<p>Grade ≥ 3 adverse events (28 patients)</p>

Top-25 probesets differentially expressed between irradiated (2Gy) and control (0Gy) lymphocytes.

Description of additional methods and procedures used in the study. Also includes Supplementary References.

<p>A CAMERA geneset test was performed to identify sets consisting of genes that are highly ranked in terms of differential expression upon irradiation relative to genes not in the set.</p>

<p>Differential response to irradiation between Grade 3 and Grade 0 patients for the probesets part of the HR geneset.</p>

Receiver operating characteristic (ROC) curve and foci decay ratios from our retrospective study ; Induction of gene expression upon irradiation calculated within each individual patient (indicated by the index on the x-axis) for three selected radiation-sensitive genes ; Enrichment of the set of 439 probesets included in the HALLMARK P53 PATHWAY geneset that was strongly induced upon irradiation ; Volcano plots for the comparison of response to irradiation between Grade 3, 2, 1 and Grade 0 patients ; Receiver operating characteristic curve for the mean log2 fold inductions of the HR geneset .

Differential response to irradiation between Grade 3 and Grade 0 patients for the probesets part of the NHEJ/BEJ geneset.

<p>Top-10 probesets with a different response to irradiation between the four patient groups.</p>

<p>Differential response to irradiation between Grade 3 and Grade 0 patients for the probesets part of the HR geneset.</p>

Abstract Severe late damage to normal tissue is a major limitation of cancer radiotherapy in prostate cancer patients. In a recent retrospective study, late radiation toxicity was found to relate to a decreased decay of γ-H2AX foci and reduced induction of DNA double-strand break repair genes. Here, we report evidence of prognostic utility in prostate cancer for γ-H2AX foci decay ratios and gene expression profiles derived from ex vivo–irradiated patient lymphocytes. Patients were followed ≥2 years after radiotherapy. Clinical characteristics were assembled, and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. No clinical factor was correlated with late radiation toxicity. The γ-H2AX foci decay ratio correlated negatively with toxicity grade, with a significant difference between grade ≥3 and grade 0 patients (P = 0.02). A threshold foci decay ratio, determined in our retrospective study, correctly classified 23 of 28 patients with grade ≥3 toxicity (sensitivity 82%) and 9 of 14 patients with grade 0 toxicity (specificity 64%). Induction of homologous recombination (HR) repair genes was reduced with increasing toxicity grade. The difference in fold induction of the HR gene set was most pronounced between grade 0 and grade ≥3 toxicity (P = 0.008). Notably, reduced responsiveness of HR repair genes to irradiation and inefficient double-strand break repair correlated with severe late radiation toxicity. Using a decay ratio classifier, we correctly classified 82% of patients with grade ≥3 toxicity, suggesting a prognostic biomarker for cancer patients with a genetically enhanced risk for late radiation toxicity to normal tissues after radiotherapy. Cancer Res; 77(6); 1485–91. ©2017 AACR.

Objective. The aim of this study is to investigate the impact of treatment policy changes in cervical cancer patients treated with adjuvant (chemo) radiotherapy.Methods. Between 1970 and 2007, 292 patients received adjuvant radiotherapy after a radical hysterectomy with pelvic lymphadenectomy for early stage cervical carcinoma. All patients received pelvic radiotherapy (40 Gy-46 Gy in 1.8 Gy-2 Gy/fraction). Vaginal vault brachytherapy boost (10-14 Gy) was increasingly used for patients with high-risk factors, and since 1993 systematically applied in patients with at least 2 of the 3 risk factors: adenocarcinoma, nodal involvement and parametrial invasion. Cisplatin-based chemotherapy was introduced in this group of patients from 2000.Results. The 5-year cumulative risk of local recurrence (CRLR) was 13% (95%CI 9%-17%), resulting in an overall 5-year survival (OS) of 78% (95%CI 83%-73%). Since 1970, the OR for the 5-year locoregional recurrence risk (LRR) decreased from 2.5 to 1.15 (linear-OR = -0.02/year). The OR for the 5-year mortality risk reduced from 2.2 in 1970 to 1.0 in 2007 (linear-OR = -0.03/year). The largest risk reductions were observed before 1990 with a minor rise after 2002. The risk of severe late toxicity reduced from 1.8% to 1.5% (linear-OR = -0.03/year). The addition of concomitant adjuvant chemotherapy since 2000 may have benefited a subgroup of patients with squamous cell carcinoma, but not the patients with adenocarcinoma, and after introduction of chemotherapy the risk of severe late toxicity tripled from 2% to 7%.Conclusion. Since 1970, tumour recurrence risk and mortality have decreased, as radiation dose increased. The potential benefit of concomitant adjuvant chemotherapy could not be demonstrated in this nonrandomized study. (C) 2014 Elsevier Inc. All rights reserved.

