 25 × 2.0 Gy + BT: 2 × 10.0 Gy). The proposed method used information from the EBRT DVH to estimate OAR BT doses (with or without fractionation correction). Coefficients of determination (R2) were calculated for linear relationships between several EBRT DVH parameters and a BT DVH parameter of interest. The largest R2 value decided the relationship that best predicted the BT DVH parameter. The composite dose value was then calculated by adding the EBRT DVH and the estimated BT DVH parameter values and was compared to the reference composite value (in 1200 OAR/patient/parameter cases). Results. The linear relationships had an average R2 of 0.68 (range 0.42-0.88). Only one ninth of the 1200 estimated composite DVH values differed more than 2 Gy from their reference values. Conclusion. Given a successful implementation, the proposed method only requires original or simulated BT plan data for a subset of patients to estimate composite doses for large study populations in a time-efficient manner. This can assist in evaluating radiation-induced late toxicity in multimodality treatments with limited OAR dose data. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future. Material and methods. Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model. Results. The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs. Conclusions. In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom. [ABSTRACT FROM AUTHOR]

Background. For many tumour sites, external beam radiation therapy (EBRT) is delivered with a sequential two-phase treatment regime. Yet, there is a lack of consensus of how to add two different non-uniform dose distributions in order to evaluate the late radiation effect for normal tissue. The purpose of this novel investigation is to quantify the dose differences between non-corrected and fractionation-corrected combined non-uniform dose distributions. Material and methods. We used a model of an organ at risk (OAR) located in six different positions relative the treated volume giving 16 clinically representative two-phase treatment situations (46 Gy + 22 Gy). The linear-quadratic model was applied to correct for fractionation effects in each voxel before the doses were added. Dose differences were quantified using mean and maximum doses with corresponding fractionation-corrected doses as reference. Results. Non-corrected doses were higher than fractionation-corrected doses in all treatment situations (mean dose: p<0.001; maximum dose: p=0.003). With the OAR outside the treated volume, non-corrected doses were 3-6 Gy higher representing 10-50% of the reference dose (10-25 Gy); with the OAR included in the treated volume, 1-6 Gy higher representing 1-15% (30-60 Gy). Mean dose differences were generally larger than maximum dose differences. Conclusion. Substantial dose differences were present in all of the simulated treatment situations but more apparent when the OAR was located outside the treated volume in both phases. Our findings require verification in clinical cases but nevertheless indicate a need for fractionation-corrected doses in two-phase treatments both in the daily clinical routine as well as in the modelling of late radiation effects. Our data suggest that adjusting for fractionation effects would lead to lower tolerance doses than currently suggested, in particular for OARs with parallel tissue architecture. [ABSTRACT FROM AUTHOR]

