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Background Radical treatment for oligometastatic non-small-cell lung cancer (NSCLC) has a curative potential for selected patients. The present retrospective study was designed to examine the relevance of synchronous vs. metachronous manifestations as a potential prognostic factor when ablative treatments are performed in oligometastatic disease. Methods Seventy-five patients with radically treated oligometastatic NSCLC were identified, of whom 39 presented with synchronous and 36 with metachronous metastatic manifestations. For patients with synchronous metastases, an additional therapy of the thoracic locoregional disease with a curative intent (either surgery or radiochemotherapy) was required. All patients with metachronous metastases had a documented remission of the primary tumor. Ablative treatment of the complete extent of oligometastatic disease consisted (as a minimum requirement) of either complete surgical resection or definitive ablative stereotactic radiotherapy. A comparative survival analysis of two groups of patients with oligometastatic NSCLC (synchronous vs. metachronous) and a complementary analysis of prognostic factors for the whole group of patients (by means of Cox regression analysis) was performed. Endpoints were median overall and progression-free survival (OS, PFS, respectively). Results Of the 75 patients, 57 presented with a solitary metastasis, in only 7 patients metastastatic lesions were present in ≥2 organs and 66 patients had a Karnofsky performance score (KPS) of 80 % or 90 %. The median follow-up was 54.0 months (95 % CI 28–81), the median OS 21.8 months (16.1–27.6) and the median PFS 13.7 months (9.7–17.6). In univariable Cox regression analysis, no single clinical factor was significantly associated with OS. For PFS both ‘metastatic involvement of ≥2 organs vs. 1 organ’ (hazard ratio (HR) 0.43, 0.23–0.83, p  = 0.012) and a ‘KPS of 90 % vs. 70–80 %’ (HR 4.32, 1.73–10.89, p  = 0.02) were significant prognostic factors as calculated by multivariable analysis. Comparing the cohorts with synchronous ( n  = 39) vs. metachronous oligometastases ( n  = 36), no differences in median OS and PFS were found. Both cohorts were well-balanced except for the KPS, which was significantly superior in patients with synchronous oligometastases. Conclusions Radical treatment of oligometastatic NSCLC was associated with acceptable long-term survival rates in patients with good KPS and it was equally effective for synchronous and metachronous manifestations.

Background Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC. Methods Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT. Results There was no significant difference regarding LD and tumor volume between MRI and CT ( p  ≥ 0.6221, respectively p  ≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 ( r  = 0.8750) and 12 months ( r  = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders. Conclusions DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.

PurposeRandomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regimePatients and methodsPatients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used.ResultsA total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment.ConclusionWe found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

Background We explored the interaction between the oral microbiome and the development of radiation‐induced mucositis in patients with head and neck squamous cell cancer (HNSCC) undergoing chemoradiotherapy (CRT). We prospectively studied the oral microbiome and compared it to healthy controls. Additionally, we compared patients with low‐grade (LGM) vs. high‐grade mucositis (HGM). Methods Ten HNSCC patients scheduled for CRT were included. Saliva samples were characterized prior to, during, and nine months after CRT using metagenomic sequencing. We similarly characterized samples from seven healthy controls. We assessed alpha and beta diversity and examined abundances at different taxonomic levels between (sub)groups. Results Patients exhibited significantly reduced alpha diversity compared to controls at all times (p ⟨ 0.05). Differential abundance of taxa between patients and controls was observed at baseline. In patients, the relative abundance of Staphylococcus aureus and Escherichia coli increased significantly during CRT. Capnocytophaga spp. was associated with the definitive CRT patients' subgroup. At baseline, two fungal families (Melampsoraceae and Herpotrichiellaceaea) were more abundant in patients who later developed HGM. No differentially abundant taxa were found between LGM vs. HGM during irradiation. Conclusion Our findings support the hypothesis that CRT, as well as HNSCC itself, influences the composition of the oral microbiome. Microbial markers found in patients who later developed HGM should be evaluated using independent cohorts to qualify their specific biomarker potential.

