Doses to the right coronary artery and the left anterior descending coronary artery and death from ischemic heart disease after breast cancer radiotherapy: a case-control study in a population-based cohort.

BACKGROUND AND PURPOSE: Doses to the coronary arteries in breast cancer (BC) radiotherapy (RT) have been suggested to be a risk predictor of long-term cardiac toxicity after BC treatment. We investigated the dose-risk relationships between near maximum doses (Dmax) to the right coronary artery (RCA) and left anterior descending coronary artery (LAD) and ischemic heart disease (IHD) mortality after BC RT. PATIENTS AND METHODS: In a cohort of 2,813 women diagnosed with BC between 1958 and 1992 with a follow-up of at least 10 years, we identified 134 cases of death due to IHD 10-19 years after BC diagnosis. For each case, one control was selected within the cohort matched for age at diagnosis. 3D-volume and 3D-dose reconstructions were obtained from individual RT charts. We estimated the Dmax to the RCA and the LAD and the mean heart dose (MHD). We performed conditional logistic regression analysis comparing piecewise spline transformation and simple linear modeling for best fit. RESULTS: There was a linear dose-risk relationship for both the Dmax to the RCA (odds ratio [OR]/Gray [Gy] 1.03 [1.01-1.05]) and the LAD (OR/Gy 1.04 [1.02-1.06]) in a multivariable model. For MHD there was a linear dose-risk relationship (1,14 OR/Gy [1.08-1.19]. For all relationships, simple linear modelling was superior to spline transformations. INTERPRETATION: Doses to both the RCA and LAD are independent risk predictors of long-term cardiotoxicity after RT for BC In addition to the LAD, the RCA should be regarded as an organ at risk in RT planning.

Epidermal Keratinocyte Depletion during Five Weeks of Radiotherapy is Associated with DNA Double-Strand Break Foci, Cell Growth Arrest and Apoptosis: Evidence of Increasing Radioresponsiveness and Lack of Repopulation; the Number of Melanocytes Remains Unchanged.

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.

Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7weeks of radiotherapy.

BACKGROUND AND PURPOSE: Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. MATERIALS AND METHODS: 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05-1.10Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies (n=452) were collected at 30min, and 2, 3, 24, and 72h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. RESULTS: HRS in keratinocytes was evidenced by the dose-response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3Gy, persistent foci could be observed even at 72h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose-response relationships. CONCLUSIONS: These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions.

Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial.

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) (1.1Gy+2Gy per day, 5days/week for 4.5weeks, total dose 68Gy) and conventional fractionation (CF) (2Gy per day, 5days/week for 7weeks, total dose 68Gy). 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 5years 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 5years 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.

Radiation Therapy to the Plexus Brachialis in Breast Cancer Patients: Analysis of Paresthesia in Relation to Dose and Volume.

PURPOSE: To identify volume and dose predictors of paresthesia after irradiation of the brachial plexus among women treated for breast cancer. METHODS AND MATERIALS: The women had breast surgery with axillary dissection, followed by radiation therapy with (n=192) or without irradiation (n=509) of the supraclavicular lymph nodes (SCLNs). The breast area was treated to 50 Gy in 2.0-Gy fractions, and 192 of the women also had 46 to 50 Gy to the SCLNs. We delineated the brachial plexus on 3-dimensional dose-planning computerized tomography. Three to eight years after radiation therapy the women answered a questionnaire. Irradiated volumes and doses were calculated and related to the occurrence of paresthesia in the hand. RESULTS: After treatment with axillary dissection with radiation therapy to the SCLNs 20% of the women reported paresthesia, compared with 13% after axillary dissection without radiation therapy, resulting in a relative risk (RR) of 1.47 (95% confidence interval [CI] 1.02-2.11). Paresthesia was reported by 25% after radiation therapy to the SCLNs with a V40 Gy ≥ 13.5 cm(3), compared with 13% without radiation therapy, RR 1.83 (95% CI 1.13-2.95). Women having a maximum dose to the brachial plexus of ≥55.0 Gy had a 25% occurrence of paresthesia, with RR 1.86 (95% CI 0.68-5.07, not significant). CONCLUSION: Our results indicate that there is a correlation between larger irradiated volumes of the brachial plexus and an increased risk of reported paresthesia among women treated for breast cancer.

A method to estimate composite doses for organs at risk in prostate cancer patients treated with EBRT in combination with HDR BT.

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.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

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/ß = 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.

Urethral pain among prostate cancer survivors 1 to 14 years after radiation therapy.

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.

Dose-response relationships for an atomized symptom of fecal incontinence after gynecological radiotherapy.

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.

Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region.

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.

The effect of air cavity size in cylindrical ionization chambers on the measurements in high-energy radiotherapy photon beams--an experimental study.