In preparation for studies of dose volume of ionizing radiation and long-term side effects, we assessed both variation in position and volume of organs at risk in the small pelvis. Material and methods. On 10 men and seven women we delineated the sigmoid, rectum, anal sphincter, bladder, penile bulb, and cavernous bodies in two CT scans taken between five to 69 days apart. Results. The measured overlap of the two delineated volumes divided by the maximum possible overlap, was below 50% for the sigmoid in six of 17 patients, for the distal 4 cm of the sigmoid in five of 17 patients, for the rectum in none of 17 patients, for the anal sphincter in three of 17 patients and for the urinary bladder in none of 17 patients. The smaller volume divided by the larger volume was below 50% in three of 17 patients for the sigmoid, in six of 17 patients for the 4 distal cm of the sigmoid, in two of 17 patients for the rectum, in two of 17 patients for the anal sphincter and in seven of 17 patients for the urinary bladder. For the urinary bladder the largest deviation was found cranially, 4.0 cm (SD 2.0 cm), the caudal part being relatively fixed. For the rectum the largest deviation was found in the anterior wall, 1.8 cm (SD 0.7 cm), with maximum documented variation in cranial direction of 3.2 cm (SD 1.8 cm). Conclusions. The sigmoid varies considerably in documented position with the largest deviation anteriorly, the urinary bladder change in volume with the extension mainly located cranially and for the rectum the anterior wall is the most mobile with the distension becoming more pronounced cranially. In modeling dose-volume effects one may consider our results. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a rare disease in Sweden. For evaluation of the treatment outcomes in our NPC patients, 52 new cases that were referred to our department between 1991 and 2002 were retrospectively analysed. Tumor stage, according to the 1997 AJCC staging system, was I in five, II in ten, III in 12 and IV in 25 patients. Majority of the patients (87%) had World Health Organization type II-III tumors. Neoadjuvant chemotherapy was delivered in 33 patients. Thirty-two patients received hyperfractionated accelerated radiation therapy with a median dose of 64.6Gy (1.7Gy/fr bid). Conventional external irradiation with a median dose of 66Gy (2Gy/fr) was delivered to 18 patients. An intracavitary brachy-boost of 4.5-12Gy was delivered to 40 patients. Two patients were excluded from the analysis due to treatment refusal. For the patients with tumor stages I-IVB, the 5-year disease-free and overall survival rates were 61% and 55%, respectively. The 5-year local, regional, and distant relapse-free survival rates were 70%, 92% and 77%, respectively. The most frequent late side effects were xerostomia (98%), otitis (70%) and hearing deterioration (64%). Our data suggest that optimization of the treatment outcomes in NPC patients requires implementation of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The use of untraditional treatment modalities for external beam radiotherapy such as intensity modulated radiation therapy (IMRT) and proton beam therapy is increasing. This review focuses on the changes in the dose distribution and the impact on radiation related risks for long-term cancer survivors. We compare conventional radiotherapy, IMRT, and proton beam therapy based on published treatment planning studies as well as published measurements and Monte Carlo simulations of out-of-field dose distributions. Physical dose parameters describing the dose distribution in the target volume, the conformity index, the dose distribution in organs at risk, and the dose distribution in non-target tissue, respectively, are extracted from the treatment planning studies. Measured out-of-field dose distributions are presented as the dose equivalent as a function of distance from the treatment field. Data in the literature clearly shows that, compared with conventional radiotherapy, IMRT improves the dose distribution in the target volume, which may increase the probability of tumor control. IMRT also seems to increase the out-of-field dose distribution, as well as the irradiated non-target volume, although the data is not consistent, leading to a potentially increased risk of radiation induced secondary malignancies, while decreasing the dose to normal tissues close to the target volume, reducing the normal tissue complication probability. Protons show no or only minor advantage on the dose distribution in the target volume and the conformity index compared to IMRT. However, the data consistently shows that proton beam therapy substantially decreases the OAR average dose compared to the other two techniques. It is also clear that protons provide an improved dose distribution in non-target tissues compared to conventional radiotherapy and IMRT. IMRT and proton beam therapy may significantly improve tumor control for cancer patients and quality of life for long-term cancer survivors. [ABSTRACT FROM AUTHOR]

We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996–2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56–90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30–48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2–4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50–100 Gy. Mean gross tumour volume (GTV) was 39 cm 3 (2–436), and planning target volume was 101 cm 3 (11–719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1–107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3–4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (> v.s. [ABSTRACT FROM AUTHOR]

In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT) compliance with volume and dose prescriptions will be mandatory to avoid unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres participated. Each centre received CT-scans covering the whole lung volumes of two patients with instructions to follow the study protocol when outlining tumour and target volumes, prescribing doses and creating dose plans. Volumes and doses of the 12 dose plans were evaluated according to the study protocol. For the two patients the GTV volume range was 24 to 39&ThickSpace;cm 3 and 26 to 41&ThickSpace;cm 3 , respectively. The PTV volume range was 90 to 116&ThickSpace;cm 3 , and 112 to 155&ThickSpace;cm 3 , respectively. For all plans the margin between CTV and PTV in all directions followed in detail the protocol. The prescribed dose was for all centres 45&ThickSpace;Gy/3 fractions (isocentre dose about 66&ThickSpace;Gy). The mean GTV doses ranged from 63 to 67&ThickSpace;Gy and from 63 to 68&ThickSpace;Gy, respectively. The minimum doses for GTV were between 50–64&ThickSpace;Gy and between 55–65&ThickSpace;Gy, respectively. The dose distribution was conformed to PTV for 10 of 12 plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most of the volume and dose parameters for the participating centres showed fully acceptable compliance with the study protocol. [ABSTRACT FROM AUTHOR]

The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT). CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative. [ABSTRACT FROM AUTHOR]

Background and purpose: This is an investigation of a dose-based conjugated gradient optimization method (implemented in the CadPlan/Helios system) applied for head and neck tumours. Optimized field fluence distributions are created and transformed into dynamic multileaf collimator (MLC) movements. The aim was to gain knowledge about the influence of different parameters on the dose distribution and how to use the optimization algorithm in an optimum way.Material and methods: Parameters such as the number of beams, collimator angle and constraints and weight factors have been investigated. Dose escalation to the target volume, the target volume in the build-up region and the way of prescribing the target dose were also investigated. The dose distributions were mainly analysed with physical parameters.Results and conclusions: The optimization algorithm is well suited to create clinical Intensity modulated radiation therapy (IMRT) treatment plans for head and neck tumours even when the target volume is situated in the build-up region. The number of beams is a critical parameter and has a great influence on the dose distribution. The choice of collimator angles is not a critical parameter. The constraints and weight factors have a great influence on the dose distribution and varying these could easily control priorities regarding dose to the target volume or to the surrounding critical organs. Because of dose variations inside the target volume, prescribing to, normalizing to and reporting the mean dose in the target volume for IMRT treatment plans is preferable to the absorbed dose at a point, for example the isocentre point. [Copyright &y& Elsevier]

