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  • 1
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; MODEL ; MODELS ; THERAPY ; CT ; IMAGES ; VOLUME ; POPULATION ; RISK ; RISKS ; TISSUE ; radiation ; INDUCTION ; PROTON ; AGE ; chemotherapy ; SWEDEN ; BEAM ; treatment planning ; TARGETS ; CHILDREN ; IMRT ; proton therapy ; CHILDHOOD ; CRANIOSPINAL IRRADIATION ; DOSE DISTRIBUTIONS ; intensity ; SURVIVORS ; SOCIETY ; 3D ; complication ; CT images ; BEAMS ; CHILDHOOD MEDULLOBLASTOMA ; 2ND MALIGNANT NEOPLASMS ; PEDIATRIC TUMORS
    Abstract: Aim. The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy ( IMET) and proton therapy (IMPT). Material and methods. CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Results. Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. Conclusion. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative
    Type of Publication: Journal article published
    PubMed ID: 16165914
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  • 2
    Keywords: IRRADIATION ; radiotherapy ; tumor ; Germany ; MODEL ; THERAPY ; CT ; DISEASE ; liver ; TISSUE ; TUMORS ; radiation ; TIME ; RAT ; TOLERANCE ; TRIAL ; RADIATION-THERAPY ; INDUCED HEPATIC-INJURY ; animal model ; INTRAOPERATIVE RADIATION-THERAPY ; LIVER-TUMORS
    Abstract: Background: A focal reaction of the liver is radiologically seen after stereotactic high dose radiotherapy of liver tumors. The histological counterpart of this reaction should be clarified using an animal model. Materials and Methods: Six New Zealand white rabbits were positioned on a special stereotactic set-up. Parts of the liver (1.5 - 8 ml) were irradiated with either 20 - 24 Gy/80% (n = 3) or 36 Gy/80% (n = 3). The animals were followed by CT examination up to 2 years after radiotherapy. Finally, the animals were sacrificed and the liver macroscopically and microscopically inspected. Results: No focal reaction could be observed in any liver at any time by CT examination. The liver macroscopically and microscopically showed no changes 6 months or 2 years after radiotherapy. Conclusion: Up to a single dose of 36 Gy/80%, rabbits seem to show no focal tissue reaction after high dose radiation therapy of small parts of the liver
    Type of Publication: Journal article published
    PubMed ID: 16982551
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  • 3
    Keywords: PROSTATE ; DIAGNOSIS ; COHORT ; SURGERY ; HEALTH ; NATIONWIDE ; EUROPEAN-ORGANIZATION ; PERSISTENCE ; EORTC QLQ-C30 ; Mastectomy
    Abstract: Abstract Background. Breast cancer survivors may experience adverse effects of cancer and/or treatment years after completion of therapy, which can considerably decrease quality of life (QoL). Little is known about the time course of QoL in breast cancer survivors beyond the fifth year post-diagnosis, when routine follow-up care has usually terminated. We therefore explored in detail whether and to what extent restrictions in breast cancer survivors persist and whether changes or aggravations in QoL occurred over time. Material and methods. QoL was assessed 1, 3, 5, and 10 years post-diagnosis in a population-based cohort of initially 387 female breast cancer patients from Saarland (Germany), using the EORTC QLQ-C30 and QLQ-BR23. Time course of QoL over 10 years post-diagnosis was assessed for survivors and survivors' QoL was compared cross-sectionally to the German general population after adjustment for age. Results. A total of 182 out of 238 patients alive (76.5%) responded in the 10-year, 160 patients (67.2%) participated in all follow-ups. Although breast cancer survivors and controls reported comparable general health and overall QoL, survivors reported significantly more restrictions on most functioning and symptom scales at each follow-up. Detriments in various QoL dimensions (e.g. physical and social functioning; pain, financial difficulties) aggravated from year 5 to 10. Generally, restrictions were largest for the youngest survivors. Conclusion. Relevant restrictions in QoL persist over years in breast cancer survivors and affect predominantly younger women. The aggravation of restrictions in QoL beyond the fifth year may indicate deficits in health care and psychosocial support of breast cancer patients after completion of routine follow-up care.