The present investigation is a continuation of a previous study on the effect of the diameter of the air cavity in cylindrical ionization chambers on perturbation correction factors. Measurements were made using high-energy radiotherapy photon beams (4, 6 and 15 MV) in a water phantom. Two different pairs of cylindrical ionization chambers were used. The chambers in each pair had identical materials and construction but different air cavity diameters. The same methods were employed as in our previous investigation. The diameter of the air cavity in cylindrical ionization chambers influences the mass ionization (the measured ionization expressed per unit mass of air in the chamber air cavity) at the depth where the maximum ionization is observed and a normalization at this depth is therefore not correct. The corrections obtained at depths of 50 and 100 mm in the phantom showed that the air cavity diameter in cylindrical ionization chambers has a greater effect on the perturbation effects than the photon beam quality. The corrections found at depths of 50 and 100 mm are smaller than those currently used in dosimetry protocols.

Relative importance of hip and sacral pain among long-term gynecological cancer survivors treated with pelvic radiotherapy and their relationships to mean absorbed doses.

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.

Long-term symptoms after radiotherapy of supraclavicular lymph nodes in breast cancer patients.

BACKGROUND AND PURPOSE: Irradiation of the supraclavicular lymph nodes has historically increased the risk of brachial plexopathy. We report long-term symptoms after modern radiotherapy (based on 3D dose planning) in breast cancer patients with or without irradiation of the supraclavicular lymph nodes. MATERIAL AND METHODS: We collected information from 814 women consecutively treated with adjuvant radiotherapy for breast cancer. The women had breast surgery with axillary dissection (AD) or sentinel node biopsy (SNB). The breast area was treated to 50 Gy in 2.0 Gy fractions. Women with >three lymph node metastases had regional radiotherapy (RRT) to the supraclavicular lymph nodes. Three to eight years after radiotherapy, they received a questionnaire asking about paraesthesia, oedema, pain, and strength in the upper limb. RESULTS: Paraesthesia was reported by 38/192 (20%) after AD with RRT compared to 68/505 (13%) after AD without RRT (relative risk [RR] 1.47; 95% confidence interval [CI] 1.02-2.11) and by 9/112 (8%) after SNB without RRT (RR 2.46; 95% CI 1.24-4.90). Corresponding risks adjusted for oedema (RR 1.28; 95% CI 0.93-1.76) and (RR 1.75; 95% CI 0.90-3.39). In women ≤ 49years with AD and RRT, 27% reported paraesthesia. No significant pain or decreased strength was reported after RRT. CONCLUSION: Radiotherapy to the supraclavicular lymph nodes after axillary dissection increases the occurrence of paraesthesia, mainly among younger women. When adjusted for oedema the contribution from radiotherapy is no longer formally statistically significant indicating that there is also an indirect effect mediated by the oedema.

Risk factors of developing long-lasting breast pain after breast cancer radiotherapy.

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.

Experimental investigation of the effect of air cavity size in cylindrical ionization chambers on the measurements in 6°Co radiotherapy beams.

In the late 1970s, Johansson et al (1978 Int. Symp. National and International Standardization of Radiation Dosimetry (Atlanta 1977) vol 2 (Vienna: IAEA) pp 243-70) reported experimentally determined displacement correction factors (p(dis)) for cylindrical ionization chamber dosimetry in 6°Co and high-energy photon beams. These p(dis) factors have been implemented and are currently in use in a number of dosimetry protocols. However, the accuracy of these factors has recently been questioned by Wang and Rogers (2009a Phys. Med. Biol. 54 1609-20), who performed Monte Carlo simulations of the experiments performed by Johansson et al. They reported that the inaccuracy of the p(dis) factors originated from the normalization procedure used by Johansson et al. In their experiments, Johansson et al normalized the measured depth-ionization curves at the depth of maximum ionization for each of the different ionization chambers. In this study, we experimentally investigated the effect of air cavity size of cylindrical ionization chambers in a PMMA phantom and 6°Co γ-beam. Two different pairs of air-filled cylindrical ionization chambers were used. The chambers in each pair had identical construction and materials but different air cavity volume (diameter). A 20 MeV electron beam was utilized to determine the ratio of the mass of air in the cavity of the two chambers in each pair. This ratio of the mass of air in each pair was then used to compare the ratios of the ionizations obtained at different depths in the PMMA phantom and 6°Co γ-beam using the two pairs of chambers. The diameter of the air cavity of cylindrical ionization chambers influences both the depth at which the maximum ionization is observed and the ionization per unit mass of air at this depth. The correction determined at depths of 50 mm and 100 mm is smaller than the correction currently used in many dosimetry protocols. The results presented here agree with the findings of Wang and Rogers' Monte Carlo simulations and show that the normalization procedure employed by Johansson et al is not correct.

Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer.

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 2-14 years). 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.

Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma--the ARTSCAN study.

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.

Pain and mean absorbed dose to the pubic bone after radiotherapy among gynecological cancer survivors.

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.

Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial.

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.