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and prospects were described by an expert group for each of nine major areas of radiation research. A summary of the investigation is presented in this report. A more extensive summary (in Swedish) can be found at www.Cancerfonden.se. It is concluded that radiation therapy plays an increasingly important role in curative and palliative tumour treatment and presents a considerable challenge to research. Several suggestions are made that could improve the possibilities for high-quality radiation therapy research in Sweden. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate normal tissue response by molecular markers to multifraction low doses of ionizing radiation, with the focus on changes in repopulation, estimated using Ki-67 as the proliferation marker, and on expressions of the p53 and p21 proteins, identified as key proteins in the DNA damage checkpoint. Repeated skin biopsies were taken from patients treated for prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the keratinocytes in the basal cell layer of the epidermis were quantified immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given five times per week for seven weeks. The indices of the three markers were determined over the whole period. A significant suppression of the Ki-67 index was observed during the first weeks, followed by a significant gradual increase in the Ki-67 index over the last weeks. The p53 and p21 protein levels were almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21 index increased in a pattern very congruent to the Ki-67 index. In conclusion, daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in the basal layer, a cell growth arrest for a couple of weeks and a subsequent acceleration in repopulation during the following weeks of irradiation. The present findings also provided novel insights into the role of the p53/p21 pathway in the response of a normal epithelium to ionizing radiation as it is applied in radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer. Methods: We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months. Results: We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2–14years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2–2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2–6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3–3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3–9.7). Conclusion: Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region. [Copyright &y& Elsevier]

Following induction of double strand breaks the histone H2AX is rapidly phosphorylated at regions flanking the breaks resulting in nuclear γH2AX foci. The purpose of this study was to use this endogenous signalling system to quantify the in vivo response to radiation in normal tissue.Skin biopsies were taken from prostate cancer patients undergoing radiotherapy with a curative intent. Biopsies were taken at locations corresponding to 5 different doses in the range below 1.1Gy per fraction. Biopsies were taken from patients 30min following the first fraction and then once again following the fraction given after the first weekend break in the treatment course. The DNA double strand breaks were visualised as γH2AX foci using immunohistochemistry. Images were acquired using a CCD-camera and a fluorescence microscope and the γH2AX foci were quantified using digital image analysis including the basic procedures of top-hat transformation, threshold setting and labelling.Repeated assessments of the biopsies showed a high reproducibility in quantifying the number of foci per DNA area of the nucleated cells in epidermis. The reproducibility was equally good for the two biopsy occasions. A linear dose response was observed for the epidermis in the dose region 0–1Gy.We have established a method to measure the relative amount of DNA double strand breaks by detecting γH2AX foci in patients exposed to radiotherapy. The method provides a tool to study induction and repair of DNA double strand breaks and has the potential to predict individual radiosensitivity. [Copyright &y& Elsevier]

Background and purpose: There is a general concern about intensity modulated radiation therapy (IMRT) treatments being more sensitive to patient positioning than conventional treatments. The aim of this study was to evaluate the International Commission on radiation units and measurements (ICRU) method for taking systematic set-up errors into account for IMRT treatments and to compare the effects on the dose distribution with the effects of conventional treatments.Material and methods: A planning margin to account for set-up errors was added to the clinical target volumes and to the spinal cords, for three head and neck patients, according to the ICRU. No margin was added to organs at risk with mainly parallel structure if they were situated adjacent to the target volume, for example, the parotid glands. The effects of set-up errors in six IMRT plans and three conventional plans were simulated in the planning system and analysed with physical dose parameters.Results and conclusions: In general, the ICRU method of taking set-up errors into account works satisfactorily for IMRT treatments as well as for conventional treatments with no difference between the treatment techniques. The sensitivity to set-up errors regarding the target volume is dependent on the quality of the treatment plan, i.e. the part of the target covered with a dose >95 and <105% and the effect in the critical organs is dependent on the sharpness of the dose gradients outside the critical organ. However, the method makes it difficult to include organs at risk with mainly parallel structure if they are situated adjacent to the target volume. [Copyright &y& Elsevier]

Background and purpose This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methods Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1–2, N0 glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms ( p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) ( p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16− tumours. Conclusion This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect. [ABSTRACT FROM AUTHOR]