    Type of Publication: Journal article published
    PubMed ID: 23514583
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  • 4
    Keywords: neoplasms ; POPULATION ; PERFORMANCE ; UPDATE ; colonoscopy ; OCCULT BLOOD-TESTS ; ADENOMA DETECTION ; AVERAGE RISK ; CUTOFF LEVELS
    Abstract: Background. Faecal immunochemical tests (FITs) for haemoglobin are increasingly used for non-invasive screening for colorectal cancer (CRC) but large scale comparative studies of different FITs for detection of CRC, overall and by stage, are sparse. We aimed to determine and compare performance of different FITs for the detection of CRC, and to assess their stage-specific sensitivities. Material and methods. We assessed sensitivity, specificity and their corresponding 95% confidence intervals for six qualitative FITs among 74 CRC cases (59% stage I or II cancers) and 1480 controls free of colorectal neoplasm. Overall and stage-specific receiver operating characteristic curves were derived for three quantitative FITs. The areas under the curves (AUCs) were calculated and compared. Results. Pairs of overall sensitivity and specificity of the qualitative FITs ranged from 66% and 96% to 92% and 62%, respectively. For the three quantitative tests, AUCs ranged from 0.90 to 0.92, with sensitivities ranging from 80% to 87% at cut-offs yielding 90% specificity. AUCs ranged from 0.85 to 0.92, 0.94 to 0.96, and 0.86 to 0.93 for stage I, stage II and advanced stages (stage III and IV) cancers, respectively. At a specificity of 90%, the tests detected 65%-85% of stage I cancers. Conclusion. The diagnostic performance of FITs regarding detection of CRC is promising, even though the pre-defined cut-offs of some of the qualitative FITs need to be adjusted to limit false-positive rates in screening setting. At cut-off levels yielding 90% specifi city, the quantitative tests detected the vast majority of CRCs, even at early stages.
    Type of Publication: Journal article published
    PubMed ID: 23617541
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  • 5
  • 6
    Keywords: VOLUME ; HEAD ; NECK-CANCER ; GUIDANCE ; DEFORMABLE IMAGE REGISTRATION ; GUIDED RADIOTHERAPY ; CONE-BEAM CT ; ADAPTIVE RADIATION-THERAPY ; CONTOUR PROPAGATION ; CORRECTION STRATEGIES
    Abstract: Background. To present a new method that determines an optimised IGRT couch correction vector from a displacement vector field (DVF). The DVF is computed by a deformable image registration (DIR) method. The proposed method can improve the quality of volume-of-interest (VOI) alignment in image guided radiation therapy (IGRT), and can serve as a decision-making aid for re-planning. Material and methods. The proposed method was demonstrated using the CT data sets of 11 head-and-neck cancer patients with daily kilovoltage control-CTs. A DVF was computed for each control-CT using a DIR method. The DVF was used for voxel tracking and re-contouring of the VOIs in the control-CTs. Then a rigid body transformation, which could be used as couch correction vector, was optimised. The aim of the optimisation process was to find a vector and rotations that map the deformed VOIs into a specified territory. This territory was defined by a margin extension of the VOIs at the time of the planning process. Within this extension, VOI motion and deformation was tolerated. The objective function in the optimisation process was the sum of all volume fractions outside the defined territories. Results. The proposed method was able to find a correction vector, which resulted in a coverage of the target volumes of at least 98% in 52.3% of all fractions. In contrast, a standard IGRT correction using a rigid registration method only fulfilled this criterion in 22.6% of all fractions. The optimisation process took an average of 1.5 minutes per fraction. Conclusion. The knowledge of the deformation of the anatomy allows the determination of an optimised rigid correction vector using our method. The method ensures controlled mapping of the VOIs despite small deformations. If no optimised vector can be determined, re-planning should be considered. Thus, our method can also serve as a decision-making aid for re-planning.
    Type of Publication: Journal article published
    PubMed ID: 23614778
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  • 7
    Keywords: MORTALITY ; POPULATION ; COUNTRIES ; UNITED-STATES ; TRENDS ; EUROPE ; PERIOD ANALYSIS ; TESTICULAR CANCER ; UP-TO-DATE
    Abstract: Background. Following restoration of political independence in 1990, Lithuania underwent rapid societal and economic changes. We aimed to assess trends in cancer survival in the first two decades following these changes. Material and methods. We used population-based data from the Lithuanian Cancer Registry and period analysis techniques to examine trends in one-, 2-5- and five-year relative survival between 1995-1999 and 2005-2009 for 24 common cancers in Lithuania. Results. Between 1995-1999 and 2005-2009, five-year relative survival increased significantly for 20 of 24 cancers, and for 10 cancers the increase exceeded 10% units. Five-year relative survival estimates reached 46%, 69% and 91% for colorectal, breast and prostate cancer in 2005-2009, respectively, while patients with testicular cancer, Hodgkin's or non-Hodgkin's lymphoma had a five-year relative survival of 77%, 75% and 50%, respectively. Conclusion. We found a rapid increase in survival for most forms of common cancers in Lithuania between 1995 and 2009. Nevertheless, several cancers with effective therapies exhibit considerable gaps compared with Northern and Western European countries. Despite ongoing rises in survival, mortality declines are not yet manifesting for important common cancers such as breast and colorectal cancer. Rapid incidence rises suggest that increases in survival for prostate and thyroid cancers are massively influenced by early detection-related effects. Improving the availability of effective therapies, and carefully planned early detection programs may help to increase cancer survival in Lithuania in the future.