2nd ESTRO Forum 2013 S259 resulting in a very high anaerobic glycolytic rate.Despite the fact that squamous cell carcinomas have a higher 18 FDG-uptake, in general regarded as a poor prognostic factor, adenocarcinomas had a higher metastatic potential and a worse DFS.Therefore, the prognostic potential of 18 FDG-PET should be interpreted in relation to histology.

Ruim 400.000 mensen leven in Nederland met kanker. Jaarlijks wordt de ziekte bij 70.000 mensen gediagnosticeerd. De verwachting is dat de incidentie van kanker tot 2015 met 40% en de prevalentie met 90% zal toenemen. De perceptie van kanker als ziekte is veranderd in de laatste decennia. Kanker heeft een chronisch karakter gekregen en de prevalentie daarvan is vergelijkbaar met andere veel voorkomende chronische aandoeningen, zoals hart- en vaatziekten, diabetes, depressie, enzovoort.

The extent to which self-assessed work ability collected during treatment can predict return-to-work in cancer patients is unknown. In this prospective study, we consecutively included employed cancer patients who underwent treatment with curative intent at 6 months following the first day of sick leave. Work ability data (scores 0–10), clinical and sociodemographic data were collected at 6 months, while return-to-work was measured at 6, 12 and 18 months. Most of the 195 patients had been diagnosed with breast cancer (26%), cancer of the female genitals (22%) or genitourological cancer (22%). Mean current work ability scores improved significantly over time from 4.6 at 6 months to 6.3 and 6.7 at 12 and 18 months, respectively. Patients with haematological cancers and those who received chemotherapy showed the lowest work ability scores, while patients with cancer of urogenital tract or with gastrointestinal cancer had the highest scores. Work ability at 6 months strongly predicted return-to-work at 18 months, after correction for the influence of age and treatment (hazard ratio=1.37, CI 1.27–1.48). We conclude that self-assessed work ability is an important factor in the return-to-work process of cancer patients independent of age and clinical factors.

Methods: One hundred and fifty-eight patients were randomised to receive two courses of Gemcitabine (1250 mg/m(2) days 1, 8) and Cisplatin (75 mg/m(2) day 2) prior to, or daily low-dose Cisplatin (6 mg/m(2)) concurrent with radiotherapy, consisting of 24 fractions of 2.75 Gy in 32 days, with a total dose of 66 Gy.Results: Acute haematological toxicity grade 3/4 was more pronounced in the sequential (S) (30% versus 6%), oesophagitis grade 3/4 more frequent in the concurrent (C) arm (5% versus 14%). Late oesophagitis grade 3 was 4% (S and C), pneumonitis grade 3/4 14% (S) and 18% (C). Because of the poor power of the study no significant differences in median survival (MS), overall survival (OS) and progression-free survival (PFS) could be detected. MS was 16.2 (S) and 16.5 (C) months, 2-year OS was 34% (S) and 39% (C), 3-year OS was 22% (S) and 34% (C).Conclusion: Radiotherapy 66 Gy given concurrently with daily low-dose Cisplatin or after two courses of Gemcitabine/Cisplatin was well tolerated. Due to early closure no conclusions can be reached on the relative merits; both arms showed good OS. (c) 2006 Elsevier Ltd. All rights reserved.

The aim of this study was to investigate the improvement of quality of radiotherapy and compliance to the protocol amendment of EORTC study 08941. The radiotherapy-specific data were analysed from 154 patients with stage IIIA-N2 Non-Small-Cell Lung Cancer who were actually irradiated after response to 3 cycles of platinum-based induction chemotherapy. The parameters of quality, assessed in 93 patients before and in 61 after protocol amendment, included: time interval between last chemotherapy course and start of thoracic radiotherapy, the use of a 3-D planning CT, dose and fractionation scheme to the primary tumour, the involved and uninvolved mediastinum, duration of radiotherapy and toxicity. A significant improvement of all quality parameters was noted, except for the overall treatment time, which decreased slightly. Protocol amendment resulted in an improvement of the quality and the compliance of most observed parameters, at the cost of some increase in overall treatment time. The latter reflects logistical problems rather than poor compliance.