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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]

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]

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials in each of nine major areas of radiation therapy research were described by an expert group. The report presented here deals with radiation therapy dose delivery, dose distributions, beam shaping and intensity modulation. [ABSTRACT FROM AUTHOR]

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]

Abstract: Background and purpose: Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. Materials and methods: Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1–T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. Results: The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III–IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p =0.07) and for large tumours (T3–T4) (p =0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. Conclusion: Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated. [Copyright &y& Elsevier]

Purpose: To investigate how treatment-related and non-treatment-related factors impact urethral pain among long-term prostate cancer survivors. Methods and Materials: Men treated for prostate cancer with radiation therapy at the Sahlgrenska University Hospital in Göteborg, Sweden from 1993 to 2006 were approached with a study-specific postal questionnaire addressing symptoms after treatment, including urethral burning pain during urination (n=985). The men had received primary or salvage external-beam radiation therapy (EBRT) or EBRT in combination with brachytherapy (BT). Prescribed doses were commonly 70 Gy in 2.0-Gy fractions for primary and salvage EBRT and 50 Gy plus 2 × 10.0 Gy for EBRT + BT. Prostatic urethral doses were assessed from treatment records. We also recruited 350 non-pelvic-irradiated, population-based controls matched for age and residency to provide symptom background rates. Results: Of the treated men, 16% (137 of 863) reported urethral pain, compared with 11% (27 of 242) of the controls. The median time to follow-up was 5.2 years (range, 1.1-14.3 years). Prostatic urethral doses were similar to prescription doses for EBRT and 100% to 115% for BT. Fractionation-corrected dose and time to follow-up affected the occurrence of the symptom. For a follow-up ≥3 years, 19% of men (52 of 268) within the 70-Gy EBRT + BT group reported pain, compared with 10% of men (23 of 222) treated with 70 Gy primary EBRT (prevalence ratio 1.9; 95% confidence interval 1.2-3.0). Of the men treated with salvage EBRT, 10% (20 of 197) reported urethral pain. Conclusions: Survivors treated with EBRT + BT had a higher risk for urethral pain compared with those treated with EBRT. The symptom prevalence decreased with longer time to follow-up. We found a relationship between fractionation-corrected urethral dose and pain. Among long-term prostate cancer survivors, the occurrence of pain was not increased above the background rate for prostatic urethral doses up to 70 Gy3. [Copyright &y& Elsevier]

Purpose: To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose., Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models., Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months)., Conclusion: In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs., Methods and Materials: We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2-15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors., Results: Of the survivors, one in three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy., Conclusions: Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy., Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking., Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers., Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting breast pain compared to older women. Time since treatment may decrease the occurrence of pain., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors., Methods and Materials: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire., Results: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence., Conclusions: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Postoperative radiotherapy decreases the risk for local recurrence and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy., Material and Methods: Between 1991 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups., Results: For six symptom groups (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurrence after radiotherapy was observed for pain in the breast or in the skin, reported to occur "occasionally" by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p=0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p=0.001). Daily life and analgesic use did not differ between the groups., Conclusions: Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweigh the risk for long-term symptoms for most women., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT., Materials and Methods: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results., Results and Discussion: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations., Conclusions: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.

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 cm3 (2-436), and planning target volume was 101 cm3 (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.<55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials were described by an expert group for each of nine major areas of radiation therapy research. The present report deals with the potential of proton and light ion beams in radiotherapy.