    Type of Publication: Journal article published
    PubMed ID: 24669773
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  • 8
    Keywords: THERAPY ; FLUOROURACIL ; OXALIPLATIN ; PROGRESSION-FREE SURVIVAL ; METASTATIC COLORECTAL-CANCER ; LEUCOVORIN ; CETUXIMAB PLUS IRINOTECAN ; PLACEBO-CONTROLLED PHASE-2 ; DIFFERENT SCHEDULES ; III NONINFERIORITY
    Abstract: Abstract Purpose. To evaluate progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) as potential surrogate endpoints (SEP) for overall survival (OS) in second-line treatment for metastatic colorectal cancer (mCRC). Methods. A systematic literature search of randomised trials of second-line chemotherapy for mCRC reported from January 2000 to July 2013 was performed. Correlation coefficients weighted by number of patients in the treatment arms between median PFS, ORR and DCR with median OS were estimated. Results. Twenty-three trials reflecting 10 800 patients met the inclusion criteria. Median PFS and OS across all trials were 4.5 months and 11.5 months and median ORR and DCR were 11.4% and 65%, respectively. PFS showed moderate correlation with OS [RPFS = 0.73; 95% confidence interval (CI) 0.61-0.82]. In contrast, ORR only weakly correlated with OS (RORR = 0.58; 95% CI 0.38-0.72, n = 22). Despite a small number of studies (n = 10) reporting on DCR, moderate correlation with OS was observed (RDCR = 0.74; 95% CI 0.56-0.86). Conclusion. Based on the available trial-level data, PFS may serve as an appropriate SEP in second-line chemotherapy for mCRC. A small number of studies revealed moderate correlation of DCR with OS that justifies further investigation.
    Type of Publication: Journal article published
    PubMed ID: 25017379
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  • 9
    Abstract: BACKGROUND: To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. MATERIALS AND METHODS: For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (NTCPIMXT-Mix) were calculated. RESULTS: Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, NTCPIMXT-Mix values were a factor 2-10 smaller than NTCPIMXT-IMPT. Assuming a threshold of 〉/= 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, NTCP 〉/= 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. CONCLUSIONS: The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.
    Type of Publication: Journal article published
    PubMed ID: 26340301
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  • 10
    Abstract: BACKGROUND: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial. MATERIAL AND METHODS: FMISO PET/CT was performed four hours post-injection in 22 patients with advanced HNSCC in a phase II FMISO dose escalation study. PET background regions of interest (ROIs) were manually defined in deep neck muscles. TBRmax was calculated as the mean of the highest-valued voxels within the high risk RT planning target volume. Its predictive power with respect to local control was tested, classifying patients using median TBRmax as threshold. The influence of systematically varying quantification between institutions was studied in silico by applying offsets of +/- 10% and +/- 20% to the TBRmax of all patients, while the threshold remained constant. The effect was analyzed using a receiver operating characteristic (ROC). True positive and false positive rates (TPR/FPR) as well as positive and negative predictive values (PPV/NPV) were evaluated. RESULTS: For the reference condition without an offset the median TBRmax was 2.0 (1.4-3.5). Patients were classified using this threshold and TPR = 0.7, FPR = 0.4, PPV = 0.5 and NPV = 0.8 were observed. Accuracy declined with increasing offsets. Negative offsets of -10% and -20% resulted in TPR = 0.43 and 0.14, FPR = 0.20 and 0.13, PPV = 0.50 and 0.33 and NPV = 0.75 and 0.68, respectively. Positive offsets of + 10% and + 20% resulted in TPR = 1.00 and 1.00, FPR = 0.53 and 0.67, PPV = 0.47 and 0.41 and NPV = 1.00 and 1.00, respectively. CONCLUSIONS: Using a common pre-defined TBRmax threshold in multicenter trials requires careful standardization and harmonization of all steps from patient preparation to image analysis. Our results indicate that TBRmax should deviate less than 10% from reference conditions (absolute value in this dataset +/- 0.2). This conclusion likely applies to all low contrast nitroimidazole hypoxia PET tracers.
    Type of Publication: Journal article published
    PubMed ID: 26481464
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