Ionizing radiation can lead to a variety of deleterious effects in humans, most importantly to the induction of cancer. DNA double-strand breaks (DSBs) are among the most significant genetic lesions introduced by ionizing radiation that can initiate carcino-genesis. We have enumerated γ-H2AX foci as a measure for DSBs in lymphocytes from individuals undergoing computed tomography examination of the thorax and/or the abdomen. The number of DSBs induced by computed tomography examination was found to depend linearly on the dose-length product, a radiodiagnostic unit that is proportional to both the local dose delivered and the length of the body exposed. Analysis of lymphocytes sampled up to 1 day postirradiation provided kinetics for the in vivo loss of γ-H2AX foci that correlated with DSB repair. Interestingly, in contrast to results obtained in vitro, normal individuals repair DSBs to background levels. A patient who had previously shown severe side effects after radiotherapy displayed levels of γ-H2AX foci at various sampling times postirradiation that were several times higher than those of normal individuals. γ-H2AX and pulsed-field gel electrophoresis analysis of fibroblasts obtained from this patient confirmed a substantial DSB repair defect. Additionally, these fibroblasts showed significant in vitro radiosensitivity. These data show that the in vivo induction and repair of DSBs can be assessed in individuals exposed to low radiation doses, adding a further dimension to DSB repair studies and providing the opportunity to identify repair-compromised individuals after diagnostic irradiation procedures.

Background The initial training of Radiation Oncology professionals can vary widely across Europe. The aim of this study was to assess the status and content of the initial training programs currently implemented in the Greater Region: Lorraine (Nancy, France), Saarland (Homburg, Germany), Luxembourg, and Liège (Wallonia, Belgium). Methods A survey was developed to investigate (1) the overall satisfaction, learning objectives, and teaching methods used during initial training programs and (2) the perceptions of the importance of key professional competencies as described by the CanMEDS (a framework that identifies and describes the abilities physicians require to effectively meet the health care needs of the people they serve). In addition, open-ended questions were used to elicit opinions on room for improvement. Participants ( N  = 38) were physicians (radiation oncologists (RO) seniors and residents) and radiation therapists (RTTs). Results Only 21.1% of the respondents declared having acquired all the competencies required for their professional practice during their initial training. Heterogeneity in teaching methods was noted within professional programs but there is no difference between those from RO and RTT in the teaching of technical and relational skills. Relational skills were not addressed in a range of 39.5–57.9% of respondent’s curricula. More practical lessons were deemed necessary to improve radiotherapy (RT) training programs. Conclusions Radiation oncology professionals expressed the need for more practical teaching, especially in the training of non-technical skills. Regarding the perceived importance of professional aptitudes, radiation oncology professionals highlighted medical and relational skills as the most important competencies.

Purpose53BP1 foci detection in peripheral blood lymphocytes (PBLs) by immunofluorescence microscopy (IFM) is a sensitive and quantifiable DNA double-strand break (DSB) marker. In addition, high-resolution transmission electron microscopy (TEM) with immunogold labeling of 53BP1 and DSB-bound phosphorylated Ku70 (pKu70) can be used to determine the progression of the DNA repair process. To establish this TEM method in the PBLs of patients with cancer, we analyzed and characterized whether different modes of irradiation influence the formation of DSBs, and whether accompanying chemotherapy influences DSB formation.MethodsWe obtained 86 blood samples before and 0.1, 0.5, and 24 h after irradiation from patients (n = 9) with head and neck or rectal cancers receiving radiotherapy (RT; n = 4) or radiochemotherapy (RCT; n = 5). 53BP1 foci were quantified by IFM. In addition, TEM was used to quantify gold-labelled pKu70 dimers and 53BP1 clusters within euchromatin and heterochromatin of PBLs.ResultsIFM analyses showed that during radiation therapy, persistent 53BP1 foci in PBLs accumulated with increasing numbers of administered RT fractions. This 53BP1 foci accumulation was not influenced by the irradiation technique applied (3D conformal radiotherapy versus intensity-modulated radiotherapy), dose intensity per fraction, number of irradiation fields, or isodose volume. However, more 53BP1 foci were detected in PBLs of patients treated with accompanying chemotherapy. TEM analyses showed that DSBs, indicated by pKu70, were present for longer periods in PBLs of RCT patients than in PBLs of RT only patients. Moreover, not every residual 53BP1 focus was equivalent to a remaining DSB, since pKu70 was not present at every damage site. Persistent 53BP1 clusters, visualized by TEM, without colocalizing pKu70 likely indicate chromatin alterations after repair completion or, possibly, defective repair.ConclusionIFM 53BP1 foci analyses alone are not adequate to determine individual repair capacity after irradiation of PBLs, as a DSB may be indicated by a 53BP1 focus but not every 53BP1 focus represents a DSB.

