Systematic review and meta-analysis comparing surgical site infection in abdominal surgery between triclosan-coated and uncoated sutures.

PURPOSE: Surgical site infection (SSI) is a frequent complication after abdominal surgery and impacts morbidity, mortality and medical costs. This systematic review evaluates whether the use of triclosan-coated sutures for closing the fascia during abdominal surgery reduces the rate of SSI compared to uncoated sutures. METHODS: A systematic review and meta-analysis were conducted using the PRISMA guidelines. On February 17, 2024, a literature search was performed in Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Embase. Randomized controlled trials (RCTs) on abdominal fascial closure in human adults, comparing triclosan-coated and uncoated sutures, were included. The risk of bias was assessed using the Cochrane RoB 2 tool. Pooled meta-analysis was performed using RevMan. RESULTS: Out of 1523 records, eleven RCTs were included, with a total of 10,234 patients: 5159 in the triclosan-coated group and 5075 in the uncoated group. The incidence of SSI was statistically significantly lower in the triclosan-coated group (14.8% vs. 17.3%) with an odds ratio (OR) of 0.84 (95% CI [0.75, 0.93], p = 0.001). When polydioxanone was evaluated separately (coated N = 3999, uncoated N = 3900), triclosan-coating reduced SSI; 17.5% vs. 20.1%, OR 0.86 (95% CI [0.77; 0.96], p = 0.008). When polyglactin 910 was evaluated (coated N = 1160, uncoated N = 1175), triclosan-coating reduced the incidence of SSI; 5.4% vs. 7.8%, OR 0.67 (95% CI [0.48; 0.94], p = 0.02). CONCLUSION: According to the results of this meta-analysis the use of triclosan-coated sutures for fascial closure statistically significantly reduces the incidence of SSI after abdominal surgery with a risk difference of about 2%.

Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

BACKGROUND AND PURPOSE: Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. MATERIAL AND METHODS: Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. RESULTS: All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. INTERPRETATION: The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

Clinical decision rules for appendicitis are not used by surgeons in training: A survey.

BACKGROUNDS: We aimed to investigate surgeons in training knowledge of clinical decision rules (CDR) for diagnosing appendicitis and their attitudes toward implementing them. METHODS: We included surgeons in training practicing in East Denmark who independently could decide to perform a diagnostic laparoscopy for suspected appendicitis. The survey was developed in Research Electronic Data Capture and face-validated before use. It consisted of three parts: (1) the characteristics of the surgeons, (2) their diagnostic approach, and (3) their knowledge and attitude toward introducing CDR in the clinic. Data were collected in January 2023. RESULTS: We achieved 83 (90%) responses, and 52% of surgeons in training believed that appendicitis was difficult to diagnose. Their diagnostic approach mostly included symptoms and physical examinations for abdominal pain, and C-reactive protein. A total of 48% knew of at least one clinical decision rule, and 72% had never used a clinical decision rule. Regarding the necessity of CDR in clinical practice, surgeons in training options were divided into thirds: not needed, neither needed nor not needed, and needed. Surgeons in training indicated that CDR needed to be validated and easily applied before they would implement them. CONCLUSION: Approximately 3/4 of surgeons in training had never utilized a clinical decision rule to diagnose appendicitis, and only half knew of their existence. The symptoms and findings incorporated in most CDR aligned with their diagnostic approach. They were conflicted if CDR needed to be implemented in clinical practice.

Plan robustness evaluation strategies in whole-pelvic proton therapy for high-risk prostate cancer patients within a randomised clinical trial.

BACKGROUND: Inter-fractional anatomical changes challenge robust delivery of whole-pelvic proton therapy for high-risk prostate cancer. Pre-treatment robust evaluation (PRE) takes uncertainties in isocenter shifts and distal beam edge in treatment plans into account. Using weekly control computed tomography scans (cCTs), the aim of this study was to evaluate the PRE strategy by comparing to an off-line during-treatment robust evaluation (DRE) while also assessing plan robustness with respect to protocol planning constraints. MATERIAL AND METHODS: Treatment plans and cCTs from ten patients included in the pilot phase of the PROstate PROTON Trial 1 were analysed. Treatment planning followed protocol guidelines with 78 Gy to the primary clinical target volume (CTVp) and 56 Gy to the elective target (CTVe) in 39 fractions. Recalculations of the treatment plans were performed for a total of 64 cCTs and dose/volume measures corresponding to clinical constraints were evaluated for this DRE against the simulated scenario interval from the PRE. RESULTS: Of the 64 cCTs, 59 showed DRE CTVp measures within the robustness range from the PRE; this was also the case for 39 of the cCTs for the CTVe measures. However, DRE CTVe coverage was still within constraints for 57 of the 64 cCTs. DRE dose/volume measures for CTVp fulfilled target coverage constraints in 59 of 64 cCTs. All DRE measures for the rectum, bladder, and bowel were inside the PRE range in 63, 39, and 31 cCTs, respectively. CONCLUSION: The PRE strategy predicted the DRE scenarios for CTVp and rectum. CTVe, bladder, and bowel showed more complex anatomical variations than simulated by the PRE isocenter shift. Both original and recalculated nominal treatment plans showed robust treatment delivery in terms of target coverage.

Proton therapy planning and image-guidance strategies within a randomized controlled trial for high-risk prostate cancer.

The Danish Prostate Cancer Group is launching the randomized trial, PROstate PROTON Trial 1 (NCT05350475), that compares photons and protons to the prostate and pelvic lymph nodes in treatment of high-risk prostate cancer. The aim of the work described in this paper was, in preparation of this trial, to establish a strategy for conventionally fractionated proton therapy of prostate and elective pelvic lymph nodes that is feasible and robust. Proton treatments are image-guided based on gold fiducial markers and on-board imaging systems in line with current practice. Our established proton beam configuration consists of four coplanar fields; two posterior oblique fields and two lateral oblique fields, chosen to minimize range uncertainties associated with penetrating a varying amount of material from both treatment couch and patient body. Proton plans are robustly optimized to ensure target coverage while keeping normal tissue doses as low as is reasonably achievable throughout the course of treatment. Specific focus is on dose to the bowel as a reduction in gastrointestinal toxicity is the primary endpoint of the trial. Strategies have been established using previously treated patients and will be further investigated and evaluated through the ongoing pilot phase of the trial.

Treatment of postgestational rectus diastasis.

Rectus diastasis is defined by thinning and widening of linea alba and is a part of pregnancy. In some patients, the diastasis persists giving symptoms such as core instability, and cosmetic complaints. Treatment consists of exercise and surgery by either a plastic surgeon or a general surgeon. Lately, rectus diastasis has gained both national and international attention but it is not clear which patients will benefit from surgery or which operative technique has the best outcome. This review describes postgestational rectus diastasis and summarizes treatment possibilities based on the latest literature.

Towards range-guidance in proton therapy to detect organ motion-induced dose degradations.

Introduction.Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential ofrange guidanceusing water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT.Materials and methods. Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2-5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95% < 95%) using spatial agreement measures between the iso-WEPLs and isodoses in the pCT was evaluated.Results. The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65%-88% for a 2 mm threshold, 83%-96% for 3 mm, 90%-99% for 4 mm, and 94%-99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82%-100% sensitivity and 75%-80% specificity using a 2 mm Hausdorff threshold for the lateral fields.Conclusion. Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range.

Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients.

BACKGROUND: The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. MATERIAL AND METHODS: Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. RESULTS: The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5-3.4 Gy, 50 Gy) and 1.1 Gy (0.0-1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3-5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. CONCLUSION: This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.

A phase I/II study of acute and late physician assessed and patient-reported morbidity following whole pelvic radiation in high-risk prostate cancer patients.