The study was designed to evaluate diffusion-weighted magnetic resonance imaging (DWI) vs. PET-CT of the thorax in the determination of gross tumor volume (GTV) in radiotherapy planning of non-small-cell lung cancer (NSCLC). Eligible patients with NSCLC who were supposed to receive definitive radio(chemo)therapy were prospectively recruited. For MRI, a respiratory gated T2-weighted sequence in axial orientation and non-gated DWI (b = 0, 800, 1,400 and apparent diffusion coefficient map [ADC]) were acquired on a 1.5 Tesla scanner. Primary tumors were delineated on FDG-PET/CT (stGTV) and DWI images (dwGTV). The definition of stGTV was based on the CT and visually adapted to the FDG-PET component if indicated (e.g., in atelectasis). For DWI, dwGTV was visually determined and adjusted for anatomical plausibility on T2w sequences. Beside a statistical comparison of stGTV and dwGTB, spatial agreement was determined with the \"Hausdorff-Distance\" (HD) and the \"Dice Similarity Coefficient\" (DSC). Fifteen patients (one patient with two synchronous NSCLC) were evaluated. For 16 primary tumors with UICC stages I (n = 4), II (n = 3), IIIA (n = 2) and IIIB (n = 7) mean values for dwGTV were significantly larger than those of stGTV (76.6 ± 84.5 ml vs. 66.6 ± 75.2 ml, p<0.01). The correlation of stGTV and dwGTV was highly significant (r = 0.995, p<0.001). Yet, some considerable volume deviations between these two methods were observed (median 27.5%, range 0.4-52.1%). An acceptable agreement between dwGTV and stGTV regarding the spatial extent of primary tumors was found (average HD: 2.25 ± 0.7 mm; DC 0.68 ± 0.09). The overall level of agreement between PET-CT and MRI based GTV definition is acceptable. Tumor volumes may differ considerably in single cases. DWI-derived GTVs are significantly, yet modestly, larger than their PET-CT based counterparts. Prospective studies to assess the safety and efficacy of DWI-based radiotherapy planning in NSCLC are warranted.

The recently implemented mARC-rotation-technique is capable to deliver high dose rate bursts. For the case of hypopharynx cancer plans we evaluate whether the mARC can achieve an advantage in treatment time in comparison to IMRT. These plans consider two arcs with flat and flattening filter free (FFF) beam energies. For 8 hypopharynx-cancer patients step-and-shoot-IMRT and mARC plans were created retrospectively using flat and FFF beam energy. The comparison of the plan scenarios considered measures of quality for PTV coverage and sparing of organs at risk. All plans were irradiated on an anthromorphic phantom equipped with thermoluminescent dosimeters to measure scattered dose and treatment times. A visual comparison of the dose distribution did not show a marked preference for either technique or energy. The statistical evaluation yielded significant differences in favor of the mARC technique and the FFF energy. Scattered dose could be decreased markedly by the use of the mARC technique. Treatment times could be reduced up to 3 minutes with the use of mARC in comparison to IMRT. The high dose rate energy results in another time advantage of about 1 minute. All four plan scenarios yielded equally good quality plans. A combination of the mARC technique with FFF 7 MV high dose rate resulted in a decrease of treatment times from about 9 minutes to 5-6 minutes in comparison to 6 MV IMRT.

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