BACKGROUND: The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial. MATERIAL AND METHODS: A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30. RESULTS: Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p < .05) at 60 months compared to baseline. CTCAE grade 2+ GU and sexual morbidity were unchanged. GU PROs on obstructive and irritative GU items (≥daily episode) increased during RT and normalized at 24 months. No clinically significant differences were found in sexual, hormonal, and QoL scores compared to baseline. CONCLUSIONS: Whole pelvic RT resulted in a mild to the moderate burden of late GI morbidities demonstrated by a relatively high prevalence of PROs. Whereas, physician-assessed morbidity revealed a low prevalence of late GI morbidity scores. This emphasizes the importance of using both PROs and physician-reported scoring scales when reporting late morbidity in clinical trials.

Androgen Deprivation Therapy Combined With Particle Therapy for Prostate Cancer: A Systematic Review.

PURPOSE: There is high-level evidence for addition of androgen deprivation therapy to photon-based radiotherapy of the prostate in intermediate- and high-risk prostate cancer. Little is known about the value of ADT in particle therapy of prostate cancer. We are conducting a systematic review on biochemical disease-free survival, overall survival, and morbidity after combined particle therapy and ADT for prostate cancer. METHODS: A thorough search in PubMed, Embase, Scopus, and Web of Science databases were conducted, searching for relevant studies. Clinical studies on prostate cancer and the treatment combination of particle therapy and androgen deprivation therapy were included. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD42021230801). RESULTS: A total of 298 papers were identified. Fifteen papers reporting on 7,202 patients after proton or carbon-ion therapy for localized prostate cancer where a fraction or all patients received ADT were selected for analysis. Three thousand five hundred and nineteen (49%) of the patients had received combined ADT and particle therapy. Primarily high-risk (87%), to a lesser extent intermediate-risk (34%) and low-risk patients (12%) received ADT. There were no comparative studies on the effect of ADT in patients treated with particles and no studies identified ADT as an independent prognostic factor related to survival outcomes. CONCLUSIONS: The review found no evidence to support that the effects on biochemical disease-free survival and morbidity of combining ADT to particle therapy differs from the ADT effects in conventional photon based radiotherapy. The available data on the topic is limited.

Development of a supervised exercise programme for immigrant women: Feasibility study of a practical intervention in a physiotherapy setting.

BACKGROUND: While Denmark is facing growing inequality between Danish women and immigrant women in relation to exercise and health, research on interventions and targeted exercise programmes is limited. This study aimed to test the feasibility of a physiotherapeutic supervised exercise programme for immigrant women. METHODS: Inspired by improvement research a programme was developed in cooperation with the immigrant women. The intervention was modified continuously according to the women's wishes and needs. INTERVENTION: Baseline focus-group interviews, completion of questionnaire and physical-strength tests, was followed by a 12-week supervised training period. After completion of the training the participants were re-interviewed and re-tested. RESULTS: Twenty-nine women were recruited to the training programme, and 10 attended follow-up. Mean body mass index was 34 kg/m2. Attendance rate among follow-up tested participants was 70%. The women gained knowledge about their bodies, a healthier lifestyle, and awareness of the importance of active living. CONCLUSION: It was possible to recruit and maintain immigrant women in the exercise programme. This study demonstrated the importance of involving the women in the process, and revealed important factors, such as privacy, a local setting and trust in the physiotherapists.

Anatomically robust proton therapy using multiple planning computed tomography scans for locally advanced prostate cancer.

BACKGROUND: Proton therapy (PT) is sensitive towards anatomical changes that may occur during a treatment course. The aim of this study was to investigate if anatomically robust PT (ARPT) plans incorporating patient-specific target motion improved target coverage while still sparing normal tissues, when applied on locally advanced prostate cancer patients where pelvic irradiation is indicated. MATERIAL AND METHODS: A planning computed tomography (CT) scan used for dose calculation and two additional CTs (acquired on different days) were used to make patient-specific targets for the ARPT plans on the eight included patients. The plans were compared to a conventional robust PT plan and a volumetric modulated arc therapy (VMAT) photon plan, which were derived from the planning CT (pCT). Worst-case robust optimisation was used for all proton plans with a setup uncertainty of 5 mm and a range uncertainty of 3.5%. Target coverage (V95% and D95%) and normal tissue doses (V5-75 Gy) were evaluated on 6-8 rCTs per patient. RESULTS: The ARPT plans improved the prostate target coverage for the most challenging patient compared to conventional robust PT plans (20% point increase for V95% and 31 Gy increase for D95%). Across the whole cohort the estimated mean value for V95% was 97% for the ARPT plans and 95% for the conventional robust PT plans. The ARPT plans had a slight, statistically insignificant increase in normal tissue doses compared to the conventional robust proton plans. Compared to VMAT, the ARPT plans significantly reduced the normal tissue doses in the low-to-intermediate dose range. CONCLUSIONS: While both proton plans reduced the low-to-intermediate normal tissue doses compared to VMAT, ARPT plans improved the target coverage for the most challenging patient without significantly increasing the normal tissue doses compared to conventional robust PT plans.

[Multidisciplinary treatment of acute iron poisoning due to suicide attempt].

Intentional iron overdoses have an insidious and potentially fatal clinical course. This is a case report of a young woman, who deliberately ingested 300 tablets ferrous fumarate 330 mg, i.e. 400 mg elementary iron per kg body weight. Plain abdominal radiographs showed a conglomerate of iron tablets in the ventricle. Treatment consisted of endoscopic removal of tablets, deferoxamine antidote treatment, and whole bowel irrigation with macrogol laxatives. Toxicological risk evaluation of intentional iron overdoses is necessary to timely effectuate life-saving multidisciplinary empiric treatments.

Schizophrenia is associated with increased risk of subsequent substance abuse diagnosis: A nation-wide population-based register study.

AIMS: We aimed to investigate whether or not a diagnosis of schizophrenia increases the risk of a substance abuse diagnosis. DESIGN: Prospective cohort study using a longitudinal study design. SETTING AND PARTICIPANTS: Individuals born in Denmark from 1955 to 1999 and registered in the Danish registers between 1 January 1968 and 1 July 2013. MEASUREMENTS: We investigated the associations between schizophrenia and ICD diagnoses of substance abuse, both established through various Danish registers. The Cox regression model was used and adjusted for calendar year, gender, urbanicity, co-abuse, other psychiatric diagnoses, parents' substance abuse and psychiatric history, parents' immigration and parents' socio-economic position. Individuals diagnosed with substance abuse less than a year after diagnosis of schizophrenia were classified as not diagnosed with schizophrenia. FINDINGS: The cohort consisted of 3 133 968 individuals. During follow-up (103 212 328 person-years at risk), a total of 14 007 individuals developed schizophrenia, with 2885 subsequently diagnosed with substance abuse. A diagnosis of schizophrenia was positively associated with the risk of developing substance abuse [hazard ratio (HR) = 3.69, 95% confidence interval (CI) = 3.56-3.83]. Additionally, adjusting for a co-abuse markedly affected the associations, making schizophrenia primarily associated with an increased risk of abuse of cannabis, alcohol, stimulants and other substances (adjusted HR = 2.48, 95% CI = 2.34-2.64 for cannabis; HR = 1.94, 95% CI = 1.87-2.02 for alcohol; HR = 1.77, 95% CI = 1.61-1.95 for stimulants; HR = 1.36, 95% CI = 1.20-1.54 for other substances). The association was still significant 10-15 years subsequent a diagnosis of schizophrenia (HR = 2.50, 95% CI = 2.26-2.76). CONCLUSIONS: In Denmark a diagnosis of schizophrenia is significantly associated with increased risk of subsequent diagnosis of substance abuse.

Inter-institutional analysis demonstrates the importance of lower than previously anticipated dose regions to prevent late rectal bleeding following prostate radiotherapy.

PURPOSE: To investigate whether inter-institutional cohort analysis uncovers more reliable dose-response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy. MATERIAL AND METHODS: Data from five institutions were used. Rectal dose-volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70-86.4 Gy@1.8-2.0 Gy/fraction were obtained, and corrected for fractionation effects (α/ß = 3 Gy). Cohorts with best-fit Lyman-Kutcher-Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose-response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability. RESULTS: Two cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts (n = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p = 0.0002; Hosmer-Lemeshow p-value, pHL = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p < 0.0001; pHL = 0.63), indicating a logistically shaped dose-response. CONCLUSION: We have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose-volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy.

Spatial rectal dose/volume metrics predict patient-reported gastro-intestinal symptoms after radiotherapy for prostate cancer.

BACKGROUND: Gastro-intestinal (GI) toxicity after radiotherapy (RT) for prostate cancer reduces patient's quality of life. In this study, we explored associations between spatial rectal dose/volume metrics and patient-reported GI symptoms after RT for localized prostate cancer, and compared these with those of dose-surface/volume histogram (DSH/DVH) metrics. MATERIAL AND METHODS: Dose distributions and six GI symptoms (defecation urgency/emptying difficulties/fecal leakage, ≥Grade 2, median follow-up: 3.6 y) were extracted for 200 patients treated with image-guided RT in 2005-2007. Three hundred and nine metrics assessed from 2D rectal dose maps or DSHs/DVHs were subject to 50-times iterated five-fold cross-validated univariate and multivariate logistic regression analysis (UVA, MVA). Performance of the most frequently selected MVA models was evaluated by the area under the receiving-operating characteristics curve (AUC). RESULTS: The AUC increased for dose-map compared to DSH/DVH-based models (mean SD: 0.64 ± 0.03 vs. 0.61 ± 0.01), and significant relations were found for six versus four symptoms. Defecation urgency and faecal leakage were explained by high doses at the central/upper and central areas, respectively; while emptying difficulties were explained by longitudinal extensions of intermediate doses. CONCLUSIONS: Predictability of patient-reported GI toxicity increased using spatial metrics compared to DSH/DVH metrics. Novel associations were particularly identified for emptying difficulties using both approaches in which intermediate doses were emphasized.

Validation of genetic predictors of late radiation-induced morbidity in prostate cancer patients.

INTRODUCTION: Normal tissue morbidity sets the dose limit for radiotherapy (RT) in cancer treatment and has importance for quality of life for cancer survivors. A previous study of prostate cancer patients treated with RT generated clinical data for radiation-induced morbidity measured by anorectal physiological methods and validated questionnaires. Other studies have identified genetic predictors associated with late radiation-induced morbidity outcome. We have expanded biobank material aiming to validate single nucleotide polymorphisms (SNPs) and a gene expression classifier with endpoints on patient-reported outcomes and biomechanical properties of the anorectum from our cohort matching originally published endpoints. MATERIALS AND METHODS: The present cohort of prostate cancer patients was treated with RT curative intent in 1999-2007. Nine SNPs associated with late radiation-induced morbidity were tested in 96 patients (rs2788612, rs1800629, rs264663, rs2682585, rs2268363, rs1801516, rs13035033, rs7120482 and rs17779457). A validated gene expression profile predictive of resistance to radiation-induced skin fibrosis was tested in 42 patients. An RT-induced anorectal dysfunction score (RT-ARD) served as a fibrosis-surrogate and a measure of overall radiation-induced morbidity. RESULTS: The lowest p-value found in the genotype analyses was for SNP rs2682585 minor allele (A) in the FSHR gene and the RT-ARD score with odds ratios (OR) = 1.76; 95% CI (0.98-3.17) p = .06, which was out of concordance with original data showing a protective effect of the minor allele. The gene expression profile in patients classified as fibrosis-resistant was associated with high RT-ARD scores OR 4.18; 95% CI (1.1-16.6), p = .04 conflicting with the hypothesis that fibrosis-resistant patients would experience lower RT-ARD scores. CONCLUSIONS: We aimed to validate nine SNPs and a gene expression classifier in a cohort of prostate cancer patients with unique scoring of radiation-induced morbidity. One significant association was found, pointing to the opposite direction of originally published data. We conclude that the material was not able to validate previously published genetic predictors of radiation-induced morbidity.

Late urinary morbidity and quality of life after radical prostatectomy and salvage radiotherapy for prostate cancer.

OBJECTIVE: There is a paucity of knowledge of long-term urinary morbidity in patients treated for prostate cancer (PCa) with radical prostatectomy (RP) and salvage radiotherapy (SRT). Improved long-term survival calls for heightened awareness of late effects from radiotherapy after RP. The purpose of this study was to assess late urinary morbidity and its potential impact on quality of life (QoL) in patients treated with RP plus SRT compared with patients treated with RP alone. MATERIALS AND METHODS: Long-term morbidity and QoL were evaluated using a cross-sectional design with validated questionnaires in urinary morbidity [Danish Prostatic Symptom Score (DAN-PSS)] and QoL [European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)]. Included were a total of 227 patients treated with SRT and 192 treated with RP in the periods 2006-2010 and 2005-2007, respectively. RESULTS: Weak stream, straining, frequency and nocturia were significantly more prevalent in patients treated with RP + SRT than in patients treated with RP alone. Patients treated with RP + SRT generally suffered from more severe urinary symptoms. The QoL scores of the two treatment groups were not statistically significantly different, but a high level of urinary morbidity was significantly related to decreased QoL (p = 0.000). CONCLUSIONS: Patients treated with SRT have a higher rate of urinary morbidity than do patients treated with RP alone. Severe urinary morbidity was significantly related to decreased QoL, but did not differ between the two treatment groups.

Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient-reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose. MATERIALS AND METHODS: Data were taken from two Scandinavian studies (N=207/276) including men treated with external-beam RT (EBRT) to 78/70Gy (2Gy/fraction; median time-to-follow-up: 3.6-6.4y). Within and across cohorts, bladder dose-volume parameters were tested as predictors for GU symptom domains identified from two study-specific questionnaires (35 questions on frequency, incontinence, obstruction, pain, urgency, and sensory symptoms) using univariate and multivariate logistic regression analysis (MVA) with 10-fold cross-validation. Performance was evaluated using Area Under the Receiver Operating Characteristic Curve (Az). RESULTS: For the identified Incontinence (2-5 symptoms), Obstruction (3-5 symptoms), and Urgency (2-7 symptoms) domains, MVA demonstrated that bladder doses close to the prescription doses were the strongest predictors for Obstruction (Az: 0.53-0.57) and Urgency (Az: 0.60). For Obstruction, performance increased for the across cohort analysis (Az: 0.61-0.64). CONCLUSIONS: Our identified patient-reported GU symptom domains suggest that high urinary bladder doses, and increased focus on both obstruction and urgency is likely to further add to the understanding of GU tract RT responses.

Salvage radiation therapy following radical prostatectomy. A national Danish study.

BACKGROUND: The purpose of this observational cohort study was to evaluate the outcome and prognostic factors following salvage radiotherapy (SRT) in a consecutive national cohort. MATERIAL AND METHODS: Between 2006 and 2010, 259 patients received SRT in Denmark. Patient- and cancer-related characteristics were retrospectively retrieved from patient charts. The primary end point was biochemical progression-free survival (b-PFS). RESULTS: At the end of follow-up, 51% of the patients displayed a prostate-specific antigen (PSA) level <0.1 ng/ml. The three-year b-PFS rate for the total cohort was 57.0%. Nearly half of the patients (44%) received androgen deprivation therapy (ADT) in combination with SRT. Positive surgical tumour margins (p = 0.025) and ADT (p = 0.001) were the only markers independently correlated with b-PFS. In patients who received SRT without ADT, both a pre-SRT PSA level ≤0.5 ng/ml (p = 0.003) and pathological tumour stage T1-T2 (p = 0.036) independently correlated with b-PFS. Moreover, a duration between radical prostatectomy (RP) and SRT ≤29 months (p = 0.035) independently correlated with b-PFS in patients treated with ADT in combination with RT. CONCLUSIONS: In patients treated for biochemical failure after RP, positive surgical tumour margins and PSA levels ≤0.5 ng/mL at the time of SRT were associated with a favourable outcome. Despite less favourable tumour characteristics, patients receiving SRT and ADT demonstrated improved b-PFS, and in particular, patients with PSA levels >0.2 ng/ml benefitted from additional ADT.